Intensive insulin therapy is frequently complicated by excessive weight gain. The purpose of this study was to determine the cause and composition of this weight gain. Therefore, changes in body composition, energy expenditure, glycosuria, 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 studied on conventional insulin therapy and after 2 mo of intensive insulin therapy while maintaining constant caloric intake and were compared with a group of 6 matched nondiabetic volunteers. Body composition was determined by underwater weighing. Energy expenditure was measured during 24-h stays in a whole-room calorimeter. Whole-body turnover rates of glucose, glycerol, palmitate, and leucine were determined by isotope dilution methods. Intensive insulin therapy lowered the mean daily blood 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 glycosuria (428 ± 116 to 39 ± 22 mmol/day, P < 0.05). Body weight increased 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 energy expenditure decreased 5% (118 ± 32 kcal/day) with intensive insulin therapy (P < 0.05). The rates of glucose, glycerol, free fatty acid, and leucine turnover, triglyceride/free fatty acid cycling, and nonoxidative glucose and protein disposal were reduced in the diabetic volunteers during intensive insulin therapy. Thus, intensive insulin therapy causes an increase in body fat as a result of the elimination of glycosuria and reduction in 24-h energy expenditure. The elimination of glycosuria contributed 70% to the positive energy balance during intensive insulin therapy, and the reduction in 24-h energy expenditure contributed the remainder. The reduction in 24-h energy expenditure was the result of the decrease in triglyceride/free fatty acid cycling and nonoxidative glucose and protein metabolism.

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