INTENSIVE INSULIN THERAPY AND WEIGHT-GAIN IN IDDM

Intensive insulin therapy is frequently complicated by excessive weigh t gain. The purpose of this study was to determine the cause and compo sition of this weight gain. Therefore, changes in body composition, en ergy expenditure, glucosuria, and substrate kinetics were evaluated in patients with IDDM who transferred from conventional insulin therapy to intensive insulin therapy. Six adult patients with IDDM were studie d on conventional insulin therapy and after 2 mo of intensive insulin therapy while maintaining constant caloric intake and were compared wi th a group of 6 matched nondiabetic volunteers. Body composition was d etermined by underwater weighing. Energy expenditure was measured duri ng 24-h stays in a whole-room calorimeter. Whole-body turnover rates o f glucose, glucerol, palmitate, and leucine were determined by isotope dilution methods. Intensive insulin therapy lowered the mean daily bl ood glucose concentration and HbA1 (14.8 +/- 1.6 to 7.7 +/- 0.6 mM and 12.9 +/- 0.9 to 9.6 +/- 0.6%, both P < 0.01) and almost eliminated gl ucosuria (428 +/- 116 to 39 +/- 22 mmol/day, P < 0.05). Body weight in creased 2.6 +/- 0.8 kg with intensive insulin therapy (P < 0.05) as a result of an increase in fat mass (2.4 +/- 0.8 kg, P < 0.05). Daily en ergy expenditure decrease 5% (118 +/- 32 kcal/day) with intensive insu lin therapy (P < 0.05). The rates of glucose, glucerol, free fatty aci d, and leucine turnover, triglyceride/free acid cycling, and nonoxidat ive glucose and protein disposal were reduced in the diabetic voluntee rs during intensive insulin therapy. Thus, intensive insulin therapy c auses an increase in body fat as a result of the elimination of glucos uria and reduction in 24-h energy expenditure. The elimination of glyc osuria contributed 70% to the positive energy balance during intensive insulin therapy, and the reduction in 24-h energy expenditure contrib uted the remainder. The reduction in 24-h energy expenditure was the r esult of the decrease in triglyceride/free acid cycling and nonoxidati ve glucose and protein metabolism.