EFFECT OF OBESITY ON THE RESPONSE TO INSULIN THERAPY IN NONINSULIN-DEPENDENT DIABETES-MELLITUS

An initial improvement in glycemic control is often followed by gradua l deterioration of glycemia during insulin treatment of patients with noninsulin-dependent diabetes mellitus (NIDDM). We examined the causes of such worsening in a 12-month follow-up analysis of 100 insulin-tre ated NIDDM patients in the Finnish Multicenter Insulin Therapy Study w ho were treated with either combination therapy with insulin or insuli n alone. In the entire study group, glycemic control averaged 9.7 +/- 0.2% at 0 months and 8.0 +/- 0.1%, 8.0 +/- 0.1%, 8.2 +/- 0.1%, and 8.5 +/- 0.2% at 3, 6, 9, and 12 months (P < 0.001 for each time point us. 0 months). Glycemic control at 12 months was significantly worse than that at 3 (P < 0.001), 6 (P < 0.001), and 9 months (P < 0.02). Baseli ne body mass index was the most significant predictor of deterioration in glycemic control. During 1 yr, hemoglobin A(1c) decreased almost 3 -fold more (by 1.7 +/- 0.2%; P < 0.001 vs. 0 months) in patients whose baseline weight was below the mean baseline body mass index of 28.1 k g/m(2) (nonobese patients) than in those whose weight exceeded 28.1 kg /m(2) (obese patients; 0.5 +/- 0.2%; P = NS vs. 0 months; P < 0.01 vs. obese patients). Glycemic control improved similarly over 1 yr in the nonobese subjects and deteriorated similarly in the obese patients re gardless of their treatment regimen. Insulin doses, per body weight, w ere similar in the nonobese and obese patients. The nonobese patients consistently gained less weight during 12 months of combination therap y with insulin (3.5 +/- 0.6 kg at 12 months) than during insulin thera py alone (5.1 +/- 0.6 kg; P < 0.05). The treatment regimen did not inf luence weight gain in the obese group, who gained 4.4 +/- 1.0 kg durin g combination therapy with insulin and 4.5 +/- 1.1 kg during insulin t herapy alone. We reached the following conclusions: 1) after an initia l good response, glycemic control deteriorates more in obese than in n onobese patients with NIDDM; 2) in obese patients, weight gain per se cannot explain the poor glycemic response to combination or insulin th erapy, but it may induce a disproportionately large increase in insuli n requirements because of greater insulin resistance in the obese than in the nonobese; 3) in nonobese patients, glycemic control improves e qually during 1 yr with combination therapy with insulin and insulin a lone, but combination therapy with insulin is associated with less wei ght gain than treatment with insulin alone; 4) weight gain appears har mful, as it is associated with increases in blood pressure and low den sity lipoprotein cholesterol.