insulin--isophane and Body-Weight

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

To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin.. We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes.. Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified.. The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Our aim was to compare the effects of an intermediate acting human insulin (NPH) and a long-acting insulin analog, insulin glargine, in insulin naïve type 2 diabetes patients, stratified by the type of hyperglycemia (fasting or postprandial type). Based on different action profiles, we hypothesized that patients having different hyperglycemia types would react differently when treated with these insulins. This is a post hoc analysis of the Lanmet study data. The Lanmet study was a randomized, 36-week controlled insulin initiation study in type 2 diabetes patients. 109 subjects with baseline HbA1c >8.0% (64 mmol/mol) completed the study. The patients were divided into two groups according to fasting glucose (mmol/l)/HbA1c (%) ratio. Patients with a ratio ≥1.3 were defined as having fasting type and those with a ratio <1.3 as having postprandial type hyperglycemia. The main outcome measures were change in HbA1c and body weight, and final insulin dose. Independently of insulin type, compared to patients with postprandial type hyperglycemia, those with fasting type hyperglycemia had 2.1 kg/m(2) greater initial BMI (p = 0.044), gained 2.0 kg more weight (p = 0.020, adjusted for baseline BMI p = 0.035), and had 36% greater final insulin dose/kg (p = 0.001). With respect to hyperglycemia type, there was no difference between NPH and glargine in their effects on HbA1c. When starting bedtime insulin in type 2 diabetes patients, those with fasting type hyperglycemia are prone to greater weight gain. Hyperglycemia type does not help in identifying patients who would benefit specially from either NPH insulin or insulin glargine.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Statistics, Nonparametric

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

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

To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.. This was an exploratory, post hoc analysis by race (White vs. Black/African-American) and ethnicity (Hispanic/Latino vs. non-Hispanic/Latino) of data from the INITIATEplus trial. Participants were treated twice-daily with BIAsp 30 over 24 weeks.. NCT00101751.. Efficacy endpoints included reductions in mean glycated hemoglobin (A1C) and fasting plasma glucose (FPG). Safety endpoints included hypoglycemia rates (events/patient-year) and adverse events. Body weight changes were also measured.. Glycemic control improved by a similar extent for all demographic groups. Observed mean decreases in A1C ranged from 2.4% to 2.6% after 24 weeks' treatment. Baseline-adjusted mean A1C decreases for White vs. Black/African-American subjects were 2.56% and 2.13% (p < 0.0001), and for Hispanic/Latino vs. non-Hispanic/Latino subjects were 2.45% and 2.42% (p = 0.677), respectively. Final FPG values were similar among all groups (141-146 mg/dL [7.83-8.10 m mol/L]), and baseline-adjusted FPG decreases were not significantly different (p > 0.025) between groups. Hypoglycemia was low for White, Black/African-American, Hispanic/Latino, and non-Hispanic/Latino subjects (0.08, 0.04, 0.03, and 0.07 major events/patient-year, with 0.60, 0.30, 0.37, and 0.52 minor events/patient-year, respectively). Body weight increases were 3.17 and 3.06 kg (White vs. African-American) and 2.69 and 3.19 kg (Hispanic/Latino vs. non-Hispanic/Latino). Final weight-adjusted total daily insulin doses were 0.60 U/kg for Black/African-American subjects vs. 0.78 U/kg for White subjects (p < 0.0001), and 0.71 U/kg for Hispanic/Latino subjects vs. 0.74 U/kg for non-Hispanic/Latino subjects (p = 0.42).. The trial was not designed or powered for comparisons across racial or ethnic groups, subjects were not stratified for pre-baseline medication regimens between each race and ethnic group, and unequal subject numbers and baseline A1C disparities existed between the pairs of groups being compared.. Diabetes self-management with BIAsp 30 using an easily followed self-titration algorithm produced low hypoglycemia rates. All subgroups achieved A1C reductions >2.1% and FPG declines >82 mg/dL that were similar across groups, demonstrating that self-titration of BIAsp 30 can successfully be pursued in a primary care setting by patients who had previously failed to meet ADA A1C targets under oral antidiabetes therapy, with race or ethnicity not an obstacle to achieving better glycemic control.

Topics: Biphasic Insulins; Black or African American; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Hispanic or Latino; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; United States; White People

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 evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes.. The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 0 Therapy Korea study was a 6-month, prospective, observational study. No study-specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients > or years (n = 1720).. BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post-prandial plasma glucose levels of 1.2 +/- 1.6%, 2.3 +/- 3.5 mmol/l and 4.8 +/- 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 +/- 1.7%, 10.7 +/- 3.4 mmol/l and 16.7 +/- 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either 'very satisfied' or 'satisfied' with BIAsp30 treatment.. In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Postprandial Period; Prospective Studies; Treatment Outcome

PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy) is the largest, multinational, open-labelled, uncontrolled and completed observational study of the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) treatment in clinical practice. We present results of 3 months of treatment in Chinese patients with type 2 diabetes mellitus who were inadequately controlled on current treatment.. Patients received BIAsp 30 treatment with or without oral antidiabetic drugs (OADs). Patients were categorized according to their treatment prior to entering the study: drug-naive (n = 3697), OAD (n = 4754), insulin (n = 2392) or OAD + insulin (n = 817).. At 3 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-2.24 +/- 1.67, -2.04 +/- 1.57, -1.82 +/- 1.49 and -1.86 +/- 1.61%), fasting plasma glucose (-3.93 +/- 3.12, -3.51 +/- 2.55, -2.99 +/- 2.93 and -3.38 +/- 3.16 mmol/l) and postprandial plasma glucose (-7.09 +/- 4.92, -6.51 +/- 4.02, -5.20 +/- 4.31 and -5.50 +/- 4.32 mmol/l) in the drug-naive, OAD, insulin and insulin + OAD groups respectively (p < 0.001). The proportions of patients in each group achieving target HbA(1c) of less than 7% were higher at 3 months (49.5, 51.8, 51.0 and 48.3%) compared with baseline (3.2, 4.2, 7.1 and 8.3%). The rates of hypoglycaemic episodes (events per patient-year) were lower at the end of the study in all the groups compared with baseline. Hypoglycaemic episodes were mostly minor and diurnal in nature. A total of 151 adverse drug reactions were reported, of which five were serious adverse drug reaction (SADRs). These SADRs were all symptoms of local hypersensitivity.. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was efficacious and safe in Chinese patients with poorly controlled type 2 diabetes.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Treatment Outcome

To assess the effects of a structured in-patient diabetes training programme in people with Type 2 diabetes mellitus on a basal-bolus regimen using insulin glargine or NPH insulin and rapid-acting insulin analogues with respect to glycaemic control, weight development and incidence of hypoglycaemia in an outpatient-clinic setting.. This was a prospective, non-randomized, single centre, comparative observational study including 119 subjects. Pre-study treatment was a basal-bolus regimen with NPH insulin and a rapid-acting insulin analogue. Subjects either continued with NPH insulin (n=56) or were switched over to insulin glargine (n=63) at the discretion of the investigator (aiming at equal numbers in each group). Patients then attended routine out-patient follow up visits for 18 months.. HbA1c in the insulin glargine group improved statistically significant by -0.49%; [95%CI, -0.26, -0.71; p<0.001; HbA1c at endpoint 6.95+/-0.71%], whereas in the NPH group the reduction by -0.12% [95%CI, -0.31, 0.06; p=0.189; HbA1c at endpoint 7.22+/-0.74%] was statistically not significant. After 18 months of treatment the difference between treatment groups was 0.37% (p<0.015). Mean weight gain was significantly higher in the NPH group than in the glargine group (2.1 vs. 0.25 kg; p=0.025). A lower risk of hypoglycaemia in the glargine group (0.50 vs. 0.71 episodes/patient/month) did not reach statistical significance (p=0.081).. Following a structured in-patient diabetes training programme glycaemic control in people with Type 2 diabetes mellitus on a basal-bolus regimen improved significantly only with insulin glargine suggesting that training alone may not be sufficient to further improve metabolic control in relatively well controlled patients on NPH insulin. Therefore, in addition to a structured training programme also the insulin regimen should be optimized, e.g. by introduction of an insulin analogue.

Topics: Adult; Aged; Ambulatory Care Facilities; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Education as Topic; Prospective Studies

This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin.. In this multinational, open-labelled, parallel group, 16-week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA(1c) at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored.. In the total population (HbA(1c) 7.5-13.0% at screening), end-of-trial HbA(1c) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (+/-s.e.m), 0.39 +/- 0.15%, p = 0.007]. In a subpopulation (HbA(1c) > or = 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c) levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 +/- 0.21%, p = 0.027). Mean body weight (+/-s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 +/- 13.3 kg vs. 88.9 +/- 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups (0.03-0.04 events/patient/week).. BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA(1c) > or = 9%.

Topics: Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Treatment Outcome

In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.. In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.. During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).. Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.

Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Lipid Metabolism; Liver; Male; Metformin; Middle Aged

To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.. Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight.. At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C

Topics: Administration, Oral; Adult; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

To show that a thrice daily meal-time biphasic insulin aspart (BIAsp) treatment regimen is as efficacious as a 4 times daily basal-bolus regimen with human isophane insulin (NPH) and insulin aspart (IAsp).. A multinational, randomised, open-label parallel-group trial in 394 patients with type 2 diabetes on a once or twice daily insulin regimen. Patients were randomised 1:1 to BIAsp or IAsp+NPH for 16 weeks. The BIAsp group was treated according to individual needs using BMI as a surrogate index of insulin resistance. Subjects administered BIAsp 70 (BMI< or =30 kg/m (2)) or BIAsp 50 (BMI>30 kg/m (2)) with breakfast and lunch and BIAsp 30 with dinner. The IAsp+NPH group injected IAsp at meals and NPH at bedtime as basal insulin. HbAlc levels after 16 weeks were compared between treatments using a predefined non-inferiority criterion of 0.4%. The incidence of hypoglycaemic episodes and adverse events was evaluated.. Mean HbAlc (+/-SD) decreased from 9.1+/-0.7% to 7.8+/-1.0% with both treatments. Glycaemic control provided by BIAsp was non-inferior to that obtained by the IAsp+NPH (intention to treat ITT) population: diff, HbAlc -0.05%; 95% CI (-0.24; 0.14); per protocol (PP) population: diff, HbAlc -0.03%; 95% CI (-0.23; 0.16). Similar improvements in glycaemic control in both groups were confirmed by self-measured 8-point plasma glucose (PG) profiles, average and fasting PG concentrations, and average prandial PG increments. The incidence of adverse events and hypoglycaemic episodes was similar in the two treatment groups.. A thrice daily meal-time BIAsp regimen is a suitable alternative to an intensified insulin regimen in people with inadequately controlled type 2 diabetes mellitus, and requires fewer daily injections than a basal-bolus therapy without compromising efficacy and safety.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients.. In this randomized, open-label parallel study, twice-daily biphasic insulin aspart 30 (30% soluble and 70% protaminated insulin aspart; BIAsp 30) plus metformin (met) was compared with once-daily insulin glargine (glarg) plus glimepiride (glim) in 255 insulin-naïve patients (131 male; mean+/-SD age, 61.2+/-9.1 years). Mean baseline HbA (1c) (+/-SD) was 9.2+/-1.4% and 8.9+/-1.3% for BIAsp 30 plus met ( N=128) and glarg plus glim ( N=127), respectively ( P=0.0747). Primary endpoint was the difference in absolute change in HbA (1c) between groups after 26 weeks of treatment.. HbA (1c) change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group (between-group difference: -0.5% (95% CI: -0.8; -0.2); P=0.0002). Mean prandial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim: 1.4+/-1.4 mmol/l vs. 2.2+/-1.8 mmol/l; P=0.0002. During the maintenance phase (weeks 6-26), one major hypoglycemic episode occurred in each group; 20.3% and 9% of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups, respectively ( P=0.0124). At end-of-trial, mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg. Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg (95% CI: 0.84; 2.19; P<0.0001). Weight change with BIAsp 30 plus met of +0.7 kg was not statistically significant (95% CI: -0.07; 1.42; P=0.0762).. Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA (1c) and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

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

Postprandial hyperglycemia contributes to glycation of hemoglobin A1c and has been associated with cardiovascular risk in people with diabetes. We investigated the impact of injection timing of Humalog Mix25 (Mix25, known as Humalog Mix75/25 in the U.S.: 25% insulin lispro and 75% neutral protamine lispro) on glycemia and postprandial blood glucose (BG) excursions in elderly individuals. Seventy-three patients aged 60 to 80 years were randomized to Mix25 (Mix25 group, 37 participants) or a continuation with maximum dose glibenclamide (control group, 36 participants). The Mix25 group was subdivided into a group of 18 patients who were injecting insulin after meals and 19 who were injecting before.. At baseline, the absolute postprandial BG concentrations and postprandial BG excursions after breakfast were high (Mix25 group: 15.3+/-4.8 mmol/l and 3.5+/-2.7 mmol/l, respectively; controls: 15.4+/-3.9 mmol/l and 4.7+/-2.7 mmol/l, respectively). In both groups improvement was observed at the endpoint, but it was greater with Mix25 (Mix25 group: 10.3+/-3.6 mmol/l, p<0.0001 vs. baseline, p<0.003 vs. controls, and 2.0+/-2.5 mmol/l, p<0.008 vs. baseline, p=ns vs. controls; control group: 13.3+/-2.9 mmol/l, p<0.006 vs. baseline, and 4.7+/-2.7 mmol/l, p<0.006 vs. baseline). The two Mix25 subgroups had similar postprandial BG levels and BG excursions after breakfast.. Mix25 improves postprandial BG and yields a greater effect on BG excursions compared with monotherapy with glibenclamide. The timing of Mix25 did not impact the level of BG or BG fluctuations after meals, which may be important for individuals with changing dietary pattern.

Topics: Aged; Aged, 80 and over; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period

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 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

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

This study set out to define relationships between changes in plasma leptin and changes in body weight, plasma insulin and blood glucose control during a 12-month crossover study of once-daily Ultratard or twice-daily Insulatard insulin.. Fasting plasma leptin and insulin were measured during a multicentre cross-over study involving 60 subjects with type 2 diabetes (fasting glucose > 8 mM). After a 2-month run-in, there were two 6-month periods of treatment with Insulatard or Ultratard insulin.. Mean plasma leptin increased significantly in both groups after insulin therapy was instigated (12.8 +/- 8.1 to 22.9 +/- 13.1 ng/ml in the Insulatard group; 12.1 +/- 7.2 to 19.2 +/- 12.3 ng/ml in the Ultratard group). Weight also increased significantly in both groups (82.4 +/- 14.3 kg to 88.8 +/- 14.3 kg and 82.2 +/- 15.3 kg to 85.3 +/- 15.2 kg respectively). The increase in plasma leptin correlated well with the increase in weight (R = 0.416, p = 0.001), and this correlation continued after the crossover point. Plasma leptin correlated with BMI throughout the study (R = 0.540, p = 0.000).. The sustained rise in body weight despite a substantial increase in plasma leptin suggests that either resistance to the hypothalamic action of leptin develops when insulin therapy is begun in type 2 diabetes, or that resetting of the set point for body weight occurs such that a larger body mass is tolerated for a given level of plasma leptin.

Topics: Body Mass Index; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Leptin; Male; Middle Aged

To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c).. In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG)

Topics: Administration, Oral; Adult; Aged; Algorithms; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

To study the effect on body weight and glycaemic control of two insulin treatment regimens in patients with Type 2 diabetes and moderate failure to oral hypoglycaemic agents.. Sixteen patients treated with oral hypoglycaemic agents (6 men and 10 women) were included in this open-label, randomized, parallel group study. Their age was 62 +/- 2 (mean +/- SEM) years (range 44-79 years), body weight 71.3 +/- 2.9 kg, body mass index (BMI) 24.6 +/- 0.8 kg/m(2). The patients were switched to insulin treatment with bedtime NPH insulin combined with daytime sulphonylurea (combination group) or twice daily injections of a premixed combination of regular human and NPH insulin (insulin twice daily group) with measurements as given below before and after 12 and 24 weeks of treatment.. HbA(1c) was lowered from 8.3 +/- 0.3% to 7.0 +/- 0.2% in the insulin twice daily group (p<0.05) and from 8.3 +/- 0.3% to 6.8 +/- 0.5% in the combination group (p<0.03; ns between treatment groups). Body weight increased from 71.7 +/- 4.0 kg to 77.6 +/- 4.4 kg in the insulin twice daily group (p<0.001) and from 70.8 +/- 4.6 kg to 72.7 +/- 5.1 kg in the combination group (ns; p<0.02 between groups). The dose of insulin at 24 weeks in the insulin twice daily group was 45.8 +/- 4.2 U and 29.4 +/- 5.4 U in the combination group (p=0.03). Combination treatment reduced fasting and stimulated C-peptide levels.. Both treatments improved glycaemic control to the same extent but the combination of bedtime NPH insulin and daytime sulphonylurea gave a very small increase of body weight over a 6 months period. We conclude that combination therapy is an attractive alternative when starting insulin treatment in patients with Type 2 diabetes as this is a critical period for weight gain in such patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin, Isophane; Middle Aged; Sulfonylurea Compounds; Weight Gain

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

To directly compare the rate of hypoglycemia and metabolic control achieved on once-daily ultralente insulin administration with twice-daily NPH insulin administration in patients with type 2 diabetes. Patient treatment satisfaction and quality of life were also examined before and during each treatment.. A crossover study was performed involving five centers and 79 patients with type 2 diabetes (fasting blood glucose > 8 mmol/l) with a 2-month run-in followed by two 6-month periods of either NPH or ultralente insulin administration. Patients were managed by a specialist nurse using a dosage adjustment protocol.. HbA1c was lower with NPH insulin therapy during each of the 6-month periods (9.7 +/- 0.2 vs. 9.1 +/- 0.3 and 9.8 +/- 0.2 vs. 9.0 +/- 0.3 mmol/l; both P < 0.01). The difference was accounted for by higher evening glucose levels with ultralente insulin (fasting 8.2 +/- 0.3 vs. 8.2 +/- 0.3 mmol/l, 6:00 P.M. 11.5 +/- 0.4 vs. 10.6 +/- 0.4 mmol/l). Despite worse control, the total number of hypoglycemic episodes was greater with ultralente insulin (220 vs. 171), and hypoglycemic episodes requiring third-party assistance occurred almost entirely with ultralente (14 vs. 1). Treatment satisfaction scores increased more with NPH insulin compared with ultralente and rose further upon changing to NPH insulin, but fell upon changing to ultralente insulin. These changes were highly significant (P < 0.001). Diabetes quality of life improved on both regimens.. These data clearly demonstrate the lower hypoglycemia rate, better glucose control, and greater treatment satisfaction accompanying therapy for type 2 diabetes with twice daily NPH compared with once daily ultralente insulin.

Topics: Blood Glucose; Blood Pressure; Body Weight; Circadian Rhythm; Comorbidity; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas.. Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA1c levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity.. FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized ( < 6.4 mmol/l) within 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until the end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The insulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA1c (10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0.2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- 1/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P < 0.01). Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P < 0.001) and in the second phase (P < 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting enhanced insulin sensitivity.. NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM.

Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Glucose; Glycated Hemoglobin; Humans; Insulin, Isophane; Liver; Male; Middle Aged; Obesity; Reference Values; Time Factors; Triglycerides

To compare the effect of bedtime NPH insulin or preprandial regular insulin combined with glibenclamide on metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure to sulfonylurea therapy.. Eighty NIDDM patients were randomized to treatment with either three preprandial doses of regular insulin (daytime group D) or a bedtime dose of NPH insulin (nocturnal insulinization, group N), both regimens being combined with 10.5 mg of glibenclamide. Metabolic profiles were obtained at 0, 6, 16 weeks.. Glycemic control had improved significantly in both groups after 4 months. Fasting blood glucose was significantly lower compared with baseline in both groups. The mean change +/- SD in group D was -2.8 +/- 3.5 mmol/l and in group N -6.4 +/- 3.0 mmol/L, the reduction being more pronounced in group N compared with group D (P < 0.0001). HbA1c was lowered similarly, from 9.2 +/- 1.4 to 7.1 +/- 1.2% in group D (P < 0.0001) and from 9.1 to 1.1 to 7.5 +/- 1.5% in group N (P < 0.0001). The total daily insulin doses were similar, 29 +/- 11 U in group D and 26 +/- 9 U in group N, and the circulating insulin levels during daytime were higher in group D than in group N. Total serum cholesterol and triglycerides were similarly and significantly lowered compared with baseline in both groups. Weight gain was more pronounced in group D (3.4 +/- 0.3 kg) than in group N (1.9 +/- 1.9 kg; D vs. N, P < 0.002), and the change was inversely correlated with initial eight but not with the improvement in HbA1c.. The two insulin regimens exert similar effect on glucose metabolism and serum lipids in NIDDM patients on combination therapy. Weight gain is more pronounced in patients given insulin during the daytime when preprandial doses of short-acting insulin are used.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Glyburide; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Middle Aged; Time Factors; Treatment Failure; Triglycerides

To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.. A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.. Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.. The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Fasting; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Metformin; Middle Aged; Obesity

To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus.. Randomized, double-blind, placebo-controlled trial with a 9-month treatment period.. University hospital.. Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone.. Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia.. Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin.. Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.

Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Male; Middle Aged; Random Allocation; Triglycerides

Long-term, high dosage protamine zinc insulin (PZI) treatments produce adverse reactions. The trace element selenium (Se) is a candidate for the prevention of diabetes due to anti-oxidative stress activity and the regulation of glycometabolism. In this study, we aimed to investigate the anti-diabetic effects of a combination of PZI and Se on type 2 diabetes. Diabetic KKAy mice were randomized into the following groups: model group and groups that were subcutaneously injected with PZI, Se, high or low dose PZI + Se for 6 weeks. PZI combined with Se decreased the body weight and fasting blood glucose levels. Moreover, this treatment also improved insulin tolerance, as determined by the reduced values from the oral glucose tolerance test and insulin tolerance test, and increased insulin levels and insulin sensitivity index. PZI combined with Se ameliorated skeletal muscle and β-cell damage and the impaired mitochondrial morphology. Oxidative stress was also reduced. Furthermore, PZI combined with Se upregulated phosphatidylinositol 3-kinase (PI3K) and downregulated protein tyrosine phosphatase 1B (PTP1B). Importantly, the low dosage combination produced effects similar to PZI alone. In conclusion, PZI combined with Se improved glycometabolism and ameliorated the tissue and mitochondrial damage, which might be associated with the PI3K and PTP1B pathways.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Gene Expression Regulation; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Insulin, Isophane; Mice; Mitochondria; Muscle Cells; Muscle, Skeletal; Oxidative Stress; Random Allocation; Sodium Selenite

The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs.. Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models.. A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant.. Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.

Topics: Body Mass Index; Body Weight; Comorbidity; Costs and Cost Analysis; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Propensity Score; United Kingdom

Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake.

Topics: Animals; Appetite Depressants; Biological Transport; Body Composition; Body Weight; Brain; Eating; Hypoglycemic Agents; Injections, Intraperitoneal; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Wistar

The aim was to observe the effects of switching from neutral protamine Hagedorn (NPH) insulin to insulin glargine on glycaemic control in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice in Italy. This multicenter, observational, retrospective study included 1,011 patients with T2DM who switched from NPH insulin to glargine or were maintained on NPH insulin. The primary outcome was change in HbA1c over 4-8 months. Secondary outcomes included fasting blood glucose (FBG), insulin dose, and hypoglycaemia. The intention-to-treat population consisted of 996 patients (glargine 496; NPH 500). Prior to switching, HbA1c was higher in the glargine than the NPH group [mean (±SD) 8.8 ± 1.4 vs. 7.9 ± 1.2%; p < 0.001]. HbA1c decreased after 4-8 months with glargine (8.2 ± 1.4%; p < 0.001) but not with NPH (8.0 ± 1.4%; p = 0.20). Similar results were observed for FBG. The daily dose of glargine increased from 0.22 ± 0.10 U/kg at the switch to 0.26 ± 0.11 U/kg at study end, while the NPH dose remained stable (0.19 ± 0.09-0.20 ± 0.09 U/kg). While not statistically significant, the percentage of patients with hypoglycaemic episodes during the last month of treatment tended to be less with glargine. No significant change in body weight occurred in either group. Switching patients from NPH insulin to insulin glargine in a real-life setting was associated with significant improvement in glycaemic control. The increase in glargine dose was not accompanied by increased hypoglycaemia or weight gain.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Italy; Male; Retrospective Studies

To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.. People included in THIN United Kingdom primary care record database who began insulin (2000-2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A(1c) (HbA(1c)) and weight change.. Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio 1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA(1c) had reduced less in basal versus pre-mix or NPH at 6-8 and at 9-11 months, and versus pre-mix at 12-14 months.. We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA(1c) compared to other insulins.

Topics: Analysis of Variance; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin, Isophane; Insulins; Proportional Hazards Models; Regression Analysis; Risk Assessment; United Kingdom; Vascular Diseases

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

Despite a wealth of clinical trial data supporting use of the premixed insulin analogue, biphasic insulin aspart 30 (BIAsp 30) in the treatment of type 2 diabetes mellitus (T2DM), there is limited documentation of its use in primary care-based clinical practice.. An observational study investigating the safety and efficacy of BIAsp 30 in routine clinical practice was conducted. Patients were followed up 3 and 6 months after initiating insulin treatment. Safety and efficacy measures were documented.. During the course of the study, 1154 patients were included (age range 20-95 years), of whom 89% completed the 6-month follow-up period. Mean HbA(1c) at baseline was 8.8% (73mmol/mol), and had improved to 7.2% (55mmol/mol) after 6 months of treatment. The rate of total hypoglycaemia at completion of the study was 4.1 events per patient year. Major hypoglycaemic events were rare (two in total).. BIAsp 30 was initiated safely and effectively in insulin-naïve patients with T2DM. The safety and efficacy profile observed in clinical trials was confirmed in this largely primary care-based setting in Sweden.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Services Research; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Primary Health Care; Prospective Studies; Sweden; Time Factors; Treatment Outcome; Young Adult

To compare hypoglycaemic events, glycated haemoglobin (HbA1c) and changes in body weight in Muslim patients with Type 2 diabetes receiving Humalog Mix 50 and human Mixtard 30 twice daily during Ramadan fasting.. Data were collected from Muslim patients with Type 2 diabetes attending primary care practices in North-West London, who were on Mixtard 30 insulin twice daily before Ramadan. Group 1 had their evening insulin changed to Humalog Mix 50 (n = 26) 2 weeks before Ramadan, i.e. taking Mixtard 30 at predawn meal and Humalog Mix 50 at the sunset meal during Ramadan. As the major proportion of the daily caloric intake was consumed at the sunset meal, the rationale of switching the evening dose from human Mixtard 30 to Humalog Mix 50 was to provide more rapid-acting insulin that has shorter time of onset and peak time for the large evening meal to improve the postprandial glucose control without increasing the risk of hypoglycaemia. Group 2 continued on Mixtard 30 twice daily (n = 26). All patients received structured education about how to identify and manage hypoglycaemia during Ramadan.. Group 1 had a mean HbA1c reduction of 0.48% (p = 0.0001) before and after Ramadan, whereas group 2 had a mean HbA1c increase of 0.28% (p = 0.007). Group 1 was associated with a small reduction of 0.04 (p = 0.81) in the mean number of hypoglycaemic events during Ramadan compared with before Ramadan, whereas group 2 was associated with an increase of 0.15 (p = 0.43), although these differences between the groups were not statistically significant following adjustment for baseline factors [LSM difference between groups = 0.135, p = 0.36, 95% confidence limits (-0.16, 0.43)].. Changing to humalog Mix 50 during Ramadan resulted in improvement in glycaemic control without increasing the incidence of hypoglycaemia.

Topics: Aged; Biphasic Insulins; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Islam; Male; Middle Aged; Risk Factors; Young Adult

This study reports on the effectiveness of exenatide compared to insulin glargine or NPH insulin in patients with type 2 diabetes mellitus, unable to achieve glycemic control with oral glucose-lowering therapies in a clinical care setting.. Patients with type 2 diabetes mellitus (n = 47) whose glycemia was not controlled adequately with oral hypoglycemic agents at maximum recommended therapeutic doses were initiated on exenatide therapy. Age-, sex-, and body mass index-matched patients receiving insulin glargine (n = 54) or NPH insulin (n = 23) served as controls. Data analysis included glycated hemoglobin, fasting and postprandial plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia.. A statistically significant reduction in glycated hemoglobin value was noted after initiating exenatide (pre-exenatide 9.7 +/- 1.4% vs. post-exenatide 8.7 +/- 1.5%; P < 0.05), which was comparable to values after insulin glargine (9.8 +/- 1.1% vs. 9.0 +/- 1.5%, respectively; P < 0.05) and NPH insulin (9.6 +/- 1.4% vs. 8.9 +/- 1.3%, respectively; P < 0.05). Exenatide therapy was associated with net weight loss (mean, 1.6 kg), but therapy with insulin glargine and NPH insulin was associated with weight gain (1.8 and 2.3 kg, respectively).. In a group of select Asian Indian type 2 diabetes patients with secondary failure to oral hypoglycemic agents seen at a diabetes center, exenatide treatment in combination with oral drug regimens resulted in significant lowering of glycated hemoglobin similar to insulin glargine or NPH insulin but with the additional benefit of weight loss, albeit a small amount.

Topics: Adult; Aged; Asian People; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Peptides; Surveys and Questionnaires; Treatment Outcome; Venoms

Premixed insulin is effective to improve glycemic control; however, clinicians may be less likely to know which premixed insulin is appropriate for which patients. This study aimed to evaluate the effects of twice-daily injections of premixed insulin lispro on glycemic control in type 2 diabetic patients.. Forty type 2 diabetic patients, who had been treated with twice-daily injections of human protamine mixture 30/70 insulin for at least 12 months, were divided into two groups; one group whose blood glucose 2 hours after breakfast was greater than 200 mg/dL, was switched to lispro mix50, and the other group whose blood glucose 2 hours after breakfast < 200 was switched to lispro mix25.. Glycated haemoglobin (HbA1c) significantly improved in the Mix50 group from 8.3% to 7.5% (at 12 weeks; p < 0.05), and to 7.5% (at 24 weeks; p < 0.05). On the other hand, HbA1c levels in the Mix25 group were slightly decreased from 8.1% to 7.7% at 12 weeks (p < 0.05), and to 7.9% at 24 weeks (not significant). Both postprandial plasma glucose and fasting plasma glucose levels were significantly improved in the Mix50 group, but not in the Mix25 group. Overall, 95% of subjects preferred premixed lispro insulin from human insulin in the viewpoint of the timing of insulin injection by questionnaire analysis.. Switching from human protamine mixture 30/70 insulin to lispro mix50 twice-daily injection therapy in patients with high postprandial plasma glucose could improve their glycemic control and quality of life.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Protamines; Treatment Outcome

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

Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. We report a patient with permanent neonatal diabetes mellitus and severe exocrine pancreatic insufficiency. Ultrasound examination revealed pancreatic agenesis with a suggestion of a small amount of tissue in the head of the pancreas. Genetic testing revealed that the neonate had a homozygous Pro63fsX60 IPF-1 mutation. This is the second reported case of neonatal diabetes mellitus secondary to a homozygous mutation in the IPF-1 gene and supports the previously proposed biological role of IPF-1 in the pancreatic development in human.

Topics: Birth Weight; Blood Glucose; Body Height; Body Weight; Cesarean Section; Chromosomes, Human, Pair 6; Diabetes Mellitus; Diabetes, Gestational; Female; Homeodomain Proteins; Homozygote; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin, Isophane; Male; Mothers; Mutation; Pancreas; Pregnancy; Trans-Activators; Young Adult

Long-term studies involving large number of type 2 diabetic patients supplied evidence that constant adequate metabolic control may prevent the late (micro- and macrovascular) diabetic complications. In the present non-interventional, retrospective study, authors performed an analysis of type 2 diabetic patients who had been previously treated with biphasic human insulin (BHI) and their therapy was changed to biphasic analog insulin aspart 30/70 (BIAsp = NovoMix 30). The switch of the insulin therapy was carried out in years 2007 and 2008 with the cooperation of 50 accredited diabetes centers. Data were obtained at the time of therapeutical change and six months later. The number of suitable patients was 2898 with an age of 66.20 +/- 10.10 year, and the duration of diabetes was >10 years in 43% of the patients. After the six-month therapy with NovoMix 30, the mean HbA 1c level decreased statistically significantly from the initial value of 9.10 +/- 1.44% to 7.62 +/- 1.00% ( p < 0.001). The lipid profile also improved although target values were not always attained. A reduction was also observed in both systolic and diastolic blood pressure. Mean body weight decreased from 84.2 +/- 14.9 kg to 82.6 +/- 13.9 kg ( p < 0.01). All these changes occurred in spite of a significantly reduced daily insulin dose (48.4 +/- 17.6 IU) as compared with the initial value (49.0 +/- 17.4 IU, p < 0.001). A marked decrement was also observed in the frequency of hypoglycemic reactions. These results confirm that treatment with NovoMix 30 insulin leads to a significant amelioration of glycemic control as reflected by the decreased level of HbA 1c and the higher proportion of patients attaining the target value, as well as the lower frequency of hypoglycemic episodes. The significant improvements in cardiovascular risk factors are also important, but the explanation is still missing and would require the accomplishment of prospective, controlled studies.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hungary; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Risk Factors; Time Factors; Weight Gain

To evaluate the long-term cost-effectiveness of transferring type 2 diabetes patients to an insulin detemir regimen after failure to achieve adequate control with oral antidiabetic agents (OADs) alone, or in combination with neutral protamine hagedorn (NPH) insulin, or with insulin glargine in Germany.. A computer simulation model of diabetes was used to make long-term projections of future clinical outcomes and direct medical costs based on findings from a German subanalysis of the PREDICTIVE trial. The study analysed the impact of converting patients failing their current treatments to an insulin detemir regimen. Therapy conversion to insulin detemir +/- OADs was associated with a significant reduction in glycosylated haemoglobin (HbA(1)c) compared with OADs alone, NPH insulin +/- OADs, and insulin glargine +/- OADs. Across all three groups, hypoglycaemia rates decreased by 80% and patients lost an average of 0.9 kg of body weight during treatment with insulin detemir +/- OADs.. Therapy conversion to insulin detemir +/- OADs was projected to improve life expectancy by 0.28 years compared with OADs alone, and by 0.13 years compared with the NPH and glargine regimens. Transfer to insulin detemir was associated with improvements in quality-adjusted life expectancy of 0.21 quality-adjusted life years (QALYs) over OADs alone, 0.28 QALYs over NPH +/- OADs, and 0.29 QALYs over glargine +/- OADs. Insulin detemir was associated with savings over patient lifetimes due to reduced diabetes-related complications in all three comparisons.. Therapy conversion to insulin detemir +/- OADs in type 2 diabetes patients failing OADs alone, NPH or insulin glargine regimens was associated with improvements in life expectancy, quality-adjusted life expectancy and cost savings in all three scenarios evaluated.

Topics: Administration, Oral; Body Weight; Costs and Cost Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Quality-Adjusted Life Years

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: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glipizide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Metformin; Peptides; Pioglitazone; Thiazolidinediones; Venoms

We previously reported that lipoprotein lipase mass level in preheparin serum (preheparin LPL mass) was significantly lower in type 2 diabetes mellitus compared to healthy subjects and increased by conventional insulin therapy using NPH (intermediate-acting) insulin. The aim of this study was to investigate the effects of intensive insulin therapy on preheparin LPL mass. Thirty-two subjects (total group) with type 2 diabetes receiving treatment by NPH insulin injection twice a day in the morning and evening were switched to basal bolus insulin (BBI) therapy (fast-acting insulin after each meal and NPH insulin before bedtime). In 14 subjects, the total daily insulin dose was not change after switching to BBI therapy (iso-dose group). After 3 months of BBI therapy, preheparin LPL mass increased significantly from 47 to 56 ng/ml in total group. Glycosylated hemoglobin and serum triglyceride levels decreased significantly, and high-density lipoprotein-cholesterol increased significantly. Low-density lipoprotein levels did not changed but increase in size was suggested by PAG disc electrophoresis. Similar changes were observed in the iso-dose group. These results suggest that BBI therapy enhances preheparin LPL mass, accompanied by antiatherogenic changes in glucose and lipid metabolism.

Topics: Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Lipids; Lipoprotein Lipase; Male; Middle Aged

Mechanism of protection against cisplatin nephrotoxicity in streptozotocin-diabetic rats is unclear but is associated with decreased renal platinum accumulation. This study was designed to determine whether normalization of hyperglycaemia by insulin treatment to six week streptozotocin-diabetic rats reversed protection against cisplatin nephrotoxicity. Male Sprague-Dawley rats divided into 3 groups (n=10/group) (1) non-diabetic (2) untreated streptozotocin-diabetic and (3) insulin-treated streptozotocin-diabetic groups were rendered diabetic using streptozotocin (65 mg/kg body weight, intravenous). At the end of 6 weeks, Group 3 animals were treated with insulin (subcutaneously) for 21 days to normalize glucose. After 21 days of insulin treatment, the mean +/- S.D. plasma glucose (mg%) in Group 3 animals at 144.8 +/- 22.03, was significantly lower than Group 2 animals (412 +/- 24.69) and comparable to age-matched non-diabetic (Group 1) animals. Blood urea nitrogen at 24 hr after intraperitoneal administration of cisplatin (5 mg/kg body weight) increased by a factor 2.5 in Group 3 compared to 1.1 and 1.3 in Group 1 and Group 2 animals respectively. In the same animals, at 96 hr the blood area nitrogen increased by a factor of 3.2 and 2.9 in Group 1 and Group 3 respectively compared to 1.14 for Group 2 animals. Renal platinum levels in Group 1, Group 2 and Group 3 after 96 hr after cisplatin administration were 6.92 +/- 0.83, 3.46 +/- 0.77 & 6.20 +/- 0.64 (microg/g wet weight of tissue) respectively. Results indicate that 21 day insulin treatment to streptozotocin-diabetic animal reverses protection against cisplatin toxicity. Moreover, insulin treatment increased the susceptibility of streptozotocin-diabetic rats to cisplatin-induced renal toxicity.

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Body Weight; Cisplatin; Diabetes Mellitus, Experimental; Drug Administration Schedule; Glycated Hemoglobin; Hyperglycemia; Injections, Intraperitoneal; Injections, Subcutaneous; Insulin, Isophane; Kidney; Kidney Diseases; Male; Platinum; Rats; Rats, Sprague-Dawley; Streptozocin; Time Factors

To investigate the efficacy of insulin therapy in preventing cystopathic changes in diabetes using a rabbit model.. Twenty-four New Zealand white rabbits were studied in three groups: eight in group 1 as control, eight in group 2 with diabetes by administration intravenously alloxan hydrochloride and eight in group 3 administered insulin therapy after induction of diabetes. Urodynamic investigations were carried out in three groups at the end of 8 weeks. Tissue sections prepared from all groups were studied histologically.. Bladder capacity and compliance increased in diabetic non-treated group. There was no significant difference between the control group and the diabetic group treated with insulin. The neuropathic changes were observed in the diabetic group, whereas the findings of the histological study were similar in the control and in the insulin treatment group.. This animal model indicates that insulin therapy can prevent or delay urodynamic and histopathological changes in diabetes mellitus. These results must be supported by in vitro pharmacological studies.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Hypoglycemic Agents; Insulin; Insulin, Isophane; Rabbits; Urinary Bladder; Urinary Bladder Diseases; Urodynamics

A retrospective analysis was conducted to determine the effects of metformin on glycosylated hemoglobin (HbA1c), body weight, and adverse events in an African-American population. Thirty-six patients who were receiving combination therapy with metformin and either a sulfonylurea or insulin were identified from a hospital pharmacy database. Nineteen patients met the criteria for efficacy analysis. The combination of metformin with either a sulfonylurea or insulin resulted in a decrease of the average HbA1c from a baseline of 10.07% to 7.92% (delta = 2.15%). The effect of combination therapy on weight was variable; however, twice as many patients lost weight compared with those who gained weight. Metformin appeared to be well-tolerated, with gastrointestinal symptoms being the most commonly reported adverse events.

Topics: Adult; Aged; Aged, 80 and over; Black People; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glipizide; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Metformin; Middle Aged; Prognosis; Retrospective Studies

A clinical transfer trial was conducted to ascertain whether semisynthetic human NPH insulin has a full 24-hour duration of therapeutic effect comparable to that of NPH insulin from animal sources. Diabetic patients requiring insulin and stabilized on a once-a-day (QD) regimen of animal NPH insulin were enrolled and entered a two-week run-in period during which the constancy of their insulin requirements and the stability of their glycemic control were assessed. At the end of the run-in phase, baseline measurements were made of fasting blood glucose (FBG), hemoglobin A1 C, C-peptide, and insulin antibodies. Patients then were transferred to a QD regimen of semisynthetic human NPH insulin (Novolin N) in the same dose as the animal insulin. Glycemic control was reassessed after 1, 4, and 8 weeks of therapy, and a global assessment of overall glycemic control was made at the conclusion of the study. Efficacy variables were analyzed for 39 patients. Most had non-insulin-dependent diabetes mellitus (NIDDM) and most were transferred from mixed beef/pork insulin. Six (15%) patients required significant adjustments in insulin dose or regimen; the remaining 85% completed the eight weeks of treatment with minimal changes in insulin dose. Mean values for FBG and hemoglobin A1 C did not change significantly between baseline and the end of the study. The only statistically significant change was an increase in mean body weight (P less than or equal to 0.01). Results of the investigators' global assessments showed that 74% of the patients had unchanged or improved control of glycemia after transferring to semisynthetic human NPH insulin. The average frequency of hypoglycemic events was not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus; Humans; Hypoglycemia; Immunoglobulin G; Insulin Antibodies; Insulin, Isophane; Time Factors

As a model of surgical stress in the cancer-bearing animal, we resected large flank sarcomas from cachectic rats under ether anesthesia and closed wounds primarily. The metabolic cost of tumor resection was measured using a long-term continuous indirect calorimeter. In the immediate postresection period energy balance decreased and host energy expenditure increased significantly (P less than 0.005). In animals with similar tumor weights, mortality following resection was determined by the degree of cachectic depletion. We then considered whether improvement of preoperative host nutritional status with insulin treatment might improve a subsequent surgical outcome. Insulin, when administered exogenously to cachectic tumor-bearing rats, has been shown to stimulate food intake and preserve host weight and does not stimulate tumor growth. When individual rats bearing a cachexia-producing flank sarcoma demonstrated a decline in food intake to less than 75% of predicted (approximately 25 days after tumor implantation), they were randomized to receive either daily injections of NPH insulin (2 units/100 g/day) for 5 days or no treatment for 5 days. Animals then underwent tumor resection and 14-day survival was measured. All resections were performed in an unbiased manner without the surgeon's knowledge of each rat's treatment status. In an experiment using 59 rats, insulin-treated rats had a threefold higher 5-day preoperative food intake and did not lose weight in the preoperative period, while untreated rats lost 17 g (P less than 0.001). Mortality in the insulin-treated group was 10% versus 28% in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Cachexia; Energy Metabolism; Insulin, Isophane; Male; Premedication; Prognosis; Rats; Rats, Inbred F344; Sarcoma, Experimental

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

Clinical factors which might influence the absorption of subcutaneously injected 125I-NPH insulin were studied in 101 diabetics. The disappearance curve was monoexponential after a delay period of 1.5 +/- 0.8 h (mean +/- SD). Lipohypertrophy significantly prolonged insulin absorption (half life (T1/2) = 11.2 +/- 3.1 h, p = 0.0001). Low bicarbonate levels increased the absorption (T1/2 3.9 +/- 2.3 h, p less than 0.05). Lean diabetics had a faster absorption (6.2 +/- 1.9 h) than normal weight diabetics (7.5 +/- 2.0 h, p less than 0.02). Sex, age, diabetes duration and injection depth did not influence T1/2. The half life was significantly inversely correlated to the resting subcutaneous blood flow (r = 0.882, p less than 0.01). The overall interindividual coefficient of variation for insulin absorption in nonketotic diabetics was 27.4%. Also considerable intra-patient day-to-day variation was found (24.5%), and between different injection sites (30.2%). These variations emphasize the drawbacks of conventional insulin therapy in the management of insulin-requiring diabetics.

Topics: Absorption; Adult; Age Factors; Body Weight; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Half-Life; Humans; Injections, Subcutaneous; Insulin, Isophane; Iodine Radioisotopes; Male; Sex Factors

Topics: Angiotensin II; Animals; Blood Glucose; Blood Pressure; Blood Urea Nitrogen; Blood Volume; Body Weight; Diabetes Mellitus, Experimental; Hematocrit; Insulin, Isophane; Kidney; Male; Norepinephrine; Potassium Isotopes; Radioimmunoassay; Radioisotopes; Rats; Renal Artery; Renin; Streptozocin; Tyramine

Topics: Adult; Age Factors; Aged; Body Weight; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hospitalization; Humans; Hypoglycemia; Insulin; Insulin Resistance; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Topics: Animals; Antigens; Blood Glucose; Body Weight; Cattle; Cross Reactions; Diabetes Mellitus; Dogs; Electrophoresis; Fatty Acids, Nonesterified; Glucagon; Glycosuria; Immune Sera; Insulin; Insulin, Isophane; Insulin, Long-Acting; Iodine Radioisotopes; Pancreatectomy; Rabbits; Radioimmunoassay; Swine

Topics: Animals; Appetite; Behavior, Animal; Blood Glucose; Body Weight; Central Nervous System Diseases; Chickens; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Liver; Organ Size; Ovulation; Pharmacology; Poultry; Protamines; Research