Jean‐Louis Chiasson

CONTEXT: The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. OBJECTIVE: To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). DESIGN, SETTING, AND PARTICIPANTS: International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years. INTERVENTION: Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714). MAIN OUTCOME MEASURES: The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (> or =140/90 mm Hg). RESULTS: Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P =.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P =.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P =.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P =.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P =.004) associated with acarbose treatment was still statistically significant. CONCLUSION: This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

OBJECTIVE: To evaluate and validate appropriate premeal insulin dose reductions for postprandial exercises of different intensities and durations to minimize the risk of exercise-induced hypoglycemia in type 1 diabetic subjects. RESEARCH DESIGN AND METHODS: Eight male type 1 diabetic patients on a basal-bolus insulin regimen of ultralente (UL) as basal insulin and lispro (LP) as premeal insulin were tested in a randomized, crossover fashion during postprandial exercise at 25% VO2max for 60 min, 50% VO2max for 30 and 60 min, and 75% VOmax for 30 min starting 90 min after a standardized mixed breakfast (600 kcal, 75 g carbohydrates). Each subject served as his own control and was rested after a full dose of insulin LP (LP 100%) and/or 50% (LP 50%) and/or 25% (LP 25%) of the current dose. RESULTS: At all intensities, the full premeal insulin dose was associated with an increased risk of hypoglycemia. At 25% VO2max for 60 min, a 50% reduction in the premeal insulin dose resulted in plasma glucose of -0.62 mmol/l compared with baseline at the end of exercise. At 50% VO2max for 30 and 60 min, 50 and 75% reductions of the premeal insulin dose were associated with plasma glucose of -0.39 and +0.49 mmol/l, respectively, at the end of the exercise. At 75% VO2max, a 75% reduction of the premeal insulin dose was required to achieve appropriate postexercise plasma glucose (+0.71 mmol/l). Such reductions in the premeal insulin dose resulted in a 75% decrease in the incidence of exercise-induced hypoglycemia. CONCLUSIONS In well-controlled type 1 diabetic subjects on intensive insulin therapy with the basal-bolus (UL-LP) insulin regimen, risk of hypoglycemia can be minimized during postprandial exercises of different intensities and different durations by appropriate reduction of premeal insulin LP.