Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin lispro is a rapid-acting insulin analog to regular insulin. Inversion of the proline-lysine amino acid sequence at positions 28 and 29 on the B chain is responsible for its more rapid absorption, faster onset, and shorter duration of action compared with regular insulin. The fast onset of action allows for greater flexibility in dosing and mealtime scheduling. Insulin lispro provides equivalent or slightly improved glycemic control in patients with types I and II diabetes mellitus compared with regular insulin, without subsequent increases in hypoglycemic episodes. It also results in greater reduction in postprandial blood glucose excursion than regular insulin. Compared with other insulins, insulin lispro represents a more physiologic approach to exogenous insulin therapy.
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PMID:Insulin lispro, a new insulin analog. 962 Jan 4

It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macrovascular complications of diabetes mellitus. Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, alpha-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes. Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which. when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. Alpha-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption. With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.
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PMID:Drug therapy of postprandial hyperglycaemia. 995 49

Glycaemic control in Type 1 diabetes has been proven efficient in preventing microvascular and neurological complications. The assumption that good control of hyperglycaemia may also have significant impact on alleviation of complications in Type 2 diabetes has gained growing support in recent years. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is most frequently used. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase glucose disposal and decrease hepatic glucose output without causing hypoglycaemia. Acarbose helps to spread the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological treatments can improve blood glucose regulation in Type 2 diabetes patients. However, the key to strict glycaemic control with use of exogenous insulin lies in the creation of delivery methods that emulate physiologic insulin secretion. 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. Evidence suggests that patients perceive their quality of life to be improved with insulin lispro when compared with regular human insulin, and that satisfaction with treatment is greater with the insulin analogue. Numerous new pharmacological approaches are under active investigation, with the aim of promoting insulin secretion, improving the action of insulin, or slowing carbohydrate absorption. With respect to continuous subcutaneous insulin infusion therapy and implantable pumps, despite that this approach is not widely utilised, it appears to bring us as close to achieving glycaemic control as is feasible with current treatment approaches. However, general application of such technology requires significant improvements in several areas, such as improvement of patency of catheter, pump failures due to early battery depletion incidents, and pump miniaturisation. Future perspective resides on insulin analogues with longer half-lives that would provide better basal insulin coverage in association with fast-acting analogues.
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PMID:Pharmacological management of diabetes: recent progress and future perspective in daily drug treatment. 1005 Nov 77

This willingness-to-pay (WTP) analysis is the first study of its kind undertaken in Australia to support an application for listing of a new drug on the Australian national formulary. The technique offers the advantage of being able to summarise diverse outcomes of therapy in a single unit of measure. Willingness to pay is used to value benefits in cost-benefit analysis (CBA), and CBA represents an absolute decision rule. An open-ended question with a bid-up approach was used to minimise bias and elicit the maximum amount patients would be willing to pay for insulin lispro. The WTP study incorporated scenarios describing the outcomes from insulin lispro and neutral (regular) insulin, the results from a formal metaanalysis and a description of the injection characteristics of the therapies. A sample of 83 patients with type I or II diabetes mellitus were surveyed using an open questionnaire to determine their maximum willingness to pay for the therapy they preferred. Overall, 92% of patients preferred insulin lispro (referred to as insulin A) and 8% preferred neutral insulin (referred to as insulin B). The incremental benefit per patient was calculated as 452.16 Australian dollars ($A) per year. Insulin lispro was listed on the Australian national formulary at a 36% premium over neutral insulin, so the additional cost per patient would be $A70.32 per year. Therefore, costs were exceeded by the benefits and insulin lispro was deemed to offer a net benefit. A multivariate analysis indicated that those patients who were middle-aged had the strongest preference for insulin lispro.
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PMID:Economic evaluation of insulin lispro versus neutral (regular) insulin therapy using a willingness-to-pay approach. 1017 60

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

Even a small improvement in satisfaction with treatment for a chronic disease can be valuable. However, sensitive measurements instruments are needed to assess the effects of treatment changes in patients already well satisfied with baseline treatment. Such instruments were thought to be necessary to deal with ceiling effects in scores of satisfaction with functional insulin treatment (FIT) accommodating full flexibility of food intake and lifestyle in diabetes by manipulation of insulin (FIT; Howorka et al. 2000). The Status(S) version of the Diabetes Treatment Satisfaction Questionnaire (DTSQ, Bradley 1994) was extended with items measuring specific components of FIT and its psychometric properties investigated in a validation study with 171 FIT patients with diabetes. A new Change(C) version of DTSQ extended for FIT was used together with the DTSQ(S) by 52 participants in a subsequent randomised cross-over study involving new fast-acting lispro vs. regular insulin, where treatment satisfaction was the primary outcome variable. Insulin lispro use improved satisfaction (p < or = 0.001) both, on classical and extended versions of DTSQ(S) and (C), despite high baseline levels of satisfaction. However, the DTSQ(C) augmented the effects of lispro (p = 0.0001) apparent on DTSQ(S) scores and revealed significant treatment effects (p < or = 0.01) not significant with DTSQ(S). In parallel, glycaemic control improved with lispro (e.g., HbA1c, p = 0.023). Improved satisfaction with treatment was more apparent with DTSQ(C) than DTSQ(S) in patients who at baseline were at or near ceiling for treatment satisfaction.
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PMID:Dealing with ceiling baseline treatment satisfaction level in patients with diabetes under flexible, functional insulin treatment: assessment of improvements in treatment satisfaction with a new insulin analogue. 1128 11

Insulin lispro is absorbed more rapidly and has a shorter duration of action than regular human insulin. It improves glycaemic control but large-scale studies are required to identify regimens that optimise efficacy and safety with local dietary habits. This study involved 1184 Italian patients with Type 1 diabetes, randomised to insulin lispro (n=586) or regular human insulin (n=598) as pre-meal bolus for 3 months. Optimisation of basal NPH insulin was carried out in both groups. The number of administrations of NPH insulin was increased when using insulin lispro but, because basal and bolus insulins were mixed before meals, the total number of injections per day was unchanged. Compliance to administration time was significantly (p<0.001) greater with insulin lispro than with regular human insulin. Post-prandial blood glucose levels were lower with insulin lispro after breakfast (p<0.001), lunch (p<0.005) and dinner (p<0.001). The HbA1c level was decreased from baseline by both insulins, but the percent increase in patients with acceptable (<8%) HbA1c was greater with insulin lispro. While frequency of hypoglycaemia was decreased from baseline by both insulins, the proportion of episodes classified as severe was significantly increased from baseline with regular human insulin, but not with insulin lispro. Thus, compared with regular human insulin, improved glycaemic control was achieved with insulin lispro without an increase in severe hypoglyeaemia.
Diabetes Nutr Metab 2001 Jun
PMID:Italian multicentre study of intensive therapy with insulin lispro in 1184 patients with Type 1 diabetes. 1147 59

This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) using an external insulin pump. In this 24-week multicenter, randomized, two-way crossover, open-label trial, 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks, followed by the alternate treatment for another 12 weeks. Efficacy and safety measures included hemoglobin A(1c) (HbA(1c)) at baseline and endpoint, home blood glucose monitoring, hypoglycemia, and frequency of pump catheter occlusion. Patients consumed a standard test meal on three occasions, with determinations of fasting, 1- and 2-h postprandial glucose values. Insulin lispro use was associated with a significantly lower HbA(1c) than was buffered regular human insulin (7.41+/-0.97 vs. 7.65+/-0.85 mmol/l; P=.004). Fasting serum glucose values before the test meal were similar between the two therapies. The 1-h (11.16+/-4.29 vs. 13.20+/-4.68 mmol/l; P=.012) and 2-h (9.64+/-4.10 vs. 12.53+/-4.64 mmol/l; P=.001) postprandial glucose concentrations were significantly lower during treatment with insulin lispro. No differences between treatments were observed in basal or bolus insulin doses, weight gain, or the incidence and rate of hypoglycemia, hyperglycemia, or pump occlusions. When used in external pumps, insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile.
J Diabetes Complications
PMID:A comparison of insulin lispro and buffered regular human insulin administered via continuous subcutaneous insulin infusion pump. 1171 22

The results of the clinical studies of insulin lispro carried out in Japan to confirm the pharmacodynamics, pharmacokinetics, efficacy and safety, which were recently released were summarized in this article. When compared to human regular insulin, single subcutaneous injection to healthy persons showed that insulin lispro was adsorbed and disappeared more rapidly in blood stream and blood lowering action revealed more early. The potency of hypoglycemic action was stronger. Long-term multicenter, randomized, comparative, parallel, open-label study to diabetic patients of both type 1 and type 2 by multiple injection method showed that insulin lispro resulted in the significant improvement of 2 hour-postprandial blood glucose level 12 and 24 weeks after the initiation of treatment. HbA1c level did not change between two groups during the study. Insulin lispro did not give any adverse effects during 48 week-study. These studies support the conclusion that insulin lispro is useful and effective in the treatment of diabetes as a short-acting insulin.
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PMID:[Insulin lispro]. 1171 98


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