insulin--isophane and Diabetes-Mellitus--Type-1

To compare the safety and efficacy of insulin detemir versus neutral protamine Hagedorn (NPH) in pregnant women with diabetes.. MEDLINE, CENTRAL, Google Scholar databases, and ClinicalTrials.gov registry were searched from inception to December 2021 to identify randomized controlled trials (RCTs) concerning adult women with singleton pregnancies, gestational or pregestational diabetes, and the need for insulin therapy. A systematic review and a meta-analysis (weighted data, random-effects model) were performed. Continuous outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) (inverse variance method); dichotomous outcomes were expressed as risk ratio (RR) with 95% CI (Mantel-Haenszel method). Heterogeneity was quantified using the I. Insulin detemir was associated with less maternal hypoglycemic events and decreased risk for prematurity compared with NPH insulin. More research should be conducted to reach a safe conclusion about the optimal insulin regimen for women with diabetes in pregnancy.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Protamines; Randomized Controlled Trials as Topic

To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM).. Systematic review and individual patient data (IPD) network meta-analysis (NMA).. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through June 2015.. Randomised controlled trials (RCTs) on adults with T1DM assessing glycosylated haemoglobin (A1c) and severe hypoglycaemia in long-acting and intermediate-acting insulin regimens.. We requested IPD from authors and funders. When IPD were not available, we used aggregate data. We conducted a random-effects model, and specifically a one-stage IPD-NMA for those studies providing IPD and a two-stage IPD-NMA to incorporate those studies not providing IPD.. We included 28 RCTs plus one companion report, after screening 6680 titles/abstracts and 205 full-text articles. Of the 28 RCTs, 27 studies provided data for the NMA with 7394 participants, of which 12 RCTs had IPD on 4943 participants. The IPD-NMA for A1c suggested that glargine once daily (mean difference [MD]=-0.31, 95% confidence interval [CI]: -0.48 to -0.14) and detemir once daily (MD=-0.25, 95% CI: -0.41 to -0.09) were superior to neutral protamine Hagedorn (NPH) once daily. NPH once/two times per day improved A1c compared with NPH once daily (MD=-0.30, 95% CI: -0.50 to -0.11). Results regarding complications in severe hypoglycaemia should be considered with great caution due to inconsistency in the evidence network. Accounting for missing data, there was no evidence of inconsistency and long-acting insulin regimens ranked higher regarding reducing severe hypoglycaemia compared with intermediate-acting insulin regimens (two-stage NMA: glargine two times per day SUCRA (Surface Under the Cumulative Ranking curve)=89%, detemir once daily SUCRA=77%; one-stage NMA: detemir once daily/two times per day SUCRA=85%). Using multiple imputations and IPD only, complications in severe hypoglycaemia increased with diabetes-related comorbidities (regression coefficient: 1.03, 95% CI: 1.02 to 1.03).. Long-acting insulin regimens reduced A1c compared with intermediate-acting insulin regimens and were associated with lower severe hypoglycaemia. Of the observed differences, only glargine once daily achieved a clinically significant reduction of 0.30%. Results should be interpreted with caution due to very low quality of evidence.. CRD42015023511.

Topics: Adult; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Network Meta-Analysis

People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020.. We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM.. Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument.. We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-cert. Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.

Topics: Adolescent; Adult; Bias; Child; Child, Preschool; Confidence Intervals; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Myocardial Infarction; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Young Adult

To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes).. We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily.. The absolute changes in HbA. In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA

Topics: Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Network Meta-Analysis; Practice Guidelines as Topic

Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities.. A systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed.. Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and they generally were of moderate quality with bias in the studies.. There was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.

Topics: Blood Glucose; Brazil; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Patient Satisfaction; Quality of Life

Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia. Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings.

Topics: Alanine Transaminase; Blood Glucose; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Liver; Polyethylene Glycols; Treatment Outcome; Triglycerides; Weight Loss

The costs of the insulin analogue (insulin glargine) have been growing appreciably in the State of Minas Gerais in Brazil, averaging 291% per year in recent years. This growth has been driven by an increasing number of successful law suits and a 536% price difference between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One potential way to address this is to undertake a systematic review assessing the efficacy and safety of insulin glargine analogue compared with NPH insulin in patients with type 1 diabetes mellitus (T1DM), and, as a result, provide published data to support future recommended activities by the State of Minas Gerais. These could include maintaining it on the list of the Public Health System (SUS) provided there is a price reduction. Alternatively, the review could provide potential arguments to defend against future law suits should the authorities decide to delist insulin glargine.. A systematic review of published studies researching the effectiveness of insulin glargine in patients with T1DM between January 1970 and July 2009 in MEDLINE (PubMed), the Latin American and Caribbean Centre on Health Sciences Information, the Cochrane Controlled Trials Databases and the National Health Service Centre for Reviews and Dissemination. Inclusion criteria included insulin glargine on its own or combined with other insulin formulations. Only randomised controlled clinical trials were included. Initially, the titles of all studies were assessed by two independent reviewers before being potentially discarded, with the quality of papers assessed using a modified Jadad scale. The outcome measures included blood levels of glycated haemoglobin, episodes of hypoglycaemia, adverse effects and the reduction of microvascular and macrovascular end-organ complications of T1DM.. Out of 803 studies found in the selected databases, only eight trials met the inclusion criteria. Most of the studies were of poor methodological quality or had a high risk of bias, with a mean score of 2.125 on the Jadad scale. No study could be classified as double-blind, and only one study documented the increased efficacy of insulin glargine in relation to both glycaemic control and hypoglycaemic episodes. Typically, there was no significant difference between insulin glargine and NPH insulins.. This systematic review showed no therapeutic benefit of insulin glargine over other insulin formulations studied when analysing together glycaemic control and the frequency and severity of hypoglycaemia. We therefore recommend to the State Authority to delist insulin glargine or renegotiate a price reduction with the manufacturer. This systematic review provides support for this decision as well as documentation to combat potential law suits if discussions are unsatisfactory.

Topics: Brazil; Diabetes Mellitus, Type 1; Drug Costs; Drug Evaluation; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Prescription Fees; Randomized Controlled Trials as Topic

Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes. The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy. Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes. However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman's diabetes is well controlled with human insulin. There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended. Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control. A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia. The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin. There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Randomized Controlled Trials as Topic; Treatment Outcome

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Randomized Controlled Trials as Topic; Weight Gain

During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Off-Label Use; Pregnancy; Pregnancy in Diabetics

Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue.. Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed.. Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (-0.13; -0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01].. The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia.

Topics: Adolescent; Adult; Body Mass Index; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic

The purpose of this study was to review studies reporting on quality of life and treatment satisfaction of patients with diabetes mellitus being treated with long-acting insulin analogues.. A systematic literature search was made of trials published between January 1, 2000 and June 28, 2007. Retrieved studies were analysed, using predefined inclusion criteria as well as methodological and quality aspects.. Twelve studies were included, all of them dealing with insulin glargine as the trial drug or for comparison. With regard to treatment satisfaction, insulin glargine was superior in one head-to-head comparison with NPH (neutral protamine Hagedorn) and one head-to-head comparison with NPH as an add-on to oral glimepiride. There was no difference in comparisons with continuous subcutaneous insulin infusion (CSII), insulin aspart or exenatide. Regarding health related quality of life (HRQoL), insulin glargine was shown to be superior to rosiglitazone as an add-on to metformin and sulfonylurea. Again, there were no differences in comparisons with NPH, CSII or exenatide.. There are only a limited number of high quality studies showing that insulin glargine is superior regarding treatment satisfaction and HRQoL of patients with diabetes mellitus. There are fewer publications with good evidence of patient-reported outcomes than those reporting well-established outcomes using HbA1c levels or the incidence of hypoglycaemia.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Exenatide; Humans; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Patient Satisfaction; Peptides; Quality of Life; Venoms

Recent epidemiological studies suggest that treatment with insulin glargine (A21Gly,B31Arg,B32Arg human insulin) may promote cancer growth. The present meta-analysis was performed to assess the risk of cancer during treatment with insulin detemir (B29Lys(epsilon-tetradecanoyl),desB30 human insulin), another long-acting insulin analogue.. This meta-analysis was performed in a population of 8,693 patients with type 1 or type 2 diabetes, who were included in Novo Nordisk-sponsored, randomised and controlled diabetes trials of at least 12 weeks in duration that compared insulin detemir with NPH insulin or insulin glargine. In a blinded manner, the adverse events with suspected treatment-emergent malignant tumours were obtained from these studies under three system-organ classes: 'Neoplasms benign, malignant and unspecified (including cysts and polyps)', 'Neoplasm' and 'Surgical and medical procedures'. Conditional ORs were estimated applying both the Mantel-Haenzel and Peto methods to ensure robustness of results.. Separate analyses were performed for trials comparing insulin detemir with NPH insulin and insulin detemir with insulin glargine. In the first analysis, 16 studies were included with a total of 3,983 patients treated with insulin detemir and 2,661 patients treated with NPH insulin. In the second analysis, five studies were included with a total of 1,219 patients treated with insulin detemir and 830 patients treated with insulin glargine. The estimated OR for a cancer diagnosis between NPH insulin and insulin detemir was statistically significantly >1, with the ratio favouring insulin detemir. There was a more than twofold higher cancer occurrence in the NPH insulin-treated population. For the insulin detemir comparison with insulin glargine, there was a non-significant difference in ORs in favour of insulin detemir.. In these randomised controlled diabetes trials, patients treated with insulin detemir had a lower or similar occurrence of a cancer diagnosis compared with patients treated with NPH insulin or insulin glargine, respectively.

Topics: Adult; Aged; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic

Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire to novel preventive measures of, severe hypoglycaemia. Our studies confirm that severe hypoglycaemia is still a major clinical problem in type 1 diabetes. The individual susceptibility to severe hypoglycaemia is highly varying and conventional risk factors - with major contribution from hypoglycaemia unawareness - only account for a limited part of this variation. Results from a case-series suggest that the use of psychoactive substances may be as significant as alcohol for promotion of risk of severe hypoglycaemia - a finding which needs to be confirmed by case-control studies. We identified elevated renin-angiotensin system activity as a novel predictor of risk of severe hypoglycaemia in type 1 diabetes with potential clinical significance. Thus, three sequential renin-angiotensin system-related risk factors were associated with severe hypoglycaemia, and by including these factors in a common model both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin-angiotensin system activity to maintain cognitive function during hypoglycaemia. The clinical implications of this finding which, however, must await additional independent confirmation, include prediction and possibly some prevention of severe hypoglycaemia. An evaluation of renin-angiotensin system activity may - together with assessment of other risk factors - contribute to rational individualized setting of glycaemic targets and thereby open for prevention of severe hypoglycaemia. Furthermore, s

Topics: Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Renin-Angiotensin System; Risk Factors

Type 1 diabetes mellitus is associated with acute and long-term complications, to which pre- and postprandial hyperglycemia are independent contributors. The objective of this review was to evaluate evidence-based information using biphasic insulin aspart 30 in the treatment of type 1 diabetes mellitus.. The study reviewed the Cochrane Database and scientific literature (PubMed) published until January 2008 using the words biphasic insulin aspart 30 insulin or premixed aspart insulin.. Biphasic insulin aspart 30 is similar in efficacy to biphasic human insulin in improving hemoglobin A(1c) levels, with the advantage of a better postprandial glucose profile.. There is evidence supporting the efficacy and safety of biphasic insulin aspart 30 insulin. However, the need for well-designed clinical trials aimed at understanding the potential differences in safety and efficacy between patients with type 1 and type 2 diabetes is crucial.

Topics: Biphasic Insulins; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Randomized Controlled Trials as Topic

The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells.

Topics: Adolescent; Child, Preschool; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Time Factors; Young Adult

A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA(1c), hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia -- particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Randomized Controlled Trials as Topic

This analysis first modeled the interaction between hypoglycemia and glycosylated hemoglobin (HbA1c) in clinical trials that compared insulin glargine (glargine) with human neutral protamine Hagedorn insulin (NPH) in patients with type 1 or type 2 diabetes mellitus. The model was then used to compare rates of hypoglycemia associated with use of these insulins.. Patient-level data from all randomized Phase III/IV clinical trials sponsored by the manufacturer of glargine that compared glargine and NPH and were available in May 2004 were included in the model. In addition, MEDLINE, EMBASE, and BIOSIS were searched for comparative randomized controlled trials of glargine and NPH using the terms insulin glargine, HOE 901, neutral protamine Hagedorn insulin, and NPH insulin. Studies were excluded from the analysis if patient-level data were not available. Unadjusted rates of symptomatic, confirmed, and severe hypoglycemia were compared with those derived from negative binomial regression analysis, which stratified the results by HbA1c at end point (with last observation carried forward), treatment, and duration of diabetes. In addition, the analysis was stratified by Phase III studies (which focused on determining tolerability and efficacy before regulatory approval) and Phase IV studies (which compared the clinical efficacy of the 2 insulins). The first month of the study was not included in the analysis because of continual adjustment of the insulin dose and maintenance of previous NPH in some studies.. Eleven sponsored randomized trials were included in the model (total of 5074 patients). Four other sponsored trials were not included because the databases were not finalized, and 3 investigator-initiated trials were not included because patient-level data were unavailable. Rates of hypoglycemia had a curvilinear relationship with HbAlc, increasing at lower end-point HbAlc values. In combined analyses of the studies of type 1 and type 2 diabetes, unadjusted rates of hypoglycemia were lower for glargine than NPH: 6.1% lower for all symptomatic hypoglycemia, 21.6% lower for confirmed hypoglycemia, and 23.9% lower for severe hypoglycemia (all, P < 0.05). When modeled using the negative binomial distribution with end-point HbA1c as a covariate, the corresponding results were 9.1% (P < 0.05), 26.6% (P < 0.001), and 30.0% (P = 0.08), respectively. When only Phase IV trials were analyzed, the relative reductions with glargine were 16.2% (P < 0.01), 40.8% (P < 0.01), and 46.8% (P < 0.05). The results of the separate analyses of studies of type 1 and type 2 diabetes were comparable.. Based on the results of this analysis, calculated unadjusted hypoglycemia event rates appear to underestimate the differences between glargine and NPH. In most of the present analyses, unadjusted rates were significantly lower with glargine than NPH. Adjustment for end-point HbA1c resulted in greater relative reductions in the risk of hypoglycemia for glargine compared with NPH. The adjusted risk reduction with glargine was highest in the Phase IV studies.

Topics: Binomial Distribution; Blood Glucose; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Models, Statistical; Randomized Controlled Trials as Topic; Treatment Outcome

Basal insulin therapy is an integral part of the intensive management of type 1 diabetes and it is also often used in type 2 diabetes. An ideal insulin regimen in patients with diabetes would mirror the 24-h insulin profile of a non-diabetic person, thereby preventing hyperglycaemia without inducing hypoglycaemia. Until recently, available insulins have pharmacokinetic disadvantages, compared to physiological insulin secretion. Insulin detemir is a new basal insulin analogue recently available for commercial use in the UK. Clinical trials have demonstrated lower fasting plasma glucose levels, lower variability in plasma glucose, predictable action profile and a reduced risk of nocturnal hypoglycaemia and weight gain, compared to conventional basal insulins. This study reviews the properties and potential use of insulin detemir.

Topics: Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir are reviewed.. Insulin detemir is a long-acting, neutral, and soluble insulin analogue with a lower within-subject variability of fasting plasma glucose levels than isophane insulin human (NPH insulin) and insulin glargine. The lower within-subject variability of insulin detemir may decrease hypoglycemic events, especially nocturnal events, and may contribute to a decreased incidence of weight gain. In vivo, insulin detemir is 98-99% bound to albumin-one of the mechanisms contributing to its long duration of action. Several open-labeled, randomized, multicenter trials have been conducted comparing the safety and efficacy of insulin detemir to NPH insulin in patients with type 1 or type 2 diabetes mellitus. In most trials, patients were randomized to receive insulin on three different dosing schedules: basal insulin twice daily before breakfast and at bedtime, basal insulin at 12-hour intervals, or basal insulin before breakfast and dinner. Mealtime insulin was given as part of the basal-bolus therapy. Glycosylated hemoglobin values were similar in patients receiving insulin detemir or NPH insulin. Insulin detemir appears to be well tolerated. The most common adverse effects reported during clinical trials were hypoglycemia, headache, dizziness, and injection-site reactions.. Insulin detemir given once or twice daily as part of basal-bolus insulin therapy is at least as effective as NPH insulin in maintaining overall glycemic control in adult patients with type 1 or type 2 diabetes mellitus.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes between meals and overnight as well as postprandially. The most frequently used insulin for basal therapy is the intermediate-acting neutral protamin Hagedorn (NPH) insulin, although it does not correspond to a physiological profile. Insulin glargine is a new extended-action recombinant insulin analog, which is absorbed slowly into the bloodstream, reaching peak action in about 4 h and maintaining this concentration profil for 24-30 h. Some studies demonstrated that insulin glargine reduces the incidence of hypoglycemia and is at least as effective as NPH insulin given once or twice daily. It is equally effective administered before breakfast, dinner or at bedtime. Similar absorption rates were recorded after subcutaneous injection in differents part of body. The continuous subcutaneous insulin infusion utilizing an external insulin infusion pump (CSII) is one approach to intensive insulin therapy. Some studies indicate that pump therapy is associated with improved glycemic control compared with traditional insulin therapies and with significant decreases in frequency of both mild and severe hypoglycemic episodes. The author summarizes the indication, the effect and side effects of pump therapy.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting

Insulin treated diabetic patients have often to contend with variability in the action of injected insulin and to some unpredictibility in glycemic control. The variability in blood glucose control seems particularly important with long-acting insulins. Insulin detemir belongs to a new class of non-crystalline form of long-acting insulin analogs. Absorption of insulin detemir is dependent on neither appropriate resuspension before injection and dissolution of crystals in the subcutaneous tissue, as is the case for NPH insulin, nor on formation and dissolution of microprecipitates, as is the case for insulin glargine. In euglycemic glucose clamp studies, insulin detemir was associated with significantly less within-subjects variability for the pharmacodynamic endpoints than both NPH insulin and insulin glargine. Three, up to 6 months trials, carried out in patients with type 1 diabetes have shown that the day-to-day within-subject variations in plasma glucose were significantly lower with insulin detemir than with human NPH insulin. Similar results have been reported in patients with type 2 diabetes. Nightly 8-h plasma glucose recordings showed a smoother and more stable profile with insulin detemir than with NPH insulin. In patients with type 1 diabetes the combination of insulin detemir with mealtime insulin aspart, a fast-acting insulin analog, provides a smoother and more stable profile with lower post-prandial plasma glucose levels that the combination of NPH insulin with regular human insulin before each meal. In several trials, the risk of hypoglycemia, particularly of nocturnal hypoglycemia, was significantly lower with insulin detemir than with NPH insulin. In conclusion insulin detemir offers a better reproducibility as compared with other basal insulins, reduces the risk of hypoglycemia, and may lead the patients to titrate their insulin doses more easily and therefore to achieve more often glycemic objectives. The combination of rapid- and long-acting insulin analogs reproduces a more physiological insulin secretion and thereby reduces the risk of hypoglycemia and improves the overall 24-h glycemic profile.

Topics: Blood Glucose; Circadian Rhythm; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Reproducibility of Results

Biphasic insulin aspart 30 (BIAsp 30 [30% soluble, rapid-acting insulin aspart and 70% protamine-bound insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark), a premixed insulin analogue, addresses both the prandial and basal aspects of glucose regulation when used once or twice daily in patients with type 1 or type 2 diabetes. It provides overall glycemic control similar to biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin) in patients with type 1 or type 2 diabetes.. The aim of this review was to evaluate the safety profile associated with BIAsp 30 in patients with type 1 or type 2 diabetes versus that of comparator insulin products, including BHI 30 and biphasic insulin lispro 25 (Mix 25 [25% biphasic insulin lispro and 75% protaminated lispro], Humalog Mix 75/25, Eli Lilly and Company, Indianapolis, Indiana), together with the basal insulins, including NPH insulin and insulin glargine (Lantus, Sanofi-Aventis Pharmaceuticals, Paris, France).. Data from human clinical studies published in peer-reviewed journals or as conference proceedings that reported safety results in patients with type 1 or type 2 diabetes who were treated with BIAsp 30 versus comparator insulins were evaluated. To locate the appropriate articles, a MEDLINE search was performed for all years up to February 2005, using the following key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin. Additional papers were identified by examining the reference lists in these papers as well as our own personal reference files. Results from 17 publications were analyzed. The analysis included >2600 patients with type 2 diabetes (mean [range] age, 58 [36-70] years; duration of diabetes, 11.8 [9-17] years; and baseline glycosylated hemoglobin [HbA1c], 8.6% [7.5%-9.9%]). It also included 104 patients with type 1 diabetes (mean [range] age, 44.5 [30-58] years; duration of diabetes, 16 [2-30] years; and baseline HbA1c, 8.4% [7.2%-10.4%]).. Hypoglycemia occurred in 43% to 57% of patients receiving BIAsp 30 versus 32% to 57% of patients receiving BHI 30 and 28% of patients receiving NPH insulin. Major hypoglycemic events were uncommon in most studies; but when they did occur, they were reported less frequently in patients receiving BIAsp 30 (2%-8% of patients) than in patients receiving BHI 30 (2%-14% of patients). Furthermore, patients treated with BIAsp 30 were at lower risk of experiencing minor nocturnal hypoglycemia than patients receiving comparator insulin; in 1 study, the relative risk (BIAsp 30 vs BHI 30) was calculated to be 0.63 (95% CI, 0.37 to 1.09). The adverse event (AE) profile, weight gain during treatment, and formation of cross-reactive antibodies were not different between BIAsp 30 and BHI 30. AEs were reported in 36% to 90% of patients receiving BIAsp 30, 38% to 88% of patients receiving BHI 30, and 51% of patients receiving Mix 25. The use of oral antidiabetic drugs in combination with BIAsp 30 did not alter the safety profile of BIAsp 30.. The flexible and convenient treatment regimen offered by BIAsp 30, together with its ability to improve postprandial glucose control, is associated with a safety profile comparable to that of BHI 30 and NPH insulin, with a lower risk of major and nocturnal hypoglycemic events.

Topics: Adult; Aged; Biphasic Insulins; Clinical Trials as Topic; Cross Reactions; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Randomized Controlled Trials as Topic; Weight Gain

Insulin pump therapy enjoys a steadily growing number of users and is associated with an approximately 0.5% lower A1c as compared to flexible insulin injection therapy in type 1 diabetes patients. An important question is whether superiority of insulin pump therapy persists in the era of rapid acting analogs and will persist in the era of long acting analogs. Pooled data of three randomized clinical trials using rapid acting analogs in both arms shows a 0.35% lower A1c when on the pump. Treatment effect was shown to be larger in those with higher baseline A1c's. Results of three trials comparing insulin pump therapy with regimens consisting of both rapid acting and long acting analogs are inconsistent, probably indicating the advantage of pump therapy at group level is likely to have become relatively small. Therefore, the challenge for the treatment team is to identify those patients who benefit most from insulin pump treatment. Poor glycemic control merits a trial of insulin pump therapy in the motivated patient. Other indications for insulin pump therapy include the need for several basal rates, a life style characterized by unpredictable physical activity and patient preference.

Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin, Isophane; Insulin, Regular, Pork

The prescription of insulin glargine has increased in Sweden and during 2003 the cost in the county of Skåne equalled all intermediate-acting insulins (ATC-code A10AC01). To investigate the evidence behind claimed advantages of insulin glargine over existing therapy, we carried out a systematic review. We analysed the available documentation presented after registration of the drug by the drug regulatory authorities FDA and EMEA. Data presented at the authorithies' Internet sites was approached. All published studies not included in the registration file were also included in the analysis. Data on glycemic control, expressed as HbA1c, and hypoglycemia was registered. Most studies included a comparison with NPH insulin, incorporating both type 1 and type 2-diabetes. In six pivotal studies there were no significant difference between the two insulin treatments regarding HbA1c, nor was there any substancial evidence concerning differences regarding hypoglycemia. According to FDA, no claim of superiority of insulin glargine could be expressed as all studies had an open design. Studies not included at registration did not add any new evidence. The claimed advantages of insulin glargine does not seem to be substantiated by available evidence.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Meta-Analysis as Topic

A better diabetes regulation seems possible, with the aid of the recently available insulin analogs than with isophane insulin, for patients with diabetes mellitus type 1 or 2. The glycaemic regulation can be improved and/or the chances of hypoglycaemia can be reduced by reduced variability in the resorption of (insulin glargine) or by binding to the serum albumin (insulin detemir). With poor regulation it seems possible to bring about a substantial HbA1c reduction without an increase in hypoglycaemic incidents, and with reasonable to good regulation to achieve a reduction of the number of hypoglycaemias whilst HbA1c remains the same.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26 kg/m2) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients.. A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications + treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually.. Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of 1707 pounds sterling and an incremental cost-effectiveness ratio of 19,285 pounds sterling per QALY gained. Results were stable under a wide range of reasonable assumptions.. Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< 35,000 pounds sterling/QALY gained).

Topics: Adolescent; Adult; Aged; Body Mass Index; Clinical Trials as Topic; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Theoretical; United Kingdom

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Humans; Injections; Insulin; Insulin Infusion Systems; Insulin, Isophane

Tight glycaemic control (ideally, HbA1c<7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes.

Topics: Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Parenteral; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Type 1 diabetes is associated with a number of diabetes-related complications which may be minimized by maintaining good long-term metabolic control. The current guidelines recommend that glycosylated hemoglobin levels should be targeted to below 7.0% or 6.5% to reduce the incidence of diabetic complications, including micro- and macrovascular disorders. However, this intensive metabolic control is hindered by the occurrence of hypoglycemia. The episodes of hypoglycemia are problematic for patients taking intermediate-acting insulin preparations (i.e., NPH insulin), which have traditionally formed the mainstay basal insulin treatment. With NPH insulin, the pharmacokinetic profile is such that peak insulin activity occurs 4-6 hours following administration; therefore, nocturnal hypoglycemia commonly takes place after bedtime administration of the insulin. The development of the long-acting human insulin analogue insulin glargine now provides patients with an insulin that offers a longer duration of action (up to 24 hours) and a smoother time-action profile compared with those of NPH insulin. A number of clinical trials comparing the safety and efficacy of insulin glargine and NPH insulin in patients with type 1 diabetes show that, in addition to other clinical benefits over NPH insulin, insulin glargine may also improve glycemic control and satisfaction in this patient population.

Topics: Diabetes Mellitus, Type 1; Humans; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Insulin aspart (NovoLog, NovoRapid), a rapid-acting human insulin analog, provides more rapid absorption than regular human insulin after subcutaneous administration. In most randomized, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated hemoglobin (HbA1c) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomized, nonblind trial. Preliminary data from randomized, nonblind trials suggest insulin aspart had a trend towards lower HbA1c levels compared with regular human insulin in patients with type 2,diabetes mellitus. Biphasic insulin aspart (30% soluble [rapid-acting] and 70% protamine-bound insulin aspart [BIAsp30]) [NovoLog Mix 70/30, NovoMix 30(2)] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomized, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomized, nonblind trial in patients with type 2 diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall incidence of hypoglycemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycemia and severe hypoglycemic events than regular human insulin.. The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycemic control and led to a similar or lower number of hypoglycemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycemic control which offers clinical and practical advantages over regular human insulin.

Topics: Biphasic Insulins; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin Aspart; Insulin, Isophane; Randomized Controlled Trials as Topic; Treatment Outcome

The DCCT and UKPDS have established that in type 1 and in type 2 diabetes respectively, long-term near-normoglycaemia protects against the onset and/or progression of microangiopathic complications. Therefore, insulin strategies to maintain long-term near-normoglycaemia are of key importance in the management of diabetes. To successfully achieve near-normoglycaemia, insulin therapy must mimic nature by providing a bolus of insulin at meal ingestion and by replacing basal insulin between meals and overnight Mealtime insulin needs can be best met by subcutaneous (s.c.) injection of a rapid-acting insulin analogue such as insulin lispro or insulin aspart. Rapid-acting insulin analogues are preferred to human regular insulin for three reasons: convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); lower blood glucose 2 hours after meals; and less risk for late postprandial hypoglycaemia. However, in type 1 diabetes the benefits of mealtime treatment with rapid-acting insulin analogues become apparent only to the extent that replacement of basal insulin is optimised. The interprandial need for basal insulin can be best met by continuous s.c. insulin infusion (CSII). CSII is very good for basal insulin replacement because it uses a rapid-acting insulin analogue with low variability in s.c. absorption, resulting in a flat and peakless action profile. A second option for basal insulin replacement is s.c. injection of an insulin preparation with retarded action. The two most commonly used are NPH and insulin glargine. NPH exhibits an action profile with a peak 4 to 5 hours after injection and duration of action of 10 to 15 hours. Insulin glargine has a peakless action profile and lasts approximately 24 hours. To optimise replacement of basal insulin with NPH, a few units of NPH must be combined with rapid-acting analogues at meals and also given at bedtime (0.2 U/kg). With insulin glargine, 0.2 to 0.4 U/kg should be injected once or, in some patients, twice daily. Modern insulin strategies for intensive therapy should include use of a rapid-acting insulin analogue at meal-time, and use of CSII to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of CSII and should be considered for substitution of basal insulin, especially in type 1 diabetes.

Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period

Insulin aspart, a rapid-acting human insulin analogue, provides more rapid absorption than regular human insulin after subcutaneous administration. In most randomised, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated haemoglobin A(1c ) (HbA(1c)) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycaemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomised, nonblind trial. Preliminary data from randomised, nonblind trials suggest insulin aspart had a trend towards lower HbA(1c) levels compared with regular human insulin in patients with type 2 diabetes mellitus. Biphasic insulin aspart [30% soluble (rapid-acting) and 70% protamine-bound insulin aspart (BIAsp30)] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomised, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomised, nonblind trial in patients with type 2 diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall incidence of hypoglycaemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycaemia and severe hypoglycaemic events than regular human insulin.. The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycaemic control and led to a similar or lower number of hypoglycaemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycaemic control which offers clinical and practical advantages over regular human insulin.

Topics: Absorption; Adolescent; Adult; Biphasic Insulins; Child; Databases, Bibliographic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Food; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane

Nowadays, human insulin is used daily by millions of diabetic patients. The biological effect of human insulin is comparable to that of porcine insulin. However, after subcutaneous injection, pharmacological and clinical studies showed pharmacokinetic and pharmacodynamic differences between human and animal insulins. Human insulin tends to have faster absorption and shorter duration of action compared with animal insulin. These differences are more pronounced and can be of clinical relevance with intermediate- and long-acting insulin preparations. Optimal metabolic control can be achieved with either human or highly purified animal insulin preparations, provided appropriate insulin replacement strategies are used.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Glucose Clamp Technique; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Pork; Lipid Metabolism; Recombinant Proteins; Swine; Time Factors

Protamine insulin use may immunologically sensitize patients to protamine, leading to anaphylactoid reactions upon subsequent exposure to protamine sulfate during cardiac catheterization or cardiovascular surgery. The risk of such reactions in protamine insulin-dependent patients is uncertain. One catheterization study reported a 50-fold greater risk while a second showed no increased risk! To clarify the risk, the records of 7,750 cardiac catheterization procedures between 1984 and 1987 were analyzed for presence of NPH or PZI insulin use, protamine administration, and any complications or adverse reactions. Protamine was administered in 3,341/7,750 procedures (43%), including 171 in diabetics receiving NPH insulin. Adverse reactions to protamine occurred in 2/3, 170 noninsulin patients, 0.06%, and adverse reactions due to probable NPH insulin sensitization occurred in 1/171, 0.6%, of NPH diabetics, p = .034. Meta-analysis of risk showed an odds ratio of 7.96 for the NPH diabetic patients, and combining these results with the other large series in the literature (269 NPH diabetics total) showed an odds ratio of 4.19 compared to a non-NPH insulin group. Meta-analysis of the surgical literature showed the risk in surgical patients to be 2.1% in NPH patients versus 0.12% with no NPH, with an odds ratio of 15.52. The greater incidence in surgical patients may be due to protamine sensitization at prior catheterization and to the larger dose of protamine administered to surgical patients.

Topics: Anaphylaxis; Cardiac Catheterization; Cardiac Surgical Procedures; Diabetes Mellitus, Type 1; Humans; Immunization; Incidence; Insulin, Isophane; Insulin, Long-Acting; Meta-Analysis as Topic; Odds Ratio; Protamines; Risk Factors

To compare the pharmacokinetic (PK) and pharmacodynamic (PD) effects and safety of therapeutic dosages of a regular insulin (experimental drug) produced by Bioton S.A. (Warsaw, Poland) versus Humulin® R, a regular insulin (reference drug) produced by Eli Lilly (Indianapolis, Indiana).. In a single-centre, randomized, double-blinded phase 1 crossover study, we used the manual euglycaemic clamp technique to compare PK and PD profiles between single subcutaneous doses (0.3 units/kg) of the two regular insulins in participants with type 1 diabetes (T1DM) with a washout period of 14 (± 7) days between tests.. The experimental product regular human insulin and comparator Humulin® R are bioequivalent in patients with T1DM. Wider entry to the pharmaceutical market of affordable, biosimilar regular insulins may substantially improve access to insulin for many socioeconomically disadvantaged patients with diabetes.

Topics: Biosimilar Pharmaceuticals; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Regular, Human; Therapeutic Equivalency

To compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) insulin used in pregnant women with diabetes.. A randomized study was conducted in diabetic pregnant women (n=240) (including 132 with pregestational diabetes and 108 with gestational diabetes). All patients were randomly divided into two groups: IDet group (n=120) treated with IDet plus short acting insulin Novolin-R before three meals (RRR-IDet plan), and NPH group treated with NPH plus Novolin-R before three meals (RRR-NPH plan). Patients were enrolled during 12-28 gestation weeks and followed up until delivery.. Basal characteristics, such as age, enrollment gestational weeks, average HbA1c, fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) were similar between two groups. After 1 week of treatment, the FPG of IDet group were significantly lower than NPH group (p<0.05) and the time required to reach the targeted blood glucose level was significantly shorter (p<0.001). After 3 months of treatment, the HbA1c level in the two groups was normalized but there was no significant difference in HbA1c level. Maternal and neonatal outcomes were comparable between the two therapeutic approaches; however, the incidence of hypoglycemia in IDet group was remarkably lower than that of NPH group (p<0.05). The adverse drug reactions were rare and similar between the two groups.. For the treatment of gestational diabetes, both RRR-IDet plan and RRR-NPH plan were reported to control blood glucose effectively. Compared with NPH, IDet could control blood glucose and reached the targets faster and more effectively, thus reducing the number of insulin injections and the incidence of hypoglycemia in pregnant women without increasing adverse birth outcomes. Therefore, for pregnant women with gestational diabetes, who require insulin therapy, IDet would be an ideal basal insulin being worthy of promotion in clinical settings.

Topics: Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy

To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia.. During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1 mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P < 0.0001) with insulin analogue.. Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night.. This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996).. Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months.. In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Disease Susceptibility; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male; Middle Aged; Severity of Illness Index

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action resulting from reduced peripheral effects. This report provides an integrated summary of lipid changes at 26 weeks with BIL and comparator insulins (glargine, NPH) from phase III studies in type 1 diabetes (T1D), insulin-naïve patients with type 2 diabetes (T2D), patients with T2D on basal insulin only and patients with T2D on basal-bolus therapy. BIL treatment had little effect on HDL cholesterol and LDL cholesterol in all patients. The effect of both BIL and glargine treatment on triglycerides (TG) depended on whether patients had been previously treated with insulin. When BIL replaced conventional insulin glargine or NPH treatments, increases in TG levels were observed. When BIL or comparator insulins were given for 26 weeks to insulin-naïve patients with T2D, TG levels were unchanged from baseline with BIL but decreased with either glargine or NPH. The decreased peripheral action of BIL may reduce suppression of lipolysis in peripheral adipose tissue resulting in increased free fatty acid delivery to the liver and, hence, increased hepatic TG synthesis and secretion.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Lipid Metabolism; Lipids; Male; Middle Aged; Polyethylene Glycols; Retrospective Studies; Triglycerides

We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy.. This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131).. In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean ± SD of absolute change in HbA1c was-0.25 ± 1.68% (-2.69 ± 18.32 mmol/mol) in the insulin glargine group and -0.54 ± 1.67% (-5.55 ± 20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3 ± 45.8 versus32.3 ± 43.2); severe hypoglycaemia was rare (<2%).. Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.

Topics: Adolescent; Blood Glucose; Child; China; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Treatment Outcome

To compare the effectiveness of a free-mix of aspart (A) and detemir (D) insulins (ADIM) with a commonly used premixed fixed-ratio aspart and neutral protamine Hagedorn (NPH) insulin mixture (ANIM) in young children with type 1 diabetes (T1D) treated with twice-daily injections. The trial thus compares not only D vs. NPH, but also flexible, personalized insulin preparations vs. a fixed premixed preparation.. This single-center, open-label, randomized trial included 82 children with T1D. Patients stayed on ANIM for 1 yr of optimization of disease management, then were randomized to either ANIM (N = 41) or ADIM (N = 41) for another year.. Frequency of severe or symptomatic episodes, glycated hemoglobin A1c (HbA1c), and blood glucose (BG) values.. Compared with ANIM, ADIM decreases symptomatic hypoglycemia by approximately 2 fold (p < 0.001) and severe hypoglycemia by 7-10 fold (p = 0.04). ADIM somewhat reduced BG variation. Mean HbA1c was comparable on ADIM (7.9 ± 0.8 %; 63 ± 9 mmol/mol) and ANIM (8.2 ± 0.7 %; 66 ± 8 mmol/mol).. Using a free-mixing preparation of aspart and detemir insulin decreases hypoglycemia in young children with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male

To investigate, using a novel non-steady-state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal.. After a period of insulin withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m(2)) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol.. Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04).. The results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Glycerol; Humans; Hyperglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin, Isophane; Lipolysis; Male

The aim of the present study was to investigate the effects of subcutaneous detemir on glucose flux, lipid metabolism and brain function. Twelve people with type 1 diabetes received, in random order, 0.5 units/kg body weight detemir or NPH insulin. Glucose concentration was clamped at 5 mmol/l then increased to 10 mmol/l. Glucose production rate (glucose Ra), glucose uptake (glucose Rd) and glycerol production (glycerol Ra) were measured with a constant intravenous infusion of [6,6(2) H(2)]glucose and [(2)H(5)]glycerol. Electroencephalography direct current (DC) and alternating current (AC) potentials were measured. While detemir induced similar effects on glucose Ra, glucose Rd and glycerol Ra during euglycaemia compared with NPH, it triggered a distinct negative shift in DC potentials, with a significant treatment effect in frontal cerebrocortical channels (p < 0.001). AC spectral power showed significant differences in theta and alpha frequencies during euglycaemia (p = 0.03). Subcutaneous detemir exerts different effects on brain function when compared with NPH in people with type 1 diabetes. This may be an important mechanism behind the limitation of weight gain with detemir.

Topics: Adult; Blood Glucose; Brain; Cross-Over Studies; Diabetes Mellitus, Type 1; Electroencephalography; Female; Glycerol; Humans; Hypoglycemic Agents; Infusions, Intravenous; Injections, Subcutaneous; Insulin Detemir; Insulin Infusion Systems; Insulin, Isophane; Lipolysis; Male; Weight Gain

Crystalline NPH insulin comes in a two-phase solution with either a solvent or a rapid-acting insulin (in premixed formulations) and needs adequate mixing for complete resuspension before injection. The aim of this study was to establish pharmacokinetics (PK) and pharmacodynamics (PD) after injection of appropriately resuspended versus nonresuspended NPH insulin.. PK and PD were assessed after subcutaneous injection of NPH insulin 0.35 units/kg at steady state by pen either resuspended (R+, tipping of insulin pen 20 times) or nonresuspended (pen maintained in fixed position either horizontally [R- horizontal] or vertically with tip up [R- up] or tip down [R- down]). Eleven subjects with type 1 diabetes (age 31.5 ± 12 years, diabetes duration 17.5 ± 7.7 years, BMI 22.9 ± 1.5 kg/m2, A1C 7.2 ± 0.4% [55.2 ± 4.4 mmol/mol]) were studied (euglycemic clamp) with a randomized crossover design.. Compared with resuspended NPH insulin (R+), nonresuspended NPH insulin resulted in profound PK/PD differences with either reduced (R- horizontal and R- up) or increased (R- down) plasma insulin concentrations [FIRI_AUC(0-end of study) (free immunoreactive insulin area under the concentration-time curve between 0 and end of study)] and PD activity [glucose infusion rate (GIR)_AUC(0-end of study)] (all P < 0.05). Duration of NPH insulin action was shorter in R- up (9.4 ± 1.7 h) but longer in R- down (15.4 ± 2.3 h) compared with R+ (11.8 ± 2.6 h) (P < 0.05). Within-subject variability (percent coefficient of variation) among studies was as high as 23% for PK [FIRI_AUC(0-end of study)] and 62% for PD [GIR_AUC(0-end of study)].. Compared with resuspended NPH insulin, lack of resuspension profoundly alters PK/PD and may importantly contribute to day-to-day glycemic variability of type 1 diabetes.

Topics: Adult; Blood Glucose; Chemical Precipitation; Cross-Over Studies; Crystallization; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Compounding; Drug Delivery Systems; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin, Isophane; Male; Pharmaceutical Solutions; Young Adult

This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented.. Subjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8-12 gestational weeks.. For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments.. IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.

Topics: Abortion, Induced; Abortion, Spontaneous; Congenital Abnormalities; Diabetes Mellitus, Type 1; Drug Combinations; Female; Fetal Death; Gestational Age; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Live Birth; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy, Ectopic

To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes. RESEARCH DESIGN/METHOD: Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks' gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n=18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n=78); preterm delivery (n=63); and excessive fetal growth (n=88).. 18 patients experienced a malformed/lost fetus in early pregnancy - none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p=0.012). In the third trimester, elevated HbA1c, ≥ 1 plasma glucose (PG) measurement >11 mmol/L (198 mg/dL) and %PG values outside 3.9-7.0 mmol/L (70-126 mg/dL) were significant predictors of poor late-pregnancy outcomes (all p<0.05).. Elevated HbA1c, high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes.

Topics: Adult; Albuminuria; Blood Glucose; Congenital Abnormalities; Diabetes Mellitus, Type 1; Female; Fetal Death; Food; Gestational Age; Glycated Hemoglobin; Humans; Insulin; Insulin Aspart; Insulin, Isophane; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy Trimester, Third

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.. ClinicalTrials.gov NCT00626080.

Topics: Appetite Regulation; Blood-Brain Barrier; Body Weight; Brain Mapping; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Magnetic Resonance Imaging; Photic Stimulation

Insulin regulates the GH-IGF1 axis. Insulin analogs differ from human insulin in receptor affinity and possibly liver accessibility. Therefore, we compared the GH-IGF1 axis response with human NPH insulin, insulin detemir, and insulin glargine in patients with type 1 diabetes (T1D).. A total of 17 patients (seven were women) with T1D (age of 42 (24-63) years (mean and range), BMI of 24.7 (19.5-28.3) kg/m(2), HbA1c of 7.2 (6.3-8.0) % (55 (45-64) mmol/mol), T1D duration of 26 (8-45) years) were studied using a randomized, three-period crossover design. Patients received s.c. injections of equal, individual doses of NPH, detemir, and glargine at 1800 h. Plasma glucose, serum total IGF1, bioactive IGF, IGF-binding protein (IGFBPs), and GH were measured hourly for 14 h post-injection.. When compared with the area under the curve (AUC) following NPH and glargine, detemir resulted in the lowest 6-14 h AUC (mean and range) of IGFBP1 (1518 (1280-1800)) vs 1621 (1367-1922) vs 1020 (860-1210) μg/l×h) and GH (17.1 (14.1-20.6) vs 15.4 (12.7-18.6) vs 10.2 (8.5-12.3) μg/l×h), but in the highest AUC of bioactive IGF (3.8 (3.5-4.2) vs 3.7 (3.4-4.0) vs 4.4 (4.1-4.8) μg/l×h) (all P<0.01). These differences were unrelated to plasma glucose. By contrast, profiles of total IGF1, IGFBP2, and IGFBP3 were comparable.. Independent of plasma glucose, a single dose of detemir caused larger suppression in serum IGFBP1 than NPH and glargine, whereas bioactive IGF was higher, thereby explaining the lower GH levels. Thus, detemir appears to be more liver specific than NPH insulin and glargine.

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Human Growth Hormone; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin Glargine; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Linear Models; Male; Middle Aged; Time Factors; Treatment Outcome

Avoidance of hypoglycemia is a key consideration in treating young children with type 1 diabetes (T1DM).. To evaluate hypoglycemia with insulin glargine vs. neutral protamine Hagedorn (NPH) insulin in young children, using continuous glucose monitoring (CGM).. Children of 1 to <6 yr treated with once-daily glargine vs. once- or twice-daily NPH, with bolus insulin lispro/regular human insulin provided to all.. Twenty-four week, multicenter, randomized, open-label study. Primary endpoint was event rate of composite hypoglycemia [symptomatic hypoglycemia, low CGM excursions (<3.9 mmol/L) or low fingerstick blood glucose (FSBG; <3.9 mmol/L)]. Noninferiority of glargine vs. NPH was assessed for the primary endpoint.. One hundred and twenty-five patients (mean age, 4.2 yr) were randomized to treatment (glargine, n = 61; NPH, n = 64). At baseline, mean HbA1c was 8.0 and 8.2% with glargine and NPH, respectively. Composite hypoglycemia episodes/100 patient-yr was 1.93 for glargine and 1.69 for NPH; glargine noninferiority was not met. Events/100 patient-yr of symptomatic hypoglycemia were 0.26 for glargine vs. 0.33 for NPH; low CGM excursions 0.75 vs. 0.72; and low FSBG 1.93 vs.1.68. There was a slight difference in between-group severe/nocturnal/severe nocturnal hypoglycemia and glycemic control. All glargine-treated patients received once-daily injections; on most study days NPH-treated patients received twice-daily injections.. While glargine noninferiority was not achieved, in young children with T1DM, there was a slight difference in hypoglycemia outcomes and glycemic control between glargine and NPH. Once-daily glargine may therefore be a feasible alternative basal insulin in young populations, in whom administering injections can be problematic.

Topics: Blood Glucose; Child; Child, Preschool; Circadian Rhythm; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Infant; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Monitoring, Ambulatory

To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight-modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu).. Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m(2), A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu.. After 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed.. Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir.

Topics: Adolescent; Adult; Appetite; Brain; Cerebrovascular Circulation; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucose; Humans; Hypoglycemic Agents; Imaging, Three-Dimensional; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Magnetic Resonance Imaging; Male; Middle Aged; Regional Blood Flow; Retrospective Studies; Young Adult

This 52-week, randomized, multinational, open-label, parallel-group, non-inferiority trial investigated the efficacy and safety of basal-bolus treatment with insulin detemir vs. NPH (neutral protamine Hagedorn) insulin, in combination with insulin aspart, in subjects aged 2-16 years with Type 1 diabetes mellitus.. Of the 347 randomized and exposed subjects, 177 received insulin detemir and 170 NPH insulin, both administered once or twice daily in combination with mealtime insulin aspart. Glycaemic measurements and weight were followed over 52 weeks.. After 52 weeks, insulin detemir was shown to be non-inferior to NPH insulin with regard to HbA(1c) [mean difference insulin detemir-NPH: 1.30 mmol/mol, 95% CI -1.32 to 3.92 (0.12%, 95% CI -0.12 to 0.36) in the full analysis set and 1.41 mmol/mol, 95% CI -1.26 to 4.08 (0.13%, 95% CI -0.12 to 0.37) in the per protocol analysis set]. Hypoglycaemic events per subject-year of exposure of 24-h and nocturnal hypoglycaemia were significantly lower with insulin detemir than with NPH insulin (rate ratio 0.76, 95% CI 0.60-0.97, P = 0.028 and 0.62, 95% CI 0.47-0.84, P = 0.002, respectively). Weight standard deviation (sd) scores (body weight standardized by age and gender) decreased with insulin detemir, but increased slightly with NPH insulin (change: -0.12 vs. 0.04, P < 0.001). At end of the trial, median insulin doses were similar in both treatment groups.. Insulin detemir was non-inferior to NPH insulin after 52 weeks' treatment of children and adolescents aged 2-16 years, and was associated with a significantly lower risk of hypoglycaemia, together with significantly lower weight sd score when compared with NPH insulin.

Topics: Adolescent; Blood Glucose; Body Mass Index; Body Weight; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

Intensive insulin therapy (IIT) based on multiple daily injections of long plus rapid-acting insulin has been demonstrated to reduce mortality and morbidity associated with chronic hyperglycemia in T1DM patients. The objective of this study was to assess and compare the postprandial glycemic profile over a diurnal 12 h-period produced by the administration of a new NPH plus regular human DNA recombinant IIT (test regimen) relative to the reference IIT in T1DM patients. A phase IV, single-center, open-label, randomized, multiple-dose, balanced, cross-over study in 12 T1DM patients was conducted. Patients were assigned to receive either the test (Densulin® N (NPH) plus Densulin® R (regular),100 UI/ml, Denver Farma, Argentina) followed by the reference (InsulatardHM® (NPH) plus ActrapidHM®,100 UI/ml, Novo Nordisk Pharma Argentina) regimens or viceversa, according to a random sequence. Each treatment regimen consisted of 2 phases of an ambulatory run-in period of 7 days followed by 12 h confinement period. Blood glucose levels were measured. Glycemic profile was evaluated through glycemic plasma-concentration time curves, area under the time-concentration glycemic curves from basal to 2 h (GlyAUC0-2) and to 12 h (GlyAUC0-12) postprandial, and maximum glycemic postprandial concentration (GlyCmax). 12 hour glycemic concentration-time curves were similar for both test and reference regimens. Geometric least square means ratios Test/ref regimens and their 90% confidence interval for GlyAUC0-2, GlyAUC0-12 and GlyCmax were 94.33 (81.13-125.09), 107.75 (94.05-123.45) and 105 (92.89-118.68), respectively. Both regimens presented similar safety profile. This study demonstrated that the new human DNA recombinant NPH and regular insulin is equally effective to the reference regimen for postprandial diurnal glycemic profile.

Topics: Adolescent; Adult; Aged; Area Under Curve; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Recombinant Proteins; Young Adult

This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.. Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account.. A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups.. Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

This randomised (1:1), multinational, open-labelled, parallel group trial compared insulin detemir (IDet) with neutral protamine Hagedorn (NPH) insulin, in combination with mealtime insulin aspart, over 1 yr in subjects aged 2-16 yr with type 1 diabetes mellitus. Of 348 randomised subjects, 82 (23.6%) were 2-5 yr (IDet: 42, NPH: 40). This article is a descriptive subgroup analysis of these young children. Baseline characteristics (IDet vs. NPH) were similar: mean age, 4.3 vs. 4.5 yr; diabetes duration, 2.2 vs. 2.1 yr; males, 42.9 vs. 52.5%. Mean haemoglobin A1c (HbA1c) was similar between groups at baseline (8.2 vs. 8.1%), and changed little over 1 yr (8.1 vs. 8.3%). Fasting plasma glucose (FPG) was similar at baseline (8.44 vs. 8.56 mmol/L) and decreased during the study (-1.0 vs. -0.45 mmol/L). A lower rate of hypoglycaemia was observed with IDet compared with NPH (24-h; 50.6 vs. 78.3 episodes per patient-year; nocturnal hypoglycaemia, 8.0 vs. 17.4 episodes per patient-year). No severe hypoglycaemic episodes occurred with IDet, while 3 subjects reported 6 episodes with NPH. Change in weight standard deviation score standardised by age and gender was -0.17 with IDet and +0.03 with NPH. A slightly lower proportion of subjects in this age group reported adverse events with IDet than with NPH (69.0 vs. 77.5%). Serious adverse events were few (5 with IDet, 7 with NPH). In conclusion, long-term treatment with IDet in children aged 2-5 yr suggested similar glycaemic control, greater reduction in FPG, lower rates of hypoglycaemia, no inappropriate weight gain, and fewer adverse events compared with NPH.

Topics: Body Weight; Child, Preschool; Diabetes Mellitus, Type 1; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter-regulatory responses to spontaneous hypoglycaemia.. Glycaemic control, hypoglycaemic frequency, p-insulin concentrations, insulin dosages and patients' satisfaction were examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed by hospitalization where episodes of spontaneous hypoglycaemia and counter-regulatory hormone responses were evaluated from frequently obtained blood samples.. No difference between soluble insulin and insulin Aspart was found regarding HbA1c (7.0 ± 0.2 vs. 7.0 ± 0.2%, ns), hypoglycaemic frequency (1.1 ± 0.2 vs. 0.9 ± 0.1 events per patient per week, ns), nocturnal hypoglycaemia, severe hypoglycaemic events, dosages of bolus insulin (31.8 ± 0.4 vs. 30.0 ± 0.6 IU day(-1), ns), or NPH insulin (26.7 ± 1.8 vs. 26.0 ± 1.7 IU day(-1) , ns) or in patients satisfaction (ns). Modest differences existed in the counter-regulatory responses regarding growth hormone, glucagon and ghrelin whereas no differences were found in relation to free fatty acid, cortisol, insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins 1 and 2. Treatment with insulin Aspart resulted in well-defined peaks in serum insulin concentrations as compared with more blunted insulin peaks using human soluble insulin.. Although insulin Aspart treatment was associated with clear postprandial insulin peaks, no improvement in glycaemic control was obtained and no difference in the hypoglycaemic frequency was observed. However, insulin Aspart elicited a slightly different physiological response to spontaneous hypoglycaemia compared with human insulin.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Fatty Acids, Nonesterified; Female; Ghrelin; Glucagon; Hormones; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Young Adult

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Off-Label Use; Pregnancy; Pregnancy in Diabetics

Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure.. A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured.. After 16 weeks, weight change was -0.69±1.85 kg with insulin detemir and +1.7±2.46 kg with NPH insulin (P<0.001). Total energy intake was significantly less with insulin detemir (2,016±501 kcal/day) than with NPH insulin (2,181±559 kcal/day) (P=0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P=0.039, P=0.047). After the meal, ghrelin and pancreatic polypeptide levels (P=0.002, P=0.001) were higher with insulin detemir.. The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Eating; Energy Intake; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Weight Gain

The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen.. This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months.. Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia.. The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Weight Loss

To compare switching from NPH insulin (NPH) to insulin glargine (glargine) with continuing NPH for changes in fasting blood glucose (FBG) in patients with Type 1 diabetes on basal-bolus therapy with insulin lispro as bolus insulin. Secondary objectives included self-monitoring blood glucose, mean daily blood glucose (MDBG) and mean amplitude glucose excursion (MAGE) values alongside changes in HbA(1c) and safety profiles.. This was a 30-week, parallel, open-label, multicentre study. Seven-point profiles were used to calculate MDBG and MAGE. Hypoglycaemia and adverse events were recorded by participants. FBG improved significantly with both glargine (baseline-endpoint change: -28.0 mg/dL; 95% CI: -37.3, -18.7 mg/dL; p<0.001) and NPH (-9.8 mg/dL; 95% CI: -19.1, -0.5 mg/dL; p=0.0374). The improvement was significantly greater with glargine than NPH (mean difference: -18.2 mg/dL; 95% CI: -31.3, -5.2 mg/dL; p=0.0064). MDBG (-10.1 mg/dL; 95% CI: -18.1, -2.1 mg/dL; p=0.0126) and MAGE (-20.0 mg/dL; 95% CI: -34.5, -5.9 mg/dL; p=0.0056) decreased significantly with glargine, but not NPH although endpoint values were no different with the two insulins. Baseline to endpoint change in HbA(1c) was similar (-0.56 vs -0.56%) with no differences at endpoint. Overall hypoglycaemia was no different, but glargine reduced nocturnal hypoglycaemia ("serious episodes" with BG < 42 mg/dl, p=0.006) whereas NPH did not (p=0.123), although endpoint values were no different.. Switching from NPH to glargine is well tolerated and results into lower FBG, and lower glucose variability while reducing nocturnal hypoglycaemia. These data provide a rationale for more aggressive titration to target with glargine in Type 1 diabetes.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Diabetes Mellitus, Type 1; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Italy; Male; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

To compare the glucose variability associated with insulin glargine and NPH/Lente insulin used as the basal insulin component of a multiple daily injection (MDI) regimen in pediatric patients with type 1 diabetes.. Continuous glucose monitoring data were collected from a subset of patients (n = 90) who agreed to use a continuous glucose monitoring system during an active-controlled, randomized, open-label study evaluating the safety and efficacy of insulin glargine and NPH/Lente insulin used with insulin lispro as part of an MDI regimen.. Treatment with insulin glargine resulted in significant reductions in glucose variability as measured by the SD of glucose values (adjusted mean change from baseline to week 24: -13.4 mg/dl [-0.74 mmol/l]; P

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

The purpose of this study was to evaluate pharmacokinetic and pharmacodynamic profiles of pure insulin aspart and three different formulations of insulin aspart and protaminated insulin aspart: biphasic insulin aspart 30 (BIAsp30), biphasic insulin aspart 50 (BIAsp50) and biphasic insulin aspart 70 (BIAsp70). Nineteen type 1 diabetes patients received individually identical doses of the four different insulin aspart preparations on 4 separate days in this randomized crossover study. Having achieved overnight stable blood glucose control by intravenous infusions of human insulin, one of the trial insulins was injected subcutaneously and a standard meal was given in the morning. Plasma glucose and serum insulin aspart were recorded the following 12 hr. During the first 4 hr after injection with the trial insulin, the area under the curve for levels of insulin aspart (AUC(ins)) was significantly higher during insulin aspart treatment as compared to the other three insulin treatments, followed by BIAsp70, BIAsp50 and BIAsp30 (P < 0.05). Over the last 4 hr, the AUC(ins) for BIAsp30 was significantly higher as compared to the other insulin preparations (P < 0.05). By contrast, during the initial 4 hr, the area under the curve for levels of glucose (AUC(glu)) was highest after injection with BIAsp30 compared to the other three treatments (P < 0.05), while during the last 4 hr the highest AUC(glu) was seen following insulin aspart (P < 0.05). We conclude that when insulin aspart is pure or formulated with protamine in three different ratios, the pharmacokinetic profiles are readily distinguishable. These differences in pharmacokinetics are reflected in the pharmacodynamic profiles.

Topics: Adult; Aged; Area Under Curve; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Time Factors; Young Adult

We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(epsilon-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake.. After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-(2)H(2)]glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration.. During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir.. In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counter-regulation are similar.. ClinicalTrials.gov NCT00760448.

Topics: Blood Glucose; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Epinephrine; Glucose; Growth Hormone; Heart Rate; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Liver; Patient Selection; Reaction Time

To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old.. Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention).. Mean A1C at the study entry was 8.68% and after 12 months of glargine, was 8.64% (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002).. The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

Topics: Analysis of Variance; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome

The aim of this study was to compare the effects of exercise on plasma glucose excursions when using each of three basal insulins in people with Type 1 diabetes.. This was a multinational, open-label, randomized, three-period, crossover clinical trial. People with Type 1 diabetes [n = 51, age 39 +/- 10 (+/- sd) years, 67% men] managed with mealtime plus basal insulin regimens, were exercised for 30 min, 5 h after the last mealtime and basal insulin injection when using insulin detemir, insulin glargine or neutral protamine Hagedorn (NPH) insulin.. There were no significant differences in the plasma glucose excursions during or for 150 min after exercise. During 30 min exercise, five (11%) participants on insulin detemir developed minor hypoglycaemia, six (12%) for NPH and 18 (38%) for glargine. From the end of exercise to 150 min, five (11%) on insulin detemir developed minor hypoglycaemia, seven (14%) for NPH and nine (19%) for glargine. In total, from start of exercise to 150 min after exercise, 10 (21%) participants on insulin detemir experienced minor hypoglycaemia as compared with 13 (27%) for NPH and 27 (57%) for glargine (P < 0.001 glargine vs. detemir and NPH). Maximum plasma cortisol levels were lower on detemir and NPH than glargine.. Insulin detemir was associated with less hypoglycaemia than insulin glargine but not NPH insulin in relatively well-controlled people with Type 1 diabetes during and after exercise.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Exercise; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

The purpose of this study was to compare the efficacy and safety of insulin glargine and detemir with NPH insulin in children and adolescents with type 1 diabetes mellitus (DM).. Thirty four children and adolescents with type 1 DM (mean age 12.7 ± 3.4 years, diabetes duration 5.4 ± 3.0 years) were included in the study. All patients had been receiving intensive insulin therapy with insulin aspart and NPH for at least 6 months before switching from NPH to insulin glargine (Group 1, n=19) or detemir (Group 2, n=15). The medical records obtained within 6 months before and after treatment with insulin glargine and detemir were retrospectively reviewed and the data were compared in each group.. The mean age and duration of DM were similar in two groups (p>0.05). In both groups, switching from NPH to insulin glargine or detemir, resulted in a reduction in HbA(1c) (p0.05, for both). Patients in the detemir treated group had less increment in body mass index (BMI) SDS at the end of 6 months of therapy compared to NPH and glargine treated patients (p>0.05, for both). No side effects were noted throughout the study.. Both insulin glargine and detemir improved HbA(1c) at short-term and proved to be safe and well tolerated in children and adolescents with type 1 DM.

Topics: Adolescent; Blood Glucose; Body Mass Index; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Retrospective Studies; Treatment Outcome

To compare long-acting insulin glargine (Lantus) with intermediate-acting insulin (neutral protamine Hagedorn [NPH]/Lente) when used as the basal component of a multiple daily injection (MDI) regimen with prandial insulin lispro (Humalog) in adolescents with type 1 diabetes mellitus (T1DM).. This was an active-controlled, randomized, open-label, sex-stratified, 2-arm, parallel-group comparison of once-daily insulin glargine with twice-daily NPH/Lente in an MDI regimen. Changes in glycated hemoglobin A1C (A1C), occurrence of hypoglycemia, and adverse events were assessed in 175 patients (age 9 to 17 years) with T1DM.. The overall mean change in A1C from baseline to week 24 was similar in the 2 groups: insulin glargine (n = 76), -0.25% +/- 0.14%; NPH/Lente (n = 81), 0.05% +/- 0.13% (P = .1725). However, an analysis of covariance, adjusting for baseline A1C, revealed a strong study arm effect on the slopes of the regression lines, indicating that the reduction in A1C was significantly greater with insulin glargine in those patients with higher baseline A1C values. The rate of confirmed glucose values <70 mg/dL was higher in the patients receiving insulin glargine (P = .0298). No differences in the rate of severe hypoglycemia (P = .1814) or the occurrence of glucose levels <50 mg/dL (P = .82) or <36 mg/dL (P = .32) were found between the 2 groups.. Insulin glargine is well tolerated in MDI regimens for pediatric patients with T1DM and may be more efficacious than NPH/Lente in those with elevated A1C.

Topics: Adolescent; Body Mass Index; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

Type 2 diabetes patients on premixed insulin are commonly prescribed biphasic insulin with low prandial insulin content, such as biphasic insulin aspart (BIAsp) 30, comprising 30% insulin aspart (IAsp). The new formulations BIAsp 50 and BIAsp 70 contain 50% and 70% soluble IAsp, respectively. We compared the pharmacodynamics (PD) and pharmacokinetics (PK) of BIAsp 30, 50, and 70 and IAsp in a glucose clamp trial.. In this randomized, double-blind, crossover study at a clinical research institute, 32 type 1 diabetes patients on basal-bolus therapy each underwent four glucose clamps (clamp level 5 mmol/L, duration 28 h post-dosing [12 h for IAsp]) and received a single dose of 0.4 U/kg BIAsp 30, 50, or 70 and IAsp. Main PD/PK outcome parameters measured were early- and late-phase glucose disposal (area under the curve of glucose infusion rate [AUC(GIR)]), nonesterified fatty acid concentrations, and IAsp concentrations.. With increasing proportions of soluble IAsp, the insulin formulations showed significantly higher early metabolic activity (ratio of AUC(GIR) 0-6 h: BIAsp 50/BIAsp 30 = 1.28 [P < 0.001], BIAsp 70/BIAsp 50 = 1.18 [P < 0.001), IAsp/BIAsp 70 = 1.15 [P < 0.01]) and lower late metabolic activity (ratio of AUC(GIR) 12-28 h: BIAsp 50/BIAsp 30 = 0.17 [P < 0.01], BIAsp 70/BIAsp 50 = 0.21 [P < 0.05]). Likewise, early IAsp levels were significantly greater and late PK concentrations were significantly lower with increasing proportion of soluble IAsp.. There are significant differences between the early and late PD and PK effects among BIAsp 30, 50, and 70 and IAsp that should allow tailored treatment with the convenience of prandial and basal insulin in each injection.

Topics: Adult; Area Under Curve; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Young Adult

Insulin glargine is difficult to use for children due to the number of injections required because it is claimed to be immiscible with rapid-acting insulin analogs. For this study, we hypothesized that treating new-onset type 1 diabetes with twice-daily insulin glargine plus a rapid-acting insulin analog mixed in the same syringe would result in better glycosylated hemoglobin than twice-daily neutral protamine Hagedorn with a rapid-acting insulin analog (standard treatment).. Forty-two patients with new-onset type 1 diabetes were started on standard treatment. Three months after diagnosis, if patients were found compliant and had a glycosylated hemoglobin level of < or = 9%, then they were randomly assigned either to receive insulin glargine twice daily mixed with a rapid-acting insulin analog or to continue on standard treatment for 3 more months. Additional lunchtime rapid-acting insulin analog injections were given for the insulin glargine group as necessary.. Nineteen patients in the insulin glargine group and 17 in the neutral protamine Hagedorn group completed the study. The glycosylated hemoglobin level at baseline was 6.8% +/- 1% vs 6.9% +/- 1% and at poststudy was 6.7% +/- 1.3% vs 7.6% +/- 1% in the insulin glargine versus neutral protamine Hagedorn group, respectively. Two patients in the insulin glargine group required lunch rapid-acting insulin analog in the last month of the study. Although both groups were encouraged to contact the principal investigator with all queries, more in the insulin glargine arm opted to do so.. Glycemic control with insulin glargine mixed with a rapid-acting insulin analog given twice daily seems significantly more effective than the standard therapy in newly diagnosed type 1 diabetes. Furthermore, it decreases pain and burden of injections for children with diabetes by allowing patients to mix glargine with rapid-acting insulin analog.

Topics: Adolescent; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Probability; Prospective Studies; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome

The purpose of this study was to compare quality of life (QoL) and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed with multiple injection regimens.. As part of a 32-week, five-center, two-way crossover study in 56 individuals with type 1 diabetes randomized to evening insulin glargine plus mealtime insulin lispro or to NPH insulin (once or twice daily) plus mealtime unmodified human insulin, the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Audit of Diabetes Dependent Quality of Life questionnaire were completed at baseline and at weeks 16 and 32, with additional interim DTSQ measurements.. For all patients combined, the mean baseline present QoL score was 1.3, reflecting "good" QoL. Present QoL improved with glargine + lispro but did not change with NPH + human insulin (1.6 +/- 0.1 [mean +/- SEM] vs. 1.3 +/- 0.1, difference 0.3 [95% CI 0.1-0.6]; P = 0.014). Baseline mean average weighted impact score (AWI) of diabetes on QoL was -1.8, indicating a negative impact of diabetes on QoL. The AWI score at end point improved significantly with glargine + lispro but changed little with NPH + human insulin (-1.4 +/- 0.1 vs. -1.7 +/- 0.1, 0.3 [0.0-0.6]; P = 0.033). Treatment satisfaction (DTSQ 36-0 scale score) at end point was markedly greater with glargine plus lispro compared with that for NPH plus human insulin (32.2 +/- 3.4 vs. 23.9 +/- 7.2, 8.6 [6.5-10.6]; P < 0.001).. Insulin glargine plus insulin lispro improves treatment satisfaction, reduces the negative impact of diabetes on QoL, and improves QoL in comparison with NPH insulin plus unmodified human insulin in type 1 diabetes.

Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Life Style; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires

This 24-month, multi-national, open-label, parallel group trial investigated the long-term efficacy and safety of insulin detemir and Neutral Protamine Hagedorn insulin in combination with mealtime insulin aspart in patients with Type 1 diabetes using a treat-to-target concept.. Patients were randomized 2 : 1 to detemir (n = 331) or NPH (n = 166) groups. Basal insulin was initiated once daily (evening) and titrated individually based on self-measured plasma glucose (PG) levels, aiming for pre-breakfast and pre-dinner targets < or = 6.0 mmol/l. A second basal morning dose could be added according to pre-defined criteria.. After 24 months, superiority of glycated haemoglobin (HbA(1c)) was achieved with detemir compared to NPH (detemir 7.36%, NPH 7.58%, mean difference -0.22% points) [95% confidence interval (CI) -0.41 to -0.03%], with reductions of 0.94% and 0.72% points, respectively. Fasting PG (FPG(lab)) was also lower with detemir (detemir 8.35 mmol/l, NPH 9.43 mmol/l; P = 0.019). Twenty-two per cent of patients treated with detemir reached an HbA(1c) < or = 7.0% in the absence of confirmed hypoglycaemia during the last month of treatment vs. 13% on NPH (P = 0.019). Risk of major and nocturnal hypoglycaemia was 69% and 46% lower with detemir than with NPH (P < 0.001), respectively; patients treated with detemir gained less weight (detemir 1.7 kg, NPH 2.7 kg; P = 0.024). The overall safety profile was similar in the two groups and treatment with detemir did not result in any unexpected findings.. Long-term treatment with the insulin analogues detemir + aspart was superior to NPH + aspart in reducing HbA(1c), with added benefits of less major and nocturnal hypoglycaemia and less weight gain.

Topics: Adolescent; Adult; Aged; Antibodies; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

Our goal was to investigate blood glucose and lipometabolism control in type 1 diabetes patients who missed breakfast and the accompanying insulin injection of NPH insulin (NPH) or insulin glargine (glargine) as part of a basal-bolus regimen. This was a multi-center, open-label, controlled study in adults (> or =18 years) with HbA (1c)< or =11.5% on insulin therapy with NPH as basal insulin. Patients were randomized to receive prandial insulin plus either bedtime glargine (n=28) or NPH (n=32). Insulin was titrated to target fasting blood glucose levels 80-130 mg/dl at 06:00-07:00. Patients had no intake of insulin or food between 22:00 and 12:00 the next day. The change in blood glucose levels (07:00-11:00) was similar (27.5 mg/dl vs. 35.4 mg/dl), but the mean blood glucose level was higher with glargine vs. NPH at 22:00 (158.2 mg/dl vs. 130.2 mg/dl). During the period without insulin or food intake, blood glucose decreased with glargine (-25.8 mg/dl) and increased with NPH (+9.1 mg/dl; p=0.0284). Nonesterified fatty acid (07:00 and 09:00-12:00) and beta-hydroxybutyrate (07:00 and 10:00-12:00) levels were lower with glargine vs. NPH (both p<0.05). For patients who miss a morning meal, glargine is associated with maintained glycemic and lipometabolic control compared with NPH insulin.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Eating; Fatty Acids, Nonesterified; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Lipid Metabolism; Male

The aim of the study was to compare the efficacy of insulin glargine and aspart with NPH insulin and aspart in a basal bolus regimen in type 1 diabetes. In this 36-week randomised open-label two-period cross-over trial, subjects received 16 weeks' treatment with either once-daily insulin glargine or twice-daily NPH insulin after 4-week run-in. Primary outcome was HbA1c and secondary outcomes were fasting plasma glucose (FPG), weight change, incidence of hypoglycaemia, effect on lipid profile and patient satisfaction. Sixty patients with type 1 diabetes were recruited (33 male, mean age 42.7 years, mean HbA1c 8.53%) with 53 completing the study. At completion, HbA1c was lower with glargine and aspart than with NPH and aspart (8.07% versus 8.26%, difference -0.19 [95% CI 0.37-0.01]%, p=0.04). FPG was significantly different between glargine and NPH (p=0.002), with mean FPG on glargine 3mmol/L lower than on NPH at the end of the study. There were no differences in hypoglycaemia rate (p=0.63), weight (p=0.45) or lipid profile (p=0.18). Patient satisfaction was greater with glargine (DTSQ, p=0.001). Three patients discontinued as they wished to remain on glargine. We suggest that glargine combined with aspart is an effective basal bolus regimen in type 1 diabetes.

Topics: Adult; Blood Glucose; Blood Pressure; Cholesterol; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

This study compared the effect of insulin detemir on glycaemic control (HbA(1c), fasting plasma glucose and variability thereof) with that of Neutral Protamine Hagedorn human isophane (NPH) insulin, both combined with insulin aspart, in children with Type 1 diabetes mellitus, and compared the safety of these treatments.. In this 26-week, open-label, randomized (2 : 1), parallel-group study, 347 (140 prepubertal and 207 pubertal) children with Type 1 diabetes, aged 6-17 years, received insulin detemir (n = 232) or NPH insulin (n = 115) once or twice daily, according to the prestudy regimen, plus premeal insulin aspart.. The mean HbA(1c) decreased by approximately 0.8% with both treatments. After 26 weeks, the mean difference in HbA(1c) was 0.1% (95% confidence interval -0.1, 0.3) (insulin detemir 8.0%, NPH insulin 7.9%). Within-subject variation in self-measured fasting plasma glucose was significantly lower with insulin detemir than with NPH insulin (SD 3.3 vs. 4.3, P < 0.001), as was mean fasting plasma glucose (8.4 vs. 9.6 mmol/l, P = 0.022). The risk of nocturnal hypoglycaemia (22.00-07.00 h) was 26% lower with insulin detemir (P = 0.041) and the risk of 24-h hypoglycaemia was similar with the two treatments (P = 0.351). The mean body mass index (BMI) Z-score was lower with insulin detemir (P < 0.001).. Basal-bolus treatment with insulin detemir or NPH insulin and premeal insulin aspart in children and adolescents with Type 1 diabetes mellitus improved HbA(1c) to a similar degree. The lower and more predictable fasting plasma glucose, lower risk of nocturnal hypoglycaemia and lower BMI observed with insulin detemir are clinically significant advantages compared with NPH insulin.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Risk Factors

We sought to compare and evaluate the impact of inhaled versus injected insulin on potential mediators of patient acceptance of insulin therapy while maintaining comparable A1C levels.. During a noninferiority efficacy trial conducted in 40 centers in the U.S., we surveyed treatment satisfaction, quality of life, and adherence barriers at weeks -4, -1, 6, 12, 20, and 24 in adolescents aged 12-17 years and adults with type 1 diabetes who received premeal regular plus twice-daily NPH insulin during a 4-week run-in; then, subjects were randomized to premeal inhaled human insulin plus twice-daily NPH (adults, n = 102; adolescents, n = 60) (inhaled) or remaining on run-in therapy (n = 105 and 60, respectively) (subcutaneous injection).. Overall treatment satisfaction (0-100) increased by 13.2 +/- 1.1 units for inhaled insulin (baseline = 63.3 +/- 1.2) compared with 1.7 +/- 0.8 for subcutaneous insulin injection (baseline = 64.1 +/- 1.2, P < 0.0001). All 12 satisfaction subscales favored inhaled insulin (all P < 0.01), and effects did not vary by age or sex. Despite similar baseline-adjusted end point A1C for inhaled (7.7 +/- 0.1%) and subcutaneous (7.9 +/- 0.1%) regimens, quality-of-life scales of mental health, symptoms, health status, cognitive functioning, and adherence barriers during treatment were more favorable for inhaled insulin (all P < 0.05). Greater satisfaction was associated with fewer barriers to insulin adherence (rho = -0.78, P < 0.0001) and a greater reduction in A1C (rho = -0.18, P < 0.001).. Treatment satisfaction was substantially more favorable, adherence barriers moderately lower, and quality of life moderately higher for inhaled compared with subcutaneous regimen. It remains to be demonstrated whether these patient-reported outcomes will translate into improved adherence and glycemic control.

Topics: Administration, Inhalation; Adolescent; Adult; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Female; Glycated Hemoglobin; Humans; Injections, Subcutaneous; Insulin, Isophane; Male; Middle Aged; Occupations; Patient Compliance; Patient Satisfaction; Quality of Life

To assess the safety and efficacy of insulin aspart (IAsp) versus regular human insulin (HI) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes.. Subjects (n = 322) who were pregnant or planning pregnancy were randomized to IAsp or HI as meal-time insulin in an open-label, parallel-group, multicenter study. Subjects had A1C < or =8% at confirmation of pregnancy. Insulin doses were titrated toward predefined glucose targets and A1C <6.5%. Outcomes assessed included risk of major maternal hypoglycemia, A1C, plasma glucose profiles, and maternal safety outcomes.. Major hypoglycemia occurred at a rate of 1.4 vs. 2.1 episodes/year exposure with IAsp and HI, respectively (relative risk 0.720 [95% CI 0.36-1.46]). Risk of major/major nocturnal hypoglycemia was 52% (RR 0.48 [0.20-1.143]; P = NS) lower with IAsp compared with HI. A1C was comparable with human insulin in second (IAsp-HI -0.04 [-0.18 to 0.11]) and third (-0.08 [-0.23 to 0.06]) trimesters. A total of 80% of subjects achieved an A1C < or =6.5%. At the end of first and third trimesters, average postprandial plasma glucose increments were significantly lower with IAsp than HI (P = 0.003 and P = 0.044, respectively), as were mean plasma glucose levels 90 min after breakfast (P = 0.044 and P = 0.001, respectively). Maternal safety profiles and pregnancy outcomes were similar between treatments.. IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postprandial glucose control and preventing severe hypoglycemia.

Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 1; Drug Administration Schedule; Europe; Female; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Quality of Life

Early worsening of diabetic retinopathy, characterized by cotton wool spots, intraretinal microvascular abnormalities and/or macular edema, can occur following improvement of glycemic control. In four randomized 28- to 52-week clinical trials comparing insulin glargine and NPH insulin in regard to glycemic control and frequency of hypoglycemia, ophthalmologic examinations and fundus photographs were included to assess frequency of early worsening of retinopathy or other early adverse ocular effects. Retinopathy progression rates at 28 weeks were 7-12% by clinical examination and 3-8% by photographic grading; corresponding rates of clinically significant macular edema (CSME) were 1-8% and 1-4%, respectively. Optic disc swelling was not observed clinically or in photographs. Two of the 24 possible comparisons (four trials, three outcomes, two assessment methods), both of which were photographic assessments in type 2 diabetes, were in/near the nominally significant range and favored NPH insulin: 28-week rates of >or=3-step retinopathy progression (insulin glargine: 16/213, 7.5%; NPH insulin: 6/220, 2.7%; p=0.028) and 52-week CSME rates (26/233, 11.2% and 14/214, 6.5%, respectively; p=0.098). Because the between-treatment differences were small and inconsistent across trials and assessment methods, and because overall rates were consistent with the natural course of diabetic retinopathy, we conclude that it is unlikely that insulin glargine carries a higher risk of early worsening or other early adverse effect than NPH insulin. These trials tended to exclude a large early adverse effect, such as optic disc swelling, but cannot assess longer-term effects; a 5-year randomized trial of insulin glargine versus NPH insulin has been initiated. Data from this manuscript have been presented as posters and published in abstract form at the European Association for the Study of Diabetes 2001 ( DIABETOLOGIA 44(Suppl 1):I-IV(A287), 2001) and the Latin American Diabetes Association 2001 (11-15 November 2001, Punta del Este, Uruguay; Poster 180) congresses.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Fluorescein Angiography; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

This study examined the impact of insulin glargine introduction in basal-bolus therapy in type 1 and type 2 diabetic patients with inadequate metabolic control (A1c > 6.9%) using previous NPH insulin regime. In this uncontrolled, retrospective study, 49 patients (28F/21M), average age 24.7 +/- 16.5, mean duration of DM 13.2 +/- 10.1 yrs., 93.1% DM1 patients, received insulin glargine plus mealtime rapid-acting insulin (lispro or aspart) followed by 90-day treatment. We analyzed mean total insulin dose, incidence of hypoglycemic events, convulsive crisis, hyperglycemic complications and A1c levels before and after three months of introduction of glargine therapy. A1c values were determined using the HPLC instrument, with a normal range of 4.3% to 6.9%. After switching to insulin glargine therapy, mean A1c dropped from 10.2 +/- 2.0 to 9.1 +/- 1.8%, with significant impact (p= 0.019). We observed a significant reduction of 0.11 U/kg/day in total insulin dose, dropped from 0.75 U/kg of NPH to 0.64 U/kg of glargine, with significant correlation (p< 0.05). The introduction of glargine therapy was coincident with a decrease of hypoglycemic crisis (p= 0.02), convulsive events due to hypoglycemia (severe hypoglycemic crisis) (p= 0.023) and ketosis (p= 0.001) switching MDI-treated patients with improvement of metabolic control (reduction of A1c levels). This therapy improved quality of life in these patients due to a significant reduction of hypoglycemic (including severe) events, ketosis episodes and total daily insulin dose, with important impact on health public services.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome

In this open study of clinical practice, 142 paediatric patients with type 1 diabetes mellitus (>1 year duration), stratified by age, received prandial insulin (regular or lispro) and either once daily insulin glargine (GLAR; n=74), titrated to target fasting blood glucose (FBG) levels 4.4-7.8 mmol/l, or NPH/semilente insulin (NPH insulin, administered once, twice or three times daily; n=68), titrated to target FBG 4.4-8.9 mmol/l. Both groups were treated for 20 +/- 10 months. HbA(1c) significantly increased in GLAR (7.3 +/- 1.0% to 7.6 +/- 1.1%; p = 0.003) and NPH/semilente insulin (7.7 +/- 1.6% to 8.3 +/- 1.5%; p = 0.0001) treated patients. The incidence of symptomatic hypoglycaemia was comparable between GLAR versus NPH/semilente insulin at endpoint (2.19 vs. 1.94 episodes/week); however, the overall incidence of severe hypoglycaemia was significantly lower with GLAR versus NPH/semilente insulin (0.14 vs. 0.73 events/patient-year; p = 0.002). The daily insulin dose was similar between the treatment groups; however, perceived quality of life (QoL) was better with GLAR. GLAR is associated with equivalent glycaemic control, less severe hypoglycaemia and improved QoL compared with NPH/semilente insulin.

Topics: Adolescent; Adult; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Hemoglobins; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Quality of Life

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes.. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups.. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05).. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

This study was conducted to evaluate the dose ratio of insulin detemir and neutral protamine Hagedorn (NPH) insulin over a range of therapeutically relevant subcutaneous doses.. The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of insulin detemir (0.15, 0.3, 0.6 U/kg) and NPH insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6- (2)H (2)] glucose).. Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U insulin detemir equals 1 IU NPH insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUC (GIR)) and the maximal GIR (GIR (max)) values, when comparing U (insulin detemir) to IU (NPH insulin). The pharmacodynamic within-subject profile was lower with insulin detemir in regard to AUC (GIR 0-24 h), GIR (max) and duration of action ( P<0.05). There was a tendency for a greater reduction of EGP with insulin detemir than with NPH insulin in regard to the area over the curve (AOC) of EGP in 24 hours (AOC (EGP 0-24 h)) ( P=0.07) and minimal EPG (EGP (min)) ( P=0.02).. These data show that insulin detemir is dose-proportional to NPH insulin in type 1 diabetic patients at clinically relevant doses. The data indicate that insulin detemir has a lower degree of within-subject variability.

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Preprandial insulin injection in preschool children is complicated by irregular eating habits. Postprandial injection of rapid-acting insulin analogs such as insulin aspart (IAsp) offers the convenience of adjusting insulin dose to match food consumed. This trial compared safety and efficacy - including parental treatment satisfaction - of two basal-bolus regimens [IAsp plus Neutral Protein Hagedorn (NPH) insulin vs. regular human insulin (HI) plus NPH] in preschool children with type 1 diabetes.. This study is a randomized, 12-wk, crossover trial comparing IAsp and regular HI in 26 children (17 boys and 9 girls; age: 2.4-6.9 yr). Regular HI was injected 30 min before and IAsp after or shortly before meals. Treatment satisfaction was assessed by a modified version of the WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ-M).. Glycemic control for IAsp treatment was not different from that for regular HI treatment as assessed by mean postprandial blood glucose increment (IAsp vs. regular HI: 2.0 vs. 1.6 mmol/L), fructosamine (300 vs. 302 micromol/L), and hemoglobin A(1c) (HbA(1c)) (7.7 vs. 7.6%). The relative risk of hypoglycemia was not significantly different [relative risk for IAsp/regular HI (95% CI): 1.06 (0.96-1.17), p = 0.225]. Mean total daily insulin dose (0.7 U/kg) remained constant throughout the trial with both treatments. The DTSQ-M score tended to be better for IAsp and reached statistical significance regarding the parental satisfaction with continuing IAsp treatment (p < 0.05).. In preschool children, a basal-bolus treatment scheme with postprandial IAsp as bolus insulin was equally effective and safe compared with preprandial regular HI, although the parents showed a preference for the IAsp treatment.

Topics: Blood Glucose; Child, Preschool; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Eating; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Patient Satisfaction; Surveys and Questionnaires

The results of using status measures to identify any changes in treatment satisfaction strongly suggest a need for specific change instruments designed to overcome the ceiling effects frequently observed at baseline. Status measures may leave little room to show improvement in situations where baseline ceiling effects are observed. A change version of the DTSQ (DTSQc) is compared here with the original status (now called DTSQs) version to test the instruments' comparative ability to demonstrate change.. Two multinational, openlabel, randomised-controlled trials (one for patients with type 1 diabetes, the other for type 2) compared new, longer-acting insulin glargine with standard NPH basal insulin. The DTSQs was completed at baseline and the DTSQs and DTSQc at final visit by 351 English- and German-speaking patients. DTSQc scores were compared with change from baseline for the DTSQs, using 3-way analysis of variance, to examine Questionnaire, Treatment and Ceiling effects (i.e. baseline scores at/near ceiling).. Significant Questionnaire effects and a Questionnaire x Ceiling interaction (p < 0.001) in both trial datasets showed that the DTSQc detected more improvement in Treatment Satisfaction than the DTSQs, especially when patients had DTSQs scores at/near ceiling at baseline. Additionally, significant Treatment effects favouring insulin glargine (p < 0.001) and a Treatment x Questionnaire interaction (p < 0.019), with the DTSQc showing more benefits, were found in the type 1 trial. Results for Perceived Hyper- and Hypoglycaemia also demonstrated important differences between the questionnaires in the detection of treatment effects. Tests of effect sizes showed these differences in response to change to be significantly in favour of the DTSQc.. The DTSQc, used in conjunction with the DTSQs, overcomes the problem of ceiling effects encountered when only the status measure is used and provides a means for new treatments to show greater value than is possible with the DTSQs alone.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Endpoint Determination; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Outcome Assessment, Health Care; Patient Satisfaction; Psychometrics; Surveys and Questionnaires; Time Factors

The aim of this prospective cross-over study was to compare glycemic control on NPH insulin (NPH) and on glargine in unsatisfactorily controlled type 1 diabetic prepubertal children.. 14 patients, aged 6-12 years, on multiple insulin injections regimen were included. The study protocol: (i) a 6-month therapy with NPH as basal insulin and (ii) a 6-month therapy with glargine as basal insulin, in a random order.. After 4 and 6 months mean blood glucose levels were similar on glargine and on NPH. After 6 months on NPH fasting blood glucose levels were similar to baseline (9.3+/-1.5 and 9.8+/-1.6 mmol/l respectively), while on glargine they were significantly lower compared to baseline (8.0+/-1.4 vs. 9.8+/-1.6 mmol/l, p=0.04) and markedly lower than after 6 months on NPH (8.0+/-1.4 vs. 9.3+/-1.5 mmol/l, p=0.077). HbA1c was lower on glargine compared to NPH, but only after 4 months the difference was statistically significant (7.1+/-0.16 vs. 7.74+/-0.25%, p=0.007). No severe hypoglycemia or ketoacidosis occurred.. In preadolescent children with unsatisfactorily controlled type 1 diabetes glargine constitutes a useful and safe alternative to NPH, providing better early morning and good total glycemic control, not increasing the risk of severe hypoglycemia; taking it into account the health care systems should participate in its costs for those who can not afford or tolerate an insulin pump.

Topics: Blood Glucose; Child; Child, Preschool; Cross-Over Studies; Diabetes Mellitus, Type 1; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Puberty; Treatment Outcome

Overweight and obesity are overrepresented in adolescents with type 1 diabetes mellitus (T1DM). Exogenous insulin administration often poorly reproduces normal insulin patterns and may less effectively regulate leptin and ghrelin, two hormones involved in the control of appetite and adiposity.. The objective of the study was to determine whether insulin regimens that better replicate normal insulin patterns and augment postprandial nutrient disposal may help normalize leptin and ghrelin and improve body weight regulation.. Ten young women with T1DM were studied in this 2-wk prospective, balanced crossover-design study at the University of California, Davis.. Participants received either a single injection of regular + NPH insulin (R+N) or two mealtime injections of Lispro insulin in randomized order on 2 separate days. Meal composition and total insulin administered were the same on both treatment days.. Plasma glucose, insulin, leptin, and ghrelin concentrations were monitored over the 10-h study period.. Lispro produced two distinct mealtime peaks of insulin, compared with one prolonged rise with R+N. Lispro reduced postprandial hyperglycemia and total glucose area under the curve. Leptin increased more on the Lispro (2.7 +/- 0.7 vs. 0.7 +/- 0.5 ng/ml, P = 0.02). Ghrelin was more suppressed after lunch with Lispro (P = 0.004).. Injection of Lispro insulin with meals produces more physiological insulin patterns, better glucose control, and improved leptin and ghrelin regulation than R+N. More closely mimicking normal insulin, leptin, and ghrelin responses to meals with fast-acting insulin may have implications for body weight regulation in T1DM.

Topics: Adolescent; Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Ghrelin; Humans; Insulin; Insulin Lispro; Insulin, Isophane; Leptin; Obesity; Peptide Hormones; Postprandial Period; Prospective Studies

This study evaluated the effect of aerobic versus resistance training on metabolic control in type-1 diabetes patients. Thirteen non-active patients, ranging in age from 13-30, were submitted to a 12-week aerobic exercise (Group A, n = 7) or resistance training (Group B, n = 6) period. Group A training consisted of a 40 min walk or run and Group B training consisted of resistance exercises three times a week. Blood samples were obtained before and after the 12-week training period. When these samples were compared, results showed that in Group A there were no changes in glycated hemoglobin, lipid profile, fast glucose level or body mass index (BMI). There was, however, a reduction in waist circumference and in average self-monitored blood glucose levels, measured after each exercise session. In Group B, there were no changes in the parameters evaluated. In both groups the total insulin dosage was reduced. As other authors have shown, resistance/aerobic training did not improve glycated hemoglobin in type-1 diabetes patients.

Topics: Adolescent; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Combined Modality Therapy; Diabetes Mellitus, Type 1; Exercise; Exercise Therapy; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Lispro; Insulin, Isophane; Lipids; Male; Physical Endurance; Waist-Hip Ratio

To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen.. In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 +/- 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile.. HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference -0.5 (95% CI -0.7, -0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l(-1) h(-1), P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l(-1) h(-1), P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l(-1) h(-1), P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001).. Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia.

Topics: Adult; Area Under Curve; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state.. Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (+/- sd) 39 +/- 12 years, body mass index 24 +/- 3 kg/m(2)] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7-14 days, after which the third clamp was performed to investigate IDet at steady state.. At steady state, the metabolic effect of IDet was constant over 24 h while a clear peak in the metabolic effect [expressed as glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the metabolic effect (maximum GIR divided by the average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation(12-24 h) 1.27 +/- 0.17 vs. 1.56 +/- 0.72, P < 0.05). The overall metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)(0-24 h): 5697 +/- 1861 vs. 5929 +/- 1965 mg/kg] whereas a significantly lower effect (5187 +/- 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIR(trough 24 h) 3.7 +/- 1.7 vs. 3.8 +/- 1.6 mg/(kg x min) NS], indicating that IDet had reached steady state after the first two injections.. IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects.

Topics: Adult; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Infusions, Parenteral; Injections; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

Hypoglycaemia remains a major barrier preventing optimal glycaemic control in Type 1 diabetes due to the limitations of conventional insulin preparations. We investigated whether basal-bolus therapy with insulin detemir (detemir), a new soluble basal insulin analogue, was more effective in reducing the risk of hypoglycaemia compared with NPH insulin (NPH).. In this multinational, open-label, cross-over trial, 130 individuals with Type 1 diabetes received detemir and NPH twice daily in a randomized order in combination with premeal insulin aspart (IAsp) during two 16-week treatment periods. Risk of hypoglycaemia was based on self-measured plasma glucose (SMPG) and self-reported episodes during the last 10 weeks of each period.. Risk of nocturnal and overall hypoglycaemia was, respectively, 50% and 18% lower with detemir than with NPH (P < 0.001). A total of 19 severe hypoglycaemic episodes occurred during treatment with detemir compared with 33 with NPH (NS). HbA(1c) decreased by 0.3% point with both treatments and was comparable at 7.6% (+/- sem 0.06%, 95% confidence interval -0.106, 0.108) after 16 weeks with similar doses of basal insulin. Within-person variation in mean plasma glucose was lower with detemir than with NPH (sd 3.00 vs. 3.33, P < 0.001), as was prebreakfast SMPG (P < 0.0001).. Detemir was associated with a significantly lower risk of hypoglycaemia compared with NPH at similar HbA1c when used in combination with mealtime IAsp. The more consistent plasma glucose levels observed with detemir may allow people to aim for tighter glycaemic control without an increased risk of hypoglycaemia.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

The aim of this study was to compare the effect of multiple mealtime injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on glycaemic control in patients with type 1 diabetes.. Twenty-three patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range) with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All eligible patients were randomly assigned to BIAsp30 thrice daily supplied with bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then switched to the alternative regimen for another 12 weeks. The insulin dose adjustments were made by patients on the basis of advice from a diabetes nurse. At end of each treatment period, the patients attended two profile days, 1 week apart for pharmacodynamic and pharmacokinetic assessments. HbA1C was measured at baseline and at the end of each treatment period. A seven-point self-monitored blood glucose (SMBG) was obtained twice weekly.. In comparison with HI, multiple mealtime injections of BIAsp30 resulted in a significant reduction in HbA1C[HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7-9.8), p = 0.013]. During treatment with BIAsp30, nighttime glycaemic control was significantly improved. Day-to-day variation in pharmacodynamics and pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30 compared with HI.. In type 1 diabetics, multiple mealtime administration of BIAsp30 compared with traditional basal-bolus human insulin treatment significantly improves long-term glycaemic control without increasing the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day variations in insulin pharmacokinetics and pharmacodynamics.

Topics: Adult; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

Pain resulting from injections has a potential influence on the acceptance and thus on the success of insulin treatment. Systematic investigation in humans has suggested that individuals perceive more pain during SC injection of acidic solutions than neutral solutions. Insulin glargine is a long-acting (up to 24-hour duration of effect), parenteral blood glucose-lowering agent. Unlike other insulins, it is injected as an acidic solution (pH 4).. The aim of this study was to assess whether the SC injection of insulin glargine is more painful than neutral insulin in a clinical setting.. This single-center, prospective, controlled, noninterventional study was performed in consecutively enrolled male and female pediatric patients (7-21 years) with type 1 diabetes mellitus who self-injected insulin >or=3 times per day and who had diabetes duration of >or=6 months. The study was conducted from September 1, 2005, to December 30, 2005, at the Diabetes Clinic, University Children's Hospital, Ulm, Germany. No changes to the patients' current insulin regimen were made. Based on their existing insulin treatment, patients were assigned to 1 of 2 treatment groups: (1) the acidic insulin group, which injected insulin glargine, and (2) the neutral insulin group, which injected neutral protamine Hagedorn or Semilente insulin. All patients also injected shortacting regular insulin or insulin analogs. Pain during SC insulin injection and during self-monitoring of blood glucose (SMBG) (the internal control) was assessed using a standardized, noninterventional protocol and optimized combined 10-cm visual analog scale and 5-point verbal rating scale (minimum = I cannot feel it at all; maximum = it hurts me). Patients were instructed to document pain immediately after insulin injection and SMBG at home 3 times a day on 3 different days.. A total of 112 patients (mean [SD] age, 14.6 [3.0] years; sex, 60 [53.6%] male; mean [SD] glycosylated hemoglobin [HbA(1c)], 8.0% [1.4%]; mean [SD] diabetes duration, 6.1 [3.9] years) completed the study. Pain scores reported by the acidic group (n = 76) were not significantly different when compared with those of the neutral group (n = 36) (4.0 [2.0] vs 4.2 [1.9]). Pain scores were also similar for the injection of short-acting insulin in those from the acidic group when compared with those from the neutral group (3.7 [1.7] vs 4.1 [2.1]). Insulin injections were generally perceived as more painful than SMBG (3.9 [1.7] vs 2.9 [1.8]; P < 0.001). Using the Spearman rank correlation coefficient, pain perception was determined to be independent of age, gender, HbA(1c) level, and duration of diabetes.. Despite its acidic formulation (pH 4), insulin glargine was not perceived as more painful during SC injection than neutral long-acting or shortacting insulin in these pediatric patients with type 1 diabetes mellitus.

Topics: Adolescent; Adult; Blood Glucose Self-Monitoring; Case-Control Studies; Child; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Pain; Pain Measurement; Prospective Studies; Self Administration

The aim of this study was to compare the long-term safety and efficacy of twice-daily insulin detemir or NPH insulin as the basal component of basal-bolus therapy in people with type 1 diabetes.. A multicentre, open-label, parallel-group study was conducted over 12 months and completed by 308 people (from an original randomized cohort of 428). Patients were randomized in a 2:1 ratio to receive insulin detemir or NPH insulin before breakfast and dinner, with insulin aspart at mealtimes.. Glycaemic control improved in both groups with HbA(1c) decreasing by 0.64 and 0.56% point in the insulin detemir and NPH insulin groups, reaching baseline-adjusted final values of 7.53 +/- 0.10% and 7.59 +/- 0.13%, respectively. No significant difference was apparent between treatments in terms of HbA(1c), fasting plasma glucose or 9-point blood glucose profiles. Fewer hypoglycaemic events (major and minor) occurred in association with insulin detemir compared with NPH insulin, but the overall hypoglycaemic risk did not differ statistically significantly (RR for detemir, 0.78 [0.56-1.08]). However, the risk of nocturnal hypoglycaemia during the maintenance phase (month 2-12) was 32% lower in the detemir group (p = 0.02) and lower in every month. This risk reduction remained statistically significant after correction for HbA(1c). After 12 months, baseline-adjusted mean body weight was significantly lower in the insulin detemir group than in the NPH insulin group (p < 0.001).. In long-term basal-bolus therapy, insulin detemir with insulin aspart as mealtime insulin is well tolerated and reduces the risks of nocturnal hypoglycaemia and weight gain compared to NPH insulin.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

To compare pharmacokinetic characteristics of two biphasic insulin aspart (BIAsp) formulations: BIAsp30 and BIAsp70 (30% and 70%, respectively, of fast-acting insulin aspart) during 15 days of multiple dosing (thrice daily).. A total of 22 patients with Type 1 diabetes (nine women, 13 men) aged 41.4 +/- 9.9 years (mean +/- sd) with a diabetes duration of 18.9 (2.3-40.3) years (median and range) completed the randomized, double-blinded, two-period crossover study. On day 1 and day 15 of each treatment period, 24-h serum insulin and glucose profiles were evaluated. Total area under the insulin aspart concentration-time curve (AUC(0-24 h)), AUC after dinner administration stratified into early (AUCdinner(0-6 h)) and intermediate-phase (AUCdinner(6-14 h)), maximum insulin concentration (Cmax), time to maximum insulin concentration (Tmax) after each meal were recorded.. On day 15 BIAsp70 was associated with a shorter Tmax, and more than 40% elevated Cmax. Comparing with BIAsp30, AUC(0-24 h) and AUCdinner(0-6 h) were increased by 25% and 28%, respectively, but AUCdinner (6-14 h) was markedly lower for BIAsp70 [BIAsp30/BIAsp70: 1.9; 95% CI (1.42, 2.55)]. Similar findings were also observed on day 1. The fasting or pre-meal serum insulin levels on day 15 tended to be higher with BIAsp30, but the differences were not statistically significant. CONCLUSIONS The pharmacokinetic properties of BIAsp30 and 70 remain constant during 2 weeks of daily administration in patients with Type 1 diabetes. In comparison with BIAsp30, the administration of BIAsp70 results in a shorter time to and larger maximum insulin aspart concentration. Furthermore, total and early post-dinner insulin AUC were greater, whereas late-phase insulin exposure was lower with BIAsp70.

Topics: Adult; Area Under Curve; Biphasic Insulins; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Time Factors

To investigate the pharmacodynamic profile and duration of action for five subcutaneous doses of insulin detemir (0.1, 0.2, 0.4, 0.8, and 1.6 units/kg; 1 unit = 24 nmol) and one subcutaneous dose of NPH insulin (0.3 IU/kg; 1 IU = 6 nmol).. This single-center, randomized, double-blind, six-period, crossover study was carried out as a 24-h isoglycemic clamp (7.2 mmol/l) in 12 type 1 diabetic patients.. Duration of action for insulin detemir was dose dependent and varied from 5.7, to 12.1, to 19.9, to 22.7, to 23.2 h for 0.1, 0.2, 0.4, 0.8, and 1.6 units/kg, respectively. Interpolation of the dose-response relationships for AUC(GIR) (area under the glucose infusion rate curve) revealed that a detemir dose of 0.29 units/kg would provide the same effect as 0.3 IU/kg NPH but has a longer duration of action (16.9 vs. 12.7 h, respectively). Lower between-subject variability was observed for insulin detemir on duration of action (0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, P < 0.05) and GIR(max) (maximal glucose infusion rate) (0.2 and 0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, both P < 0.05). Assessment of endogenous glucose production (EGP) and peripheral glucose uptake (PGU) resulted in an AOC(EGP) (area over the EGP curve) of 636 mg/kg (95% CI 279-879) vs. 584 (323-846) and an AUC(PGU) (area under the PGU curve) of 173 (47-316) vs. 328 (39-617) for 0.29 units/kg detemir vs. 0.3 IU/kg NPH, respectively.. This study shows that insulin detemir provides a flat and protracted pharmacodynamic profile.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

This trial investigated the efficacy and safety of two different administration-time regimens with insulin detemir (IDet) to that of a conventional basal insulin regimen with NPH insulin (NPH).. This multinational, 16-week, open, parallel group trial included 400 people with Type 1 diabetes mellitus (DM) randomized to IDet either morning and before dinner (IDetmorn+din) or morning and bedtime (IDetmorn+bed), or to NPH morning and bedtime (NPHmorn+bed), all in combination with mealtime insulin aspart (IAsp).. HbA1c was comparable between the three groups after 16 weeks (P = 0.64), with reductions of 0.39-0.49% points. Lower fasting plasma glucose (FPG) was observed with IDetmorn+din and IDetmorn+bed compared with NPHmorn+bed (9.8 and 9.1 vs. 11.1 mmol/l, P = 0.006), whereas the IDet groups did not differ (P = 0.15). Within-person variation in self-measured FPG was significantly lower for both IDet regimens (sd IDetmorn+din 2.5, IDetmorn+bed 2.6 mmol/l) than for NPHmorn+bed (sd 3.1 mmol/l, P < 0.001), but was comparable between the IDet groups (P = 0.48). Ten-point plasma glucose profiles were lower between dinner and breakfast in the IDetmorn+din group (P = 0.043), compared with the two other groups. Risk of overall and nocturnal hypoglycaemia was similar for the three groups. Lower mean bodyweight was observed with IDet compared with NPH after 16 weeks (difference: (IDetmorn+din)-1.3 kg, P < 0.001, (IDetmorn+bed)-0.6 kg, P = 0.050).. Both IDet regimens were well tolerated and provided lower and less variable glucose levels with no, or less, weight gain than NPH at comparable HbA1c. IDet can be administered either at dinner or bedtime, with similar glycaemic control according to the need of the individual person.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome; Weight Loss

To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1 diabetes patients.. Patients (n = 125) received preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a multicentre, randomized, single-blind (a blinded investigator made titration decisions) study. Basal insulin dosage was titrated to achieve fasting blood glucose (FBG) values < 5.5 mmol/L.. Baseline characteristics were similar for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3 versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a significant treatment benefit of 0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of glargine (P < 0.05). There were similar total numbers of daytime mild, moderate or severe hypoglycaemia episodes in the two treatment arms. However, significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group (P = 0.04 and P = 0.02).. Glargine is superior to NPH for improving HbA(1c) and FBG levels during intensive insulin therapy in patients with type 1 diabetes, and is associated with less severe nocturnal hypoglycaemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Fasting; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Retrospective Studies; Single-Blind Method; Treatment Outcome

This study aimed to evaluate the impact of insulin antibodies on insulin aspart pharmaco-kinetics and pharmacodynamics after 12-week multiple daily injections of biphasic insulin aspart 30 (30% fast-acting and 70% protamine-crystallised insulin aspart, BIAsp30) in patients with type 1 diabetes.. Twenty-three patients (8 women, 15 men) aged 44.8 (20.6-62.5) years (median and range) with diabetes duration of 19.5 (1.6-44.6) years and haemoglobin (Hb)A(1C) of 9.2% (8.1-12.3%) participated in the study, which consisted of 12-week treatment with multiple injections of BIAsp30. At the end of the treatment period, all patients attended two 24-h profile days 1 week apart for pharmacokinetic and pharmacodynamic assessments. HbA(1C) and insulin antibodies were also determined.. Patients were stratified into two groups depending on whether the level of insulin binding to insulin antibodies was below or above 75% (moderate vs high (%, median and range): 62 (15-74) vs 80 (75-89)). High levels of insulin antibodies resulted in about threefold increase in AUC((0 - 24 h)) (the area under the concentration-time curve during 24 h) for total insulin aspart (analysis of variance, P < 0.05). The differences in free insulin aspart pharmacokinetics, insulin pharmacodynamics and HbA(1C) were not statistically significant between patients with different levels of insulin antibodies. Total daily insulin dosage was significantly lower in patients with high than moderate levels of insulin antibodies.. In type 1 diabetic patients, high levels of circulating insulin antibodies result in elevated total, but not free, insulin aspart profiles. Consistent with the finding of similar insulin pharmacodynamics, the long-term glycaemic control is not significantly different between patients with different levels of insulin antibodies.

Topics: Adult; Biphasic Insulins; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Antibodies; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Reproducibility of Results; Treatment Outcome

Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.. People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.. With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040).. Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean +/- SD], BMI 24 +/- 2 kg/m(2), HbA(1c) 7.5 +/- 1.2%, diabetes duration 18 +/- 9 years) participated in this parallel group comparison. Each subject received four single subcutaneous doses of 0.4 units/kg of either insulin detemir (n = 18), insulin glargine (n = 16), or human NPH insulin (n = 17) under euglycemic glucose clamp conditions (target blood glucose concentration 5.5 mmol/l) on four identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and pharmacokinetic (serum concentrations of insulin detemir, human insulin, and insulin glargine) properties of the basal insulin preparations were recorded for 24 h postdosing. Insulin detemir was associated with significantly less within-subject variability than both NPH insulin and insulin glargine, as assessed by the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR-AUC((0-12 h)) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC((0-24 h)) 27 vs. 68 vs. 48%; GIR(max) 23 vs. 46 vs. 36%; P < 0.001 for all comparisons]. Insulin detemir also provided less within-subject variability in the pharmacokinetic end points: maximal concentration (C(max)) 18 vs. 24 vs. 34%; INS-AUC((0- infinity )) 14 vs. 28 vs. 33%. The results suggest that insulin detemir has a significantly more predictable glucose-lowering effect than both NPH insulin and insulin glargine.

Topics: Adult; Carrier Proteins; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Time Factors; Treatment Outcome

Individuals at high risk of developing type 1 diabetes mellitus can be identified using immunologic, genetic, and metabolic parameters. In the Diabetes Prevention Trial-1 (DPT-1), annual intravenous infusions of low doses of regular insulin, together with daily subcutaneous injection of a single low dose of Ultralente insulin at nighttime, failed to prevent or delay the onset of type 1 diabetes in high-risk non-diabetic relatives. In our study, we attempted to achieve beta-cell rest by administering higher doses of neutral protamine Hagedorn (NPH) insulin twice daily to high-risk non-diabetic subjects in an effort to prevent or delay the onset of the disease. The maximum tolerable dose was given with the dose reduced for any hypoglycemia (mean dose 0.33 +/- 0.15; range 0.09-0.66 units/kg/d). We treated 26 subjects who were confirmed to have islet cell antibodies (ICAs) and a low first-phase insulin response (FPIR) to intravenous glucose. Fourteen had normal glucose tolerance and 12 impaired glucose tolerance (IGT). The median duration of follow-up was 5.5 yr. Diabetes occurred in 10 of 12 subjects with IGT and five of 14 subjects with normal glucose tolerance. The cumulative incidence of diabetes was the same as with that seen in a matched, observation group (subjects followed prospectively as part of the University of Florida natural history studies) (age, sex, ICA, insulin autoantibodies, duration of ICA prior to enrollment, FPIR, and glucose intolerance; p = 0.39), as was the rate of progression (p = 0.79). There was a higher rate of progression to diabetes in the group with abnormal glucose tolerance at baseline than in those with normal baseline glucose tolerance (p = 0.003). Interestingly, in non-progressors, as opposed to progressors, there was no fall in C-peptide (peak and area under the curve) production regardless of the type of tolerance testing (mixed meal, oral or intravenous) over time (p < 0.001). In this study, in the dose and regimen of NPH insulin used, insulin did not delay or prevent the development of type 1 diabetes. However, preservation of C-peptide production in the prediabetic period appears to indicate non-progression to clinical disease and may serve as a new surrogate for determining response to preventative efforts.

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Middle Aged; Pilot Projects; Prediabetic State; Risk

Injection of insulin lispro (LP) before meals provides a more physiologic insulin activity profile than regular human insulin, but the relatively short duration of action of LP may allow the blood glucose (BG) level to increase during the late postprandial period (4-7 hours after meals) unless basal insulin is optimally replaced. One approach to basal insulin optimization has been to combine small doses of NPH with LP before meals. When used in a similar fashion, premixed, fixed-ratio insulin preparations containing LP and NPL (an LP-based intermediate-acting insulin) may provide the basis for an optimized basal-bolus insulin regimen.. This study assessed mean late postprandial glycemic control during treatment with a premixed formulation consisting of a high proportion of LP (75% LP/25% NPL; H) and a premixed formulation consisting of a medium proportion of LP (50% LP/50% NPL; M). The H/M formulation was given before meals and was compared with treatment with preprandial LP + NPH (LP + N) in patients with type 1 diabetes mellitus (DM).. This multicenter, randomized, open-label, 2-period crossover study was conducted at 4 centers in Italy and 1 center in France. Patients eligible for the study had type 1 DM, were > or = 18 years of age, and had a glycosylated hemoglobin (HbA(1c)) <150% of the upper limit of normal. Patients were randomly assigned to 1 of 2 treatment sequences: LP self-mixed with NPH before meals plus NPH alone at bedtime for 8 weeks (LP + N) followed by preprandial H or M, plus NPH alone at bedtime for 8 weeks (H/M), or the opposite sequence. Assessments included 8-point self-monitored BG profiles, HbA(1c), and hypoglycemia (any sign or symptom of hypoglycemia or BG < 3.0 mmol/L [<54.0 mg/dL]). The primary outcome measure was the late postprandial BG value, calculated as the mean of the combined prelunch (late postbreakfast), predinner (late postlunch), and bedtime (late postdinner) values.. A total of 89 patients with type 1 DM were enrolled (44 men, 45 women; mean [SD] age, 38.3 [12.8] years; mean [SD] body weight, 70.8 [11.6] kg; mean [SD] body mass index, 24.6 [3.0] kg/m(2); mean [SD] duration of diabetes, 17.8 [10.5] years; mean HbA(1c), 7.9% [0.88%]). The mean (SD) late postprandial BG values were similar between treatments (8.9 [2.1] mmol/L [160.3 (37.8) mg/dL] for H/M vs 9.0 [1.8] mmol/L [162.1 (32.4) mg/dL] for LP + N), as were the end point HbA(1c) values (7.8% [0.9%] for H/M vs 7.9% [0.8%] for LP + N). The rate of hypoglycemia was significantly higher during treatment with H/M, primarily because of episodes occurring between 12 PM and 6 PM, but was relatively low in both groups (mean/median rate per patient per 30 days: 2.87/2.14 for H/M and 2.11/1.07 for LP + N; P < 0.05).. In this population of patients with type 1 DM, preprandial H/M provided an effective alternative regimen for prandial and basal insulin replacement. Late postprandial BG control, an indicator of basal insulin sufficiency, was similar to that achieved with an intensified regimen of LP + N injected separately before meals, and the end point HbA(1c) was similar between the 2 treatments.

Topics: Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Male; Postprandial Period; Time Factors

To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy.. In this multinational, double-blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA(1c) < 8.0%) were symmetrically randomised to two 16-week treatment periods on either type of insulin, both injected 0-5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4-week washout.. The rate of major nocturnal (24.00-06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47-1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA(1c) remained constant, slightly below 7.7% on both treatments.. The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.

Topics: Adolescent; Adult; Aged; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

The purpose of this trial was to compare the effects of QD basal insulin replacement using insulin detemir versus neutral protamine Hagedorn (NPH) insulin in basal-bolus therapy in combination with regular human insulin (HI) in patients with type 1 diabetes mellitus (DM).. This was a 6-month, prospective, randomized, open-label, controlled, parallel-group trial conducted at 92 sites in Europe and Australia. The trial population included men and women with type 1 DM for at least 1 year aged > or = 18 years with glycosylated hemoglobin (HbA(1c)) <== 12% already taking QD basal-bolus treatment with an intermediate- or long-acting insulin and a fast-acting human insulin or insulin analogue as bolus insulin. Patients were randomly assigned (2:1) to 6 months of treatment with insulin detemir or NPH at bedtime in combination with HI with main meals. Main outcome measures were blood glucose control as assessed by HbA(1c), fasting plasma glucose (FPG), 9-point self-monitored blood glucose (SMBG) profiles, 24-hour continuous blood glucose profiles, hypoglycemia, weight gain, and adverse events.. Of the 749 patients randomized to treatment, 747 were exposed to trial products and included in the intent-to-treat analysis set. Seven hundred patients completed the trial: 465 (94.7%) in the insulin detemir group and 235 (91.8%) in the NPH group. After 6 months, FPG was lower with insulin detemir than with NPH (-1.16 mmol/L difference; P = 0.001), whereas HbA(1c) did not differ significantly between treatments (-0.12% [95% CI, -0.25 to 0.02]; P = NS). Day-to-day variability in self-measured fasting blood glucose was lower with insulin detemir (SD, 2.82 vs 3.60 mmol/L; P < 0.001). The overall shape of the 9-point SMBG profiles differed significantly between treatments (P = 0.006), with lower glucose levels before breakfast with insulin detemir than with NPH (P < 0.001). There was a 26% reduction in the relative risk of nocturnal hypoglycemia with insulin detemir compared with NPH (P = 0.003). Gain in body weight was significantly lower after 6 months with insulin detemir than with NPH (-0.54 kg difference; P = 0.024). The frequency and type of adverse events were similar between treatment groups.. In this study, QD administration of insulin detemir at bedtime resulted in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from ean blood glucose levels over 24 hours than NPH insulin, combined with an overall reduction in the risk of nocturnal hypoglycemia. These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets.

Topics: Adult; Blood Glucose; Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies

The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin.. In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively.. Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001).. Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH.. One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment.. Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05).. The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cognition; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male

This trial compared the long-term safety and efficacy of the basal insulin preparations, insulin detemir and NPH insulin, in basal-bolus therapy for patients with type 1 diabetes.. This multinational open, parallel-group trial randomized patients to receive insulin detemir or NPH insulin twice daily in addition to mealtime human soluble insulin. Doses were titrated towards predefined glycemic targets. After an initial 6-month treatment period, patients were invited to participate in a 6-month extension period. A total of 289 from 421 elected to continue in the trial, of which 252 completed.. Glycemic control as assessed by hemoglobin A1c (insulin detemir, 7.88%; NPH insulin, 7.78%; difference not significant) and fasting plasma glucose (insulin detemir, 10.1 mmol/L; NPH insulin, 9.84 mmol/L; difference not significant) was similar in both treatment groups at end point, with hemoglobin A1c little changed from baseline and fasting plasma glucose slightly decreased. There was some evidence for a risk reduction for hypoglycemia in association with insulin detemir, although this was not statistically significant (relative risk overall hypoglycemia, 0.71, P = 0.139; relative risk nocturnal hypoglycemia, 0.71, P = 0.067), and hypoglycemic events were fewer in each of the 12 months. There was a significant treatment difference with regard to weight outcome; NPH insulin was associated with weight gain (1.4 kg), but there was no mean weight gain (-0.3 kg) in the insulin detemir cohort (baseline-adjusted between-group difference at 12 months, 1.66 kg, P = 0.002). There were no obvious between-group differences in other safety parameters.. Glycemic control is maintained with insulin detemir during long-term treatment. At equivalent glycemic control to NPH insulin, insulin detemir is associated with a lack of weight gain and a trend towards a reduced risk of nocturnal hypoglycemia when used in basal-bolus therapy with mealtime soluble human insulin.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Middle Aged

The goal of new therapies introduced for type 1 diabetes should be to decrease hypoglycemic episodes while improving glycemic control.. A database was used to computer match the baseline A1C values in 196 subjects with type 1 diabetes receiving multiple daily injections (MDI) consisting of four or more injections per day. There were 98 patients transferred from NPH to insulin glargine (Lantus, Aventis Pharmaceuticals, Bridgewater, NJ), and 98 patients remained on NPH throughout the study. The gender distribution and mean age (approximately 32 years), duration of diabetes (approximately 16 years), and duration of treatment (approximately 13 months) were not significantly different between the groups. The majority of patients were well controlled (>50% in both groups had an A1C <7%).. The mean A1c values were not significantly different in the groups at baseline or at follow-up. Severe hypoglycemic episodes per patient per year were significantly lower in the glargine group compared with the NPH group (0.5 vs. 1.2, respectively; P = 0.04). The mean end-of-study total (P = 0.03) and long-acting (P = 0.0001) doses were significantly reduced from baseline in the group that switched to glargine, but not in the group that remained on NPH, with no change in the short-acting dose in either group. The weight gain was significantly higher in the NPH group at the end of the study (P = 0.004) with no significant change in the glargine group.. Transfer to glargine treatment from NPH in MDI regimens significantly reduces severe hypoglycemic episodes despite a decline in long-acting basal insulin without significant weight gain.

Topics: Adult; Databases, Factual; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Time Factors

Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals.. This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively.. After 6 months, comparable HbA(1c) levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (-0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300-0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P = 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001).. Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.

Topics: Adult; Blood Glucose; Body Weight; Carrier Proteins; Diabetes Mellitus, Type 1; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Risk Factors

To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin.. In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study.. Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13).. Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.

Topics: Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male

To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime.. A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4-7.2 mmol/l and 2 h after meals at 8.0-9.2 mmol/l. The primary end point was HbA(1c).. Mean daily blood glucose was lower with dinnertime glargine (7.5 +/- 0.2 mmol/l) or bedtime glargine (7.4 +/- 0.2 mmol/l) versus NPH (8.3 +/- 0.2 mmol/l) (P < 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P < 0.05). HbA(1c) at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 +/- 0.2 to 6.4 +/- 0.1%) and glargine at bedtime (from 7.0 +/- 0.2 to 6.6 +/- 0.1%) (P < 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P < 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose < or =4.0 mmol/l) was lower with glargine (dinnertime 8.1 +/- 0.8 mmol/l, bedtime 7.7 +/- 0.9 mmol/l) than with NPH (12.2 +/- 1.3 mmol/l) (episodes/patient-month, P < 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P < 0.05). There were no differences between glargine given at dinnertime and at bedtime.. Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA(1c) level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; Postprandial Period

This trial aimed to characterize for the first time the pharmacokinetic profile of insulin detemir, the novel soluble basal insulin analog, in children and adolescents compared with adults. Comparisons were also made with NPH insulin to determine any between-treatment difference in the effect of age on pharmacokinetic profile.. This single-center, open-label, randomized, crossover trial included children (aged 6-12 years, n = 13), adolescents (aged 13-17 years, n = 10), and adults (aged 18-65 years, n = 11) of both sexes. Subjects were given single doses of 0.5 units/kg s.c. insulin detemir or 0.5 IU/kg NPH insulin on 2 separate days. Serial blood sampling was performed for 24 h for analysis of serum insulin detemir, human insulin, and glucose concentrations.. The mean pharmacokinetic profile of insulin detemir was similar across all three age-groups. This was determined by statistical analyses of the data, which showed no overall age effect or between-group differences when pairwise comparisons were made between children (or adolescents) and adults on the parameters of the area under the curve (AUC), AUC from zero to infinity, AUC from 0 to 24 h [AUC((0-24 h))], and the maximum concentration measured during the 24 h after closing. No overall age effect for AUC((0-24 h)) and C(max) was detected for NPH insulin, but data were only analyzable from seven adults and pairwise comparisons did indicate that children and adults had different pharmacokinetic profiles. Less total variability in the pharmacokinetics of insulin detemir than NPH insulin was indicated by lower coefficients of variation in AUC, C(max), and time to maximum concentration in all three age-groups.. The data suggest that insulin detemir can be used in children and adolescents with type 1 diabetes using titration guidelines similar to those used in adults. Moreover, insulin detemir may offer the advantage of greater predictability of response in comparison to NPH insulin due to lower total variability and a lesser degree of kinetic disparity across age-groups.

Topics: Adolescent; Adult; Age Factors; Aged; Carrier Proteins; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

The purpose of this study was to evaluate the use of a new long-acting basal insulin, insulin glargine (IG), in children with type 1 diabetes. Study design Data from 114 subjects, age 2 to 18 years (mean, 12.2 years; 54 boys, 60 girls), were collected for 9 months before and 9 months after IG treatment. During IG therapy, all subjects received morning neutral protamine Hagedorn insulin (given with insulin lispro; Humalog) to provide daytime insulin coverage. The numbers of nonsevere and severe hypoglycemic events, hemoglobin A1c values, body weight, and daily insulin dose were recorded at each clinic visit.. The mean (+/-1 SEM) frequency of nonsevere hypoglycemic events per week decreased from 2.0+/-0.1 to 1.3+/-0.1 (P<.001). Severe hypoglycemic episodes were reduced from a total of 22 in the 9 months before IG to nine in the 9 months after IG. Severe nocturnal events were similarly reduced from 14 to four episodes. The mean (+/-1 SEM) hemoglobin A1c levels were 9.6+/-0.1% (baseline), 9.4+/-0.1% at 3 months (P=.18), 9.3+/-0.1% at 6 months (P=.03), and 9.3+/-0.1% at 9 months (P=.01).. Insulin glargine therapy can reduce hypoglycemic episodes in children and adolescents with suboptimal glucose control without jeopardizing glycemic control.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Topics: Biphasic Insulins; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Feeding Behavior; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Italy; Male; Middle Aged; Research Design; Time Factors

This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night.. The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 x NPH) or twice (2 x NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA(1c) levels <8.5%. Efficacy measures were HbA(1c) levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials.. In all, 104 patients completed the trial. The mean HbA(1c) level before randomization was 7.1 +/- 0.85%. The HbA(1c) levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] -0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 x NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 x NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively.. Equal HbA(1c) levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 x NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.

Topics: Adult; Blood Glucose; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male

Intensive insulin treatment of type 1 diabetes mellitus increases the risk for nocturnal hypoglycemia.. To demonstrate that splitting the evening insulin regimen reduces the risk for nocturnal hypoglycemia in intensive treatment of type 1 diabetes mellitus.. Randomized, open, two-treatment crossover trial in two 4-month periods.. University research center in Italy.. 22 C-peptide-negative persons with type 1 diabetes mellitus (mean age [+/-SD], 29 +/- 3 years).. Each patient was randomly assigned to one of two insulin regimens for 4 months and then switched to the other regimen for another 4 months. The two treatment regimens were 1) mixed treatment--a mixture of human regular and neutral protamine Hagedorn (NPH) insulin administered before dinner and 2) split treatment--human regular insulin administered at dinner and NPH insulin administered at bedtime.. Frequency of nocturnal hypoglycemia. Secondary end points were levels of fasting blood glucose and hemoglobin A1c and responses to experimental hypoglycemia.. During the split-regimen treatment period, patients had fewer episodes of nocturnal hypoglycemia (mean [+/-SE], 0.10 +/- 0.02 episode/patient-day vs. 0.28 +/- 0.04 episode/patient-day; P = 0.002), a lower fasting blood glucose level (mean [+/-SE], 7.6 +/- 0.2 mmol/L vs. 8.3 +/- 0.5 mmol/L [137 +/- 4 mg/dL vs. 160 +/- 8 mg/dL]; P = 0.030), less variable fasting blood glucose levels (SD range, 2.0 +/- 0.4 vs. 3.5 +/- 0.6; P = 0.001), and lower hemoglobin A1c value (mean [+/-SE], 7.0% +/- 0.11% vs. 7.5% +/- 0.15%; P = 0.004) than during the mixed regimen. Responses to experimental hypoglycemia were better preserved with the split regimen than with the mixed regimen.. When the goal of insulin therapy in type 1 diabetes mellitus is near-normoglycemia, splitting the evening insulin treatment regimen into short-acting insulin at dinner and NPH insulin at bedtime reduces the risks for nocturnal hypoglycemia and hypoglycemia unawareness and decreases the hemoglobin A1c value compared with mixing short-acting insulin and NPH insulin at dinner.

Topics: Adult; Analysis of Variance; Blood Glucose; Circadian Rhythm; Cognition Disorders; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Prospective Studies; Regression Analysis

Topics: Adult; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Prospective Studies

Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human-soluble insulin but reduces rates of hypoglycaemia. We tested the hypothesis that the use of rapid-acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy.. Ten patients with type 1 diabetes (four female, mean age 33 +/- 3 years, diabetes duration 12 +/- 2 years) participated in an open, randomized cross-over study, with 2 months run-in and 4-month treatment periods using either lispro or human-soluble insulin before meals and human NPH insulin (NPH) at night. The total of reported hypoglycaemic episodes (lispro vs. soluble, 123 vs. 128) and HbA(1c) (6.1 +/- 0.2 vs. 6.6 +/- 0.2%) were similar during both treatments. At the end of each period, we measured symptomatic, counterregulatory and cognitive responses, and glycaemic thresholds during hypoglycaemia, induced with a hyperinsulinaemic clamp (blood glucose of 5, 4.5, 3.5 and 2.5 mmol/l).. We found similar overall responses of adrenaline, cortisol, growth hormone and total symptom score. Glycaemic thresholds for rises in adrenaline (3.1 +/- 0.2 vs. 3.1 +/- 0.2 mmol/l, p = 0.76), cortisol (2.2 +/- 0.1 vs. 2.2 +/- 0.1 mmol/l, p = 0.16), growth hormone (3.3 +/- 0.15 vs. 2.9 +/- 0.2 mmol/l, p = 0.13), symptoms (3.2 +/- 0.2 vs. 3.3 +/- 0.1 mmol/l, p = 0.051) and impaired cognitive function (3.0 +/- 0.2 vs. 3.0 +/-0.2 mmol/l, p = 0.20) were also similar.. Four months of intensive treatment, with insulin lispro used pre-prandially and isophane at night, produced relatively preserved but equivalent physiological responses to hypoglycaemia as those on soluble insulin. Longer periods of treatment or alternative regimens may be necessary to demonstrate beneficial effects on hypoglycaemic physiological responses.

Topics: Adult; Blood Glucose; Cognition; Cross-Over Studies; Diabetes Mellitus, Type 1; Epinephrine; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Norepinephrine; Reaction Time

The objective of this study was to compare the efficacy and safety of insulin glargine, a long-acting insulin analog, with NPH insulin in children and adolescents with type 1 diabetes mellitus (T1DM). In a multicenter, open-label, randomized, 6-month study, 349 patients with TIDM, aged 5-16 years, received insulin glargine once daily or NPH insulin either once or twice daily, based on their prior treatment regimen. Although there was no significant difference between the NPH insulin and insulin glargine treatment groups with respect to baseline to endpoint change in HbA1c levels, fasting blood glucose (FBG) levels decreased significantly more in the insulin glargine group (-1.29 mmol/l) than in the NPH insulin group (-0.68 mmol/L, p = 0.02). The percentage of symptomatic hypoglycemic events was similar between groups; however, fewer patients in the insulin glargine group reported severe hypoglycemia (23% vs 29%) and severe nocturnal hypoglycemia (13% vs 18%), although these differences were not statistically significant (p = 0.22 and p = 0.19, respectively). Fewer serious adverse events occurred in the insulin glargine group than in the NPH insulin group (p < 0.02). A once-daily subcutaneous dose of insulin glargine provides effective glycemic control and is well tolerated in children and adolescents with T1DM.

Topics: Adolescent; Age of Onset; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Hypersensitivity; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Multicenter Studies as Topic; Puberty

To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes.. People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level.. BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments.. Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.

Topics: Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

We sought to investigate the ability of biphasic insulin aspart 30 (BIAsp 30) to control postprandial hyperglycemia and hyperlipidemia in a meal-test comparison with biphasic human insulin 30 (BHI 30). In this randomised crossover trial, 50 patients with type 1 diabetes (mean age, 35.7 +/- 9.4 years; body mass index [BMI], 24.0 +/- 2.6 kg/m(2); HbA(1c), 8.6% +/- 1.1%) were studied on 3 separate days, where the following treatments were given in random order: BIAsp 30 injected immediately before a standard breakfast, BHI 30 injected 30 minutes before breakfast (BHI 30(t=-30)), and BHI 30 injected immediately before breakfast (BHI 30(t=0)). The dose was 0.40 U/kg for all 3 treatments. BIAsp 30 reduced the area under the baseline adjusted 4-hour postprandial serum glucose curve (AUC(0-4h)) by 23% compared with BHI 30(t=0) (P <.0001) and by 9% compared with BHI 30(t=-30) (P =.013). Maximum serum glucose concentration (C(max)) was lower for BIAsp 30 compared with BHI 30(t=0) (14.0 +/- 2.4 v 16.5 +/- 2.8 mmol/L, P <.0001), and time to maximal serum glucose concentration (t(max)) was approximately 20 minutes shorter for BIAsp 30, irrespective of timing of BHI 30 injection (P <.0001). There were no significant differences among the 3 treatments with respect to postprandial levels of free fatty acids or triglycerides. The pharmacokinetic results were consistent with the above observations, ie, significantly larger insulin AUC(0-4h), higher C(max) and shorter t(max) were observed for BIAsp 30 compared with BHI 30, irrespective of timing of BHI 30 injection. We conclude that postprandial glycemic control was more effective with BIAsp 30 than with BHI 30, irrespective of timing of BHI 30 injection.

Topics: Adult; Area Under Curve; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Dosage Forms; Fatty Acids, Nonesterified; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin, Isophane; Postprandial Period; Treatment Outcome; Triglycerides

Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety.. This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin.. The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049).. Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.

Topics: Adolescent; Adult; Blood Glucose; Carrier Proteins; Cross-Over Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Kinetics; Middle Aged; Solubility

Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injections. Previous studies have shown poor bioavailability (less than 15%) with nasal insulin administration with various absorption enhancers. The aim of the study was to evaluate in type 1 diabetic patients, the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters.. The study was conducted in 16 type 1 diabetic patients (HbA1c 8.6+/-0.2%) in a cross-over trial including 2 six month randomized periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily + 3 pre-prandial regular insulin injections. End points were HbA1c levels, hypoglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clinical symptoms and objective nasal assessments.. Four patients were withdrawn because of nasal burning (3 cases) and persistent sinusitis (1 case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM, NS) for nasal and subcutaneous period respectively. The number of hypoglycaemic events was identical during the 2 periods (88 episodes). Nasal tolerance with the gelified form was better than with the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance.. 1) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients. 2) Other galenic forms should be investigated to improve nasal tolerance and bioavailability.

Topics: Administration, Intranasal; Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Injections, Subcutaneous; Insulin, Isophane; Nasal Mucosa; Sinusitis

Insulin lispro is absorbed more rapidly and has a shorter duration of action than regular human insulin. It improves glycaemic control but large-scale studies are required to identify regimens that optimise efficacy and safety with local dietary habits. This study involved 1184 Italian patients with Type 1 diabetes, randomised to insulin lispro (n=586) or regular human insulin (n=598) as pre-meal bolus for 3 months. Optimisation of basal NPH insulin was carried out in both groups. The number of administrations of NPH insulin was increased when using insulin lispro but, because basal and bolus insulins were mixed before meals, the total number of injections per day was unchanged. Compliance to administration time was significantly (p<0.001) greater with insulin lispro than with regular human insulin. Post-prandial blood glucose levels were lower with insulin lispro after breakfast (p<0.001), lunch (p<0.005) and dinner (p<0.001). The HbA1c level was decreased from baseline by both insulins, but the percent increase in patients with acceptable (<8%) HbA1c was greater with insulin lispro. While frequency of hypoglycaemia was decreased from baseline by both insulins, the proportion of episodes classified as severe was significantly increased from baseline with regular human insulin, but not with insulin lispro. Thus, compared with regular human insulin, improved glycaemic control was achieved with insulin lispro without an increase in severe hypoglyeaemia.

Topics: Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Patient Compliance; Safety; Treatment Outcome

To assess satisfaction with treatment and psychological well-being associated with insulin glargine and Neutral Protamine Hagedorn (NPH). Insulin glargine, a new long-acting insulin analogue, provides constant, peakless insulin release following once-daily administration and is associated with fewer hypoglycaemic episodes, despite metabolic control equivalent to that achieved with NPH human basal insulin.. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Well-being Questionnaire (W-BQ) were completed at baseline and at weeks 8, 20 or 28 by 517 patients with Type 1 diabetes participating in a randomized, controlled European trial comparing insulin glargine and NPH. Analysis of covariance was performed on change from baseline scores (main effects: treatment and pooled site; covariate: baseline scores).. Treatment satisfaction improved with insulin glargine at all time points, including endpoint, but deteriorated slightly with NPH. These differences were significant throughout the study (change from baseline to endpoint: +1.27 vs. -0.56; P = 0.0001). Outcomes were better with insulin glargine for the DTSQ items, Perceived Frequency of Hyperglycaemia and Hypoglycaemia, with statistically significant differences at week 28 and endpoint for hyperglycaemia (P = 0.0373 and 0.0379) and at week 20 for hypoglycaemia (P = 0.0024). There was no difference in psychological well-being between the treatment groups, with mean scores increasing in both.. Study participants had treatment-independent improvements in General Well-being. Advantages for insulin glargine were seen in significantly improved Treatment Satisfaction throughout the study, together with lower Perceived Frequency of Hyperglycaemia than for patients on NPH, without a significant increase in Perceived Frequency of Hypoglycaemia.

Topics: Adolescent; Adult; Aged; Attitude to Health; Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Surveys and Questionnaires; Treatment Outcome

While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients.. Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001).. Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.

Topics: Adolescent; Adult; Blood Glucose; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Lipids; Male; Middle Aged; Time Factors

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Adult; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 1; Dietary Sucrose; Drug Administration Schedule; Drug Therapy, Combination; Feeding Behavior; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Middle Aged

Because of age-related developmental and cognitive issues, children <10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision. The purpose of this study was to determine if insulin pump therapy at nighttime only, when children are at home, could improve fasting and nighttime blood glucose levels without adverse effects.. The study cohort consisted of 10 children aged 7-10 years. A randomized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night, combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin, with 3 insulin injections per day. Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range (70-150 mg/dl) before meals, at bedtime, and at 3:00 A.M.; serum fructosamine levels; and scores on measures of adherence and fear of hypoglycemia.. Compared with baseline levels, the use of the pump resulted in a significant decrease in the mean average (P < 0.001), breakfast (P < 0.0001), and 3:00 A.M. (P < 0.003) blood glucose levels. There was a decrease in the percentage of blood glucose values less than the target range (P < 0.01) and in fructosamine (P < 0.01) values and an increase in the percentage of blood glucose levels within the target range (P < 0.03).. Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump.

Topics: Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Humans; Injections; Insulin; Insulin Infusion Systems; Insulin Lispro; Insulin, Isophane; Sleep

To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI).. This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals.. Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups.. Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Female; Food; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin.. This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l.. A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin.. Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Time Factors

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Infant; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

HOE 901 (Hoechst Marion Roussel, Frankfurt, Germany) is a biosynthetic insulin with a prolonged action. The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes.. A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial. Subjects were randomized either to two different formulations of HOE 901 (the formulations differed only in zinc content) or to NPH insulin. The study was only partially blinded because patients can distinguish HOE 901 (a clear solution) from NPH (a cloudy suspension). In addition to premeal injections of regular insulin, patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime.. Fasting plasma glucose levels were significantly lower with HOE 901 (-1.88 mmol/l. P = 0.0005) as were fasting self-monitored blood glucose levels (-0.80 mmol/l, P = 0.0020). HbA1c levels also showed a significant reduction with HOE 901 (-0.14%) versus NPH (P = 0.030). The overall frequency of hypoglycemia did not differ, but the frequency of nocturnal hypoglycemia was significantly (P = 0.0037) lower with HOE 901 (36 vs. 55%). However, this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily. The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH.. This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Female; Fructosamine; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Safety; Single-Blind Method

Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes.. In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose.. At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin.. Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.

Topics: Adult; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Fasting; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Time Factors

To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes.. Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime.. Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034).. Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Ethnicity; Fasting; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; United States

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; Osmolar Concentration

To establish whether the short-acting insulin analog lispro can be successfully implemented in long-term intensive insulin therapy in type 1 diabetes, and if so, what its effects are on glycemic control and frequency and awareness of hypoglycemia.. We randomized 56 type 1 diabetic patients to treatment with either lispro (n = 28) or human regular insulin (Hum-R; n = 28) as mealtime insulin for 1 year (open design, parallel groups). Lispro was injected at mealtime and Hum-R was given 10-40 min before meals (bedtime NPH was continued on both occasions). With lispro, NPH was added at breakfast (approximately 70/30), lunch (approximately 60/40), and supper (approximately 80/20) (mixing percentage of lispro/NPH) to optimize premeal and bedtime blood glucose.. Total daily insulin units were no different in the two treatment groups, but with lispro approximately 30% less short-acting insulin at meals and approximately 30% more NPH was needed versus Hum-R (P < 0.05). The bedtime NPH dosage was no different. With lispro + NPH, the mean daily blood glucose was lower than with Hum-R (8.0 +/- 0.1 vs. 8.8 +/- 0.1 mmol/l; P < 0.05), HbA1c was lower (6.34 +/- 0.10 vs. 6.71 +/- 0.11%, mean value over 1 year; P < 0.002), and hypoglycemia (blood glucose < or = 3.8 mmol/l) was less frequent (7.4 +/- 0.5 vs. 11.5 +/- 0.7 episodes/patient-month) and tended to occur more within 90 min after meals than in the postabsorptive state (P < 0.05 vs. Hum-R). After 1 year, plasma adrenaline and symptom responses to experimental, stepped hypoglycemia improved with lispro and were closer to the responses of 12 nondiabetic control subjects versus Hum-R both in terms of thresholds and magnitude (P < 0.05).. We concluded that mealtime injection of lispro + NPH improves the 24-h blood glucose and the percentage HbA1c as compared with Hum-R. The improvement can be maintained long term. Intensive therapy with lispro + NPH results in less frequent hypoglycemia and better awareness and counterregulation of hypoglycemia.

Topics: Adult; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Time Factors

To evaluate a multiple daily injections (MDI) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally.. Twenty-five C-peptide negative Type 1 patients already trained to MDI were randomized to lispro (lispro + NPH 5 min before breakfast and lunch, lispro before dinner, NPH at bedtime) or soluble insulin (20-30 min before each meal and NPH at bed-time) for 3 months before crossing over to the other regimen for another 3 months. The mean initial HbA1c level was 8.32+/-1.5%.. The variability of capillary blood glucose values was significantly lower with lispro (MAGE 0.75+/-0.36 g/l vs. 0.99+/-0.50, P<0.01; MODD 0.64+/-0.26 g/l vs. 0.80+/-0.40, P<0.05). There was a nonsignificant reduction in HbA1c with lispro: -0.40+/-0.86 vs. -0.08+/-0.71. Mean daily blood glucose levels were significantly lower with lispro (1.53+/-0.48 g/l vs. 1.82+/-0.57 g/l, P<0.05). The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro, P = 0.048. At the end of the study, 75% of the patients chose the lispro associated with multiple NPH regimen for their own treatment. The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro (53% vs. 34%).. An MDI regimen using lispro combined with multiple NPH compared to a standard MDI regimen using soluble insulin reduced day-to-day blood glucose fluctuations, was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Patient Satisfaction; Solubility; Treatment Outcome

Topics: Adult; Blood Glucose; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Male

Regular insulin given with the evening meal could contribute to the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes using a multiple injection regimen. To test this hypothesis, we compared glucodynamics and free insulin levels on two separate study nights.. A total of 14 adolescents were recruited. On both nights, identical doses of regular insulin or insulin lispro were administered 30 min or 10 min, respectively, before the evening meal, using a double-blind randomized crossover study design. Doses of NPH insulin and carbohydrate content of the evening meal and snack were kept identical. Blood samples were taken every 15 min for blood glucose and every 60 min for free insulin and ketones.. After insulin lispro administration, glucose levels were significantly lower between the evening meal and the bedtime snack (analysis of variance [ANOVA] P = 0.02), and four hypoglycemic episodes were recorded. This corresponded to a higher (458 +/- 48 vs. 305 +/- 33 pmol/l, P = 0.02), earlier (64 +/- 4.6 vs. 103 +/- 12 min, P = 0.01), and shorter-lasting (245 +/- 21 vs. 365 +/- 39 min, P = 0.01) insulin peak in contrast to regular insulin. After the bedtime snack, glucose levels increased dramatically during the lispro night and stayed higher, up to 0300 in the morning (ANOVA P = 0.01), corresponding to lower mean insulin levels (146 +/- 20 vs. 184 +/- 27 pmol/l, P = 0.04). No differences were seen in glucose and insulin levels between 0300 and 0800. Four episodes of nocturnal hypoglycemia were documented after the bedtime snack during the regular insulin night, in contrast to one episode after insulin lispro. No differences in ketone levels were observed.. The replacement of regular insulin with insulin lispro may reduce the risk of late hypoglycemia, but redistribution of the evening carbohydrate may be needed to ensure good metabolic control and prevent early postprandial hypoglycemia.

Topics: Activity Cycles; Adolescent; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Ketones; Life Tables; Male; Postprandial Period

In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean+/-SEM): 16.1+/-3.1 vs 23.6+/-3.3) episodes during the last 6 weeks of treatment, p=0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA1c 7.2+/-0.2 vs 7.1+/-0.2 %, p=0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study.

Topics: Adult; Blood Glucose; Circadian Rhythm; Cognition Disorders; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glucose; Glucose Clamp Technique; Hormones; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infusion Pumps; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin, Isophane; Male; Middle Aged; Nervous System Diseases; Patient Acceptance of Health Care; Perception

To compare insulin administration using premixed insulin (70% NPH/30% Regular) by an injectable pen with traditional self-mixed insulin administered by syringe.. In this study, 93 women were enrolled into four groups: 1) self-mixed/syringe, 2) premixed/syringe, 3) self-mixed/pen, and 4) premixed/pen.. Women in the premixed pen group had significantly less cesarean deliveries for failure to progress in labor and a decrease (not significant) in postpartum infection and infant macrosomia. Patients felt premixed insulin administered by the pen was easier to use. No significant differences were noted in glucose control, compliance among the four groups, or cost.. Premixed insulin administration via the pen is safe, effective and no more costly than traditional treatment for pregnant diabetic women.

Topics: Blood Glucose; Cesarean Section; Diabetes Mellitus, Type 1; Drug Combinations; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin, Isophane; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Prospective Studies; Syringes

A three-way, crossover, open-label, randomized study was designed to compare the evening and night (1800-0800) glycemic control when the evening premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared with the control arm on standard premeal human regular insulin and pre-bedtime NPH insulin.. A total of 13 type 1 diabetic patients who use a premeal plus basal insulin regimen were studied on three separate days, with identical meals and snacks at the same times on each study day. On the control study day, patients received human regular insulin before dinner and NPH at bedtime in their usual doses. On another day, lispro was given before dinner with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the third regimen, the lispro and NPH were administered together in their usual dose before the evening meal by separate injections. The three regimens were tested in random order.. Postprandial (1800-2200) blood glucose concentrations were lower after reduced-dose lispro compared with human regular insulin (6.0 +/- 0.3 [SEM] vs. 7.4 +/- 0.3 mmol/l, P < 0.05). Nighttime (2400-0400) blood glucose concentrations were not different (8.6 +/- 0.3 vs. 9.2 +/- 0.3 mmol/l, NS), and prebreakfast concentrations were also unchanged (7.7 +/- 0.9 vs. 8.7 +/- 0.8 mmol/l) after lispro with increased-dose NPH compared with standard insulin. By contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did not differ between study days, but it was more frequent postprandially after dinner usual-dose lispro plus early NPH (2 vs. 7 patients, P = 0.062).. With lower mealtime and higher basal bedtime insulin doses, patients using insulin lispro may be able to gain an overall improvement in evening blood glucose control without deteriorated nighttime glucose levels. Earlier basal NPH dosage alone does not ameliorate the nighttime hyperglycemia of short-acting insulin analog regimens.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydroxybutyrates; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period

Insulin lispro improves early postprandial blood glucose control but can result in late interprandial hyperglycemia. As an approach to resolving this problem, we performed a randomized, crossover study with four treatment arms, comparing the daytime metabolic profile after either premeal lispro alone or premeal lispro with optimal daytime NPH insulin and with standard human regular insulin.. Twelve C-peptide negative type 1 diabetic patients were studied on four separate study days, at least 7 days apart. On each study day, patients received one of the four study insulin treatments, in random order, with identical meals and snacks. The four treatments were 1) premeal human regular insulin before lunch and supper at unchanged dose; 2) premeal lispro (unchanged dose) at lunchtime and dinner; 3) pre-lunch reduced-dose lispro (70%) before lunch and supper with supplemental lunchtime NPH and with a 6-h interval until dinner; and 4) pre-lunch reduced-dose lispro (70%) before lunch and supper with supplemental lunchtime NPH and with a 8-h interval until dinner. All patients were using their usual premeal plus basal insulin regimen during the period of the study, with human regular insulin before meals and NPH insulin at bedtime.. Postprandial blood glucose concentrations (1230-1500) were lower after reduced or usual lispro dose compared with human regular insulin (5.5+/-0.2 and 5.6+/-0.2 vs. 8.2+/-0.5 mmol/l, P < 0.001), with no difference between the lispro doses. However, prepran-Dial (1800) blood glucose levels deteriorated to higher levels after usual-dose lispro alone compared with either human regular insulin (P < 0.05) or reduced-dose lispro plus NPH (P < 0.05) (8.9+/-0.3 vs. 7.1+/-0.8 and 6.4+/-0.4 mmol/l), with no difference between human regular insulin and reduced-dose lispro plus NPH. During the 2 h between the usual and delayed mealtime, blood glucose concentrations remained controlled on lispro plus NPH (2000: 6.5+/-0.4 mmol/l).. Reduced-dose lunchtime lispro plus NPH maintained the improvement in postprandial blood glucose control with no deterioration in interprandial blood glucose control, even up to a late meal.

Topics: Adult; Blood Glucose; C-Peptide; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Postprandial Period

Topics: Adult; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Male; Prospective Studies; Weight Gain

To determine insulin kinetics and overnight glycemic control after bedtime administration of a new intermediate-acting insulin preparation called neutral protamine lispro (NPL).. We studied 12 patients with well-controlled type 1 diabetes. The study had a double-blind, randomized, crossover design. After a lead-in period of 10-14 days two experiments were carried out with an interval of 2-7 days. During these experiments overnight insulin kinetics and fasting blood glucose levels were studied after evening administration of NPH insulin and NPL. Blood glucose levels < 3.8 mmol/l were treated by means of a variable infusion of a 20% glucose solution.. A trend toward a shorter time to peak insulin concentration was observed after administration of NPL (P = 0.07). No differences between NPH and NPL were detected in the total area under the curve (AUC) for insulin, in insulin levels before breakfast, or in glucose levels before breakfast (P = 0.5, 0.6, and 0.4, respectively).. We detected no major differences between NPH and NPL in the total AUC for insulin, prebreakfast glucose levels, or prebreakfast insulin levels. Therefore, we conclude that NPH and NPL are equally effective in controlling overnight glycemia.

Topics: Adult; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Combinations; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Kinetics; Male; Middle Aged; Protamines

The dawn-phenomenon causes high fasting glucose values in IDDM patients during puberty. Even a bedtime injection of intermediate-acting insulin does not reliably suppress glucose rises during the morning hours. We therefore examined whether Semilente, an amorphous zinc insulin with kinetics different from NPH insulin, is better suited to alleviate the dawn-phenomenon in adolescent patients with long-standing diabetes. This prospective study included 15 adolescent patients (age 15.5 +/- 0.4 years; mean +/- SE) well beyond the remission phase of diabetes (mean duration: 7.5 +/- 0.8 years). On an inpatient basis, blood glucose profiles following bedtime injections of NPH or semilente insulin were compared, using a sequential cross-over design for intra-patient comparison. Fasting blood glucose was significantly lower following bedtime injections of Semilente (183 +/- 21 mg/dL [10.2 +/- 1.1 mmol/L]) compared to nights where NPH had been injected (235 +/- 22 mg/dL [13.1 +/- 1.2 mmol/L]). In addition, the morning postprandial blood glucose was significantly improved. The frequency of nocturnal hypoglycemia was not different, and the dose of Semilente insulin was slightly lower compared to the dose of NPH-insulin injected. For adolescent IDDM patients with suboptimal metabolic control due to a marked dawn-phenomenon, with high fasting glucose concentrations despite a bedtime injection of NPH insulin, bedtime injection of Semilente insulin may result in reduced fasting hyperglycemia on the next morning.

Topics: Adolescent; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies; Time Factors

To test whether a suppertime injection of human ultralente insulin in patients with type I diabetes would result in a larger inhibition of basal hepatic glucose production (HGP) and improvement in fasting and mean daily plasma glucose levels.. We studied 16 type I diabetic patients (41 +/- 4 years of age; body mass index [BMI] = 23.3 +/- 0.3 kg/m2; diabetes duration > 3 years) with a crossover protocol of therapy with an intermediate and ultralente insulin. All patients were already treated with three injections per day of regular insulin in addition to intermediate-acting (NPH) insulin at suppertime. After a 14-day run-in period, patients were randomly assigned to treatment with equivalent doses (10.8 +/- 0.8 U, at 1900) of intermediate (Humulin I) or ultralente (Humulin U) insulin. After 1 month of treatment, patients were crossed over. No change of the insulin dosage was performed during the study period. Basal HGP was measured by D-(6,6-2H2)-glucose infusion. Plasma glucose concentration was measured in the fasting state and monitored during the day.. Before starting the study period, fasting plasma glucose was 13.4 +/- 1.1 mM and plasma free-insulin was 48.0 +/- 4.8 pM. Daily plasma glucose concentration averaged 10.3 +/- 0.3 mM and the area under the curve (AUC) was 1.41 +/- 0.05 mol/14 h. NPH insulin, given at suppertime for a month, did not induce significant changes in fasting plasma insulin (40.2 +/- 4.8 pM), glucose concentration (14.0 +/- 0.9 mM) or HGP (20.2 +/- 2.2 mumol.kg-1.min-1). Accordingly, no change occurred in the average daily plasma glucose (10.3 +/- 0.3 mM) or AUC (1.41 +/- 0.9 mol/14 h). Glycated hemoglobin also was not affected (8.2 +/- 0.4 vs. 8.2 +/- 0.3%). On the contrary, a 4-week treatment with ultralente insulin, also given at suppertime, was associated with a decline in the basal HGP (16.0 +/- 1.3 mumol.kg-1.min-1), fasting (11.3 +/- 0.9 mM) and average daily (9.4 +/- 0.3 mM) plasma glucose concentrations, and AUC (1.29 +/- 0.07 mol/14 h) of plasma glucose level (all P < 0.05). Glycated hemoglobin was reduced (7.9 +/- 0.4%). In each condition, fasting plasma glucose concentration was correlated with the average daily plasma glucose level (basal = 0.78; intermediate = 0.89; ultralente = 0.62; all P < 0.05), which suggests that ultralente insulin likely induces the improvements of metabolic control through reducing fasting plasma glucose.. Our results suggest that treating type I diabetic patients with ultralente insulin at suppertime provides a better modulation of basal HGP so that lower fasting plasma glucose levels are ensured. The reduction of fasting hyperglycemia is likely to affect positively daily plasma glucose control.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glucose; Humans; Hyperglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Liver; Male; Recombinant Proteins

This study investigated the effect on blood sugar control and weight gain of a multiple injection therapy (MIT) regimen in 22 established adolescent diabetics using a pre-prandial 50:50 mixture of Isophane/soluble insulin with night-time Isophane. This regimen was compared in a cross-over study with MIT using pre-prandial soluble insulin and night-time Isophane. After 4 wk for stabilization, there were 2 periods of 16 wk on each regimen. Throughout the study, blood sugar control was monitored by regular HbA1 and fructosamine measurements. The total daily dose of insulin was unchanged throughout the study, 1.0 +/- 0.3 iu/kg/day for Penmix/Isophane and 1.1 +/- 0.3 iu/kg/day for soluble/Isophane. The mean HbA1 and fructosamine did not alter significantly on either regimen. There was no significant weight gain during the Penmix therapy, despite the increased proportion of longer-acting despite the increased proportion of longer-acting insulin. Lean body mass (LBM) measured by skinfold thickness and electrical impedance only changed marginally on either regimen; the correlation between the 2 measuring techniques for LBM was good. Patient acceptance of the 50:50 Penmix insulin was high, 13 of 19 children preferring it to the conventional regimen.

Topics: Adipose Tissue; Adolescent; Body Mass Index; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Male; Sex Characteristics; Skinfold Thickness; Weight Gain

The aim of this study was to assess the immunocompetence of T cells from patients with poorly controlled diabetes with respect to Candida albicans antigen and to compare the relative immunogenicity of human insulin, bovine insulin and protamine at the T-cell level during 6 months treatment with human or bovine NPH insulins. T-cell proliferation was measured in vitro in response to C. albicans, bovine and human insulin, bovine and human NPH and protamine in 17 patients with newly-diagnosed type 1 (insulin-dependent) and 12 with poorly-controlled type 2 (non-insulin-dependent diabetes) before and after 0.5, 1, 3 and 6 months of treatment with either bovine or human NPH insulin. The following results were found: Baseline responses to C. albicans (as a recall antigen) were similar for patients and controls despite marked hyperglycaemia in the patients. No patient had a response greater than mean + 2 S.D. of controls to human or bovine insulin before starting treatment, or had insulin autoantibodies. Treatment with human NPH insulin did not induce T-cell responses to human or bovine insulin, but 3/13 (23%) patients treated with bovine NPH responded to bovine and human insulin after 6 months, of whom one responded exclusively to human. In contrast, 6 (46%) bovine and 3 (19%) human NPH-treated patients responded to protamine. It was concluded that there is no evidence of T-cell immunosuppression in poorly-controlled diabetes or of T-cell autoimmunity to insulin in newly-diagnosed type 1 diabetes. Treatment with bovine NPH insulin immunizes T cells to insulin, but human NPH does not.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Animals; Antigens, Fungal; Autoantibodies; Candida albicans; Cattle; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; HLA-DR Antigens; Humans; Immunophenotyping; Insulin, Isophane; Islets of Langerhans; Lymphocyte Activation; Middle Aged; Protamines; Recombinant Proteins; T-Lymphocytes

To evaluate whether an insulin regimen with a long-acting zinc insulin (Ultratard HM) could help control fasting hyperglycemia in insulin-dependent diabetes mellitus (IDDM) patients.. A randomized sequential crossover trial with 6-wk treatment periods was used. Ten IDDM patients from the diabetes clinic at the Medical School who had persistent fasting hyperglycemia (greater than 10 mmol/L) were studied. Patients with nocturnal hypoglycemia were excluded. All patients completed the study. Insulin regimens consisted of three daily injections of a short-acting insulin (Actrapid HM) before meals and either a long-acting zinc insulin (Ultratard HM) or an intermediate isophane insulin (Protaphane HM) before the evening meal. Each regimen was followed for 6 wk.. Fasting blood glucose levels (at 06:00 and 08:00) were significantly lower after the long-acting insulin regimen (6.26 +/- 0.88 vs. 10.82 +/- 4.27 mM, P less than 0.05 and 9.26 +/- 1.02 vs. 14.03 +/- 1.08 mM, P less than 0.05, respectively). Plasma-free insulin levels mirrored blood glucose concentrations because they were significantly higher at 06:00 and 08:00 after the long-acting insulin regimen (49.5 +/- 10.1 vs. 20.1 +/- 4.3 pM, P less than 0.05 and 31.6 +/- 5.0 vs. 16.5 +/- 3.4 pM, P less than 0.05, respectively). At any other time of the day, blood glucose and plasma insulin levels were not significantly different with either one of the two insulin regimens.. A long-acting zinc human insulin injected before the evening meal can help to control persistent fasting hyperglycemia in IDDM patients.

Topics: Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hyperglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Pork

Fasting hyperglycemia is common in patients with insulin-dependent diabetes mellitus (IDDM) treated with twice-daily subcutaneous insulin regimens. We postulated that substituting human ultralente insulin for the presupper dose of intermediate-acting insulin would improve overnight glycemic control in children and adolescents with IDDM.. This 6-mo double-blind crossover study compared a conventional insulin regimen, a mixture of human NPH and regular given before both breakfast and supper (NPH), with a novel twice-daily regimen in which human ultralente replaced NPH before the evening meal (ultralente). This study was comprised of 20 children and adolescents (mean age and duration of IDDM 11.3 +/- 2.9 and 2.4 +/- 1.3 yr, respectively) from the Youth Clinic of the Joslin Diabetes Center, all of whom regularly performed self-monitoring of blood glucose (SMBG) and had been treated exclusively with human insulin (mean daily dose 0.75 +/- 0.22 U/kg). Subjects performed SMBG on a prescribed schedule with a glucose meter with an electronic memory, and recorded results of blood glucose measurements, insulin dosages, and episodes of hypoglycemia. Monthly measurements were obtained for height, weight, and HbA1, and mean daily insulin dosages and average blood glucose level before breakfast, lunch, supper, bedtime snack, and between 0200 and 0300 were calculated. Nonfasting serum lipids were measured at entry, crossover, and the end of the study.. After 3 mo, mean HbA, did not differ significantly (9.1 +/- 1.7 vs. 9.5 +/- 1.4%, NPH and ultralente, respectively). Mean fasting blood glucose was significantly lower on ultralente (9.6 +/- 1.9 vs. 10.3 +/- 2.2 mM, P less than 0.05, and blood glucose showed a similar trend (0.05 less than P less than 0.1) before lunch (8.9 +/- 1.7 vs. 9.8 +/- 2.6 mM. Mean blood glucose before bedtime snack was significantly lower (P less than 0.01) on NPH (8.4 +/- 1.9 vs. 10.0 +/- 2.1 mM) but did not differ significantly before supper or between 0200 and 0300. On the two regimens, growth and serum lipids were normal and similar, and no differences were observed in the incidence or severity of hypoglycemia.. Compared with a mixed dose of regular and NPH, a similar dose of a mixture of regular and human ultralente insulin before supper caused a modest reduction in fasting blood glucose levels but was associated with higher blood glucose levels before the bedtime snack. Overall glycemic control, reflected in HbA1 values, was not significantly improved.

Topics: Child; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Insulin, Isophane; Insulin, Long-Acting; Lipids; Male; Recombinant Proteins

The absorption of isophane (NPH) insulin from subcutaneous and intramuscular injection sites was measured in seven healthy volunteers using the euglycaemic clamp technique. Human Insulatard (Nordisk, Gentofte, Denmark) was administered in a dose of 0.25 U kg-body-weight-1 into the anterior compartment of the thigh. In random order injections were given either subcutaneously, via 12 mm needle at 45 degrees to the skin into a skinfold, or intramuscularly by 25 mm needle perpendicularly to the skin. Insulin concentrations rose more rapidly after intramuscular injection than after subcutaneous injection, being significantly higher as early as 60 min after injection (19.7 +/- 1.6 (+/- SE) vs 8.7 +/- 1.4 mU l-1; p less than 0.001). Thereafter insulin concentrations remained significantly higher for the remaining 360 min of study, reflected by a significantly greater area under the insulin concentration curve for the 420 min study (IM 8630 +/- 1256 vs SC 4908 +/- 465 mU l-1 min, p less than 0.05). A significantly greater quantity of infused glucose was required to maintain euglycaemia after intramuscular injection than after subcutaneous injection (923 +/- 256 vs 216 +/- 71 mg kg-1 min, p less than 0.05). These results demonstrate a striking difference in the pharmacokinetics of an isophane (NPH) insulin when injected into subcutaneous fat and muscle.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Humans; Injections, Intramuscular; Injections, Subcutaneous; Insulin, Isophane; Male

Continuous subcutaneous insulin infusion (CSII) and multiple injections (MI) have been shown to have metabolic advantages in highly-selected insulin-dependent diabetics (IDDs), but there have been few comparative studies in self-selected IDDs. With MI, the optimal insulin preparation for overnight insulin delivery has not been defined. We compared conventional 2-3 injection therapy (CT), CSII and MI with human isophane insulin (MI/human isophane) and human ultralente insulin (MI/human ultralente), respectively, at bedtime in self-selected IDDs. Of 275 IDDs who were invited to participate, 52 individuals (18.9%) entered the study. Most indices of glycaemic control showed better values on CSII and also on MI compared to CT, but the differences were small. Fasting blood glucose was higher on MI/human ultralente than on MI/human isophane. Only one subcutaneous abscess and one case of ketoacidosis requiring hospitalization occurred on CSII. Serious hypoglycaemic episodes were non-significantly increased on intensified therapy. Most patients clearly preferred intensified insulin therapy; approximately one half CSII.

Topics: Adult; Blood Glucose; Consumer Behavior; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Infusion Pumps, Implantable; Insulin; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Male

Fifty two children with insulin dependent diabetes mellitus were randomised to receive human isophane or lente insulin preparations in combination with soluble insulin in a double blind trial. Patients were seen every two months, and crossed over after four months of treatment. Control assessed by glycated haemoglobin was significantly lower in children on human isophane insulin, but fasting blood glucose and fructosamine concentrations and the number of episodes of hypoglycaemia were similar on both regimens. In five children on twice daily insulin regimens, insulin profiles throughout a 24 hour period demonstrated greater variability on lente compared with isophane insulin despite identically administered insulin doses. A questionnaire completed at the end of the study showed that two thirds of the children and/or their parents preferred the isophane insulin, and they gave perceived improvement of metabolic control as the major reason for their choice.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Insulin, Isophane; Insulin, Long-Acting; Male; Patient Participation

In Switzerland it is still a debatable point whether diabetics whose treatment has been changed from animal to human insulin notice premonitory symptoms of hypoglycemia to a lesser degree and whether this could be hazardous for them. In a prospective study, 18 longstanding type 1 and type 2 diabetics, treated with insulin Lente MC, were selected and observed at frequent intervals for three months. This first period was followed by a transfer to human insulin (Protaphan HM) and a close observation for another three months. Before the transfer, all patients were well informed about a possible change in premonitory symptoms of hypoglycemia. The initial dose of Protaphan HM was 10% lower than in the treatment with Lente MC. During the three month period with human insulin, we observed no change with regard to blood-sugar regulation or Hb-A1. The most important observation was that the number of hypoglycemic episodes did not change after the transfer to human insulin. There were only mild to moderate degrees of hypoglycemia, the average being three episodes per patient. The change to human insulin was without any problems for the patients: they all preferred to stay on Protaphan HM for future treatment. Also, in general practice, patients can be changed without difficulties from animal to human insulin, provided that the above-mentioned precautions are respected.

Topics: Adult; Aged; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Although insulin and sulfonylureas often have additive clinical effects when used in combination for type II (non-insulin-dependent) diabetes, these results are variable and a clinical role for this approach is not yet established. This study tests the efficacy of a specific combined regimen for a subpopulation of patients with a randomized double-masked placebo-controlled crossover design and under conditions similar to those of clinical practice. Twenty subjects with limited duration (less than 15 yr) type II diabetes who were moderately obese (less than 160% ideal wt) and proved imperfectly controlled on 10 mg glyburide twice daily completed two 4-mo crossover protocols, comparing a single injection of NPH insulin in the evening plus 10 mg glyburide in the morning with insulin plus placebo. Insulin dose was adjusted by experienced endocrinologists seeking the best glycemic control consistent with safety. All subjects had glycosylated hemoglobin values less than or equal to 150% of the control mean on combined therapy, and combined therapy was superior to insulin alone (fasting plasma glucose 8.0 +/- 0.3 vs. 11.1 +/- 0.6 mM, P less than .01; glycosylated hemoglobin 9.8 +/- 0.1 vs. 10.6 +/- 0.2%, P less than .01). Despite greater weight gain on combined therapy, blood pressure and plasma lipid concentrations were the same on the two regimens. These results suggest this simple regimen offers another option, besides multiple injections of insulin, for patients of this kind who are unsuccessful with a sulfonylurea or a single injection of insulin alone.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Eating; Fasting; Glucagon; Glyburide; Humans; Insulin, Isophane; Middle Aged; Random Allocation

Isophane (NPH) and lente insulin preparations have been the basis of insulin-injection regimens for many decades but were never formally compared. After a 2-mo run-in period, 82 patients were randomized to NPH (Protaphane) or lente (Monotard) insulin preparations given together with Actrapid as a twice-daily injection regimen in a double-blind study. Patients were seen monthly and crossed over after 5 mo of treatment. Control as assessed by glycosylated hemoglobin (NPH 9.2 +/- 0.1%, lente 9.3 +/- 0.1%, mean +/- SE) and fructosamine (1.55 +/- 0.02 and 1.57 +/- 0.02 mM) concentrations was identical for the two regimens as were home-collected laboratory-measured fasting blood glucose (BG) (NPH 8.8 +/- 0.5 mM, lente 9.0 +/- 0.5 mM) and mean BG (8.2 +/- 0.3 and 7.6 +/- 0.3 mM) concentrations. For both regimens, the major control problem was the BG concentration before and after breakfast. Total insulin dosage was similar (NPH 56.3 +/- 0.6 U/day, lente 57.2 +/- 0.6 U/day) with no tendency for a difference in the evening intermediate-acting dose (NPH 17.0 +/- 0.3 U/day, lente 17.0 +/- 0.3 U/day) to counter fasting hyperglycemia. Serum lipid concentrations and body weight confirmed the equivalence of control. Hypoglycemic events were recorded in personal diaries and graded by predetermined criteria. Self-treated, relative-assisted, and hospital/doctor-treated hypoglycemic events did not differ in frequency. We conclude that lente- and NPH-based twice-daily human insulin regimens give indistinguishable metabolic control.

Topics: Adult; Blood Glucose; Cholesterol; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Triglycerides

In an open randomized cross-over study 50 patients with insulin-dependent diabetes were allocated to 3 months of treatment with NPH insulin either by means of a pen injector (Insuject-X) or by conventional syringes. The needle of the NPH pen injector was removed immediately after use to avoid possible leakage of solvent. Ambulatory control was assessed every 6 weeks, including blood sampling (HbA1c and insulin antibodies) and recording of hypoglycaemia. NPH insulin containers were collected for insulin potency measurement by HPLC. A seven-point blood glucose profile was performed fortnightly by means of home blood glucose monitoring. At the end of the 6 months a questionnaire was completed. No significant changes occurred in HbA1c (difference 0.1 +/- 0.7 (SD)%), blood glucose profile, or the incidence of hypoglycaemic episodes on the two regimens. The concentration of NPH insulin in the containers remained constant. All but two of the patients preferred to continue to use the pen injector. This NPH pen injector is a reliable and efficacious tool which may also prove more convenient for the patients.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Injections, Subcutaneous; Insulin Antibodies; Insulin, Isophane; Random Allocation

Three 'pen'-administered multiple injection regimens have been compared with twice daily insulin injection regimens by means of 24-h profiles of plasma glucose and free insulin concentrations. Ten Type 1 diabetic patients received their usual twice daily insulin regimen and were then randomized to receive the same total daily insulin dose in four divided doses using (1) 50:50 premixed soluble and isophane, (2) 30:70 premixed soluble and isophane, and (3) preprandial soluble and evening crystalline-zinc insulins. Profiles were performed after 1 week on each regimen. Plasma glucose concentrations were similar during the twice daily regimen and the two premixed regimens, rising during the early hours of the morning to a peak between 0900 and 0930 h of 13.8 +/- 2.8 (+/- SD) mmol l-1 on the twice daily regimen, 13.6 +/- 5.3 mmol l-1 on the premixed 50:50 regimen, and 13.5 +/- 4.2 mmol-1 on the premixed 30:70 regimen. With the basal and prandial regimen, overnight plasma glucose concentrations were higher than with the other regimens between 2400 and 0300 h (p less than 0.05). Concentrations then fell until breakfast, and rose after this meal to a peak of 9.5 +/- 4.3 mmol l-1 (p less than 0.01). Mean plasma glucose concentrations were significantly lower than on the other three regimens between 0830 and 1100 h (p less than 0.05). Less variability was observed in 24-h mean plasma glucose concentrations during the basal and prandial regimen than during the other three regimens.

Topics: Adult; Blood Glucose; Circadian Rhythm; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hyperglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Pork; Male; Recombinant Proteins

Porcine and semisynthetic human insulin preparations (Nordisk) having the same content of regular insulin, same galenic characteristics and same degree of purity, were tested in type I, type IIa and type IIb diabetics. There was no difference as to the duration of action. This is contrary to some earlier reports stating that protamine-bound biosynthetic human insulin has a shorter duration of action than porcine preparations. The onset of the hypoglycaemic action in type IIa diabetics is significantly more rapid with isophane human insulin than with isophane pork insulin. The use of an insulin pump prior to testing the duration of action of intermediate insulin preparations appears to be superior to other methods.

Topics: Aged; Animals; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin Infusion Systems; Insulin, Isophane; Male; Middle Aged; Swine; Time Factors

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Combinations; Humans; Injections, Subcutaneous; Insulin; Insulin, Isophane; Insulin, Long-Acting; Middle Aged

Ten insulin-dependent diabetics taking twice-daily mixtures of soluble and isophane insulin were studied in a double-blind crossover trial to examine the effect on their glycaemic control of a fixed-mixture preparation (containing either 50% soluble, 50% isophane or 30% soluble, 70% isophane) given in the same total dose as each patient's usual mixture. The mean (+/- S.E.M.) of eight daily blood glucose determinations when the patients' usual mixtures were pre-mixed by the hospital pharmacy was 7.6 +/- 0.7 mmol/l, 7.8 +/- 0.8 mmol/l when the fixed-mixture preparation was used and 8.0 +/- 0.5 mmol/l when the patients drew up and mixed the insulins themselves. Individual glucose profiles on each of the three regimens expressed as mean modified log 'M' indices were 1.26 +/- 0.14, 1.29 +/- 0.16 and 1.37 +/- 0.14, respectively. Thus, the patients studied were as well controlled on a fixed-mixture preparation as on their usual 'tailormade' insulin regimens.

Topics: Adult; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Combinations; Female; Humans; Insulin; Insulin, Isophane; Male; Middle Aged; Random Allocation

A double-blind cross-over study of the sc absorption of radiolabelled semi-synthetic human (SHI) and purified porcine (PPI) insulin was made. Absorption of both isophane (n = 10) and soluble insulin (n = 8) was studied. There was no significant difference between the disappearance from the injection site, the plasma free insulin concentrations, or blood glucose levels after sc injection of the isophane preparations. A faster disappearance of the soluble SHI (as judged from T/50 and AUC) was found (both P-values less than 0.01). However, no difference was observed between the plasma insulin concentrations at any time point (P less than 0.05). Blood glucose levels showed no statistical differences between the two soluble preparations. The data indicate minor differences between the pharmacokinetics of SHI and PPI, but these seem of no clinical importance.

Topics: Absorption; Adult; Animals; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Insulin; Insulin, Isophane; Male; Middle Aged; Receptor, Insulin; Swine

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group.. Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group.. • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic.. • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Child, Preschool; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane

Few studies addressed the efficacy of human insulin regimens (mostly premix insulin) used in many low-and-middle income countries on glycemic control of children and adolescents with diabetes. The aim of this study was to assess the efficacy of the premix insulin on the glycated hemoglobin (HbA. A retrospective study was carried out from January 2020 to September 2022 on patients with type 1 diabetes aged below 18 years followed in Burkina Life For A Child program. They were categorized into three groups, on regular with NPH insulin (Group A), on premix insulin (Group B) and on regular with premix insulin (Group C). Outcome was analyzed based on HbA. Sixty-eight patients with a mean age of 15.38 ± 2.26 years and the sex ratio (M/W) 0.94 were studied. There were 14 in Group A, 20 in Group B, and 34 patients in Group C. The mean HbA. Our results indicate that the use of premix insulin gives a better glycemic control than NPH insulin. However, further prospective study of these insulin regimens with a strengthening education strategy and glycemic control by continuous glucose monitoring and HbA

Topics: Adolescent; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Prospective Studies; Retrospective Studies

In Type 1 diabetes patients, even ultra-rapid acting insulins injected subcutaneously reach peak concentrations in 45 minutes or longer. The lag time between dosing and peak concentration, as well as intra- and inter-subject variability, render prandial glucose control and dose consistency difficult. We postulated that insulin absorption from subcutaneously implantable vascularizing microchambers would be significantly faster than conventional subcutaneous injection. Male athymic nude R. norvegicus rendered diabetic with streptozotocin were implanted with vascularizing microchambers (single chamber; 1.5 cm2 surface area per side; nominal volume, 22.5 μl). Plasma insulin was assayed after a single dose (1.5 U/kg) of diluted insulin human (Humulin®R U-100), injected subcutaneously or via microchamber. Microchambers were also implanted in additional animals and retrieved at intervals for histologic assessment of vascularity. Following conventional subcutaneous injection, the mean peak insulin concentration was 22.7 (SD 14.2) minutes. By contrast, when identical doses of insulin were injected via subcutaneous microchamber 28 days after implantation, the mean peak insulin time was shortened to 7.50 (SD 4.52) minutes. Peak insulin concentrations were similar by either route; however, inter-subject variability was reduced when insulin was administered via microchamber. Histologic examination of tissue surrounding microchambers showed mature vascularization on days 21 and 40 post-implantation. Implantable vascularizing microchambers of similar design may prove clinically useful for insulin dosing, either intermittently by needle, or continuously by pump including in "closed loop" systems, such as the artificial pancreas.

Topics: Animals; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin, Isophane; Insulin, Regular, Human; Male; Mice; Mice, Nude; Rats

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Pregnancy; Protamines

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Pregnancy; Protamines

This study includes modeling and simulation of insulin aspart pharmacokinetics (PK). The authors used PK data of biosimilar insulins-insulin aspart and biphasic insulin aspart 30/70-to develop a predictive population PK model for the insulins. The model was built via Monolix software, taking into account the weight-based dosing and the dose and body-weight effects on the parameters. The model-based simulations were performed using the R package mlxR for various administered doses and various ratios of insulin aspart forms for a better understanding of the insulin behavior. The optimal model was a 1-compartment model with a combination of zero- and first-order absorptions, with absorption lag for the soluble form of insulin aspart and first-order absorption for the insulin aspart protamine suspension. The assumption of identical behavior of 2 insulins at the distribution and elimination phases was made. The developed PK model was fitted successfully to the experimental data, and all fitted parameters displayed a moderate coefficient of variation. The PK model allows us to predict PK profiles for various doses and formulations of insulin aspart and can be used to improve the accuracy, safety, and ethics of novel clinical trials of insulin.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulins

Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use.. To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings.. This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019.. Insulin glargine, insulin detemir, and NPH insulin.. The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age.. Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use.. In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

Topics: Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Proportional Hazards Models; Retrospective Studies

Published studies have challenged the cost-effectiveness of insulin glargine versus neutral protamine hagedorn (NPH) insulins in Brazil with limited evidence of increased effectiveness despite considerably higher acquisition costs. However, still a controversy. Consequently, there is a need to address this.. Retrospective cohort study of Type I diabetes patients receiving insulin glargine in Brazil following NPH insulin who met the criteria.. 580 patients were enrolled. HbA. Limited differences between NPH insulins and insulin analogs in routine clinical care do not justify an appreciable cost difference.

Topics: Adult; Blood Glucose; Brazil; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

To assess the cost-effectiveness of basal insulin regimens for adults with type 1 diabetes mellitus in England.. A cost-utility analysis was conducted in accordance with the National Institute for Health and Care Excellence reference case. The UK National Health Service and personal and social services perspective was used and a 3.5% discount rate was applied for both costs and outcomes. Relative effectiveness estimates were based on a systematic review of published trials and a Bayesian network meta-analysis. The IMS CORE Diabetes Model was used, in which net monetary benefit (NMB) was calculated using a threshold of £20,000 per quality-adjusted life-year (QALY) gained. A wide range of sensitivity analyses were conducted.. Insulin detemir (twice daily) [iDet (bid)] had the highest mean QALY gain (11.09 QALYs) and NMB (£181,456) per patient over the model time horizon. Compared with the lowest cost strategy (insulin neutral protamine Hagedorn once daily), it had an incremental cost-effectiveness ratio of £7844/QALY gained. Insulin glargine (od) [iGlarg (od)] and iDet (od) were ranked as second and third, with NMBs of £180,893 and £180,423, respectively. iDet (bid) remained the most cost-effective treatment in all the sensitivity analyses performed except when high doses were assumed (>30% increment compared with other regimens), where iGlarg (od) ranked first.. iDet (bid) is the most cost-effective regimen, providing the highest QALY gain and NMB. iGlarg (od) and iDet (od) are possible options for those for whom the iDet (bid) regimen is not acceptable or does not achieve required glycemic control.

Topics: Adult; Bayes Theorem; Blood Glucose; Computer Simulation; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; England; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Young Adult

Investigate contributors to treatment satisfaction in type 1 diabetes (T1D).. Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin.. Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1.13 [0.30] versus -0.04 [0.31]; p=0.006). In the overall population, treatment satisfaction improvement with all insulin regimens was related to less frequent severe hypoglycemia (coefficient-0.077; p=0.040) and HbA1c reduction (-0.066; p=0.082). By treatment regimen, relationships between treatment satisfaction and these outcomes approached or attained statistical significance for NPH insulin, but not Gla-100. In the overall population, predictors of treatment satisfaction improvement included: Gla-100 treatment (estimate 1.17, p=0.006), lower baseline DTSQs (-0.57, p<0.001), study (-1.01, p=0.019), lower severe hypoglycemia rate (0.17, p=0.012), and higher baseline HbA1c (0.44, p=0.014). By treatment regimen, these predictors remained significant for NPH insulin.. Gla-100 resulted in a significant improvement in treatment satisfaction versus NPH insulin, independent of baseline disease characteristics and clinical outcomes.

Topics: Adult; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index

The aim of this study was to study the efficacy and safety of long-acting insulin analog insulin lispro protamine suspension (ILPS) in diabetic pregnant women.. In a multicenter observational retrospective study, we evaluated pregnancy outcome in 119 women affected by type 1 diabetes and 814 with gestational diabetes (GDM) treated during pregnancy with ILPS, compared with a control group treated with neutral protamine hagedorn (NPH) insulin.. Among type 1 diabetic patients, fasting blood glucose at the end of pregnancy was significantly lower in ILPS-treated than in NPH-treated patients. HbA1c levels across pregnancy did not differ between groups. Caesarean section and preterm delivery rates were significantly lower in the ILPS-women. Fetal outcomes were similar in the ILPS and NPH groups. Among GDM women, fasting blood glucose at the end of pregnancy was significantly lower in ILPS-treated than in NPH-treated patients. Duration of gestation was significantly longer, caesarian section and preterm delivery rates were lower in the ILPS-treated group. In addition, there were significantly fewer babies with an excessive ponderal index or neonatal hypoglycemic episodes in the ILPS group than in the NPH group.. Association of ILPS with rapid-acting analogs in pregnancy is safe in terms of maternal and fetal outcomes.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Humans; Infant, Newborn; Insulin Lispro; Insulin, Isophane; Italy; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Retrospective Studies

Long-acting insulin analogues for type 1 diabetes (T1D) treatment have been available on the Brazilian market since 2002. However, the population cannot access the analogues through the public health system.. To estimate the incremental budget impact of long-acting insulin analogues coverage for T1D patients in the Brazilian public health system compared to NPH insulin.. We performed a budget impact analysis of a five-year period. The eligible population was projected using epidemiological data from the International Diabetes Federation estimates for patients between 0-14 and 20-79 years old. The prevalence of T1D was estimated in children, and the same proportion was applied to the 15-19-year-old group due to a gap in epidemiological information. We considered 4,944 new cases per year and a 34.61/100,000 inhabitants mortality rate. Market share for long-acting insulin analogues was assumed as 20% in the first year, reaching 40% in the fifth year. The mean daily dose was taken from clinical trials. We calculated the bargaining power of the Ministry of Health by dividing the price paid for human insulin in the last purchase by the average regulated price. We performed univariate and multivariate sensitivity analyses.. The incremental budget impact of long-acting insulin analogues was US$ 28.6 million in the first year, and reached US$ 58.7 million in the fifth year. The total incremental budget impact was US$ 217.9 million over the five-year period. The sensitivity analysis showed that the percentage of T1D among diabetic adults and the insulin analogue price were the main factors that affected the budget impact.. The cost of the first year of long-acting insulin analogue coverage would correspond to 0.03% of total public health expenditure. The main advantage of this study is that it identifies potential bargaining power because it features more realistic profiles of resource usage, once centralized purchasing is established as an economically sustainable strategy. Clinical guidelines restricting the use of insulin analogues would make the decision towards insulin analogue coverage more affordable.

Topics: Adolescent; Adult; Aged; Brazil; Child; Child, Preschool; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Female; Health Care Costs; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Public Health

To compare the effect on metabolic control of treatment with conventional and analogue insulins for patients with diabetes mellitus.. Retrospective cohort study held in cities of Colombia (Pereira and Manizales). People insured by the paid healthcare system, who were diagnosed with diabetes mellitus type 1 and 2, and treated with conventional and analogue insulin for at least 6 months prior to the start of the study were sampled and followed up for 18 months. Data were collected from clinical records for each patient. Treatment groups were compared according to the type of insulin received.. A total of 313 patients were included; overall, 56.9% were women and the mean age was 57.3 years. No statistically significant difference was found in glycosylated haemoglobin reduction at 3, 6 and 18 months when comparing patients receiving glargine vs NPH insulin (P=.403) and NPH plus zinc crystalline insulin vs glargine plus glulisine (P=.514). The percentage of patients with metabolic control increased from 27.8% to 34.2% during follow-up with all types of insulin.. Insulin analogues were not superior to human insulin for glycaemic control. A significant proportion of patients did not attain the treatment goals; therefore, it is necessary to implement measures to improve the monitoring and control of diabetes mellitus.

Topics: Adult; Blood Glucose; Cohort Studies; Colombia; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.. Retrospective analysis of data from 892 DAFNE participants from 11 UK centres.. Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c  ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110).. After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c , independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.

Topics: Adult; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Patient Education as Topic; Retrospective Studies; Self Care; Treatment Outcome

Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP) in rats.. Diabetic (alloxan, 42 mg/kg i.v., 10 days) and non-diabetic (control) male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a) total and differential cell counts in peritoneal lavage (PeL) and bronchoalveolar lavage (BAL) fluids; (b) quantification of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL- 6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA); (c) total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d) biochemical parameters (urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) by colorimetric analyses); and (e) lung, kidney, and liver morphological analyses (hematoxylin and eosin staining).. Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1β, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c.), 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels.. These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal inflammation in diabetic rats.

Topics: Alloxan; Animals; Blood Glucose; Cytokines; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Insulin, Isophane; Liver; Male; Rats; Rats, Wistar; Weight Gain

We performed a comparative analysis of the use of long-acting insulin (analogues) neutral protamine hagedorn (NPH), detemir (Det) and glargine (Gla), and quantified injection frequencies and daily insulin doses in patients with type 1 and 2 diabetes in daily practice.. A total number of 51 964 patients from 336 centres in Germany and Austria with type 1 and 2 diabetes with exclusive insulin therapy were retrospectively analysed.. A total number of 42.1%/75.9% (type 1/type 2) of patients used NPH, 19.9%/6.7% Det and 38.0%/17.4% Gla, with similar glycaemic control and proportion of severe hypoglycaemia for NPH/Det/Gla in type 1 (Mean HbA(1c) 7.98%/7.98%/8.07%; mean proportion of severe hypoglycaemia 11.06%/11.93%/10.86%) and type 2 diabetes (Mean HbA(1c) 7.61%/7.78%/7.61%; mean proportion of severe hypoglycaemia 5.66%/4.48%/5.03%). In type 1 diabetes, the mean daily injection frequencies of NPH versus Det versus Gla were 1.9 vs 1.8 vs 1.1, and total daily insulin injections were 5.3 vs 5.6 vs 5.0. The adjusted mean daily basal insulin doses were 0.36, 0.39 and 0.31 IU/kg, mean daily total insulin dose was lowest for Gla (0.74 IU/kg), followed by NPH (0.76 IU/kg) and Det (0.81 IU/kg). In type 2 diabetes patients, mean daily injection frequencies were 1.6 for NPH, 1.4 for Det and 1.1 for Gla, total daily insulin injections were 4.0 vs 4.1 vs 3.6. The mean daily basal insulin dosages were 0.30 IU/kg (NPH), 0.33 IU/kg (Det) and 0.29 IU/kg (Gla), mean total insulin doses per day were 0.63 IU/kg (NPH), 0.77 IU/kg (Det) and 0.67 IU/kg (Gla).. In a 'real-world' setting, the injection frequencies and doses of basal and total insulin per day are lowest with the use of insulin glargine compared with NPH-insulin or insulin detemir at similar glycaemic control and rates of severe hypoglycaemia.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM.. Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0-18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 ± 3.8 years; 53% males; diabetes duration 5.6 ± 3.5 years; HbA1c 7.9 ± 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR = 1.44; 95%CI 1.04-1.99), in patients using rapid acting analogues as compared to regular insulin (IRR = 1.48; 95%CI 0.97-2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR = 0.40; 95%CI 0.19-0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR = 4.25; 95%CI 1.01-17.86) and increased with insulin units needed (IRR = 7.66; 95%CI 2.83-20.74) and HbA1c levels (IRR = 1.63; 95%CI 1.36-1.95). Mother's age was inversely associated with the risk of both SH (IRR = 0.95; 95%CI 0.92-0.98) and DKA (IRR = 0.94; 95%CI 0.88-0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR = 1.48; 95%CI 0.97-2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect.. The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Infant; Insulin; Insulin, Isophane; Italy; Ketosis; Male; Retrospective Studies

Topics: Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Injections, Intramuscular; Injections, Subcutaneous; Insulin, Lente

We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, "H & E" staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples.

Topics: Animals; Antioxidants; Apitherapy; Apoptosis; Cell Survival; Combined Modality Therapy; Diabetes Mellitus, Type 1; Food, Organic; Hippocampus; Honey; Hypoglycemic Agents; Injections, Intraperitoneal; Injections, Subcutaneous; Insulin, Isophane; Iran; Male; Neurons; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Streptozocin

Topics: Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics

Topics: Diabetes Mellitus, Type 1; Drug Evaluation; Humans; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 1; Drug Evaluation; Humans; Insulin, Isophane; Insulin, Long-Acting

To describe (i) current bedtime nutritional practices and (ii) the association between post-dinner dietary intake and the occurrence of non-severe nocturnal hypoglycemia (NH) in real-life conditions among adult patients with type 1 diabetes using insulin analogs.. One hundred adults (median [interquartile range]: age 46.4 [36.0-55.8] years, HbA1c 7.9 [7.3-8.6] % (63 [56-70] mmol/mol)) using multiple daily injections (n=67) or insulin pump (n=33) wore a blinded continuous glucose monitoring system and completed a food diary for 72-h.. NH occurred on 28% of 282 nights analyzed. (i) Patients reported post-dinner dietary intakes on 63% of the evenings. They injected rapid-acting insulin boluses on 64 occasions (23% of 282 evenings). These insulin boluses were mostly injected with (n=37) dietary intakes. (ii) Post-dinner dietary intake was not associated with NH occurrence in univariate analyses. In multivariate analyses, the injection of rapid-acting insulin modulated the association between post-dinner dietary intake and NH: with insulin, post-dinner carbohydrate intake was positively associated with NH (odds ratio (OR): 1.16 [95% confidence interval, CI: 1.04-1.29] per 5g increase, p=0.008); without insulin, post-dinner protein intake was inversely associated with NH occurrence (OR [95% CI]: 0.88 [0.78-1.00] per 2g increase, p=0.048).. NH remains frequent in adults with type 1 diabetes. There is a complex relationship between post-dinner dietary intake and NH occurrence, including the significant role of nutrient content and rapid-acting insulin injection that requires further investigation.

Topics: Adult; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Dietary Supplements; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin, Isophane; Male; Middle Aged; Monitoring, Physiologic; Postprandial Period; Quebec; Risk Factors

The Somogyi effect postulates that nocturnal hypoglycaemia causes fasting hyperglycaemia attributable to counter-regulatory hormone release. Although most published evidence has failed to support this hypothesis, this concept remains firmly embedded in clinical practice and often prevents patients and professionals from optimizing overnight insulin. Previous observational data found lower fasting glucose was associated with nocturnal hypoglycaemia, but did not assess the probability of infrequent individual episodes of rebound hypoglycaemia. We analysed continuous glucose monitoring data to explore its prevalence.. We analysed data from 89 patients with Type 1 diabetes who participated in the UK Hypoglycaemia study. We compared fasting capillary glucose following nights with and without nocturnal hypoglycaemia (sensor glucose < 3.5 mmol/l).. Fasting capillary blood glucose was lower after nights with hypoglycaemia than without [5.5 (3.0) vs. 14.5 (4.5) mmol/l, P < 0.0001], and was lower on nights with more severe nocturnal hypoglycaemia [5.5 (3.0) vs. 8.2 (2.3) mmol/l; P = 0.018 on nights with nadir sensor glucose of < 2.2 mmol/l vs. 3.5 mmol/l]. There were only two instances of fasting capillary blood glucose > 10 mmol/l after nocturnal hypoglycaemia, both after likely treatment of the episode. When fasting capillary blood glucose is < 5 mmol/l, there was evidence of nocturnal hypoglycaemia on 94% of nights.. Our data indicate that, in clinical practice, the Somogyi effect is rare. Fasting capillary blood glucose ≤ 5 mmol/l appears an important indicator of preceding silent nocturnal hypoglycaemia.

Topics: Adult; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Cohort Studies; Diabetes Mellitus, Type 1; Drug Monitoring; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Monitoring, Ambulatory; Prevalence; Severity of Illness Index; United Kingdom

The aim of this study was to compare, from the perspective of the statutory health insurance, resource consumption and the associated adjusted treatment costs of intensified conventional therapy (ICT) with long-acting insulins in patients with type 1 diabetes mellitus (T1DM).. We identified patients with T1DM who started ICT with either insulin glargine or neutral protamine Hagedorn (NPH) insulin between July 2000 and February 2008 using a representative German database (IMS® Disease Analyzer). The variables age, gender, insurance status, diabetes duration, hemoglobin A1c level, body mass index, and geographic region and specialization of practice were collected. Resource consumption was evaluated over a time period of 12 months and included the quantities of applied basal and bolus insulin, blood glucose test strips, lancets and needles, physician visits (general practitioner, specialist), hospitalization, and antihypoglycemic therapy (intravenous glucose/glucagon).. A total of 2297 patients with T1DM were included; 1079 received ICT with insulin glargine and 1218 with NPH insulin. After adjustment, annual cost savings in favor of insulin glargine amounted to €423.94 compared with NPH insulin (p = .3019).. The adjusted results show that an ICT with insulin glargine results in lower annual costs than ICT with NPH insulin (this difference was not statistically significant). However, in the context of glucose-lowering effect and a lower hypoglycemia rate, insulin glargine is preferred to NPH insulin for patients with T1DM undergoing ICT.

Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 1; Female; Germany; Health Resources; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Proportional Hazards Models

Topics: Diabetes Mellitus, Type 1; Humans; Hypersensitivity; Hypoglycemia; Insulin; Insulin, Isophane; Male; Middle Aged

Defects in both insulin secretion and function play a fundamental role in the pathophysiologic mechanisms underlying both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). As the most physiologic treatment option available, insulin plays a central role in the management of patients with T1DM and a growing role in the management of patients with T2DM, as is reflected in current treatment guidelines.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Short-Acting; Insulins

Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study.. Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables.. The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine.. There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice.

Topics: Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Coma; Female; Finland; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Medical Record Linkage; Poisson Distribution; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk

Monitoring of blood glucose concentration is important to evaluate the diabetic status of dogs. Continuous glucose monitoring systems (CGMS) have been applied in veterinary medicine for glucose monitoring in diabetic dogs. The purpose of the study was to evaluate the daily glycemic profiles obtained with CGMS and compare glucose fluctuations between day- and night-time in diabetic dogs. Five diabetic dogs were used in this study and were treated with either NPH insulin or insulin detemir. For data analyses, day-time was defined as 9:00 am-9:00 pm and night-time as 9:00 pm-9:00 am. Using glucose profiles, we determined the mean glucose concentrations (1- and 12-hr intervals), and times spent in hyperglycemia >200 mg/dl or hypoglycemia <60 mg/dl. None of the parameters differed significantly between day-time and night-time in dogs treated with NPH insulin or insulin detemir. In conclusion, this study confirmed, using CGMS, that there are no differences in glucose fluctuations between day- and night-time, in diabetic dogs on a similar feeding regimen and insulin administration.

Topics: Animals; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dog Diseases; Dogs; Female; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Monitoring, Physiologic; Time Factors

Monkeys with insulin-dependent diabetes are important preclinical animal models for islet transplantation. Exogenous insulin should be administered to achieve good glycemic control and minimize the long-term vascular complications associated with diabetes until the graft function recovered completely. However, the effect of multiple daily injections of porcine or human insulin and the long-term effects of porcine insulin have not been studied in diabetic rhesus monkeys.. Diabetic rhesus monkeys, using a 6-month self-control insulin comparison experiment, were used to detect the incidence of adverse events and long-term diabetes complication events after long-term administration of porcine insulin.. In this study, we found that a 20% higher dose of porcine insulin results in similar glycemic control as the human insulin regimen, and adverse events were seldom reported when porcine insulin was administered. Moreover, long-term injection with porcine insulin could delay the rate and severity of diabetes-related complications.. Porcine insulin as a competent candidate for regular insulin therapy to maintain blood glucose levels in insulin-dependent diabetic monkeys during preclinical studies of islet transplantation.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Glycated Hemoglobin; Hypoglycemic Agents; Insulin, Isophane; Insulin, Regular, Human; Insulin, Regular, Pork; Macaca mulatta; Monkey Diseases

There are an estimated 1000 children with diabetes in Tanzania. Recently, the first two pediatric endocrinologists, trained in the European Society for Paediatric Endocrinology (ESPE)/International Society for Paediatric and Adolescent Diabetes (ISPAD) program in Nairobi, Kenya, entered practice. The purpose of this study was to prospectively assess the impact of a 6-month diabetes management and education program on glycemic control and acute complications in children and adolescents in Tanzania.. Eighty-one patients aged 3-19 yr were enrolled. All were on split-dose Insulatard (Neutral Protamine Hagedorn) and Actrapid (soluble, regular) insulin, and were given three glucose test strips per week. Children were seen in clinic an average of six times over 6 months and received 3 h of diabetes education. A structured questionnaire evaluated social demographic data and acute complications.. Despite regular clinic attendance, diabetes education, and provision of insulin, hemoglobin A1c (HbA1c) levels did not improve. Four children (5%) had HbA1c 7.5%, 22 (28%) HbA1c 7.5-10%, 9 (24%) HbA1c 11-12.5%, and 36 (44%) HbA1c >12.5%. There was a substantial reduction in severe hypoglycemia, with 17% of subjects experiencing this acute complication compared to 52% in the 6 months prior to study enrolment. Six children were admitted in diabetic ketoacidosis during the study compared to three during the previous 6 months. Twenty-six children (36%) reported missing >6 doses of insulin (but only two lacked insulin).. Diabetes education significantly reduced the risk of severe hypoglycemia, but better glycemic control of diabetes was not attained. Further study is needed to explore factors to improve glycemic control including increased testing, or perhaps different insulin regimens.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Therapy, Combination; Family; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin, Isophane; Insulin, Regular, Human; Insulin, Regular, Pork; Isophane Insulin, Human; Male; Medication Adherence; Outpatient Clinics, Hospital; Patient Education as Topic; Prospective Studies; Tanzania

We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51-month-old girl who presented with hyperglycemia in the neonatal period. Mutational analysis of KCNJ11 and INS was performed and this detected a novel heterozygous c.38T>G (p.Leu13Arg) INS de novo mutation. The non-conservative change substitutes the highly conserved L(13) residue within the hydrophobic core region of the preproinsulin signal peptide. Given the frequent tendency of heterozygous INS mutations to exhibit dominant negative disease pathogenesis, it is likely that the mutant preproinsulin perturbed the non-mutant counterpart progression and processing within the β-cells, and this resulted to a permanent form of congenital diabetes.

Topics: Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Potassium Channels, Inwardly Rectifying; Protein Precursors; Protein Sorting Signals

To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands.. A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€).. Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12,644 (Denmark), € 12,612 (Sweden), € 16,568 (Finland) and € 12,216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin.. Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings.

Topics: Cost-Benefit Analysis; Denmark; Diabetes Mellitus, Type 1; Female; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Netherlands; Pharmacies; Quality-Adjusted Life Years; Sweden

Basal insulin analogs are well established in the treatment of type 1 diabetes in Germany. However, little is known about their economic impact. The aim of this study for an adult population was to compare, from the perspective of the Statutory Health Insurance (SHI), the cost effectiveness of the long-acting insulin analog glargine (GLA) with intermediate-acting neutral protamine Hagedorn (NPH) insulin in basal bolus therapy, considering the interaction between glycemic control and the rate of hypoglycemia.. A validated discrete event simulation model was adapted to the German setting to project clinical and cost outcomes over 40 years. Resources were valued with German official prices in 2009/2010 Euros. Health-related disutilities were taken from UK sources. Patient characteristics and risk factors were partially extracted from German sources in a sensitivity analysis.. In the base-case analysis, GLA was dominant as it increased life expectancy by 0.196 years and improved quality-adjusted life-years (QALYs) by 0.396 units while at the same time leading to savings of €5246 each per patient after 40 years compared to NPH. These results were robust in the sensitivity analyses. Monte Carlo simulation confirmed dominance of GLA in 70% (life-years gained) and 80% (QALYs gained) of the iterations. The price of GLA had the highest impact on savings. In extreme scenarios, incremental cost-effectiveness ratios increased up to €9576 per QALY gained. Limitations of the evaluation included no myocardial re-infarction(s) and no recurrent stroke(s), patient characteristics, risk factors, and disutilities from the UK due to scarce data in Germany, and that not all diabetes-related direct costs were included, namely insulin pens and blood glucose meters.. GLA appears to be cost effective or even cost saving among type 1 diabetics with basal bolus therapy from the perspective of SHI compared to NPH depending on the scenario chosen.

Topics: Adult; Cost of Illness; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Female; Germany; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Quality-Adjusted Life Years; Young Adult

Early morning hyperglycemia is frequent among children and adolescents with type 1 diabetes. Reasons are a dawn phenomenon, a Somogyi phenomenon or a lack of insulin in the morning hours. Only few studies are published regarding incidence and relation to different modes of basal insulin treatment in this population.We analyzed all cases recorded in the DPV register from 1995 to 2010. 5 839 patients from 128 centers with at least 3 blood glucose measurements during the last night of a hospital stay were included.24.2% of patients showed a morning hyperglycemia above 200 mg/dl. 8.6% showed a dawn phenomenon, 7.0 % a lack of insulin and 2.0% a Somogyi phenomenon. A dawn phenomenon was significantly less frequent in patients treated with an insulin pump (1.1%) compared to long acting insulin analogs Glargin and Levemir (5.4%) or NPH insulin (8.2%). Lack of insulin was again less frequent during insulin pump treatment compared to other treatments (1.9% vs. 4.9% vs. 5.3%). Median rise of blood glucose levels was 33.4 mg/dl between midnight and 6 a.m. Mode of basal insulin treatment is an important factor: while treatment with an insulin pump led to a blood glucose fall of 28.5 mg/dl between 3 and 6 a.m., treatment with insulin analog or NPH insulin resulted in a rise of 28.5 or 35.9 mg/dl, respectively.This study shows that insulin pump treatment reduces the frequency of morning hyperglycemia caused by the dawn phenomenon or a lack of insulin.

Topics: Blood Glucose; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Quality Assurance, Health Care; Registries

Topics: Diabetes Mellitus, Type 1; Female; Humans; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

Standardized protocols for maintaining near-normal glycemic levels in diabetic rodent models for testing therapeutic agents to treat disease are unavailable. We developed protocols for 2 common models of spontaneous type 1 diabetes, the BioBreeding diabetes-prone (BBDP) rat and nonobese diabetic (NOD) mouse. Insulin formulation, dose level, timing of dose administration, and delivery method were examined and adjusted so that glycemic levels remained within a normal range and fluctuation throughout feeding and resting cycles was minimized. Protamine zinc formulations provided the longest activity, regardless of the source of insulin. Glycemic control with few fluctuations was achieved in diabetic BBDP rats through twice-daily administration of protamine zinc insulin, and results were similar regardless of whether BBDP rats were acutely or chronically diabetic at initiation of treatment. In contrast, glycemic control could not be attained in NOD mice through administration of insulin twice daily. However, glycemic control was achieved in mice through daily administration of 0.25 U insulin through osmotic pumps. Whereas twice-daily injections of protamine zinc insulin provided glycemic control with only minor fluctuations in BBDP rats, mice required continuous delivery of insulin to prevent wide glycemic excursions. Use of these standard protocols likely will aid in the testing of agents to prevent or reverse diabetes.

Topics: Analysis of Variance; Animals; Blood Glucose; Diabetes Mellitus, Type 1; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycemic Index; Insulin, Isophane; Mice; Mice, Inbred NOD; Rats; Rats, Inbred BB

Lipoatrophy is a rare complication of treatment with insulin analogues. It has been reported with insulin Lispro (Eli Lilly, Indianapolis, Indiana, USA) and insulin Glargine (Sanofi-Aventis, Paris, France). To our knowledge, this is one of the first reports of lipoatrophy with Aspart, biphasic Aspart and Detemir insulin analogues (Novo Nordisk, Bagsvaerd, Denmark). We report the cases of four children with type I diabetes who were commenced on NovoMix 30 or NovoRapid/Levemir insulin injections. They developed lipoatrophy at the injection sites after 2-3 years of treatment. In two of our patients, lipoatrophy resolved when the injection sites were changed, suggesting that local factors could be the cause of lipoatrophy. However, lipoatrophy developed at the new sites in the other two patients, requiring a change of insulin preparation. Regular examination of the injection sites facilitated early detection of lipoatrophy in our patients. Lipoatrophy completely resolved over 1-2 years in all patients with no recurrence after 3-4 years of follow-up.

Topics: Adolescent; Biphasic Insulins; Child; Child, Preschool; Diabetes Mellitus, Lipoatrophic; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Lipodystrophy

To evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Sweden, based on data from a two-year, multi-national, open-label, randomized, controlled trial.. Insulin detemir was associated with significant improvements in glycaemic control after 24 months (HbA1c 7.36% versus 7.58%, mean difference -0.22%, p = 0.022) and major hypoglycaemic events (69% risk reduction, p = 0.001) versus NPH. Patients treated with detemir gained less weight (1.7 versus 2.7 kg, P = 0.024). Based on these findings, a published and validated computer model (IMS CORE Diabetes Model) was used to estimate life-expectancy, quality-adjusted life expectancy and both direct medical costs and indirect costs.. Basal-bolus therapy with insulin detemir was projected to improve life expectancy by 0.14 years (15.02 ± 0.19 versus 14.88 ± 0.18 years) and quality-adjusted life expectancy by 0.53 quality-adjusted life years (QALYs) versus NPH (8.35 ± 0.11 versus 7.82 ± 0.10 QALYs). Improvements in QALYs were driven by avoided or delayed diabetes-related complications and fewer hypoglycaemic events. Direct medical costs over patient lifetimes were SEK 26,144 higher in the insulin detemir arm (SEK 995,025 ± 19,580 versus 968,881 ± 19,769), leading to an incremental cost-effectiveness ratio of SEK 49,757 per QALY gained. Capturing indirect costs led to insulin detemir being cost saving over patient lifetimes, by SEK 80,113, compared to NPH (SEK 2,959,909 ± 64,727 versus 3,040,022 ± 62,317).. Compared with NPH, insulin detemir is likely to be cost-effective from a healthcare payer perspective and dominant from a societal perspective in patients with type 1 diabetes in Sweden.

Topics: Adult; Cohort Studies; Cost of Illness; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Drug Costs; Female; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Outcome Assessment, Health Care; Quality-Adjusted Life Years; Sweden; Time Factors

To evaluate the safety and tolerability of once or twice daily neutral protamine hagedorn (NPH) insulin in fasting pregnant diabetics during Ramadan.. This was a prospective cohort study conducted during Ramadan 2006 and 2007. Twenty four pregnant diabetic women were given NPH insulin once at 5 pm or twice daily at 5 pm and 5 am. Demographic data, blood glucose control, insulin requirement, days of fasting and hypoglycemic episodes were analyzed.. Most women were parity 1 (37.5%) in their second trimester (54.2%) and worked during the daytime (87.5%). Fourteen women (58.3%) had gestational diabetes mellitus, nine women (37.5%) had type 2 and one (4.2%) had type 1 diabetes mellitus. There were significant reductions in mean fasting blood glucose (6.16 mmol/L versus 5.34 mmol/L, P = 0.001), glycosylated hemoglobin (HbA1c) (6.70% ± 0.91 versus 6.64% ± 0.96, P = 0.001) and serum fructosamine (232.4 mmol/L ± 24.0 versus 217.0 mmol/L ± 24.3, P = 0.001) after Ramadan compared to before Ramadan. Throughout the four weeks of Ramadan, home blood glucose monitoring showed a reducing trend and was within the acceptable limits. Insulin requirement was increased from the first to the fourth week with a reduction in insulin dose noted after (38.5 U/day) compared to before the start of Ramadan (40 U/day). Most women (79.2%) were able to fast for more than 15 days without any hypoglycemia or fetal demise.. Once or twice daily NPH insulin is a safe and tolerable option for pregnant diabetics who wish to fast during Ramadan.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Administration Schedule; Fasting; Female; Humans; Insulin, Isophane; Islam; Parity; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Treatment Outcome

To assess the safety and efficacy of insulin analogues versus human insulin in pregnant women with pregestational diabetes.. We collected data on pregnant women with type 1 or type 2 diabetes who were attended at the Diabetes and Pregnancy Unit between January 1998 and April 2008 (N=351). Two hundred and forty one patients were treated with regular insulin and NPH and 110 were treated with different combinations of insulins including an insulin analogue (most of them with NPH and lispro).. There was no significant difference in terms of congenital malformation rate between groups (3.3% and 3.6%). The group on insulin analogue had slightly higher mean HbA1c during the first trimester than the group on human insulin (6.6 [1.0]% vs 6.9 [1.1]%; P=0,022) and needed smaller insulin doses during whole pregnancy. Severe hypoglycaemia was significantly less frequent among women treated with a rapid insulin analogue (2.3 vs 10.0%; P=0,025). Neonatal hypoglycaemia was significantly more frequent in the group treated with a rapid insulin analogue (34.9 vs 23.6%; P=0.043) due to the concomitant use of an insulin pump. Other obstetric and neonatal variables were not different between the two groups.. Our study shows that insulin analogues are safe during pregnancy in women with pregestational diabetes mellitus. Overall, glycaemic control, maternal and foetal outcome were similar to those with human insulin. The main advantage with respect to human insulin was to importantly reduce maternal severe hypoglycaemia.

Topics: Abnormalities, Drug-Induced; Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Insulin, Regular, Human; Logistic Models; Pregnancy; Pregnancy in Diabetics; Retrospective Studies

Premixed, or biphasic, insulins containing varying proportions of rapid- and intermediate-acting insulin components have been developed to limit the number of daily injections for patients who require both prandial and basal insulin injections.. This study was conducted to determine whether there were differences in glycosylated hemoglobin (HbA(1c)), weight change, hypoglycemia occurrence, and treatment discontinuation between patients treated with biphasic insulin aspart 30 (BIAsp-30) or biphasic human insulin 30 (BHI-30) in UK general practice.. Data were from >350 general practices from the United Kingdom. Patients were stratified by treatment regimen, diabetes type, and insulin status (naive or experienced). Changes in HbA(1c) and weight were compared from baseline (the date of the first prescription for either insulin) through 180 days of follow-up using ANCOVA. Hypoglycemia incidence rate ratios were compared, and the adjusted likelihood of hypoglycemia was evaluated by logistic regression. Rates of treatment discontinuation were compared using the Cox proportional hazards model.. The study included data from 7720 patients, of whom 1333 (17.3%) had type 1 diabetes and 4457 (57.7%) were male. Patients' mean (SD) age was 57.9 (19.8) years, and their mean body mass index was 29.5 (6.2) kg/m(2). The difference in HbA(1c) reduction was significant for BIAsp-30 compared with BHI-30 in insulin-naive patients with type 1 diabetes (0.57%; P = 0.045), insulin-naive patients with type 2 diabetes (-0.17%; P = 0.003), and insulin-experienced patients with type 2 diabetes (-0.23%; P = 0.007). The difference between insulins was not significant in insulin-experienced patients with type 1 diabetes. Five hundred ninety-four patients (7.7%) experienced at least one hypoglycemic event. The incidence rate ratio for reported hypoglycemia was significantly lower with BIAsp-30 compared with BHI-30 in insulin-naive patients with type 2 diabetes (0.74; 95% CI, 0.62-0.89; P = 0.001); the difference between insulins was not significant in the other groups. The adjusted hazard ratio for treatment discontinuation was significant for BIAsp-30 versus BHI-30 in insulin-experienced patients with type 2 diabetes (0.693; 95% CI, 0.543-0.884; P = 0.003), whereas the hazard ratios for the other groups did not reach statistical significance. There were no significant differences in weight change between BIAsp-30 and BHI-30 in any of the groups.. In this analysis, BIAsp-30 was associated with improved glycemic control (HbA(1c)) compared with BHI-30 in insulin-naive patients with type 1 or type 2 diabetes and insulin-experienced patients with type 2 diabetes. BIAsp-30 was associated with reduced hypoglycemia in insulin-naive patients with type 2 diabetes and lower rates of treatment discontinuation in insulin-experienced patients with type 2 diabetes. Cambridgeshire Research Ethics Committee: REC 08/H0305/47.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Biphasic Insulins; Body Weight; Child; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United Kingdom; Young Adult

Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH, although glargine has not been shown to improve HbA1c in randomized trials. Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking.. HbA1c and insulin requirement were compared in a retrospective study of children (7-17 yr of age) with type 1 diabetes treated from diagnosis with basal insulin glargine (n = 49) or NPH (n = 49) in a multiple injection therapy (MIT) regimen with a rapid-acting insulin analogue. Patients were followed every third month for 1 yr. HbA1c, insulin dose, and weight data were retrieved.. HbA1c (mean ± SD) was lower at 3-5 months (5.5 ± 0.89 vs. 6.2 ± 0.89%, p < 0.05) and 6-9 months (5.6 ± 1.14 vs. 6.6 ± 0.99%; p < 0.001) in glargine treated. After 12 months, HbA1c was significantly lower in glargine treated (6.3 ± 1.56 vs. 7.1 ± 1.28; p < 0.01). Reported total insulin doses were similar at nadir (0.5 U/kg BW × 24 h), but significantly lower at 12 months in glargine treated (0.64 ± 0.23 vs. 0.86 ± 0.3 U/kg BW × 24 h; p < 0.001).. HbA1c 1 yr from diagnosis was lower in children treated with glargine from start as compared with those on NPH. This observation should be viewed in the light of a significantly lower dose of total daily insulin in the glargine group.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Short-Acting; Male; Retrospective Studies

Diabetes in pregnancy is associated with risks to the woman and to the developing fetus. Miscarriage, pre-eclampsia, preterm labour and congenital malformations in fetus are more common in women with pre-existing diabetes. Insulin requirement increases with each trimester of pregnancy in diabetic females. Treatment of gestational diabetes consists of medical nutrition therapy but insulin treatment forms the mainstay of the therapy. Monitoring glycemic control is essential in treatment of gestational diabetes. HbA1c level is helpful to differentiate between a pre-GDM and GDM. Majority of pregnant women with diabetes fail to achieve optimum glycemic control, mostly the postprandial plasma glucose with conventional insulin. In them, the best option is to administer ultra-short-acting analogs, insulin lispro or insulin aspart. These analogs improve the postprandial glucose control during pregnancy in both type 1 and type 2 diabetes and are considered safe and effective.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin, Isophane; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome

Insulin-like growth factor binding protein-1 (IGFBP-1) is known to regulate the bioavailability of insulin-like growth factor (IGF) and the levels of IGFBP-1 are increased in the morning in patients with type 1 diabetes mellitus. We investigated the nocturnal fluctuations of glucose, IGFBP-1, and free IGF-1 levels with three insulin regimens.. Forty-eight type 1 diabetes patients were divided into three groups according to their basal insulin therapy (continuous subcutaneous insulin infusion [CSII], insulin glargine, NPH insulin). Blood samples were obtained every 2 h between 2 300 h and 0700 h to measure plasma glucose, IGFBP-1 and free IGF-1 levels.. The dawn phenomenon was more frequent with NPH (62.1%) than with glargine (16.6%, p<0.05) and CSII (14.3%, p<0.05). In the NPH group, the serum IGFBP-1 levels were markedly increased from 21.0+/-3.6 ng/ml at 2 300 h to 200.3+/-21.8 ng/ml at 0700 h and free IGF-1 levels were inversely decreased; these changes were partially suppressed in the CSII and glargine groups.. The use of insulin regimens that provide sufficient insulin levels in the early morning can suppress the dawn phenomenon, leading to improved glycemic control. The increase in circulating IGFBP-1 in the morning, as a result of waning of insulin action, lowers free IGF-1 levels and may cause insulin resistance.

Topics: Adolescent; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Male

OBJECTIVE To investigate if long-acting insulin analogs decrease the risk of diabetic ketoacidosis (DKA) in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Of 48,110 type 1 diabetic patients prospectively studied between 2001 and 2008, the incidence of DKA requiring hospitalization was analyzed in 10,682 individuals aged /=2 years. RESULTS The overall rate of DKA was 5.1 (SE +/- 0.2)/100 patient-years. Patients using insulin glargine or detemir (n = 5,317) had a higher DKA incidence than individuals using NPH insulin (n = 5,365, 6.6 +/- 0.4 vs. 3.6 +/- 0.3, P < 0.001). The risk for DKA remained significantly different after adjustment for age at diabetes onset, diabetes duration, A1C, insulin dose, sex, and migration background (P = 0.015, odds ratio 1.357 [1.062-1.734]). CONCLUSIONS Despite their long-acting pharmacokinetics, the use of insulin glargine or detemir is not associated with a lower incidence of DKA compared with NPH insulin.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Risk Factors

Topics: Child; Child, Preschool; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Research Design

Topics: Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Eating; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Patient Education as Topic

The use of rapid-acting insulin analogs and regular insulin differs considerably in countries throughout the world. We therefore studied how glycemic control has been affected by using insulin lispro in clinical practice over 5 years in 14 hospitals in Sweden.. We used a time period when most patients had not changed the basal insulin, but only the mealtime insulin. Accordingly the most recent years were not suitable since many patients had changed basal insulin from NPH to glargine or determir. We therefore analyzed the metabolic consequences on glycosylated hemoglobin (HbA1c) when changing from regular insulin to insulin lispro from 1997 and during the following 5 years. We studied 1,069 patients with diabetes taking NPH insulin as basal insulin and at least three daily injections of regular insulin, of whom 423 changed their mealtime insulin to insulin lispro and 646 controls who continued with regular insulin.. Patients changing to insulin lispro on average decreased by 0.19% units more in HbA1c than those remaining on regular insulin. The effect was most pronounced in patients with high HbA1c even after controlling for regression to the mean. A beneficial effect of insulin lispro was also indicated since patients had the same level of HbA1c during a long period of time with regular insulin but then dropped when changing to insulin lispro.. This study indicates that insulin lispro has had a beneficial and persisting effect on glycemic control when used in patients with diabetes on multiple daily injections of insulin in clinical practice.

Topics: Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glycated Hemoglobin; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Sweden

Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data.. Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA(1c) after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables.. After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA(1c) 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05).. In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

Topics: Adult; Body Weight; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Young Adult

Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts.. The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE (a large, multinational, observational) study. The children investigated were using basal-bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians.. Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7-8.9%, p < 0.001) and mean fasting glucose [185-162 mg/dL (10.3-9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged.. Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.

Topics: Adult; Blood Glucose; Child; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Tolerance; Europe; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Safety; Turkey

We studied whether the institution of basal-bolus therapy immediately after diagnosis improved glycemic control in the first year after diagnosis for children with newly diagnosed type 1 diabetes mellitus.. We reviewed the charts of 459 children > or =6 years of age who were diagnosed as having type 1 diabetes between July 1, 2002, and June 30, 2006 (212 treated with basal-bolus therapy and 247 treated with a more-conventional neutral protamine Hagedorn regimen). We abstracted data obtained at diagnosis and at quarterly clinic visits and compared groups by using repeated-measures, mixed-linear model analysis. We also reviewed the records of 198 children with preexisting type 1 diabetes mellitus of >1-year duration who changed from the neutral protamine Hagedorn regimen to a basal-bolus regimen during the review period.. Glargine-treated subjects with newly diagnosed diabetes had lower hemoglobin A1c levels at 3, 6, 9, and 12 months after diagnosis than did neutral protamine Hagedorn-treated subjects (average hemoglobin A1c levels of 7.05% with glargine and 7.63% with neutral protamine Hagedorn, estimated across months 3, 6, 9, and 12, according to repeated-measures models adjusted for age at diagnosis and baseline hemoglobin A1c levels; treatment difference: 0.58%). Children with long-standing diabetes had no clinically important changes in their hemoglobin A1c levels in the first year after changing regimens.. The institution of basal-bolus therapy with insulin glargine at the time of diagnosis of type 1 diabetes was associated with improved glycemic control, in comparison with more-conventional neutral protamine Hagedorn regimens, during the first year after diagnosis.

Topics: Blood Glucose; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Patient Compliance; Retrospective Studies; Treatment Outcome

This study was conducted to quantify the long-term cost-effectiveness of insulin detemir (Levemir) versus intermediate-acting neutral protamine Hagedorn (NPH) insulin for the treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in Canada, and to assess the sensitivity of results to dis-utilities for hypoglycemic events. dagger Levemir is a trade name of Novo Nordisk, Princeton, NJ, USA RESEARCH DESIGN AND METHODS: The web-based IMS-CORE diabetes model has a menu-driven interface programmed in hypertext markup language (HTML). It was used to project lifetime (60 years for T1DM and 35 years for T2DM) clinical and economic outcomes for patients on detemir vs. NPH. Cohort characteristics, utilities, and costs were derived from published literature. For T1DM, clinical trial data for HbA(1c) improvement (detemir -0.94% +/- 1.07; NPH -0.82% +/- 1.01) from baseline, and rates of hypoglycemic events (major events: 0.20 vs. 0.80 per patient-year for detemir vs. NPH, respectively) were modeled. For T2DM, observational study data for HbA(1c) improvement (detemir -0.18%) from baseline, and reductions in hypoglycemic events (major events: 0.0995 vs. 1.33 per patient-year for detemir vs. NPH, respectively) were modeled. Base-case hypoglycemia dis-utilities were -0.0118 for major and -0.0035 for minor events. Sensitivity analyses were conducted on discount rate and hypoglycemia dis-utility.. Outcomes included costs of treatment/management and costs (and incidence) of diabetes-related complications. Incremental cost-effectiveness ratios (ICERs) were calculated from differences in total costs and quality-adjusted life-years (QALYs).. Average total costs for T1DM were $CAN 83 622 +/- 4585 for detemir and $CAN 72 016 +/- 4593 for NPH. QALYs increased by 0.475 years with detemir, with an ICER of $CAN 24 389/QALY. Average direct costs for T2DM were $CAN 74 919 +/- 6391 (detemir) and $CAN 69 230 +/- 6840 (NPH). QALYs increased by 0.305 years. The ICER was $CAN 18 677. Although detemir was associated with slightly lower costs for most complications, results were driven by the differences in rates and costs for hypoglycemic events, and their assumed dis-utility. Study limitations include the use of single trials for clinical assumptions and the lack of analyses for patient risk sub-groups.. Findings provide evidence for the cost-effectiveness of detemir vs. NPH in treating T1 and T2DM in Canada, and support the key role of assumptions regarding the impact of hypoglycemic events. Additional work is needed to determine the extent to which results are robust for different sub-groups of patients and for variation in assumptions around HbA(1c) improvements and hypoglycemic event rates.

Topics: Adult; Canada; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Models, Econometric; Quality of Life; Single-Payer System

The insulin analogs, glargine and detemir, are associated with reduced hypoglycemia incidence compared with NPH insulin. We assessed the impact of changing basal insulin from NPH to glargine or detemir in patients with type 1 diabetes mellitus who experienced severe hypoglycemia.. A retrospective chart review was conducted that included 73 (31 female) patients (mean age 48 years, diabetes duration 19 years) treated for 12 to 24 months with insulin glargine (n = 43) or detemir (n = 30).. There were no patients who withdrew from treatment due to side effects. The mean treatment duration in both groups was 18 months. Changing from NPH insulin was associated with a -0.3% (p = 0.036) reduction in HbA1c for glargine (baseline 8.8%) and -0.4% (p = 0.040) for detemir (baseline 8.3%) treated patients; insulin dosages increased, respectively by 4.1 (p = 0.045) and 4.3 units (p = 0.004) (mean values). Weight did not increase significantly and the 1-year rate of serious hypoglycemia was 0.25/person/year.. Switching from NPH-insulin to insulin detemir or glargine in type 1 diabetes mellitus patients with previous serious hypoglycemia was associated with a reduction in HbA1c. However, severe hypoglycemia was not completely eliminated, and few patients reached internationally accepted glycemic treatment goals.. We searched Medline, PubMed (with key search terms type 1 diabetes, NPH insulin, detemir, glargine and serious hypoglycemia), reference lists and databases of ongoing and completed trials (through July 2008) provided from the manufacturers of the drugs to identify relevant literature.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Improving the diabetes metabolic regulation decreases the risk of microvascular diabetic complications. Insulin treatment in children therefore tends to be intensified to multiple-dose insulin (MDI) or continuous subcutaneous insulin injection (CSII). Further, insulin analogues are increasingly used. The pharmacokinetics of human and analogue insulin are summarised. It is concluded that pharmacokinetic studies on analogue insulin in children are required. Yet, no clear evidence of improved glycaemic control of the intensified treatment regimes has been shown in children. Long-term randomised studies are needed.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The aim of this analysis was to evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine Hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Belgian, French, German, Italian and Spanish settings.. The published and validated IMS CORE Diabetes Model was used to make long-term projections of life expectancy, quality-adjusted life expectancy and direct medical costs. The analysis was based on patient characteristics and treatment effects from a 2-year randomised controlled trial. Events were projected for a time horizon of 50 years. Potential uncertainty using a modelling approach was addressed.. Basal-bolus therapy with insulin detemir was projected to improve quality-adjusted life expectancy by 0.45 years versus NPH in the German setting, with similar improvements in the other countries. Insulin detemir was associated with cost savings in Belgium, Germany and Spain. In France and Italy, lifetime costs were slightly higher in the detemir arm, leading to incremental cost-effectiveness ratios of 519 euro per QALY gained and 3,256 euro per QALY gained, respectively.. Compared to NPH, insulin detemir is likely to be a dominant treatment strategy in Belgium, Germany and Spain and highly cost-effective in France and Italy in patients with type 1 diabetes.

Topics: Adolescent; Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Dosage Calculations; Europe; Female; Financing, Personal; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Young Adult

Recent publications of data extracted from population registries have suggested a possible relationship between treatment with insulin glargine and increased incidence of cancer/breast cancer. The aim of the present study was investigate this possible relationship using data from the manufacturer's (sanofi-aventis) pharmacovigilance database.. We analysed the manufacturer's (sanofi-aventis) pharmacovigilance database for all randomised clinical trials (RCTs; Phase 2-4) comparing insulin glargine with any comparator in type 1 or type 2 diabetes. We identified all serious adverse events coded under the System Organ Class of 'neoplasms, benign, malignant and unspecified'. Treatment-emergent neoplasms judged to be malignant were included in this analysis.. The database included 31 studies, 12 in type 1 diabetes and 19 in type 2 diabetes. Twenty compared insulin glargine with NPH insulin, 29 were parallel-group studies and two had a crossover design. Studies were generally of 6 months' duration, except for trial reference number 4016 (n = 1,017), which had a duration of 5 years. Overall, 10,880 people were included in the analysis (insulin glargine, 5,657; comparator, 5,223). Forty-five people (0.8%) vs 46 people (0.9%) reported 52 and 48 cases of malignant cancer in the insulin glargine and comparator groups, respectively (RR 0.90, 95% CI 0.60-1.36). Skin (12 people with 16 events vs six people with seven events, RR 1.85, 95% CI 0.69-4.92), colon and rectum (six vs ten people, RR 0.55, 95% CI 0.20-1.52), breast (four vs six people, RR 0.62, 95% CI 0.17-2.18) and gastrointestinal tract (six vs four people, RR 1.38, 95% CI 0.39-4.90) were the most commonly reported sites.. In these 31 RCTs, insulin glargine was not associated with an increased incidence of cancer, including breast cancer, compared with the comparator group.

Topics: Adolescent; Adult; Child; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Random Allocation; Randomized Controlled Trials as Topic

A case of a 32-year-old woman with type 1 diabetes diagnosed 1.5 year before presention. The patient was referred to the diabetology department due to decompensation of diabetes and excessive hypodermic atrophy of both thighs. Early symptoms of lipoatrophy appeared after 1.5-2 months of insulin glargine use, in spite of frequently changed hypodermic needles and injection sites on both thighs. Simultaneously, deterioration of diabetes compensation was observed (hyperglycaemia between meals and in the morning), which was corrected by the patient with extra injections of a short acting analogue. Additional examinations confirmed type 1 diabetes (C-peptide <0.01 ng/ml) with concomitant hypothyroidism in the course oh Hashimoto disease. After change of insulin (Insulatard twice daily, Novo Rapid with meals) and injection site (administration to hypodermic tissues of arms and abdomen was started), diabetes compensation was achieved. At follow-up visit after 12 months, diabetes was still under control - HbA1c 6.8%. Moreover, progress of lipoatrophy is not observed.

Topics: Adult; Diabetes Mellitus, Type 1; Hashimoto Disease; Humans; Hypoglycemic Agents; Hypothyroidism; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Lipodystrophy; Male

To compare levels of insulin antibodies in children and adolescents after initiation of insulin therapy using either insulin aspart (IAsp) or human insulin (HI) in combination with Neutral Protamine Hagedorn (NPH) insulin, and to investigate the relationships between insulin antibodies and HbA(1c) and insulin dose.. IAsp-specific antibodies (IAsp-Ab) and antibodies cross-reacting with HI and IAsp (HI-cross-Ab) were analysed by radioimmunoassay at diagnosis of diabetes and every 3-6 months for 30 months. Seventy-two patients (HI = 30, IAsp = 42) with Type 1 diabetes, aged 2-17 years were included. Data on HbA(1c), insulin dose and serious adverse events (SAEs) were collected retrospectively.. IAsp-Ab levels remained low throughout the study. After 9 months, the level of HI-cross-Ab increased [mean (SD) HI, 48.8% (21.53); IAsp, 40.2% (17.92)] and remained elevated. Repeated measurement analysis of HI-cross-Ab levels showed no significant difference between treatments (P = 0.16). HI-cross-Ab were significantly associated with total insulin dose (U/kg) (P = 0.001) and time (P < 0.0001), but not with HbA(1c) (P = 0.24). Mean (+/- SD) HbA(1c) was similar at diagnosis (HI 9.5 +/- 1.97%; IAsp 9.6 +/- 1.62%); HbA(1c) then decreased and stabilized to about 6.0% in both groups. Few SAEs were reported, the majority being hypoglycaemic episodes.. Treatment with IAsp and with HI was associated with an increase in HI-cross-Ab in insulin-naive children, but this did not influence treatment efficacy or safety. These results support the safe use of IAsp in children and adolescents with Type 1 diabetes.

Topics: Adolescent; Antibody Formation; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Antibodies; Insulin Aspart; Insulin, Isophane; Male; Treatment Outcome

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Costs; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; United States; United States Food and Drug Administration; Weight Gain

Topics: Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

Paper presents an evaluation of diabetes control after switching from NPH insulin to detemir in children with type 1 diabetes.. We performed a non-randomized, observational, multicentre study on the first group of children whose treatment switched from NPH to insulin detemir in four centers of paediatric diabetes. A total of 72 children (39 boys and 33 girls) were included in the analysis. The average age at intervention was 10.6 +/- 4.7 yrs, the average age at diabetes onset was 6.2 +/- 4.3 yrs. Diabetes control was assessed 3 months prior to the switch and subsequently during 3-month intervals.. Mean HbA(1c) decreased from 6.9% at baseline to 6.4% after 3 months of detemir therapy (p = 0.0003). However, in the next months we observed a trend for increasing the HbA(1c), and no statistically significant difference in HbA(1c) was observed at the 6, 9 and 12 months visits vs. baseline. Fasting glycaemia decreased significantly after 3 months of treatment with detemir in comparison with the baseline (the mean value of the difference was 2.1 mmol/l, CI 95% 1.5-2.6, p = 1.4*10(-10)), and this effect was detectable during all the observational period (month 12 vs. baseline 2.6 mmol/l, p < 10(-8)).. Switching basal insulin from NPH insulin to detemir resulted in a short-term improvement of HbA(1c), and a long-term decreasing of fasting glycaemia.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Fasting; Female; Glycated Hemoglobin; Humans; Infant; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy.. The aim of this study was to retrospectively evaluate (years 2004-2007) the effectiveness and safety of insulin glargine compared with neutral protamine Hagedorn (NPH) in women affected by type 1 diabetes mellitus (T1DM) during pregnancy.. The study comprised pregnant women affected by T1DM who were followed up in the Diabetes and Pregnancy Outpatient Clinic at the University of Palermo, Palermo, Italy, within 8 +/- 3.4 weeks subsequent to a positive pregnancy test. All patients with T1DM were treated with conventional basal-bolus insulin therapy (aspart or lispro analogs at the 3 main meals plus glargine or NPH at bedtime). Healthy pregnant women were used as controls for fetal and neonatal parameters. Patients were consecutively enrolled. In all women, metabolic status was determined daily by mean glycemic values (2-hour postprandial blood glucose) and glycosylated hemoglobin (HbA1c) values (at 3-month intervals). Fetal measurements (<50th and >90th centiles of the head circumference, abdomen circumference, and femoral length) were evaluated by ultrasound at second and third trimesters. Weight and femoral length were assessed at birth, and neonates were classified according to the fetal growth curve for the Italian population (<10th centile = small for gestational age; and >90th centile = large for gestational age (LGA).. A total of 73 pregnant women (30 with T1DM and 43 healthy [control]) were included in the study. Of the 30 diabetic pregnant women included in the study, 15 (mean [SD] age, 27.4 [5.2] years; mean pregravidic weight, 59.7 [11.7] kg) maintained their preconception therapy with glargine, and 15 (mean age, 30.1 [2.4] years; mean pregravidic weight, 60.7 [8.7] kg) with NPH. No significant difference was observed between the glargine-treated group and the NPH-treated group with regard to pregravidic hypertension, third-trimester preeclampsia, maternal complications and/or their progression during pregnancy (diabetic retinopathy, micro- or macroalbuminuria) and episodes of mild hypoglycemia, severe hypoglycemia, and ketosis. There were no significant between group differences in insulin requirements (IU/kg of body weight) and glycemic profile, with the exception of better fasting and 2 hours after breakfast glycemic values in the glargine group during the first (P = 0.008 and P < 0.001, respectively) and the second (P = 0.015 and P = 0.016) trimesters, confirmed by the lower HbA1c levels in the first trimester (P = 0.037). The frequency of femoral length <50th centile at both second and third trimesters was 4/15 (26.7%) in the glargine-treated group (P = 0.033 and P = 0.013, respectively, vs control), 3/15 (20.0%) and 1/15 (6.7%), respectively, in the NPH-treated group (both, P = NS vs control), and 2/43 (4.7%) and 1/43 (2.3%), respectively, in the control group. The prevalence of LGA was 7/15 (46.7%) in the glargine group (P < 0.001 vs control), 4/15 (27.6%) in the NPH group (P = 0.033 vs control), and 2/43 (4.7%) in the control group.. Although our retrospective study involved only a small number of participants, no significant difference was found in glycemic control between glargine and NPH treatments. Use of glargine was associated with a significantly higher frequency of femoral length <50th centile. Further larger prospective studies are necessary to assess the safety profile of glargine in T1DM during pregnancy.

Topics: Adult; Blood Glucose; Body Weights and Measures; Case-Control Studies; Diabetes Mellitus, Type 1; Female; Femur; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Retrospective Studies

The PREDICTIVE study is a multinational observational study designed to follow up patients with diabetes who started insulin detemir (IDet) in routine care. Recruitment started in June 2004 and is ongoing in some countries.. We report 12-week follow-up data for patients with type 1 (T1D) or type 2 diabetes (T2D) in the European cohort who, as part of basal-bolus therapy, switched from once- (qd) or twice-daily (bid) neutral protamine Hagedorn insulin (NPH) to qd IDet. End-points - evaluated from patients' records and diaries - were incidence of serious adverse drug reactions, glycaemic parameters, hypoglycaemia and weight change.. A total of 3637 patients were included, n = 1500 T1D [mean age 40.9 years, body mass index (BMI) 25.0 kg/m(2), glycosylated haemoglobin (HbA(1c)) 7.9%] and n = 2137 T2D (mean age 60.5 years, BMI 31.9 kg/m(2), HbA(1c) 8.0%). IDet was well tolerated. Lower overall, major and nocturnal rates of hypoglycaemia were observed in T1D and T2D patients switching from NPH to IDet (overall, T1D: 38.2-18.56 episodes/patient year, p < 0.001; T2D: 13.8-3.3 [corrected] episodes/patient year, p < 0.001). Switching from bid NPH to qd IDet resulted in significant 12-week reductions in HbA(1c) (T1D: -0.40%; T2D: -0.56%; both p < 0.001). Switching from qd NPH to qd IDet, resulted in HbA(1c) reductions of: T1D -0.52%; T2D -0.56%; both p < 0.001. Fasting blood glucose levels were also significantly reduced in patients with T1D or T2D. Overall mean weight changes were: T1D: 0.0 kg, T2D: -0.2 kg after 12 weeks.. In routine care, patients with T1D or T2D may be switched from NPH to IDet qd as part of a basal-bolus regimen.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes.. We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine.. Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12-18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate.. Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1-17.5), mean duration of diabetes was 6.7 yr (range 1.8-14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for > or =12 months considered glargine better than NPH.. A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias.

Topics: Adolescent; Age of Onset; Biomarkers; Blood Glucose; Body Height; Body Weight; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Reference Values; Retrospective Studies

Topics: Administration, Oral; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Edema; Humans; Hypoglycemic Agents; Inositol; Insulin, Isophane; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Sulfonylurea Compounds

To determine how young adults with insulin therapy manage daily care of diabetes during the physically demanding conditions of conscript military service, and to evaluate the effects of military service on glycaemic control and on the incidence of acute diabetic complications.. An observational study of 47 young male volunteer conscripts receiving insulin therapy was carried out at the Signal Regiment in Riihimäki from January 2001 to July 2005. Outcome measures were drop-out rate from service, management of diabetes care, glycaemic control, and occurrence of severe hypoglycaemia or ketoacidosis during service.. Forty (85%) diabetic conscripts completed service, with service time ranging from 180 to 362 days, and seven (15%) interrupted service. One-third of conscripts reported difficulties during military training with insulin injections and blood glucose testing. The mean HbA(1c) during service increased by 0.6% units (P = 0.007) from baseline. Five events of severe hypoglycaemia in three conscripts (overall incidence rate 0.15 per patient-year) and one ketoacidosis event occurred. Diabetic conscripts were chosen for leadership training more often than non-diabetic conscripts.. Our data suggest that selected and motivated adolescents on insulin therapy can manage the daily care of diabetes and maintain appropriate glycaemic control during service, although the risk of severe hypoglycaemia exists.

Topics: Adolescent; Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Military Personnel; Risk Factors

This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials.

Topics: Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Regression Analysis; Retrospective Studies; Sensitivity and Specificity; Sex Factors

Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control.. A long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values).. The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results).. The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.

Topics: Analysis of Variance; Canada; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

We sought to test the hypothesis that start of insulin glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGF binding proteins (IGFBPs) in adolescents with type 1 diabetes-changes that may support improvement of A1C.. Twelve pubertal adolescents with type 1 diabetes and initially on NPH insulin were studied during 12 weeks of intensified treatment with glargine.. Subnormal IGF-I SD scores on NPH (-1.8 +/- 0.4) rapidly increased and remained 54 +/- 9% elevated (P < 0.001) after 12 weeks on glargine. A1C decreased from 8.3 +/- 0.6% to a nadir of 6.9 +/- 0.3% (P = 0.002) at 6 weeks and correlated with changes in IGF-I (r = -0.64, P < 0.05). The increase in IGF-I did not suppress the mean overnight growth hormone (GH) secretion at 6 weeks. The mean overnight IGFBP-1 levels decreased (P = 0.035), supporting the hypothesis that the nightly hepatic insulin action was increased. Circulating IGF-I increased in the absence of changes in both GH secretion and GH receptor numbers (assessed by growth hormone binding protein), indicating that postreceptor mechanisms are involved. IGFBP-3 proteolysis was decreased.. Increased hepatic insulin action after start of glargine was evident from a decrease in night time IGFBP-1 concentrations. This may improve GH postreceptor signaling, resulting in increased circulating IGF-I. We suggest that even in the absence of changes in GH, increased IGF-I and decreased IGFBP-1 support the improvement of metabolic control.

Topics: Adolescent; Diabetes Mellitus, Type 1; Drug Administration Schedule; Human Growth Hormone; Humans; Hypoglycemic Agents; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin, Isophane; Puberty

To evaluate the results of treatment with an insulin glargine-based regimen as compared with those of an NPH insulin-based regimen.. We reviewed the charts of 83 Japanese patients with Type 1 diabetes treated with insulin glargine for 12 months.. Median age, 56.9 years (range, 24.6-74.8 years), mean (+/-S.D.) body mass index, 21.2 (+/-2.2) kg/m2.. The average HbA1c level of the cohort was 7.8 +/- 1.2% at baseline and 7.7 +/- 1.0% at the end of the 12-month treatment (P=0.34). The average insulin requirement per day in the cohort remained unchanged after the 12-month treatment (35.0 +/- 11.6 units/day versus 35.2 +/- 11.2 units/day (P=0.58). Of the 36 patients who were receiving twice or three times daily injections of NPH insulin, 30 could be switched to a single-daily injection of insulin glargine. The frequency of severe hypoglycemia with unconsciousness became lower after switching to the insulin glargine-based regimen than during treatment with the NPH-based regimen. The average ratio of the daily usage of insulin glargine to that of total insulin after 12 months was smaller than that reported from other countries (0.34 +/- 0.09).. These results obtained from a larger number of patients as compared to previous Japanese studies confirm earlier reports that insulin glargine provides equivalent glycemic control to human NPH insulin, with a lower incidence of severe hypoglycemia. Thus, treatment with insulin glargine provides some benefits to Japanese patients with Type 1 diabetes.

Topics: Adult; Aged; Analysis of Variance; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Japan; Male; Middle Aged; Probability; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

Treatment of hematological malignancies with L-asparaginase has been associated with diabetes mellitus in about 1-2% of patients. The concomitant use of steroids has an additional deleterious effect. In this article, we report the occurrence of diabetes in a 13 year-old girl treated with L-asparaginase and dexamethasone for acute lymphoblastic leukemia. The diabetes developed 120 days after the drug was started, requiring insulin therapy for 12 months. Anti-islet autoantibody was negative, and there were no laboratory findings suggestive of pancreatitis. The DM related do L-asparaginase therapy is insulinopenic and transient, resolving with suspension of the drug. The diagnosis of this type of diabetes is based on its temporal relationship with the L-asparaginase and in the exclusion of other known causes. There is no laboratory test capable of elucidating the diagnosis. Therefore, investigation to rule out type 1A DM, type 1B DM, insulin-resistant DM induced by corticotherapy and DM secondary to toxic pancreatitis is of utmost importance. The insulin therapy must be followed closely, since this is a transient form of diabetes.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin, Isophane; Leukemia, Myeloid, Acute

To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA(1C). Mean HbA(1C) level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA(1C) level: type 1: baseline 8.9 +/- 2.6%, 18 months 7.8 +/- 1.5% (p<0.05), type 2: baseline 8.2 +/- 2.6%, 18 months 7.7 +/- 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA(1C) level at baseline exhibited more than 10% improvement in HbA(1C) level after switching both type 1 and type 2 diabetes. The HbA(1C) levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.

Topics: Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Japan; Longitudinal Studies; Male; Middle Aged; Prospective Studies

Topics: Adipose Tissue; Atrophy; Betamethasone; Child, Preschool; Diabetes Mellitus, Type 1; Drug Combinations; Female; Glucocorticoids; Humans; Hypoglycemic Agents; Insulin, Isophane

The purpose of this study was to evaluate the effect of administration time of insulin glargine (IG) on glycemic control in children and adolescents with Type 1 diabetes.. A total of 31 children and adolescents (15 F and 16 M) with Type 1 diabetes on intensive therapy (bedtime NPH and premeal insulin aspart) were randomized to receive once-daily IG either at breakfast (breakfast group, n=15) or bedtime (bedtime group, n=16) while continuing insulin aspart premeals for 6 months. Blood glucose levels were measured fasting, preprandially and bedtime. Total daily insulin dose (TDD), body mass index (BMI), glycosylated hemoglobin (HbA(1c)), and frequency of hypoglycemia in the preceding 3 months were assessed at recruitment, third month and sixth month.. The dose of IG, TDD, and fasting blood glucose levels were similar in both groups during the study period. The only significant difference in blood glucose levels between breakfast and bedtime groups was found for dinnertime at 6 months (135+/-26mg/dl versus 161+/-33mg/dl, respectively, p=0.035). In the breakfast group, the mean HbA(1c) level was significantly lower than that of baseline at month 6 (9.4+/-2.5% versus 8.0+/-0.9%, respectively, p=0.022), whereas there was no significant change in the bedtime group (9.2+/-2.1% versus 8.9+/-2.2%, respectively). The frequency of hypoglycemia was lower with IG than NPH (2.7+/-2.8/6 months versus 6.4+/-6.7/6 months, respectively, p=0.008).. Once-daily IG at breakfast in children and adolescents with Type 1 diabetes on intensive therapy is more efficacious than bedtime administration to improve metabolic control. Also, the number of hypoglycaemic events decreased with both breakfast and bedtime administrations of IG.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

The large fluctuations in blood concentrations and activity observed with insulin therapies such as NPH insulin or insulin ultralente may result in hyper- or hypoglycemia.. We compared the fluctuations of these insulins with the long-acting basal insulin analog insulin glargine as a re-analysis of three Phase I studies: (I) glargine with NPH or ultralente [single-dose (0.4 IU/kg), randomized study in healthy volunteers (n = 36)]; (II) glargine or NPH [single-dose (0.3 IU/kg), randomized study in patients with diabetes mellitus Type 1 (DMT1) (n = 20)]; and (III) glargine (tailor-made dose) plus insulin lispro in DMT1 (n = 15 over 11 days). Percent deviation around average serum concentration over 24 h (PF24) was used to determine within-patient fluctuation and mean fluctuation value for each treatment group.. Mean PF24 in healthy volunteers (Study I) was significantly lower with glargine (19.8%) than with NPH and ultralente (31.9% and 47.2%, respectively; both P < 0.001 vs. glargine). Similarly, about half the fluctuation observed with NPH (PF24 25.8%) was seen with glargine (PF24 14.2%; P < 0.001) in DMT1 (Study II). In ambulatory DMT1 patients receiving multiple glargine doses, PF24 values demonstrated that the same low fluctuations (PF24 20%) were retained throughout near-maintenance treatment (Study III).. Glargine provided less diurnal fluctuation in serum insulin levels than NPH and ultralente in healthy volunteers and patients with DMT1. This lower fluctuation of glargine over NPH or ultralente can help to reduce hyper- or hypoglycemia risks associated with insulin therapy and accordingly encourage achievement of better blood glucose control.

Topics: Adolescent; Adult; Clinical Trials, Phase I as Topic; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic

A 6-8-fold higher insulin-like growth factor 1 (IGF-1) receptor binding affinity in vitro is reported for the insulin analogue glargine compared with human insulin. This study evaluates the in vivo significance by exploring the growth hormone (GH)-IGF-1 axis. Assuming a higher binding affinity of insulin glargine to pituitary IGF-1 receptors, serum IGF-1 concentrations should decrease via negative feedback.. In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks.. Overall glycaemic control was not different between the treatment regimens. In contrast to the hypothesis, serum IGF-1 concentrations were higher during insulin glargine treatment compared with NPH insulin in patients with Type 1 diabetes (177 +/- 18 vs. 159 +/- 18 microg/l, P < 0.02, n = 17, age 28 +/- 2 years). The effect on IGF-1 was most pronounced in male patients with Type 1 diabetes (174 +/- 11 vs. 146 +/- 10 microg/l, P < 0.02, n = 10), but was not significant in patients with Type 2 diabetes (92 +/- 9 vs. 86 +/- 8 microg/l, NS, n = 25, age 66 +/- 2 years).. In contrast to our hypothesis, serum IGF-1 did not decrease, but rose during insulin glargine treatment, suggesting an absence of relevant IGF-1-like activity of glargine at the level of the pituitary. Improved plasma glucose at dawn during glargine treatment may intensify growth hormone surges and increase IGF-1 synthesis. Significant increases were seen in younger patients, compatible with the higher activity of the GH-IGF-1 axis in this age group.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Topics: Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Humans; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Retinal Diseases; Retinal Vessels; United States; United States Food and Drug Administration; Vascular Endothelial Growth Factor A

We studied a systematic program to reeducate our medical house officers on how to manage inpatient hyperglycemia without the use of sliding-scale insulin (SSI).. Patients admitted to the general medical service with diabetes or a blood glucose >140 mg/dl were included. HbA(1c) was measured in all patients, and therapy was modified if the HbA(1c) was >7.0%. For each 24 h on call, two house officers were responsible for all glucose management for their team's patients and rounded with a teaching endocrinologist twice daily for 2 weeks. Oral agent or insulin therapy was modified using blood glucoses and HbA(1c). All patients who required insulin therapy were treated with basal and bolus insulin, usually NPH and regular, adjusted twice daily.. During 8 weeks, 88 patients were identified and 16 house officers were instructed. The mean duration of diabetes was 10.4 years. Mean HbA(1c) level was 8.7%, and 48% of patients had HbA(1c) >8%. All patients with HbA(1c) >7% had diabetes therapy intensified. Overall 80% had their diabetes therapy changed by discharge. Compared with 98 historical control subjects, significantly fewer study patients had episodes of hyperglycemia, and a subgroup followed for 12 months showed a decrease in HbA(1c) from 10.1 to 8%.. Medical history, blood glucose, and HbA(1c) testing can effectively identify patients with inpatient hyperglycemia. Using direct ward-based teaching and a widely disseminated pocket set of guidelines, house officers can be taught to effectively and safely manage inpatient hyperglycemia without the use of SSI.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Education, Medical, Graduate; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Isophane; Male; Medical Staff, Hospital; Middle Aged; Staff Development

Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission.. A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected.. Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission.. Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

Topics: Adolescent; Adult; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Logistic Models; Male; Predictive Value of Tests; Remission Induction; Time Factors

In a prospective study on 11 patients with Type 1 diabetes we evaluated the glycaemic control and hypoglycaemic episodes on a combination therapy of pre-mixed and glargine insulin. Glycosylated hemoglobin (HbA1C), fasting (FPG) and Post Prandial blood glucose (PPG) levels were recorded at baseline and three monthly intervals for a period of 6 months. The mean HbA1C reduced from 9.5 to 7.3 %, incidence of hypoglycemias from 1.6 to 0.8, mean FPG from 146.5 to 90.4 and mean PPG from 258.4 to 184 over a six-month observation period. This regimen also helps to avoid injection of insulin before lunch so that child's school schedule is minimally disturbed and yet the incidence of hypoglycemia is not increased.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Education, Medical, Graduate; Humans; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Isophane; Medical Staff, Hospital

Glargine (Lantus) is a recently approved, long-acting insulin analog that is increasingly being used in children with diabetes. The aim of this retrospective chart review was to summarize our experience in starting glargine in children and adolescents with diabetes. SUBJECTS AND STUDY METHODS: We reviewed the medical records of 71 children with type 1 diabetes (29 boys and 42 girls) who initiated glargine therapy to improve glycemic control between 1 June 2001 and 30 June 2002. Data were collected for 6 months before and 6 months after adding glargine.. Subjects' mean age [+/-standard deviation (SD)] at diagnosis of diabetes was 7.5 +/- 4.1 yr. Mean age at initiation of glargine therapy was 11.5 +/- 4.9 yr. The total daily long-acting insulin dose decreased by about 20% after initiating glargine therapy. There were no significant differences in hemoglobin A1c (HbA1c) and blood glucose control prior to and after initiating glargine therapy (HbA1c at baseline 8.9 +/- 1.6% and HbA1c after 6 months of glargine therapy was 8.9 +/- 1.5%). Overall, blood glucose concentrations did not differ significantly throughout the study. Patients who switched to glargine because of nocturnal hypoglycemia had a 65% decrease in nocturnal blood glucose reading less than 50 mg/dL. There were three seizures in the first week after initiating glargine therapy.. This retrospective study suggests that glargine is at least as effective as other long-acting insulins but that care must be taken during the conversion process to avoid hypoglycemia.

Topics: Adolescent; Blood Glucose; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Osmolar Concentration; Retrospective Studies; Seizures; Treatment Outcome

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Treatment Outcome

In the last few years short-acting insulin analogs have become increasingly popular. Their introduction has unmasked serious deficiencies in the capacity of isophane insulin to provide a stable basal insulinaemia. The long-acting insulin analogs, insulin glargine and insulin detemir, have been developed as alternatives to isophane insulin. Insulin glargine has a long duration of action and has demonstrated its usefulness in diabetes type 2, specifically a lower incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical practice. Insulin detemir has a very low variability in absorption and also seems to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies are, however, needed. Because of the higher costs of these novel insulins, the decision to switch a patient from isophane insulin to an insulin analog has to be made on an individual basis.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Practice Guidelines as Topic

During the past decade several reports were published showing that intensive treatment of type 1 diabetes can prevent and delay disease-related microvascular complications. However, several problems were reported in children and adolescents such as frequent hypoglycemic episodes and weight gain. The aim of this study was to describe the results of intensified treatment for type 1 diabetes in a group of Argentinean adolescents after a follow-up of two years. Twenty five adolescents with type 1 diabetes older than 10 years with at least one year from diagnosis were selected. All patients received a one-week teaching program during admission to our center. All patients were followed-up monthly during two years. Treatment schedule included 4-5 controls in fasting conditions, two doses of NPH insulin and four doses of regular insulin according to glycemia and the amount of calculated carbohydrate intake. Median age was 13.5 years (range 10 to 19 years). Mean time from diagnosis to inclusion in the study was 3.8 years (range 1.25 to 9 years). Mean total dose of NPH insulin decreased significantly when measured at the inclusion in the study (0.9 IU/kg) and after a year of follow-up 0.8 IU/kg (p 0.04). However, there were no changes in NPH insulin dose after two years follow-up (0.85 IU/kg). On the contrary, the dose of regular insulin administered on fasting conditions with normal glycemia increased from 0 to 0.21/kg after a year (p 0.0001) and to 0.69 after two years (non significant). Median HbA1C showed a significant reduction from 10 +/- 1.62% to 8.53 +/- 1.04% after a year (p 0.03) and to 8.72 +/- 0.81% after two years. BMI Z score increased from significantly from 0.7 +/- 0.9 to 1.06 +/- 1.15 after a year (p 0.03) with a further reduction without a significant difference from the basal value after two years. We found no significant differences in the frequency of hypoglycemia or other metabolic features. Our results show that intensive treatment of type 1 diabetes in children and adolescents can achieve significant and sustained reductions of HbA1C without increasing the risk of hypoglycemia or other adverse effects.

Topics: Adolescent; Adult; Argentina; Blood Glucose; Body Mass Index; Child; Critical Care; Diabetes Mellitus, Type 1; Dietary Carbohydrates; Female; Follow-Up Studies; Humans; Insulin, Isophane; Male; Patient Education as Topic; Program Evaluation; Treatment Outcome

We report a case of Type-1 diabetes with insufficient serum immunoreactive insulin (IRI) elevation after subcutaneous NPH-insulin injection. Favorable glycemic control was achieved by a continuous subcutaneous insulin infusion (CSII) using regular insulin. A 34-year-old woman with Type-1 diabetes (height 158 cm, weight 43.4 kg) was admitted to our hospital to improve glycemic control. On admission, her glycosylated hemoglobin (HbA(1c)) level was 10.9% and her fasting plasma glucose (FPG) level was 332 mg/dl. After admission, her insulin regimen was altered from two injections a day using premixed insulin to four injections a day using regular insulin before each meal and NPH insulin at bedtime. Although the dosage of NPH insulin at bedtime was increased to 32 U/day, there was no improvement in the FPG level. The peak IRI value after NPH insulin injection was not observed but that after the regular insulin injection was observed. Therefore, her insulin administration regimen was changed to CSII, using regular insulin alone. Her fasting plasma glucose level decreased, glycosylated hemoglobin (HbA(1c)) level improved to 7.0%, her body weight increased to 46.6 kg 4 months after starting CSII.

Topics: Abdomen; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Hematocrit; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Antibodies; Insulin, Isophane; Time Factors

Topics: Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Lipodystrophy; Male

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Time Factors

Topics: Adolescent; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Monitoring, Physiologic

Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane

Administration of protamine might cause serious complications especially in patients treated preoperatively with NPH insulin.. A case report.. Administration of protamine sulphate caused fatal anaphylactic reaction to a diabetic patient undergoing femoropopliteal by-pass surgery. Care should be taken when administering protamine to a patient treated preoperatively with NPH insulin and the possibility of an anaphylactid reaction to protamine have to be kept in mind.

Topics: Anaphylaxis; Arterial Occlusive Diseases; Diabetes Mellitus, Type 1; Drug Interactions; Fatal Outcome; Femoral Artery; Heparin Antagonists; Humans; Hypoglycemic Agents; Insulin, Isophane; Intermittent Claudication; Male; Middle Aged; Postoperative Complications; Protamines

Although most patients receiving insulin produce insulin-specific IgE, significant allergic symptoms develop in very few of them. Patients receiving neutral protamine Hagedorn (NPH) insulin are at increased risk for the development of protamine hypersensitivity. The case of a 19-year-old woman with insulin-dependent diabetes and regular and NPH insulin hypersensitivity is presented.. The purpose of this study was to determine whether desensitization to NPH insulin, as well as standard insulin desensitization, could control allergic symptoms in a patient allergic to both NPH and regular insulin.. The patient required insulin desensitization for severe urticaria, angioedema, and occasional wheezing resulting from her insulin dose. She underwent a standard protocol for insulin desensitization twice in a 2-month period, with persistence in her symptoms. She was found to have high protamine-specific, as well as insulin-specific, IgE levels, and because of her poor response to regular insulin desensitization, she was desensitized to both regular and NPH insulin.. Dual desensitization resulted in marked improvement in her symptoms. The patient had recurrence of urticaria and angioedema a year and a half later, at which point the NPH was stopped and she was desensitized to regular insulin. She continued to receive regular insulin 4 times per day over the following 3 years with only occasional hives.. Patients with insulin allergy may not have complete resolution of their symptoms after standard desensitization, particularly those patients with concomitant protamine allergy. These patients may require protamine/NPH desensitization, an alternative insulin preparation, or both.

Topics: Adult; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Insulin; Insulin, Isophane; Protamines

[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed following subcutaneous (s.c.) doses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 9 subjects with IDDM. After overnight i.v. infusion of regular human insulin, morning glucose was (A) 6.9 +/- 0.1 and (B) 6.8 +/- 0.1 mmol/l. After the s.c. injection, i.v. human insulin or glucose was infused to maintain near-basal glycaemia and tracer glucose to assess hepatic glucose production (HGP). An activity profile was deduced for each study by expressing the glucose infusion rate at each time point, as a fraction (%) of the basal (measured) HGP, and the i.v. insulin infusion rate as a fraction (%) of the basal requirement. The two fractions are combined by adding the fractional glucose infusion rate and subtracting the fractional insulin infusion rate. Infusion rates of i.v. insulin in the morning were (A) 0.96 +/- 0.096 and (B) 1.22 +/- 0.09 pmol x kg(-1) x min(-1). After insulin injection, i.v. insulin requirements decreased and were below 10% of basal between 100 and 150 min. A constant activity profile of 0% represents a perfect substitution of the basal i.v. insulin infusion by the s.c. dose. The actual profile is defined by deviations from this (above) and was -17 +/- 11, 7 +/- 10, -9 +/- 6 and -18 +/- 18% for [Nepsilon-palmitoyl Lys (B29)] human insulin and 17 +/- 12, 5 +/- 6, -9 +/- 15, 22 +/- 18% for NPH insulin at 3, 6, 9 and 12 h after s.c. injection. HGP was similar for the two insulins, demonstrating similar metabolic actions and profiles both peripherally and at the liver.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Gluconeogenesis; Humans; Infusions, Intravenous; Injections, Intravenous; Insulin; Insulin, Isophane; Liver; Recombinant Proteins

Patients with diabetes mellitus type I usually are treated with a multiple injection regimen comprising rapid-acting insulin before meals and intermediate-acting insulin at bedtime. Recently, the rapid-acting insulin analogue insulin LISPRO was introduced on the Dutch market. This form of insulin is very rapidly taken up into the bloodstream from the subcutaneous tissue. The advantages of the use of insulin LISPRO are the comfort of injecting the insulin just before a meal, the more rapid correction of incidental hyperglycaemia and the slightly lower incidence of (nocturnal) hypoglycaemia in comparison with conventional rapid-acting insulin. There is no argument in favour of switching diabetics to insulin LISPRO if they are well-controlled with normal rapid-acting insulin and have few episodes of hypoglycaemia. In some persons the duration of action of insulin LISPRO may be too short, leading to preprandial hyperglycaemia. This can be avoided by using a second injection of intermediate-acting insulin, either before breakfast or before lunch.

Topics: Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane

Topics: Adrenergic beta-Antagonists; Aged; Angina Pectoris; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diet, Diabetic; Fatal Outcome; Female; Humans; Hypertension; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Propranolol

To determine the incidence of significant nocturnal hypoglycemia occurring at home in young children with insulin-dependent diabetes mellitus using conventional therapy.. Sixty-one children (aged 2.6 to 8.5 years) were studied on one night, at home, with blood collection occurring at dinner, bedtime/supper, 11 PM, 2 AM, and breakfast, with subsequent laboratory analysis.. The proportion of subjects with blood glucose levels less than 64, 55, 45, and 36 mg/dl (3.5, 3.0, 2.5, and 2.0 mmol/L) was 37.8%, 17%, 13%, and 8%, respectively. Nocturnal hypoglycemia was associated with younger age (< 5 years 57% vs 5 to 8.5 years 36%; p < 0.001) and lowered glycosylated hemoglobin levels (HbA1c) with a greater than 50% incidence of hypoglycemia seen in subjects with HbA1c levels of less than 8.5%. The average HbA1c concentration was lower in the hypoglycemic group than in the nonhypoglycemic group (7.8 vs 8.3%; p < 0.02). Nocturnal hypoglycemia occurred with increasing frequency throughout the night in subjects less than 5 years of age (dinner, supper, 11 PM, 2 AM, and breakfast incidences being 0%, 12.5%, 26%, 33%, and 30%, respectively) but not in those older than 5 years. Carbohydrate intake at supper did not prevent subsequent hypoglycemia. Blood glucose levels at 11 PM were poor predictors of subsequent hypoglycemia at 2 AM in either the group as a whole or in the children less than 5 years of age. Symptom recognition of nocturnal hypoglycemia was decreased in younger children (< 5 years (36%) > 5 years (58%)), in those with a lower HbA1c, and when hypoglycemia occurred at breakfast rather than at dinner (0% vs 50%).. The incidence of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus receiving conventional therapy is unacceptably high and is increased with lowered age and HbA1c concentration; the condition is often asymptomatic. Early-morning hypoglycemia is poorly predicted by a blood glucose determination at 11 PM and is not prevented by carbohydrate intake at supper. In younger children, blood glucose profiles should include early-morning measurements.

Topics: Age Factors; Blood Glucose; Child; Child, Preschool; Circadian Rhythm; Diabetes Mellitus, Type 1; Dietary Carbohydrates; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin, Isophane; Male; Predictive Value of Tests

Topics: Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Feeding Behavior; Glycated Hemoglobin; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane

High-dose insulin treatment in the first period after clinical onset of insulin-dependent diabetes mellitus (IDDM) has been found to reduce diabetic manifestations in humans. The aim of the present study was to examine whether high-dose insulin treatment of newly diagnosed diabetic non obese diabetic (NOD) mice would increase beta-cell insulin content after termination of treatment in this experimental IDDM animal model. Newly diagnosed diabetic female NOD mice were randomized into three groups composed of a low-dose insulin treated group (n = 10) injected subcutaneously with 15 IU/kg per day of NPH for 14 days followed by 5 days without insulin, a high-dose insulin treated group (n = 8) injected subcutaneously with 150 IU/kg per day of Actrapid for 14 days followed by 5 days without insulin and an untreated group sacrificed 3 days after diagnosis (n = 11). A reference group of age matched non-diabetic untreated female NOD mice (n = 11) was included in the study and sacrificed at the same time as the untreated diabetic mice. No significant difference in the amount of insulin extracted from the total pancreas was found by comparison of the three diabetic groups, consisting of the newly diagnosed untreated mice, the low-dose insulin treated mice and the high-dose insulin treated mice, respectively. The level was about 100-fold less than in the non-diabetic group. Blood glucose values in the two treated diabetic groups were at a high level (median > 18 mM) throughout the study. We conclude that no increase in beta-cell insulin content could be demonstrated in newly diagnosed diabetic NOD mice after early high-dose insulin treatment, at least not in the presence of high blood glucose values.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Injections, Subcutaneous; Insulin; Insulin, Isophane; Islets of Langerhans; Mice; Mice, Inbred NOD

The aim of the study was to determine the appropriate dose of subcutaneous insulin to induce "beta-cell rest" without any hypoglycemic risk, as the first stop in the investigation of its potential effect in preventing or delaying clinical diabetes mellitus onset in high-risk subjects. Four subjects at high risk for type I diabetes mellitus (first-degree relatives, islet cell antibodies (ICA)-positive, and with diminished first-phase insulin secretion) were compared with four healthy individuals. After hospitalization, urinary C-peptide excretion (UCP) and 24-hour serum profiles for glucose were measured before and after administration of NPH insulin 0.1, 0.2, and 0.3 U x kg body weight per day subcutaneously in a single dose on 4 consecutive days. After insulin 0.1 U x kg body weight, a significant inhibition of endogenous insulin secretion was observed in high-risk subjects, but not in control subjects. There was no further inhibition when a higher insulin dose (0.2 and 0.3) was administered. A sustained beta-cell rest was obtained after 3, 6, and 12 months of treatment with 0.1 U x kg body weight per day as outpatient therapy in high-risk subjects. With this dose, no subject developed hypoglycemia (plasma glucose <50 mg/dL), whereas this adverse effect was detected after 0.2 and 0.3 U x kg body weight in both groups. In conclusion, our results indicate that administration of NPH insulin 0.1 U x kg bodyweight per day induces beta-cell rest without the undesirable effect of hypoglycemic episodes. This is a preliminary study to investigate the potential beneficial effect of insulin in preventing or delaying type I diabetes mellitus in subjects at high risk for the disease.

Topics: Adolescent; Adult; Case-Control Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Secretion; Insulin, Isophane; Islets of Langerhans; Middle Aged; Prediabetic State; Risk Factors; Safety; Time Factors

We report an insulin-treated diabetic patient who suffered, in a 2-month period, three severe anaphylactic reactions immediately after self-administered subcutaneous injections of neutral protamine Hagedorn (NPH) human recombinant-DNA insulin. These reactions consisted of local and systemic symptoms, including dyspnea and hypotension. A simultaneous sensitization to human insulin and to protamine was demonstrated, both by skin tests and by the determination of serum specific IgE. Suspecting protamine allergy, we performed a test dose to human lente insulin with perfect tolerance. After a 1-year follow-up with lente-insulin treatment, no reactions have occurred, despite treatment interruptions. Therefore, protamine IgE-mediated allergy probably caused our patient's reactions. In conclusion, protamine sensitization should be ruled out in any patient with a history of reactions to subcutaneous protamine-containing insulins, even if insulin sensitization is present.

Topics: Adult; Anaphylaxis; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Immunoglobulin E; Insulin, Isophane; Insulin, Long-Acting; Male; Protamines; Skin Tests

To establish the effects of the short-acting insulin analog Lispro versus human regular insulin (Hum-R) on postprandial metabolic control in IDDM.. Four studies were performed in 10 C-peptide-negative IDDM patients. Lispro or Hum-R (0.15 U/kg) or Lispro + NPH (0.07 U/kg) or Hum-R + NPH were injected subcutaneously 30 min (Hum-R) or 5 min (Lispro) before lunch. Preprandial plasma glucose (PG) was maintained on all four occasions at approximately 7.3 mmol/l by intravenous insulin.. After subcutaneous Lispro injection, plasma free insulin (FIRI) was greater between 0 and 2 h (233 +/- 22 pmol/l) than after Hum-R (197 +/- 25 pmol/l) but lower between 2.25 and 7 h (81 +/- 10 vs. 104 +/- 13 pmol/l, P < 0.05). After Lispro, PG was lower versus Hum-R for 3 h (7.4 +/- 0.6 vs. 8.3 +/- 0.9 mmol/l) but subsequently increased more than after Hum-R (3.25-7h, 11.3 +/- 1 vs. 9.6 +/- 1.2 mmol/l), resulting in a 7-h postprandial PG greater than Hum-R (9.4 +/- 0.5 vs. 8.8 +/- 0.6 mmol/l) (all P < 0.05). Addition of NPH to Lispro increased the 2.5-to 7-h FIRI to 110 +/- 11 pmol/l and decreased the 3.25- to 7-h PG to 7.7 +/- 0.8 pmol/l, resulting in 0- to 7-h PG (7.3 +/- 0.3 mmol/l) lower than after Hum-R + NPH (7.9 +/- 0.5 pmol/l) (P < 0.05).. At meals, in order for Lispro to improve postprandial blood glucose not only at 2-h, but also over a 7-h period in C-peptide-negative IDDM, basal insulin must be optimally replaced.

Topics: 3-Hydroxybutyric Acid; Adult; Alanine; Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Fatty Acids, Nonesterified; Female; Glucagon; Glycerol; Humans; Hydroxybutyrates; Infusions, Intravenous; Insulin; Insulin Lispro; Insulin, Isophane; Lactates; Male; Postprandial Period; Recombinant Proteins

The influence of insulin binding antibodies on the pharmacokinetics of NPH insulin was studied in Type 1 diabetic patients on human insulin. Insulin-antibody binding (B(o) was measured during a screening procedure in 155 Type 1 diabetic patients. In 36 patients, B(o) was < 1.5%, and in 38 patients B(o) was > 10.0%. Of these, 6 patients, group 1 (B(o) < 1.5%) and 8 patients, group 2 (B(o) > 10.0%), respectively, subsequently participated in a pharmacokinetic study. Free insulin and the glucose infusion rate were measured using a euglycaemic clamp after subcutaneous injection of NPH insulin (0.4 U kg-1). The areas under the curve (AUC) of free insulin concentration were smaller for group 2 (p = 0.01) than for group 1 (212.2 +/- 22.0 vs 316.8 +/- 25.3 mU l-1h). The AUCs of the glucose infusion rate were also smaller for group 2 (p < 0.05) than for group 1 (2.50 +/- 0.32 vs 3.58 +/- 0.36 g kg-1). A significant negative correlation exists between the AUCs for free insulin concentration and insulin-antibody binding B(o) (r = 0.76, p = 0.001). The daily insulin dosage was higher in group 2 (p = 0.02) than in group 1 (0.66 +/- 0.03 vs 0.53 +/- 0.03 U kg-1). We conclude that insulin antibodies influence the pharmacokinetics of NPH human insulin. The demonstrable influence on the kinetics of free insulin and glucose utilization leads to a slight increase in daily total insulin requirements.

Topics: Adult; Antigen-Antibody Complex; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Male; Recombinant Proteins; Reference Values

Topics: Administration, Oral; Adolescent; Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Patient Education as Topic

A well-documented case of a 35-year-old male Type 1 diabetic patient who was admitted as an emergency after having injected 1500 international units (IU) of insulin (750 IU regular insulin,750 IU NPH-insulin) subcutaneously as a suicidal attempt is reported. Computing disappearance rates of glucose from its infused amounts necessary to maintain euglycaemia during 65 h after the insulin injection in analogy to experimental hyperinsulinaemic euglycaemic clamp examinations, a glucose consumption of 55.6 mumol kg-1 min-1 was found at peak serum insulin concentrations of about 14,400 pmol l-1. The insulin-induced glucose dynamics resemble closely those seen in healthy persons and Type 1 diabetic subjects during a 10 mU kg-1 min-1 euglycaemic clamp. This information may be useful in the handling of similar cases of insulin intoxication.

Topics: Adult; Bipolar Disorder; Blood Glucose; Diabetes Mellitus, Type 1; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin, Isophane; Male; Suicide, Attempted; Time Factors

In the past decade, human insulins have been substituting animal insulins, offering the advantage of its lesser antigenic capacity. One of the most clinically important problems with human NPH insulins is its tendency to flocculate. We present four diabetic patients who, after using flocculated human NPH insulin, encountered a deterioration in the metabolic control of their diabetes, and in two of them, there were bouts of diabetic Ketoacidosis "without any other apparent causal factors". Among those causes favoring flocculation are movement during transport, high temperatures, and probably leaving the vial open for an excessively long period of time, as with the extraction of multiple doses. Physicians, educators, diabetics, and their relatives should be informed of this phenomenon. Diabetics, especially those who carry insulin with them, should carefully inspect their vials before each injection to detect signs of flocculation.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Flocculation; Humans; Insulin, Isophane; Male; Middle Aged

A case of gas gangrene that caused intractable shoulder pain refractory to narcotics in an immunocompromised host is presented. Gas gangrene has been associated with severe trauma involving penetrating wounds, compound fractures, extensive soft-tissue injury, intramuscular injection of epinephrine, and interruption of arterial blood supply. This case describes an elderly insulin-dependent diabetic woman who developed gas gangrene in her arm and leg at the site of her subcutaneous insulin injections. The responsible organism was Clostridium septicum. Emergency medicine physicians must consider gas gangrene Clostridium infection in immunocompromised individuals without evidence of trauma who present with localized and intractable pain.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Diabetes Mellitus, Type 1; Fatal Outcome; Female; Gas Gangrene; Humans; Immunocompromised Host; Injections, Subcutaneous; Insulin, Isophane; Pain, Intractable; Radiography; Shoulder; Thigh

We studied a 26-year-old Type 1 diabetic patient who experienced recurrent episodes of ketoacidosis and who was unresponsive to subcutaneous insulin, but normally responsive to intravenous insulin as demonstrated by insulin challenge test. Attempts at intravenous and intraperitoneal insulin administration were complicated by recurrent septicaemia. We therefore investigated the hypoglycaemic effect of intramuscular insulin administration in this patient. After intramuscular injection of NPH and Ultralente human insulin (0.1 U kg-1), the lowest plasma glucose levels occurred 1 and 7 h later, respectively; the hypoglycaemic effect lasted approximately 2 and 12 h, respectively. We based insulin therapy on intramuscular NPH as a fast-acting insulin and Ultralente as an intermediate-acting insulin using four injections a day. During the next 24 months, the patient was hospitalized for 4 weeks versus 56 weeks in the 20 months preceding intramuscular insulin administration, and was able to resume full-time work. HbAlC decreased from 11.7% to 8.7% (normal range: 4.2-5.9%). Thus, long-term intramuscular insulin therapy is a feasible alternative to intravenous or intraperitoneal insulin in patients with well-demonstrated resistance to subcutaneous insulin.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Injections, Subcutaneous; Insulin; Insulin Resistance; Insulin, Isophane; Insulin, Long-Acting; Recombinant Proteins

1. The effect of the long-acting somatostatin analogue SMS-201995 on diabetes control was assessed in 6 insulin-dependent diabetic patients (3 men and 3 women aged 19-38 years). 2. Plasma glucose and triglyceride profiles were obtained on 4 consecutive days, from 8:00 a.m. to 2:00 p.m. On the first 2 days the patients received their usual dose of insulin and ate at 8:00 a.m. and at noon. On the third and fourth days they received 1/3 of their usual insulin dose together with 100 micrograms SMS-201995 injected subcutaneously. 3. Postprandial glucose and triglyceride increases were blunted during the 360 min of observation on both days after SMS-201995 administration. The areas under the glucose-time plots fell from 23.72 +/- 12.29 (mean +/- SD) to 7.98 +/- 14.26 (P < 0.05) and the areas under the triglyceride-time plots from 10.51 +/- 9.01 to -3.15 +/- 4.30 g.min.dl-1 (P < 0.01). 4. No adverse reactions were observed after SMS-201995 administration for 2 days. 5. We conclude that administration of the somatostatin analogue SMS-201995 may be beneficial for insulin-dependent diabetic patients.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Injections, Subcutaneous; Insulin, Isophane; Male; Octreotide; Time Factors; Triglycerides

For this study 54 dogs with diabetes mellitus verified by anamnesis, clinical examinations and laboratory analyses were selected in 13 Danish and Swedish small animal clinics. After instruction the owners gave isophane insulin ("Insulin Protaphan Human") injections to the dogs morning and evening followed by a commercial or homemade meal rich in fibers. The veterinarians examined the treated dogs 5 times or more in the 90 day treatment period, preferably in the morning before injection and meal. In all 54 dogs the clinical symptoms disappeared a few days after isophane insulin injections, and 54% of the dogs were clinically healthy within 8 days. Within a month 96% of the dogs were normalized after therapy. Simultaneously the blood glucose levels were normalized in 64% of the dogs within 14 days and in further 21% within 30 days. The urine glucose levels were normalized in 64% of the dogs within 14 days and for further 19% within 30 days. At the end of the study 48 out of the 54 diabetic dogs were clinically healthy, alert and free from symptoms of diabetes. The average dose of isophane insulin was for greater dogs 0.44 units per kg bw twice a day, for small dogs 0.79. Six dogs had been destroyed in the trial period for various reasons. One owner had injection troubles. Another owner was hospitalized and had to get rid of the dog. One dog developed advanced breast cancer, 1 went fierce and 2 developed cataracts. Four dogs had by 1 or 2 occasions shown hypoglycemic symptoms, which quickly disappeared after appropriate adjustments of insulin dosing, feeding schedule and exercise programme.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animal Feed; Animals; Diabetes Mellitus, Type 1; Dog Diseases; Dogs; Female; Follow-Up Studies; Insulin, Isophane; Male

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Male; Retrospective Studies

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound. NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 +/- 0.6 h and SC 10.3 +/- 0.7 h, p less than 0.05). No difference in T50% values was found for injection into the abdominal wall (9.7 +/- 1.2h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 +/- 0.3% of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 +/- 0.3% h-1) and SC into the abdominal wall (5.1 +/- 0.3% h-1) (p less than 0.01). The most constant absorption rate was obtained after SC injection into the thigh (within-study day CV of the mean absorption rate 19.9 +/- 3.2% vs 34.4 +/- 3.2% after IM injection into the thigh and 27.1 +/- 4.9% after SC injection into the abdominal wall (p less than 0.02]. The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.

Topics: Absorption; Adult; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Injections, Intramuscular; Injections, Subcutaneous; Insulin, Isophane; Male; Thigh

Reactions to intravenous protamine include rash, urticaria, bronchospasm, hypotension, and/or pulmonary artery pressure elevation. We have previously shown that in diabetic patients receiving daily protamine-insulin injections, the presence of anti-protamine IgE or IgG antibodies are significant risk factors for acute, life-threatening reactions when protamine is given intravenously. To study protamine reactions further, we measured serum anti-protamine IgE and IgG antibody levels, in-vitro basophil histamine release and intracutaneous skin testing to protamine serially in an NPH-insulin dependent diabetic who had a severe, protracted anaphylactic reaction to protamine. At the time of his protamine reaction, his serum contained 8.5 ng/ml of anti-protamine IgE and 1.3 micrograms/ml of anti-protamine IgG antibody. One month following the reaction both anti-protamine IgE and IgG increased to 16 ng/ml (twofold rise) and 90.5 micrograms/ml (70-fold rise), respectively. With time, both anti-protamine IgE and IgG antibody declined. Serial intradermal skin tests using protamine sulphate did not discriminate between the protamine reactor and nine normal control subjects who had no prior exposure nor any demonstrable serum IgE antibody to protamine. In-vitro basophil histamine release to protamine sulphate was inconclusive in discriminating between the protamine reactor and normal control subjects. We postulate that protamine may be an incomplete or univalent antigen that must first combine with a tissue macromolecule or possibly heparin to become a complete multivalent antigen capable of eliciting IgE antibody-dependent mediator release.

Topics: Aged; Basophils; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Histamine Release; Humans; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Infusions, Intravenous; Insulin, Isophane; Intradermal Tests; Male; Protamines

The absorption of isophane(NPH) insulin (Human Insulatard) from palpably abnormal thigh insulin injection sites was determined in 10 C-peptide negative diabetic patients. Absorption was compared with a control day study when the insulin was injected into normal thigh. Standard meals were given 30 and 240 min after the injection. Within 2 weeks the tissue morphology and adipose tissue depths at both injection sites were assessed by ultrasound scanning. Absorption of isophane(NPH) insulin was markedly defective from the abnormal compared with the normal injection sites (area under the free insulin curve to 10 h 115 +/- 15 vs 188 +/- 21 mU l-1 h; p less than 0.01). The area under the blood glucose curve from 270 min to the end of the study at 600 min was significantly greater after injection into the palpably abnormal injection site compared with normal thigh (80.4 +/- 5.2 vs 61.2 +/- 7.0 mmol l-1 h; p less than 0.05) representing a 22% improvement in blood glucose control on the normal injection site afternoon. The depth of abnormal injection site tissue was significantly greater than the depth of adipose tissue at the control site (17 +/- 6 vs 5 +/- 4 mm; p less than 0.001) and considerable disruption of the normal anatomy observed. These results demonstrate defective absorption of isophane(NPH) insulin from palpably abnormal injection sites and describe the morphology of the abnormal tissue.

Topics: Absorption; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Injections, Subcutaneous; Insulin, Isophane; Male; Recombinant Proteins; Skin; Ultrasonography

Topics: Adolescent; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Female; Fetal Diseases; Humans; Insulin; Insulin, Isophane; Pregnancy; Pregnancy in Diabetics

Hyperglycaemia in the afternoon is often not prevented by increasing the intermediate insulin dose in C-peptide deficient Type 1 diabetic patients, particularly children, treated with two injections of mixtures of short- and intermediate-acting insulins. To provide a better understanding of this, 19 Type 1 diabetic patients were studied using the euglycaemic clamp technique, after SC injection of either soluble, isophane (NPH) or lente insulin, or mixtures of these preparations. SC injection of 0.6 U kg-1 insulin, as either intermediate-acting (isophane (NPH) or lente) insulin alone or as a mixture of 50% soluble + 50% intermediate-acting insulins, indicates that, for the same total dose of SC insulin, a shift from soluble to intermediate-acting insulin results in a major loss of activity during the first 6 h after injection, with no compensatory increase over the next 6 h. The morning hypoglycaemic activity depends on different mechanisms with isophane (NPH) or lente insulin; the effects of soluble and isophane (NHP) insulin are superimposed, while with lente insulin, the peak of soluble insulin is blunted. For the afternoon, even large doses of isophane (NPH) or lente insulin do not meet the peak of insulin requirements following lunch.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucose Clamp Technique; Humans; Infusions, Intravenous; Injections, Subcutaneous; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male

Topics: Aged; Diabetes Mellitus, Type 1; Follow-Up Studies; Humans; Insulin, Isophane; Male

We studied morning glycaemia and metabolic consequences of delaying morning insulin/breakfast in insulin-dependent diabetics on (i) continuous subcutaneous insulin infusion (CSII) (n = 27), (ii) multiple-injection therapy (MI) with human isophane insulin at bedtime (MI/human isophane) (n = 23) and (iii) MI with human ultralente insulin at bedtime (MI/human ultralente) (n = 14). After an overnight fast, food and insulin (except for the basal infusion on CSII) were withheld, and blood glucose, serum free insulin and serum betahydroxybutyrate were followed from 0800 hours to 1300 hours. At all times blood glucose was lowest on CSII, intermediate on MI/human isophane and highest on MI/human ultralente; serum free insulin was highest on CSII, intermediate on MI/human ultralente and lowest on MI/human isophane; serum betahydroxybutyrate was lowest on CSII, intermediate on MI/human ultralente and highest on MI/human isophane. Blood glucose rose significantly on MI/human isophane (p less than 0.001) and CSII (p less than 0.02); serum free insulin declined significantly on MI/human isophane (p less than 0.001), and betahydroxybutyrate rose significantly on all regimens. Morning metabolic control is better with CSII than MI. Human isophane insulin is preferable to human ultralente insulin overnight in MI. Delaying morning insulin is not advisable on intensified insulin regimens, being most unfavourable with MI/human isophane.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Humans; Hydroxybutyrates; Infusion Pumps, Implantable; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting

The course of a diabetic patient who self-administered 2500 U of NPH insulin subcutaneously was examined in detail. Despite resumption of oral intake on day 3, she required iv glucose for 6 days, during which time serum free insulin levels remained elevated. Glucose requirements closely matched those calculated from published euglycemic clamp data on maximal glucose disposal rates during insulin infusion. We postulate that her prolonged course was due to delayed absorption of the subcutaneous insulin. This is the first case of massive insulin overdose studied in such detail, and the results may facilitate management of future cases.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Injections, Intravenous; Insulin, Isophane; Suicide, Attempted

Topics: Cardiac Catheterization; Diabetes Mellitus, Type 1; Humans; Insulin, Isophane; Protamines

Topics: Adolescent; Body Weight; Diabetes Mellitus, Type 1; Edema; Humans; Insulin, Isophane; Male; Natriuresis

Eleven adolescent diabetics, aged 15.1 +/- 1.3 years (mean +/- 1SD) in poor glycaemic control (HbA1 12.0 +/- 1.5% at entry) were commenced on a four times daily insulin injection regimen using the Penject fountain-pen syringe with Initard (50:50 mixture of porcine soluble and isophane) insulin on a sliding scale. Diabetic control improved over a 3-month period, assessed by a reduction in both the mean preprandial blood glucose concentrations (10.9 +/- 3.3 mmol/l to 7.7 +/- 2.3 mmol/l) and mean glycosylated haemoglobin concentrations (12.0 +/- 1.5% to 9.5 +/- 0.9%). Further improvement was again seen in 5 patients who remained on four daily injections for an additional 3 months (mean HbA1: 9.6 +/- 0.9% to 8.4 +/- 1.0%), whereas diabetic control in 6 patients who returned to twice daily injections deteriorated (mean HbA1 rose from 9.5 +/- 1.0% to 10.6 +/- 1.6%). Multiple insulin injections using an injection pen are acceptable to adolescent diabetics and improve their control.

Topics: Adolescent; Blood Glucose; Diabetes Mellitus, Type 1; Drug Combinations; Female; Humans; Insulin; Insulin, Isophane; Male; Monitoring, Physiologic; Patient Acceptance of Health Care; Self Care; Syringes

Metabolic rhythms were studied over 24 hours in eight adolescent diabetic patients during treatment with porcine insulin and after transfer to human insulin. Despite an increase in dose with human insulin no significant changes were found in fasting blood glucose, 24h mean blood glucose, or glycosylated haemoglobin concentrations. Significantly higher 24h mean blood lactate concentrations and lower total ketone bodies and glycerol concentrations were observed during treatment with human insulin. These findings are consistent with the increase in insulin dose and do not necessarily imply different metabolic responses to species differences in insulin.

Topics: Adolescent; Animals; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycerol; Humans; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Ketone Bodies; Lactates; Lactic Acid; Male; Pyruvates; Pyruvic Acid

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting

Insulin antibody production was studied in two groups of 9 adult diabetics each, who were never treated before with insulin. One group received Monocomponent porcine lente insulin (MC) and the other group single peak beef NPH insulin, for 3 years. Insulin antibodies were evaluated by antibody-bound immunoreactive insulin (Abl) and by the labelled insulin binding capacity (IBC) which presented a significant correlation best fitted by a logarithmic curve. The patients treated with MC insulin developed significant levels of insulin antibodies, however, at lower levels and appearing later in comparison to those with beef NPH. Only 3 patients did not produce significant levels of insulin antibodies. The highest titers occurred after different lengths of treatment in the two groups of patients. Abl decreased after continuation of treatment particularly in the MC series. While in the MC-treated patients there was some positive correlation between the insulin dose and the level of Abl no significant correlation was found between the diabetes control and insulin antibody titers in both groups of patients.

Topics: Adult; Aged; Animals; Cattle; Diabetes Mellitus, Type 1; Female; Humans; Insulin Antibodies; Insulin, Isophane; Insulin, Long-Acting; Iodine Radioisotopes; Male; Middle Aged; Swine; Time Factors

Topics: Diabetes Mellitus, Type 1; Humans; Insulin, Isophane

Topics: Absorption; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin, Isophane; Iodine Radioisotopes; Kinetics; Time Factors

Protamine is widely used for reversing systemic heparinization after cardiac catheterization. Although rare, major reactions to protamine that simulate anaphylaxis occasionally occur and have previously been associated only with an allergic reaction to fish. Because neutral protamine Hagedorn (NPH) insulin includes protamine, it might be anticipated that NPH insulin-dependent diabetic patients would develop sensitivity to protamine. Of 866 consecutive patients undergoing cardiac catheterization over a 20 month period, 651 received protamine for reversal of heparinization. Of these, 8.5% (56/651) were diabetics and 2.3% (15/651) were NPH insulin-dependent diabetics. During this period seven patients were observed immediately after administration of protamine to have major adverse reactions that required the administration of catecholamines. One death ensued. Of the seven major reactions, four occurred in NPH insulin-dependent diabetics and one occurred in a patient with an allergy to fish. The incidence of major protamine reactions was 27% (4/15) in the NPH insulin-dependent diabetics vs 0.5% (3/636) in those with no history of NPH insulin use (p less than .001). This represents a 50-fold increased risk of a major reaction to protamine if the patient was receiving NPH insulin. Accordingly, we recommend that diabetics on NPH insulin and patients with allergies to fish undergo cardiac catheterization without the use of protamine or, when necessary, that protamine be administered cautiously in anticipation of a major adverse reaction.

Topics: Anaphylaxis; Blood Pressure; Cardiac Catheterization; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Epinephrine; Female; Humans; Injections, Intravenous; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Protamines

Topics: Adolescent; Animals; Cattle; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Humans; Insulin, Isophane; Male; Protamines

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Insulin Antibodies; Insulin, Isophane; Male; Radioimmunoassay

A comprehensive approach to care of adolescents with diabetes mellitus requires knowledge of the unique characteristics of juvenile diabetes during this development period, appropriate medical goals, and awareness of the numerous psychologic and social problems encountered. Involvement of other health professionals is frequently needed. Successful adjustment of the adolescent to having diabetes includes absence of "maladaptive" coping mechanisms, realistic future goals, and acceptance of responsibility for self-care.

Topics: Adolescent; Ambulatory Care; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diet, Diabetic; Female; Humans; Insulin; Insulin, Isophane; Male; Psychology, Adolescent; Social Adjustment

Topics: Child; Diabetes Mellitus, Type 1; Enuresis; Glycosuria; Home Nursing; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Patient Compliance; Self Medication

Topics: Adolescent; Ambulatory Care; Child; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Glucose Oxidase; Glycosuria; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Methods; Specimen Handling

Topics: Adolescent; Adult; Aged; Blood Proteins; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Epitopes; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Iodine Radioisotopes; Islets of Langerhans; Male; Middle Aged; Peptides; Proinsulin; Protein Binding; Radioimmunoassay

Topics: Adolescent; Attitude to Health; Child; Child Behavior Disorders; Child, Preschool; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Humans; Hypoglycemia; Infant; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Outpatient Clinics, Hospital; Parents

Topics: Adolescent; Child; Child Behavior Disorders; Child, Preschool; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Health Education; Humans; Infant; Insulin, Isophane; Male; Parent-Child Relations; Physician-Patient Relations

Topics: Acidosis; Adolescent; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Hyperglycemia; Insulin; Insulin, Isophane; Vomiting

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 1; Humans; Insulin; Insulin, Lente