insulin--isophane and Diabetes-Mellitus

The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review.. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020.. Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD.. Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence.. The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference. This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.

Topics: Administration, Oral; Bias; Blood Glucose; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Fasting; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic

Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins

The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%.. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 18 February 2016.. Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes.. Two authors independently extracted data and assessed the risk of bias in the included studies.. The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin.Two trials with data for the comparison of insulin to placebo did not report any significant differences between groups for the primary outcomes of blood glucose levels, lung function and nutritional status. This was also true for the single trial with data for the comparison of repaglinide to placebo. Two trials (one lasting one year and one lasting two years) contributed data for the comparison of insulin versus repaglinide. There were no significant differences for the primary outcomes at any time point, except at one year (in the two-year trial) when the insulin group had significant improvement in z score for body mass index compared to the repaglinide group. The single trial comparing glargine to neutral protamine Hagedorn insulin also did not report any significant differences in the review's primary outcomes. A few cases of hypoglycemia were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment.There was an unclear risk of bias from randomization and allocation concealment in two of the four included trials as the authors did not report any details; in the remaining two studies details for randomization led to a low risk of bias, but only one had sufficient details on allocation concealment to allow a low risk judgement, the second was unclear. There was a high risk from blinding for all trials (except for the comparison of oral repaglinide versus placebo) due to the nature of the interventions. Complete data for all outcomes were not available from any trial leading to a high risk of reporting bias. The amounts of insulin and repaglinide administered were not comparable and this may lead to bias in the results. None of the included trials were powered to show a significant improvement in lung function.. This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.

Topics: Administration, Oral; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic

The majority of feline diabetic patients require insulin to stabilize their diabetes and lente insulins have been widely available for many years. Management of many cases using Lente insulins is straightforward and can produce an excellent quality and length of life.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Dose-Response Relationship, Drug; Hypoglycemic Agents; Insulin Resistance; Insulin, Lente; Quality of Life; Survival Analysis; Treatment Outcome

Hospitalized patients frequently transition between various levels of care and changing clinical situations. Optimal management of hospitalized patients with hyperglycemia includes awareness of situations that may significantly affect glucose and/or insulin metabolism. A review of published clinical trials reveals practical approaches to the management of hyperglycemia in select patient populations that may prove useful for the hospital clinician. We outline approaches to the management of hyperglycemia in hospitalized patients receiving glucocorticoids, patients with severe or end-stage renal disease undergoing hemo- or peritoneal dialysis, and patients receiving total parenteral or enteral feeding, in addition to patients transitioning from intravenous insulin infusion to subcutaneously administered insulin. Key considerations underlying these management methods include a proactive approach, frequent blood glucose monitoring, daily review of blood glucose patterns, and daily reassessment of the insulin regimen and associated orders.

Topics: Diabetes Complications; Diabetes Mellitus; Enteral Nutrition; Glucocorticoids; Hospitals; Humans; Hyperglycemia; Insulin; Insulin, Isophane; Parenteral Nutrition; Renal Dialysis; Renal Insufficiency

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.

Topics: Amino Acid Sequence; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Molecular Sequence Data

To review intermediate- and long-acting insulins with specific emphasis on the newer insulin analogs.. A MEDLINE search, in English, was conducted with a cut-off of June 30, 2006, using the terms 'NPH insulin', 'insulin analogs', 'insulin glargine', 'insulin detemir' and 'long-acting insulins'. All clinical trials from within the search period were included.. The insulin analogs, insulin glargine and insulin detemir, were introduced in an attempt to improve glycemic control among patients with diabetes, without increasing the risk of hypoglycemia. This review indicates that both insulin analogs demonstrate better glycemic control than NPH insulin, based on measurements of HbA1c, fasting glucose and intra-subject variability in blood glucose. This was accomplished with similar or reduced risk of hypoglycemia. Also, insulin detemir appears to be associated with less body weight increase than NPH insulin or insulin glargine.. The newer long-acting insulin analogs, insulin detemir and glargine, appear to provide better glycemic control than NPH insulin without increasing the risk of hypoglycemia.

Topics: Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

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

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

Tight glycaemic control is essential for reducing the risk of long-term diabetic complications in people with type I or II diabetes. Intensive blood-glucose control attempts to normalise both pre- and postprandial glycaemia, while avoiding severe hypoglycaemia. A basal insulin, providing a low level of insulin to cover postprandial and overnight fasting periods, is central to intensive blood-glucose control. However, hypoglycaemia, particularly nocturnal hypoglycaemia, is a major treatment-related complication of therapy with most basal insulins currently available for use in clinical practice. This is a result of pronounced peaks in absorption, which lead to inappropriate hyperinsulinaemia following evening administration, and especially poorly reproducible pharmacokinetic profiles when injected subcutaneously. Indeed, for many patients and health-care providers, concern around hypoglycaemia forms a critical barrier to the attainment of tight glycaemic control. Insulin detemir is a novel long-acting analogue of human insulin designed to overcome these practical limitations. Clinical evidence from comparative studies with NPH insulin shows that insulin detemir provides a consistent and clinically relevant reduction in hypoglycaemic risk, especially for nocturnal events, at equivalent or better levels of glycaemic control.

Topics: Blood Glucose; Circadian Rhythm; Delayed-Action Preparations; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.. Electronic databases.. A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.. Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia.. The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.

Topics: Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome

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

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

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Swine; Time Factors

Post-transplantation diabetes mellitus (PTDM) might be preventable.. This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant.. In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24.. At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Intention to Treat Analysis; Kidney Transplantation; Male; Middle Aged; Postoperative Care; Postoperative Period; Risk Factors; Sex Factors; Standard of Care; Time Factors

Clinical studies that compare lente insulin and neutral protamine Hagedorn (NPH) insulin in diabetic dogs are lacking. This is a prospective, randomised, controlled clinical study aimed to compare the efficacy and safety of lente insulin and NPH insulin in diabetic dogs. Thirty client-owned, newly diagnosed diabetic dogs were included. Animals were randomised into two groups and received lente insulin or NPH insulin administered every 12 hours. Follow-up re-evaluations were done at 1, 2, 4, 6, 8 and 12 weeks. At each re-evaluation, a physical exam, blood glucose curve, and serum fructosamine concentrations were performed. At the end of the study, the median insulin dose per injection was 0.61 U/kg (range, 0.34-0.92 U/kg) and 0.49 U/kg (range, 0.23-0.68 U/kg) in the lente and NPH groups, respectively. There was a significant improvement of polyuria and polydipsia and glucose concentrations in both groups. At the end of the study, the glycaemic control was considered good in 9/15 (60 per cent) and 11/15 (73 per cent) in the lente and NPH groups, respectively. These differences were not significant. Lente insulin and NPH insulin were similarly effective in the treatment of dogs with diabetes mellitus.

Topics: Animals; Diabetes Mellitus; Dog Diseases; Dogs; Female; Hypoglycemic Agents; Insulin, Isophane; Insulin, Lente; Male; Prospective Studies; Treatment Outcome

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0-13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Insulin, Isophane; Insulin, Long-Acting

To ensure patient safety when replacing insulin glargine (IG) with neutral protamine Hagedorn (NPH) insulin and to determine differences in blood glucose control, frequency of hypoglycemia, insulin dosing, health resource utilization and quality of life between users of IG and NPH insulin.. A single-site, open-label, randomized, 6-month comparative study of 66 patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Randomization was 1:1 to receive IG or NPH insulin. Data regarding blood glucose control, insulin dosage adjustment and recording of hypoglycemia episodes were obtained through telephone calls; office visits were conducted to measure weight, glycated hemoglobin, fasting plasma glucose and blood glucose profile. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to measure patients' satisfaction with their diabetes treatment.. Rates of symptomatic hypoglycemia did not differ significantly between groups: 37.5±2.2 for the IG group and 31.1±2.1 for the NPH group. However, patients treated with NPH insulin had higher frequencies of severe hypoglycemia (6.1±0.9) compared with 2.7±0.6 for the IG group. A significant difference in changes in glycated hemoglobin (A1C) was observed between the groups: the mean ± standard error A1C decreases from baseline were -0.34%±0.11 for the IG group, vs -0.01%±0.10 for the NPH insulin group. The data obtained from the DTSQ showed greater treatment satisfaction in the IG group compared with the NPH insulin group.. Switching from IG to NPH insulin resulted in more than double the rate of severe hypoglycemias and led to decreased metabolic control. Greater treatment satisfaction was observed with IG, compared with NPH insulin, as measured by change from baseline in the DTSQ scores.

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus; Drug Substitution; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Patient Satisfaction; Risk Factors; Treatment Outcome

Hyperglycaemia and diabetes mellitus are common in patients hospitalized in the orthopaedic surgery ward. However, glycaemic control obtained during hospitalization is often suboptimal. No method for achieving adequate glycaemic control in this population has been validated in an in-hospital setting.. An intervention including an intensive subcutaneous insulin protocol in the orthopaedic department.. All diabetic patients admitted to the Department of Orthopaedic Surgery were prospectively randomized during a 6-month period. One group (n = 30) received standard care with sliding scale insulin and the other group (n = 35) received the intervention protocol. During the intervention period, the staff was briefed on the importance of glucose monitoring and control. An intensive multiple-injection protocol consisting of four daily regular/neutral protamine hagedorn (NPH) insulin injections was initiated in diabetic patients. The programme was followed up by a consulting diabetologist.. Mean blood glucose levels throughout the hospitalization were 161.48 ± 3.8 mg/dL in the intervention group versus 175.29 ± 2.3 mg/dL in the control group (p < 0.0005). Hospitalization was shorter by 2 days in the intervention group (p < 0.05). The number of severe hyperglycaemic events (blood glucose level above 400 mg%) was significantly lower (p < 0.05) in the intervention group. There was no significant difference in the number of hypoglycaemic events.. The suggested four-step intervention regimen improved glycaemic control of hospitalized patients in the orthopaedic department and simplified the 'in-house' treatment of the diabetic patient. Hospital stays were reduced on average by two days (p < 0.05).

Topics: Aged; Blood Glucose; Clinical Protocols; Diabetes Mellitus; Female; Health Personnel; Humans; Hyperglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Isophane; Male; Orthopedic Procedures; Patient Education as Topic; Prospective Studies

To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT).. Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l).. Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay.. Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.

Topics: Aged; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Severity of Illness Index

Cystic fibrosis related diabetes (CFRD) with fasting hyperglycemia is found in 15% of adult and 11% of adolescent CF patients. Because of concerns about hypoglycemia, it is not common practice to treat CFRD with 24-hour basal insulin therapy, despite evidence that insulin deficiency may contribute to protein catabolism and have an adverse effect on weight, muscle mass, pulmonary function, and, ultimately, survival. We hypothesized that insulin glargine would improve blood glucose control and weight in patients with CFRD without causing hypoglycemia.. A randomized cross-over study compared 12 weeks each of bedtime NPH or glargine in 19 CFRD patients.. There was significantly greater reduction in fasting plasma glucose with glargine (P=0.03), and participants showed a non-significant trend towards weight gain with this insulin (P=0.07). No serious hypoglycemia occurred. At study end, all patients chose to continue glargine.. A study of longer duration is needed to determine whether insulin glargine impacts protein catabolism and overall clinical status in CF patients, but these initial data suggest that this is a promising therapy in CFRD.

Topics: Adult; Blood Glucose; Cross-Over Studies; Cystic Fibrosis; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

The primary objectives of this study were to assess the efficacy and safety of Lys(B28), Pro(B29) in the treatment of patients with diabetes mellitus and to compare Lys(B28), Pro(B29) to currently available regular insulin with respect to quality of life. This study was designed as an open-label, non-comparative one. The number of patients enrolled in the trial was 39. At Visit 1 (week 0), blood samples for fasting, 1- and 2-hour postprandial blood glucose, and HbA1c were taken. At Visit 2 (week 6) and Visit 3 (week 12), fasting, 1- and 2-hour postprandial blood glucose, and HbA1c levels were measured again. There was no significant change in HbA1c, fasting blood glucose and 1- and 2-hour postprandial blood glucose levels. The 1- and 2-hour postprandial blood glucose excursions decreased significantly from Visit 1 to Visit 3. There were no serious adverse events during the study. Half of the patients had less hypoglycemia with LysPro insulin, while 25% had an increase in episodes. Thirty percent of patients were more satisfied with LysPro insulin than with the short-acting insulin that they had previously used. In conclusion, LysPro therapy can be regarded as safe, since there were no unexpected adverse events and no changes in the usual physical parameters.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus; Fasting; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Middle Aged; Postprandial Period; Quality of Life; Treatment Outcome

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

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

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

To 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

Insulin requirements, C-peptide levels, and serum lipids have been assessed in 12 obese, insulin-requiring (greater than 60 U/day) patients with type II diabetes mellitus, in a randomized crossover fashion with two treatment regimens: NPH alone and combined NPH and tolazamide, over a period of 3 months each, with maintenance of weight and glycemic control (HgA1, 2hpp and mean 24h glucose profile) at comparable levels. Serum cholesterol improved in both groups compared to their respective baseline values (p less than 0.05). In addition, serum triglyceride was lower (p less than 0.05) in the combined therapy as compared with NPH alone therapy. Insulin requirements were decreased by 23% (p less than 0.002) in the combined therapy group, without significant change in weight, glycemic control, or C-peptide levels. However, C-peptide increments in the combined therapy group were significantly higher than the baseline by 70% (p less than 0.02). NPH plus tolazamide therapy as compared with NPH alone lowers insulin requirement in obese, type II diabetic women without significant alteration in glycemic control, possibly by an increased tissue sensitivity to insulin, and decreases serum triglyceride levels.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Random Allocation; Tolazamide; Triglycerides

The long-term clinical and biofhemical effects of basal-bolus insulin treatment with lispro and NPH in dogs with diabetes mellitus are undocumented.. To perform a prospective pilot field study of the long-term effects of lispro and NPH on clinical signs and serum fructosamine concentrations (SFC) in dogs with diabetes mellitus.. Twelve dogs received combined lispro and NPH insulins treatment twice a day and were examined every 2 weeks for 2 months (visits 1-4), and every 4 weeks for up to 4 additional months (visits 5-8). Clinical signs and SFC were recorded at each visit. Polyuria and polydipsia (PU/PD) were scored as absent (0) or present (1).. Median (range) PU/PD scores of combined visits 5-8 (0, 0-1) were significantly lower than median scores of combined visits 1-4 (1, 0-1, p = 0.03) and at enrolment (1, 0-1, p = 0.045). Median (range) SFC of combined visits 5-8 (512 mmol/L, 401-974 mmol/L) was significantly lower than SFC of combined visits 1-4 (578 mmol/L, 302-996 mmol/L, p = 0.002) and at enrolment (662 mmol/L, 450-990 mmol/L, p = 0.03). Lispro insulin dose was significantly and negatively, albeit weakly, correlated with SFC concentration during visits 1 through 8 (r = -0.3, p = 0.013). Median duration of follow up was 6 months (range 0.5-6) and most dogs (8, 66.7%) were followed for 6 months. Four dogs withdrew from the study within 0.5-5 months because of documented or suspected hypoglycaemia, short NPH duration or sudden unexplained death. Hypoglycaemia was noted in 6 dogs.. Long-term lispro and NPH combination therapy may improve clinical and biochemical control of some diabetic dogs with comorbidities. Risk of hypoglycaemia should be addressed with close monitoring.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Prospective Studies; Protamines

Topics: Comorbidity; COVID-19; COVID-19 Drug Treatment; Dexamethasone; Diabetes Mellitus; Glycemic Control; Humans; Hypoglycemia; Insulin, Isophane; SARS-CoV-2

To assess effects of basal-bolus insulin treatment (BBIT) with lispro and neutral protamine Hagedorn (NPH) insulins, compared with NPH insulin alone, on serum fructosamine concentration (SFC) and postprandial blood glucose concentration (BGC) in dogs with clinically well-controlled diabetes mellitus and postprandial hyperglycemia fed a high insoluble fiber-content diet.. 6 client-owned dogs with diabetes mellitus.. Blood samples were collected for BGC and SFC measurement in hospitalized dogs just before feeding and routine SC NPH insulin administration (time 0); samples were collected for BGC measurement every 30 minutes for 2 hours, then every 2 hours for up to 10 additional hours. Postprandial hyperglycemia was identified when BGC 30 minutes after insulin administration exceeded BGC at time 0 or the 1-hour time point. For BBIT, owners were instructed to continue NPH insulin administration at the usual dosage at home (q 12 h, with feeding) and to administer lispro insulin (0.1 U/Kg, SC) separately at the time of NPH injections. Two weeks later, SFC and BGC measurements were repeated; results at the start and end of the study were compared statistically.. Median SFC was significantly higher at the start (400 μmol/L) than at the end (390 μmol/L) of the study. Median 1-hour (313 mg/dL) and 1.5-hour (239 mg/dL) BGC measurements at the start of the study were significantly higher than those at the end of the study (117 and 94 mg/dL, respectively).. In this sample of dogs with well-controlled diabetes mellitus, addition of lispro insulin to an existing treatment regimen of NPH insulin and dietary management significantly decreased postprandial BGCs. Further study of BBIT for dogs with diabetes mellitus is warranted.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Fructosamine; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Protamines

Topics: Animals; Cats; Diabetes Mellitus; Insulin; Insulin, Isophane

Topics: Aged; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Diabetic Nephropathies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Predictive Value of Tests; Renal Dialysis; Time Factors

This study evaluated the outcome of cats with diabetes mellitus treated with a loose-control approach using protamine zinc insulin and identified factors that influence the likelihood of remission and survival in these cats. A total of 185 client-owned domestic cats were followed until death, lost to follow-up, or the end of the 11-year study. These cats were treated primarily basing insulin dose adjustments on clinical response. Patient records were used to examine factors suspected of influencing success of diabetes management. The remission probability was 56.2%. Survival time ranged from 0 to 3808 days with a median of 1488 days. Recent pre-diabetic corticosteroid use, lower mean blood glucose concentration during treatment, and lower mean insulin dose significantly increased the likelihood of remission. A low-carbohydrate diet, occurrence of remission, lack of diabetic ketoacidosis at diagnosis, lower mean blood glucose value during treatment, and lower blood glucose value at diagnosis were significantly associated with increased survival time.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Diabetic Ketoacidosis; Insulin; Insulin, Isophane

In vials of NPH(R+) (assumed to be 100%), Ins. Ins

Topics: Diabetes Mellitus; Dosage Forms; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin, Isophane

Topics: Animals; Cat Diseases; Cats; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Insulin, Lente; Male; Prospective Studies; Sus scrofa

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Insulin; Insulin, Isophane; Insulin, Lente

Essentials Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin. The interaction between NPH-insulin, anti-PRT/heparin antibodies and platelets was investigated. Anti-PRT/heparin antibodies activate platelets in presence of NPH-insulin dependent on heparin. Cross-reactivity seems to have no major effect on the clinical outcome of medical patients.. Background Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT/heparin complexes is common in diabetic patients. Objectives To investigate the impact of NPH-insulin on the interaction between anti-PRT/heparin antibodies and platelets. Methods The interaction between NPH-insulin and anti-PRT/heparin antibodies was tested using in-house enzyme immunoassays. The ability of anti-PRT/heparin antibodies to activate platelets in the presence of NPH-insulin (and heparin) was investigated using flow cytometry. Results Twenty-one out of 80 sera containing anti-PRT/heparin IgG showed binding to NPH-insulin. Anti-PRT/heparin IgG from immunized patients bound to platelets in the presence of NPH-insulin, but not in the presence of native insulin. Anti-PRT/heparin antibodies induced P-selectin expression in the presence of NPH-insulin in a heparin-dependent way (median mean fluorescence intensity in the presence of NPH-insulin: 55, 95% confidence interval [CI] 18.7-100.5 vs. NPH-insulin and heparin: 204, 95% CI 106.5-372.8). The clinical relevance of platelet-activating anti-PRT/heparin antibodies was assessed by investigating a multicenter study cohort of 332 acutely ill medical patients who received heparin. None of the 21 patients with anti-PRT/heparin IgG developed thrombocytopenia or thromboembolic complications. Conclusions Anti-PRT/heparin antibodies activate platelets in the presence of NPH-insulin in a heparin-dependent way. However, results from our preliminary study indicate no major impact of these antibodies on the clinical outcome in medical patients receiving heparin, particularly on thromboembolic complications.

Topics: Aged; Antibodies; Anticoagulants; Blood Platelets; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Heparin; Humans; Immunoassay; Inpatients; Insulin; Insulin, Isophane; Male; P-Selectin; Platelet Activation; Protamines

The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.. All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.. A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).. Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Topics: Adult; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Young Adult

An 18-year-old female Bali mynah (Leucopsar rothschildi) was presented for polyphagia, weight loss, and incoordination. Diabetes mellitus was diagnosed based on the history and clinical findings, including persistent hyperglycemia with concurrent hypoinsulinemia and glucosuria. A treatment protocol was developed that led to improvement of clinical signs and management of hyperglycemia over several months. Because of the advanced age of the animal, difficulty in maintaining euglycemia, and the stress of handling and treatment, euthanasia was elected 167 days after initial presentation. At postmortem examination, no pancreatic lesions were detected histologically that would account for the diabetes mellitus. To our knowledge this is the first reported case of diabetes mellitus and clinical management of this condition in a passerine species.

Topics: Animals; Animals, Zoo; Bird Diseases; Blood Glucose; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Glycosuria; Injections, Intramuscular; Injections, Subcutaneous; Insulin; Insulin, Isophane; Starlings; Sulfachlorpyridazine

Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years.. From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36-1.19).. Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data.

Topics: Diabetes Mellitus; Disease-Free Survival; Electronic Health Records; Female; Humans; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Time Factors

Topics: Animals; Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diabetes Mellitus; Dogs; History, 20th Century; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Swine

Neonatal diabetes mellitus (DM) is a rare condition that can be either transient or permanent. In this case report, we describe a novel mutation (p.L30Q) in the INS gene resulting in permanent DM in a four-month-old female who presented with polyphagia, polyuria, irritability, and hyperglycemia with glucosuria and ketonuria without acidosis.

Topics: Diabetes Mellitus; Female; Humans; Hyperglycemia; Hyperphagia; Hypoglycemic Agents; Infant; Insulin; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Mosaicism; Mothers; Mutation, Missense; Polyuria; Treatment Outcome

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8-10h while the glucose-lowering effect lasted for over 24h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Female; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male

Topics: Cystic Fibrosis; Diabetes Mellitus; Hospitalization; Humans; Insulin, Isophane; Methylprednisolone; Pilot Projects

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

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

The purpose of this observational study was to determine if switching from isophane insulin human (NPH) to insulin glargine would improve glycemic control in a medically vulnerable population with uncontrolled diabetes.. A retrospective cohort review of patients' medical records was performed that recorded events occurring between January 1, 2001, and December 31, 2003. The cohort consisted of patients with diabetes in an adult medicine clinic at a county hospital. Patients were included if they were receiving NPH insulin for a minimum of six months and subsequently switched to insulin glargine for a minimum of six months.. The study included 43 patients. There was no significant difference in mean glycosylated hemoglobin (HbA(1c)) between NPH insulin (9.6%) and insulin glargine (9.7%) regimens (p = 0.78, 95% confidence interval, -0.62%, 0.82%). Neither was there a significant difference in the frequency or severity of hypoglycemic episodes between the two treatments. Patients experienced significantly fewer diabetes-associated visits over six months while on insulin glargine. Refill frequency did not differ significantly when patients were receiving NPH insulin versus insulin glargine. When analyzing patient characteristics, those of Hispanic ethnicity experienced HbA(1c) values significantly higher than white patients. Several characteristics were associated with refill frequency.. The results of our study indicate that both NPH- and glargine-based basal insulin regimens result in similar levels of glycemic control in a medically vulnerable population with diabetes, without significant differences in the number or severity of hypoglycemic episodes or in refill frequency.

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

Topics: Diabetes Mellitus; Drug Administration Schedule; Humans; Insulin, Isophane; Insulin, Long-Acting

Topics: Blood Glucose; Diabetes Mellitus; Drug Administration Schedule; Fasting; Humans; Injections; Insulin, Isophane

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin, Isophane; Pilot Projects; Treatment Failure

In recent years, the approach to the insulin treatment of type 2 diabetics has undergone a change. Age and clinical status of the patient are decisive determinants for the selection of the appropriate form of treatment. The therapeutic strategy aims to achieve insulin substitution matched to the therapeutic objective, that is, continuous monitoring should be carried out to enable adaptation of the form and intensity of treatment to meet the target end point HbA1c < 6.5%. This necessity results in the earlier use of insulin in all, not only obese, type 2 diabetics. As a compromise solution, a certain percentage of these diabetics will have to be satisfied with simpler forms of insulin substitution and a higher HbA1c value. Attention is drawn to the other parameters of the metabolic syndrome, such as blood pressure, weight, and lipid metabolism. Particular importance attaches to non-pharmacological measures, in particular with the aim of avoiding a further increase in weight due to the treatment with insulin.

Topics: Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Obesity; Patient Education as Topic

Topics: Anaphylaxis; Angioedema; Diabetes Mellitus; Drug Hypersensitivity; Female; Heparin Antagonists; Humans; Hypoglycemic Agents; Immunoglobulin E; Insulin, Isophane; Intraoperative Complications; Middle Aged; Protamines; Urticaria; Vascular Surgical Procedures

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

To evaluate the possible benefits of the addition of intermediate-acting insulin administered at bedtime to therapy with daytime sulfonylureas in patients with non-insulin-dependent diabetes mellitus for whom maximal doses of oral hypoglycemic agents have not been successful.. Study subjects were 16 consecutive obese patients aged from 44 to 78 years (mean age, 62 years) with histories of non-insulin-dependent diabetes mellitus for a mean of 9 years. None of the subjects had been able to control their diabetes with maximal doses of oral hypoglycemic agents. All patients received 20 mg glipizide or 10 mg glyburide twice a day, as well as education about the American Diabetes Association diet. Neutral protamine Hagedorn (NPH) insulin was empirically added in doses from 0.1 to 0.2 units/kg given at bedtime. The dose was adjusted on the basis of fasting blood glucose levels.. Mean fasting blood glucose decreased from 13.7 +/- 3.4 to 8.3 +/- 2.7 mmol/L at 3 months and 7.3 + 2.0 mmol/L at 1 year. Glycosylated hemoglobin decreased from 9.0% +/- 1.9% to 6.2% +2- 1.16% at 3 months and 6.3% +/- 1.22% at 1 year.. A late-night dose of NPH insulin was added to a regimen of daytime sulfonylureas in a group of obese patients with type II diabetes whose hyperglycemia was not controlled with maximal doses of oral hypoglycemic agents. This treatment proved to be beneficial and is a useful alternative to conventional insulin therapy in this group of patients.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glipizide; Glyburide; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Time Factors

The accuracy of patients and health care professionals in drawing up the components of a split-mix insulin regimen and of premixed insulin at three dosages (30 units, 10 units, and 5 units) was assessed with both 30-U and 100-U syringes. Both patients and professionals were inaccurate with both syringes. At low doses tested and with both syringes, patients and professionals showed greater accuracy with premixed insulin than with self-mixed insulin. Errors in drawing up insulin involved errors mainly in the ratio rather than the total volume of insulin drawn. Accuracy improved with higher doses of insulin. The patients' perception of their skill level in drawing up and mixing insulin correlated with the objective measurements of their skill. The improved accuracy in dosing with premixed insulin might explain the previously observed improved glycemic control in patients taking premixed insulin.

Topics: Adult; Diabetes Mellitus; Female; Health Personnel; Humans; Insulin; Insulin, Isophane; Male; Medication Errors; Self Administration; Syringes

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

The frequency of anaphylactoid reactions to protamine sulfate was examined by reviewing the records of diabetic patients undergoing cardiac catheterization over a 5-year period, and by prospectively monitoring diabetic patients receiving NPH insulin during the infusion of protamine sulfate. No anaphylactoid reactions were noted after protamine administration (48 +/- 5 mg) in the retrospective study in either patients with prior exposure to protamine (74 catheterizations) or in diabetics with no exposure to protamine (132 catheterizations). In the prospective study, no anaphylactoid reactions were seen in the 24 NPH insulin-dependent diabetics during the infusion of protamine sulfate (45 +/- 5 mg). Five of the 42 patients (12%) from the retrospective study who underwent vascular surgery developed severe reactions to much larger doses of protamine (380 +/- 118 mg). Diabetics with prior exposure to protamine sulfate do not appear to be at increased risk of anaphylactoid reaction after the administration of protamine sulfate in the dose range of less than 50 mg at the time of cardiac catheterization.

Topics: Anaphylaxis; Cardiac Catheterization; Diabetes Mellitus; Female; Humans; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Protamines; Retrospective Studies; Risk Factors

While fibrocalculous pancreatic diabetes (FCPD) has long been recognized in neighboring Indonesia, there has been only one single case reported from Papua New Guinea. Over an eighteen month period, four new cases of FCPD were seen at this hospital, making FCPD the predominant form of diabetes seen in Papua New Guinea highlanders. Abdominal pain was prominent in only one patient. Cassava formed a small part of the diet of all patients. Control with tolbutamide alone was possible in two patients and the addition of a small dose of isophane insulin gave satisfactory control in the other two. Two patients were particularly sensitive to low doses of insulin.

Topics: Adult; Calcinosis; Diabetes Mellitus; Female; Humans; Hypoglycemia; Insulin, Isophane; Male; Middle Aged; Nutrition Disorders; Pancreatic Diseases; Papua New Guinea; Patient Compliance; Radiography; Tolbutamide

Severe hyperlipidemia was nearly completely corrected in 16 diabetic patients who were treated with regular insulin at breakfast and supper. Serum cholesterol levels fell from 572 +/- 52 mg/dl to 247 +/- 10 mg/dl, and serum triglycerides fell from 6,330 +/- 820 mg/dl to 354 +/- 40 mg/dl over a 4-month period of treatment. Establishment of comparable degrees of control of the fasting blood glucose and hemoglobin A1C levels by NPH insulin did not correct the hyperlipidemia. Regular insulin timed to act for the disposal of ingested substrates appears to provide physiologic actions important in the treatment of diabetic hyperlipidemia.

Topics: Adult; Blood Glucose; Cholesterol; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Eating; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Insulin; Insulin, Isophane; Male; Middle Aged; Triglycerides

Topics: Absorption; Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Kinetics; Solubility; Time Factors

Topics: Animals; Cattle; Diabetes Mellitus; DNA, Recombinant; HLA Antigens; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Proinsulin; Swine

Topics: Denmark; Diabetes Mellitus; History, 20th Century; Humans; Insulin, Isophane

Topics: Denmark; Diabetes Mellitus; History, 19th Century; History, 20th Century; Humans; Insulin, Isophane; Insulin, Long-Acting

Sera from patients with different types of protamine-insulin were assayed for IgG antibody to protamine. A high prevalence of circulating antibody was found in patients treated with either bovine isophane insulin (26 out of 28 patients; 26 of whom also had antibodies to insulin), or bovine protamine zinc insulin (27 out of 30 patients; all 30 had antibodies to insulin). In sera from 24 patients treated with highly purified porcine isophane insulin, protamine antibody was detected in nine; circulating insulin-antibody was detected in 12 patients, eight of whom had protamine-antibody; in the 12 patients with no detectable antibody to insulin, antibody to protamine was detected in only one (x2 = 8.7, p less than 0.01). This relationship between insulin and protamine antigenicity is of interest as it suggests that the protamine-insulin complex is itself immunogenic.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus; Epitopes; Humans; Immunoglobulin G; Insulin; Insulin Antibodies; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Protamines

Thirteen cats with diabetes mellitus were evaluated. Clinical signs included polydipsia, polyuria, polyphagia, lethargy, and weight loss. Results of physical examination included obesity, hepatomegaly, mild seborrhea sicca, muscle wasting, and dehydration. One cat walked plantigrade and was suspected of having a diabetic neuropathy. Persistent hyperglycemia, glucosuria, high liver enzyme activities, hypercholesterolemia, hyperproteinemia, and low electrolyte concentrations were the common laboratory findings. In 3 cats diabetes mellitus developed after megestrol acetate therapy; 2 of these cats required only temporary insulin treatment. In a 3rd cat, which had no history of receiving diabetogenic drug therapy, remission of diabetes mellitus also was observed. Serum insulin and plasma glucose concentrations were determined in 6 cats after administration of an intermediate-acting insulin (isophane insulin) and in 3 cats after administration of a long-acting insulin (protamine zinc insulin). The insulin concentration peaked 2 to 6 hours after the injection of intermediate-acting insulin and 6 to 12 hours after the injection of long-acting insulin. The lowest glucose concentration was recorded 4 to 8 hours after injection of intermediate-acting insulin, and 6 to 12 hours after injection of long-acting insulin. It was concluded that, although insulin therapy must be adjusted to the individual, the diabetic cat usually requires twice-daily administration of isophane insulin; however, the protamine zinc insulin can be given once daily for satisfactory control.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Cat Diseases; Cats; Diabetes Mellitus; Female; Insulin, Isophane; Insulin, Long-Acting; Male

The prolonged action of daily injections of beef ultralente insulin provides a source for the basal, steady state insulin supply which diabetics need in addition to their meal requirements. The complete distinction between basal and meal insulin requirements, provided by two or three injections of soluble insulin per day, allows simple rules to guide both the physician and patient. Thus, the required ultralente dose needs to be continued daily, irrespective of illness or missing meals, whereas the soluble insulin requirements are given according to meals. When starting ultralente insulin therapy a loading dose is required. The doses of ultralente and soluble insulin needed for different severities of diabetes and degrees of insulin resistance can be predicted. A simple regimen to cover the decreasing insulin requirements of newly presenting, ketotic juvenile-onset diabetics has been developed. During surgical operations the continued basal insulin supply, from ultralente insulin, greatly facilitates diabetes control. Whilst many patients have improved nocturnal blood glucose control after transfer to ultralente insulin, optimal control of diabetes sometimes remains difficult in view of the pre-breakfast plasma glucose rise and the longer action of subcutaneous soluble insulin than the physiological meal insulin response. Purified monocomponent beef ultralente insulin is antigenic, and human ultralente insulin might be advantageous.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Pork; Obesity; Patient Education as Topic

Topics: Adult; Animals; Blood Glucose; Diabetes Mellitus; Double-Blind Method; Drug Hypersensitivity; Female; Humans; Insulin, Isophane; Kinetics; Male; Swine

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Humans; Insulin; Insulin, Isophane; Male; Middle Aged

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Drug Combinations; Glucagon; Humans; Insulin, Isophane; Swine

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: Adult; Diabetes Mellitus; Female; Humans; Insulin, Isophane; Medication Errors

Topics: Acute Disease; Adult; Diabetes Mellitus; Drug Eruptions; Female; Humans; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Urticaria

Insulin antibodies are detectable in the sera of most patients within 3-4 months of starting treatment with conventional bovine insulins. Various factors determine the immunogenicity of insulin preparations including the genetic background of the recipient. This causes wide variation in response. Solid phase absorption studies as well as competitive binding in fluid phase indicate that the antibodies formed are almost always specific for determinants shared by the endogenous human molecule. This has important implications for the metabolic effect of insulin antibodies in vivo as well as for mechanisms of autoantibody production in man.

Topics: Animals; Antibody Specificity; Cattle; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Insulin, Long-Acting; Time Factors

Antibodies reactive with the C-peptide portion of proinsulin can be detected in the sera of patients on conventional bovine insulin regimes which include the soluble form. Direct and competitive binding studies demonstrate that C-peptide antibodies show species specificity but do not recognize free homologous C-peptide. This is likely to be due to conformational change following cleavage of C-peptide from the proinsulin molecule. Examination of sera from a large group of patients established on a standard insulin regime shows that C-peptide and insulin antibody levels do not correlate with each other and are likely to show different patterns of genetic control.

Topics: Animals; Antibody Specificity; C-Peptide; Cattle; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Insulin, Long-Acting; Peptides

Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.

Topics: Absorption; Adult; Blood Glucose; Diabetes Mellitus; Female; Half-Life; Humans; Injections, Subcutaneous; Insulin; Insulin, Isophane; Iodine Radioisotopes; Male; Middle Aged

A biotelemetric method with Geiger-Müller (GM) detectors fixed to the skin surface was used for continuous registration of the disappearance rate of subcutaneously injected 125I-NPH insulin. Methodological problems concerning counting geometry were investigated by comparing the disappearance of radioactivity, measured the GM- and NaI-detectors, respectively, and by scanning of the radioactive source. The size and position of the subcutaneous depot was unchanged throughout the study. Movement artifacts could be avoided. The coefficient of variation for distribution of ratios between count rates for GM- and NaI-detectors was 3.0% +/- 1.1 (SD) (range 0.9-4.0%) over periods of 24 h. It is concluded that the biotelemetry technique proved to be a clinically useful procedure for insulin absorption studies.

Topics: Adult; Aged; Delayed-Action Preparations; Diabetes Mellitus; Female; Humans; Injections, Subcutaneous; Insulin; Insulin, Isophane; Iodine Radioisotopes; Male; Middle Aged; Telemetry

Kinetics of subcutaneous NPH insulin were studied in newly diagnosed insulin-dependent diabetics. Using a biotelemetric technique with small Geiger-Müller detectors applied to the skin surface, the disappearance of 125I-NPH insulin fron subcutis was monoexponential with a mean half-life of 6.6 +/- 3.3 (SD) hr. A model is presented to compare the disappearance rates of subcutaneous 125I-NPH insulin and the calculated plasma appearance insulin curve derived from the actual plasma insulin concentration measurements, assuming a one-compartment model and first-order kinetics. Areas under the absorption- and appearance-time curves calculated from external measurements and from plasma insulin concentrations were identical. There was a strong correlation between plasma concentrations and absorbed amounts of labeled insulin (r = 0.8782, P less than 0.001), as there was between the blood glucose-lowering effects and percent absorbed insulin per hour (r = 0.7659, P less than 0.001). Our results indicate that the disappearance rate of iodine-labeled insulin was a relevant biological expression of insulin absorption from subcutis and a reliable noninvasive method of quantitative determination of insulin concentration in blood.

Topics: Absorption; Adolescent; Adult; Diabetes Mellitus; Female; Humans; Insulin, Isophane; Iodine Radioisotopes; Kinetics; Male; Middle Aged

A 56-year-old man developed shock and skin flush minutes after the slow administration of 25 mg of protamine sulfate. Prior protamine exposure from treatment of his diabetes with isophane insulin (NPH insulin) was believed to have sensitized this patient to protamine. A review of three other cases of reaction to low doses of protamine revealed that in each, the patient had previously been exposed to protamine. If heparin is used in a patient with a history of treatment of diabetes with isophane insulin, the heparin should be allowed to spontaneously reverse, without pharmacological assistance if possible. If protamine must be used, the patient should be pretreated with glucocorticoid and vasopressors should be immediately available.

Topics: Diabetes Mellitus; Drug Hypersensitivity; Humans; Insulin, Isophane; Male; Middle Aged; Protamines; Shock

Three patients with antibody-mediated insulin resistance were treated with U-500 regular insulin subcutaneously. Insulin requirements decreased dramatically (55% to 75%) when therapy was changed from U-100 NPH pork to equivalent doses of U-500 regular pork insulin. There was no difference in antibody affinity for the insulin in these two preparations as shown by competition experiments. These observations demonstrate that U-500 insulin is a useful alternative in the treatment of antibody-mediated insulin resistance. The mechanism for this effect is yet to be determined.

Topics: Adult; Aged; Antibody Affinity; Diabetes Mellitus; Female; Humans; Insulin; Insulin Antibodies; Insulin Resistance; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Diurnal glucose profiles have been compared in ten insulin dependent diabetics receiving, firstly, a twice-daily soluble insulin (SI): isophane insulin (NPHI) insulin (30% SI, 70% NPHI). For each patient the two regimens gave similar profiles though nocturnal blood glucose control was better on Mixtard. HbA1 values were similar on the two regimens. The findings show that, using highly purified formulations, small changes in insulin proportions in twice-daily SI: NPHI regimens may be irrelevant to diabetic control; they also suggest that highly purified NPHI may have a substantially shorter duration of action than its older counterpart and that the convenient regimen of twice-daily Mixtard is usually as good as any more complicated 'tailormade' regimen of highly purified insulins.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus; Drug Administration Schedule; Drug Combinations; Humans; Insulin; Insulin, Isophane; Middle Aged

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Female; Insulin; Insulin, Isophane; Insulin, Long-Acting

The time course of action of regular and NPH insulins injected sc was studied in 15 insulin-treated diabetics over a 24-h period during which they received a constant infusion of glucose. The blood glucose began to decline in 1.2 +/- 0.1 h (range, 0.5--2) and reached its nadir in 5.7 +/- 0.3 h (range, 4--8) after the sc injection of regular insulin. The peak effect of regular insulin usually persisted for several hours, and the total duration of action was 16.2 +/- 1.1 h (range, 9--24). Both the time of peak effect and the total duration of action were considerably prolonged compared to data provided in standard textbooks. Free insulin increased to a peak in 2.7 +/- 0.3 h (range, 1--4) after regular insulin injection and then returned to baseline by 8.8 +/- 0.96 h. Subcutaneous injection of NPH insulin decreased the blood glucose by 2.4 +/- 0.5 h (range, 1--7), with a maximal effect at 11.0 +/- 1.4 h (range, 5--19). The total duration of effect on blood glucose was 25.1 +/- 0.7 h (range, 20--29). These values are similar to those in standard textbooks. Although the total insulin levels increased after the injection of NPH insulin, there was very little if any elevation in free insulin. Recognition of the prolonged effect of regular insulin is important in establishing an insulin treatment regime for diabetic patients.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Middle Aged; Time Factors

Topics: Absorption; Adolescent; Blood Glucose; Diabetes Mellitus; Female; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Subcutaneous; Insulin, Isophane; Iodine Radioisotopes; Isotope Labeling; Pregnancy; Pregnancy in Diabetics

A young woman with diabetes mellitus developed chronic urticaria after changing from isophane been insulin suspension to isophane beef-pork insulin suspension. She reverted to treatment with her original insulin preparation, but urticaria failed to terminate. While in the hospital, her eruption began each afternoon at the site of insulin injection. Zinc single-peak beef insulin suspension, a purer preparation with different additives than isophane beef insulin, was substituted, and urticaria terminated rapidly. Intradermal skin testing using single-peak (purified) preparations indicated that the patient was sensitive to beef and pork forms of isophane insulin but not to beef and pork forms of zinc insulin. The patient later had a brief recurrence of urticaria following oral erythromycin and tetracycline therapy but did not develop lesions at sites of insulin injection.

Topics: Adult; Animals; Cattle; Chronic Disease; Diabetes Mellitus; Drug Combinations; Drug Hypersensitivity; Female; Humans; Insulin, Isophane; Recurrence; Suspensions; Swine; Urticaria

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: Adult; Animals; Cattle; Crystallization; Diabetes Mellitus; Drug Contamination; Evaluation Studies as Topic; Humans; Insulin Antibodies; Insulin, Isophane; Insulin, Long-Acting; Lipodystrophy; Proinsulin; Protein Binding; Skin Manifestations; Swine

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood Glucose; Boston; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Haptoglobins; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Male; Middle Aged; Regression Analysis

Topics: Cholesterol; Clofibrate; Dementia; Diabetes Complications; Diabetes Mellitus; Diet Therapy; Diet, Diabetic; Female; Humans; Hyperlipidemias; Insulin, Isophane; Intelligence Tests; Memory; Middle Aged; Thyroid Hormones; Triglycerides

Topics: Antigens; Blood Glucose; Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Peptides; Time Factors

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

Topics: Adult; Aged; Blood Glucose; Carbohydrate Metabolism; Chlorpropamide; Diabetes Mellitus; Drug Synergism; Female; Glycosuria; Humans; Insulin; Insulin Antibodies; Insulin Resistance; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Obesity; Phenformin; Tolbutamide

Topics: Blood Glucose; Diabetes Mellitus; Diet Therapy; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting

Topics: Adolescent; Diabetes Mellitus; Diabetic Retinopathy; Diet, Diabetic; Fluorescence; Humans; Hypercholesterolemia; Hypertension; Insulin; Insulin, Isophane; Photography; Proteinuria; Retinal Vessels

Topics: Animals; Chlorpropamide; Diabetes Mellitus; Diagnosis; Dog Diseases; Dogs; Drug Therapy; Insulin; Insulin, Isophane; Insulin, Long-Acting; Pathology; Phenformin; Protamines; Tolbutamide

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Lente; Insulin, Long-Acting; Obesity; Statistics as Topic; Zinc

Topics: Diabetes Mellitus; Geriatrics; Glucose Tolerance Test; Humans; Insulin; Insulin, Lente; Insulin, Long-Acting; Urine

Topics: Diabetes Mellitus; Diabetic Angiopathies; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Protamines

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

The intravenous infusion of 600 milligrams of glucose over 30 minutes caused a 17 percent fall in the concentration of free fatty acids in arterial blood of subjects who had fasted overnight. This response to glucose was abolished in subjects treated previously with ganglionic or adrenergic blocking agents. Small amounts of insulin were secreted in response to these glucose infusions, but in insulin-dependent diabetics incapable of altering plasma insulin to any great extent, the effect of glucose upon free fatty acids could be obtained provided the subjects were primed with long-acting insulin before the infusions were begun. The response of free fatty acids to doses of glucose which elevated the concentration of glucose in arterial blood by only 3 mg percent and the blockade of this response by autonomic and adrenergic blocking agents suggest that centers in the central nervous system exist which are capable of responding to elevations of arterial glucose by inhibiting the sympathetic tone partially responsible for sustaining lipolysis in fasting.

Topics: Autonomic Nervous System; Biomedical Research; Blood; Blood Glucose; Diabetes Mellitus; Fasting; Fatty Acids; Fatty Acids, Nonesterified; Glucose; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Negotiating; Neurophysiology; Pentolinium Tartrate; Pharmacology; Protamines

Topics: Diabetes Mellitus; Drug Therapy; Glycosuria; Humans; Insulin; Insulin, Isophane; Ketones; Ketosis; Necrobiosis Lipoidica; Steroids; Tolbutamide; Toxicology; Triamcinolone Acetonide; Urine

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Insulin; Insulin, Isophane

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

Topics: Diabetes Mellitus; Gonadotropins; Humans; Insulin; Insulin, Lente; Insulin, Long-Acting; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

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

Topics: Diabetes Mellitus; Follow-Up Studies; Humans; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente

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

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

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

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Therapeutics; Zinc

Topics: Biomedical Research; Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Female; Humans; Insulin; Insulin, Lente; Pregnancy; Zinc

Topics: Child; Diabetes Mellitus; Humans; Infant; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Child; Diabetes Mellitus; Infant; Insulin; Insulin, Lente; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

Topics: Diabetes Mellitus; Insulin; Insulin, Isophane

Topics: Diabetes Mellitus; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Therapeutics; Zinc

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

Topics: Child; Diabetes Mellitus; Humans; Infant; Injections; Insulin; Insulin, Lente

Topics: Diabetes Mellitus; Humans; Injections; Insulin; Insulin, Isophane

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Suspensions; Zinc

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

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

Topics: Diabetes Mellitus; Insulin; Insulin, Lente; Zinc

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

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Insulins; Protamines; Zinc

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

Topics: Diabetes Mellitus; Insulin, Isophane; Protamines; Therapeutics; Zinc

Topics: Child; Diabetes Mellitus; Humans; Infant; Insulin; Insulin, Isophane

Topics: Diabetes Mellitus; Insulin; Insulin, Isophane; Protamines; Zinc

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

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

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

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

Topics: Diabetes Mellitus; Disease Management; Humans; Insulin; Insulin, Isophane

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

Topics: Child; Diabetes Mellitus; Infant; Insulin, Isophane

There are several distinct types of commercial insulins available, and with combinations of these many curves of timing of insulin action may be obtained, but none can parallel the action of a normal pancreas.NPH insulin, the newest addition, has a wide range of usefulness and may supplant many of the other types and combinations.

Topics: Biphasic Insulins; Diabetes Mellitus; Humans; Insulin; Insulin, Isophane

Topics: Communication; Diabetes Mellitus; Embryo Implantation; Insulin; Insulin, Isophane

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

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

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Insulins

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Suicidal Ideation

Topics: Blood Glucose; Diabetes Mellitus; Globins; Glycosuria; Humans; Insulin; Insulin, Isophane; Urine

Topics: Biphasic Insulins; Diabetes Mellitus; Humans; Insulin, Isophane; Insulin, Long-Acting; Protamines

Topics: Diabetes Mellitus; Globins; Humans; Insulin; Insulin, Isophane