EFFECT OF INSULIN-GLIPIZIDE COMBINATION ON SKELETAL-MUSCLE CAPILLARY BASEMENT-MEMBRANE WIDTH IN DIABETIC-PATIENTS

This study investigated the long-term effect of insulin or the combina tion of insulin and an oral hypoglycemic compound (glipizide) on the s keletal muscle capillary basement membrane width in insulin-requiring diabetic patients. Seventy diabetic patients were randomized to treatm ent with either insulin-placebo or insulin-glipizide (5 mg/d) for 3 ye ars. Of these, only 61 patients completed the study; 27 patients recei ved insulin-placebo and 34 patients received insulin-glipizide. Three skeletal muscle (quadriceps femoris) biopsies were performed in all pa tients over a 3-year period. Glycosylated hemoglobin At was determined every 100 +/- 20 days, including plasma glucose levels. Muscle capill ary basement membrane width was quantitated by a previously described method. After approximately 16 months, glycosylated hemoglobin Al decr eased significantly in each group from its baseline (P < 0.001 insulin -glipizide group and P < 0.025 insulin-placebo), although no statistic ally significant difference was seen between the two groups. After 3 y ears this decrease was statistically significant (P < 0.001) only in t he insulin-glipizide group. At baseline, no statistically significant difference was found in the muscle capillary basement membrane width b etween the two groups. In spite of the significant decrease in glycosy lated hemoglobin At in both groups after 14 to 16 months, only muscle capillary basement membrane width in the insulin-glipizide group decre ased significantly compared with baseline. Patients receiving insulin- placebo showed a gradual increase in the muscle capillary basement mem brane width, which after 3 years was significantly higher than baselin e (P < 0.02). Although the mechanisms by which the addition of glipizi de to insulin treatment reduced the thickening of the muscle capillary basement membrane are not clearly understood, the current findings su ggest that diabetic microangiopathy is not necessarily progressive and that prophylaxis may be attained.