OBJECTIVE -To compare the effects of repaglinide, glipizide, and glibenclamide on insulin secretion and postprandial glucose after a single standard 500-kcal test meal.RESEARCH DESIGN AND METHODS -A total of 12 type 2 diabetic patients with early diabetes (mean HbA 1c of 6.1%) and 12 matched control subjects were enrolled in this randomized, double-blind, crossover trial. Subjects received placebo, 2 mg repaglinide, 5 mg glipizide, and 5 mg glibenclamide in a random fashion during the trial. Administration of each drug was followed by a single standard 500-kcal test meal. A washout period of 7-12 days existed between the four study visits.RESULTS -All three drugs were equally effective on the total prandial insulin secretion (area under the curve [AUC] -15 to 240 min). However, clear differences were noted in the early insulin secretion (AUC -15 to 30 min); both repaglinide and glipizide increased secretion in nondiabetic subjects by ϳ61 and 34%, respectively, compared with placebo. In the diabetic patients, the difference versus placebo was 37 and 47%, respectively. The difference between glipizide and glibenclamide reached significance in both groups of subjects, whereas repaglinide was more effective than glibenclamide only in the healthy nondiabetic subject group. All three drugs were effective in decreasing total glucose AUC in the nondiabetic and diabetic population. In the nondiabetic subjects, however, repaglinide was significantly more effective than glibenclamide. The differences disappeared in the diabetic subjects, probably as a result of increased prevalence of insulin resistance in this group.CONCLUSIONS -Repaglinide and glipizide but not glibenclamide significantly enhanced the early insulin secretion in both nondiabetic and diabetic subjects with preserved -cell function after a single standard meal.
OBJECTIVE -To assess the effects of incremental doses of repaglinide on postprandial insulin and glucose profiles after a standard 500-kcal test meal.RESEARCH DESIGN AND METHODS -Sixteen diet-treated Caucasians with type 2 diabetes (mean HbA 1c 8.4%) were enrolled in this randomized, open-label, crossover trial. Subjects received 0.5, 1, 2, and 4 mg repaglinide or placebo in a random fashion, followed by a standard 500-kcal test meal on 5 separate study days, 1 week apart.RESULTS -The insulinogenic index (⌬I30/⌬G30) and insulin area under the curve (AUC) from 0 to 30 min (AUC 0 -30 ) were higher with the 4-mg drug dose compared with the two lower doses and with 2 mg compared with 0.5 mg. On subgroup analysis, the incremental insulin responses were apparent only in the fasting plasma glucose (FPG) Ͻ9-mmol/l subgroup of subjects and not in the FPG Ͼ9-mmol/l subgroup. There was a significant dose-related increase in the late postprandial insulin secretion (insulin AUC 120 -240 ), which resulted in hypoglycemia in four subjects. Proinsulin-to-insulin ratios at 30 and 60 min improved with increasing doses of repaglinide; higher drug doses (2 and 4 mg) were more effective than the 0.5-and 1-mg doses.CONCLUSIONS -Significant dose-related increases in early insulin secretion were found only in less advanced diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg) was significant compared with placebo. Better proinsulin-to-insulin processing was noted with increasing drug doses. Diabetes Care 28:1001-1007, 2005C haracteristically, type 2 diabetic patients manifest abnormalities of insulin secretion in response to glucose or meal challenges. The insulin secretory defects are quantitative and qualitative and tend to develop early in the history of the disease (1).The normal insulin response to an intravenous glucose bolus has a typical biphasic pattern when quantified using either a hyperglycemic clamp or an intravenous glucose tolerance test. A "firstphase" insulin secretory burst occurs within 3-5 min and is over by 10 min. This is followed by a sustained "second phase" of secretion that lasts several hours in parallel with the glycemic stimulus.Following oral glucose administration, the two phases of secretion are less distinct, and a clear separation between them is virtually impossible. Several indexes of insulin secretion, derived from the insulin responses during the first 30 min of an oral glucose tolerance test or a standardized meal, correlate with the first phase of insulin secretion in response to intravenous glucose. The calculated secretion using these indexes has been called "early" insulin secretion to differentiate it from the true first phase of insulin secretion.First-phase insulin has an important physiological role in the rapid switching of the metabolic processes between fasting and postprandial states, primarily inhibiting the endogenous hepatic glucose production (2). The absence of the firstphase insulin secretory burst in type 2 diabetes leads to unsuppressed postprandial glu...
Objective-To audit the standards of secondary prevention of coronary heart disease in postmyocardial infarction patients. Design-Follow up audit, one year after acute admission with myocardial infarction. Setting-University Hospital. Subjects-For the initial admission, 153 patients were audited, with 84 patients contacted one year later. Demographic data, treatment status, and cholesterol levels were analysed both on admission and at follow up. Interventions-Total cholesterol was checked at the audit time either in the hospital or in the doctor's surgery. Main outcome measures-Statin doses and cholesterol levels. Results-Ninety six per cent of patients had their lipid profile performed on admission. Eighty three per cent of the patients with total cholesterol > 5 mmol/l were discharged from the hospital on lipid lowering medication. Forty five per cent of the subjects who were followed up had cholesterol levels > 5 mmol/l at 1 year. There was a disproportionate use of low doses of statins (lower than those shown in eVective trials: simvastatin 20 to 40 mg, pravastatin 40 mg) with a third of all patients on medication not achieving the targets at one year. Conclusion-There was a major improvement in the proportion of patients started on treatment compared with figures reported by previous studies. However, the titration of the statin doses to achieve the targets is still unsatisfactory. (Heart 2000;84:e3)
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