Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.
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PMID:Immunologic effects of insulin lispro [Lys (B28), Pro (B29) human insulin] in IDDM and NIDDM patients previously treated with insulin. 892 61

Insulin lispro, a recombinant insulin analogue, is identical to human insulin except for the transposition of proline and lysine at positions 28 and 29 in the C-terminus of the B chain. The resultant reduced capacity for self-association in solution translates into more rapid absorption of insulin lispro than human regular insulin from subcutaneous sites. Maximum insulin concentrations are higher and are reached earlier with insulin lispro than with human regular insulin, and insulin concentrations return to baseline values more quickly with insulin lispro; consequently, insulin lispro has a more rapid onset and a shorter duration of glucose-lowering activity. These pharmacological properties provided the rationale for comparative clinical trials of subcutaneous insulin lispro (administered within 15 minutes before meals, preferably immediately before meals) and subcutaneous human regular insulin (administered 20 to 45 minutes before meals) in patients with type 1 diabetes (insulin-dependent diabetes mellitus) or type 2 diabetes (non-insulin-dependent diabetes mellitus) requiring premeal insulin therapy plus basal insulin therapy. Available clinical trials are well designed and results suggest that 1- and 2-hour postprandial blood glucose levels with insulin lispro are similar to or lower than those with human regular insulin; 1- and 2-hourpostprandial glucose excursions are similar to or less pronounced than those with human regular insulin. Glycated haemoglobin A values were generally similar with both agents. Continuous subcutaneous insulin infusion was associated with greater improvements in postprandial blood glucose levels and glycated haemoglobin A1 values with insulin lispro than with human regular insulin. Confirmatory data are required. The incidence of hypoglycaemia with insulin lispro was similar to or lower than that with human regular insulin. In particular insulin lispro appears to be associated with a lower incidence of night-time and severe hypoglycaemic episodes. Evidence also suggests that patients perceive their quality of life to be improved with insulin lispro compared with human regular insulin, and that satisfaction with treatment is greater with the insulin analogue. Thus, in patients with type 1 or 2 diabetes requiring premeal insulin therapy, insulin lispro appears to provide greater postprandial glycaemic control than human regular insulin without increasing the risk of hypoglycaemia. Furthermore, the reduced injection-meal interval with this agent offers greater convenience for the patient than regular human insulin. If longer term clinical experience supports these promising results it is likely that insulin lispro will offer important advantages over human regular insulin.
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PMID:Insulin lispro: a review of its pharmacological properties and therapeutic use in the management of diabetes mellitus. 933 63

Glucose tolerance deteriorates, and the prevalence of diabetes mellitus increases, with advancing age. Most elderly diabetic patients have type 2 (non-insulin-dependent) diabetes mellitus, but the prolonged survival of young people with type 1 (insulin-dependent) diabetes mellitus increases the prevalence of type 1 diabetes among the elderly. Approximately 25 to 29% of patients with type 2 diabetes mellitus are treated with insulin. Conventional therapy with regular and intermediate-acting insulin preparations does not mimic physiological insulin secretion. Subcutaneous administration of insulin lispro, a recently introduced insulin analogue, more closely mimics the time-action curve of endogenous insulin that is produced in response to meals. Its rapid onset and short duration of action allow for adequate control of postprandial glucose levels while reducing the risk of late postprandial hypoglycaemia. Insulin lispro offers improved glycaemic control, convenience and increased flexibility in insulin-treated patients with diabetes.
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PMID:Practical guidelines on the use of insulin lispro in elderly diabetic patients. 950 89

Insulin lispro is an analog of human insulin created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed. The natural sequence in human insulin at these positions is proline at B28 and lysine at B29. At physiologic concentrations, insulin lispro exists in solution as a monomer. As such, it's rate of absorption from subcutaneous sites of injection is greater that of regular insulin. The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid-acting, and therefore a more physiological mealtime insulin than regular insulin. In addition, it shows a shorter duration of activity, approximately up to 5 hours. Insulin lispro given 0 to 15 minutes before the meal translate into better glycemic control and less hypoglycemia risk in clinical studies either in type 1 or type 2 diabetes when compare with regular human insulin given 30-45 minutes before meals.
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PMID:[Spanish experience with insulin lispro]. 971 Sep 93

The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.
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PMID:Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group. 1032 21

The importance of glucose control in reducing the complications of diabetes mellitus has been clearly demonstrated. The emergency physician routinely is expected to treat a wide range of problems related to this disease, including making the initial diagnosis of type 2 and occasionally type 1 diabetes. Also common are patients with poorly controlled diabetes. The recent introduction of new classes of agents to lower blood glucose, especially in type 2 diabetes, should improve the control in this category of patient and reduce the complication rate. Some of these agents, such as troglitazone, have potentially fatal complications and require careful monitoring. Emergency physicians should be aware of the common complications of these drugs because patients can present to the ED with them. Hypoglycemia, a common cause of 911 calls and emergency visits, is not a side effect of either metformin or acarbose. Insulin lispro has improved postprandial glycemic control for type 1 and some insulin-requiring type 2 diabetics. Hypoglycemia is less of a risk with insulin lispro, and quality of life is better with this rapidly acting insulin. Newer methods of insulin delivery, such as continuous subcutaneous infusion, have greatly improved glucose control, given greater freedom to patients, and reduced the risks of hypoglycemia.
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PMID:Recent advances in the pharmacologic management of diabetes mellitus. 1113 Sep 36

Landmark studies have confirmed the importance of intensified insulin treatment for minimizing long-term diabetic complications. Human insulin is still first-line treatment. However, even the most intensive of human insulin-based regimens can only poorly reproduce physiologically desirable insulin release, which includes rapid outbursts of insulin at mealtimes coupled with relatively low and stable basal levels between meals. Encouragingly, there are now four available or soon-to-be-available insulin analogues that offer the potential for more physiological insulin profiles. Insulin lispro and insulin aspart are rapid-acting insulin analogues intended for immediate pre-meal administration in type 1 or type 2 diabetes. Compared with injected human insulin, they improve post-prandial glucose control and reduce late post-meal and night-time hypoglycaemic episodes. Two basal insulin analogues, insulin glargine and insulin detemir, have also shown beneficial profiles with regard to night-time hypoglycaemia.Some, but not all, studies with the two rapid-acting insulins have shown improvement in overall glucose control, as assessed by HbA(1c), in comparison to human insulin. These results are encouraging and provide hope that entirely analogue-based regimens may improve overall glycaemic control and ease of use of insulin.
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PMID:New insulins in the treatment of diabetes mellitus. 1207 70

Numerous studies have established a direct relationship between maternal levels of glycemic control and neonatal outcomes for pregnancies complicated by diabetes. The past several years have seen the addition of insulin analogues as well as many new oral agents to the pharmacological armamentarium available to treat diabetes. Insulin analogs (both rapid and long acting) are of potential interest for women with insulin-requiring diabetes because of the improved control reported in non-pregnant individuals. Insulin lispro is the only insulin analog to be systematically studied in pregnancy. At this time, the majority of evidence suggests that insulin lispro does not cross the placenta and does not have adverse maternal or fetal effects during pregnancy in women with diabetes. For women with gestational diabetes mellitus (GDM) and type 2 diabetes, which are characterized by insulin resistance and relatively decreased insulin secretion, treatment with oral hypoglycemic agents is generating much excitement. Most retrospective studies and the published clinical experience have failed to demonstrate an increased risk of neonatal hypoglycemia and other neonatal morbidities with glyburide or metformin. To date there has been only one randomized controlled trial utilizing glyburide, which found it to be safe and effective in the management of GDM. More intensive investigation regarding the safety and feasibility of oral agents in pregnancies complicated by type 2 diabetes is necessary.
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PMID:Insulins and oral hypoglycemic agents in pregnancy. 1712 90

Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes. The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy. Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes. However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman's diabetes is well controlled with human insulin. There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended. Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control. A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia. The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin. There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.
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PMID:The use of insulin analogues in pregnancy. 2348 21

Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c), hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P < 0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin) were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement.
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PMID:Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes. 2384 Feb 6


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