The relationship of in vivo insulin-mediated glucose utilization to the state of physical fitness and the degree of glycemic control was examined in 27 adolescents with insulin-dependent diabetes mellitus (IDDM) compared with 10 nondiabetic adolescent control subjects. In vivo total-body insulin-mediated glucose metabolism was evaluated by the hyperinsulinemic-euglycemic clamp. Physical fitness was assessed by maximal oxygen consumption (Vo2 max) during cycle ergometry. Patients and control subjects had similar levels of Vo2 max (34.9 ± 8.6 vs. 38.6 ± 9.9 ml · kg−1 · min−1, P = 0.3). Patients had lower total-body insulin-mediated glucose metabolism compared with control subjects (33.9 ± 14.3 vs. 63.8 ± 17.2 μmol · kg−1 · min−1, P = 0.0002). Among the patients, females had lower total-body insulin-mediated glucose metabolism compared with males (24.2 ± 2.8 vs. 40.7 ± 3.4 μmol · kg−1 · min−1, P < 0.001); however, this difference disappeared after correcting for sex differences in fitness levels. Insulin-mediated glucose metabolism correlated with Vo2 max in patients and control subjects (r = 0.83, r = 0.81, P < 0.05). The regression of total-body insulin-mediated glucose metabolism on Vo2 max for patients was −2.84 ± 0.255 Vo2 max and for control subjects was 7.12 ± 0.143 Vo2 max, indicating that for similar degrees of physical fitness patients have lower total body insulin-mediated glucose metabolism levels than control subjects. In patients, total-body insulin-mediated glucose metabolism correlated with the degree of glycemic control as assessed by the level of glycosylated hemoglobin (r = −0.63, P < 0.001). In a multiple regression analysis including Vo2 max and glycosylated hemoglobin, the coefficient of determination explaining the variation in total-body insulin-mediated glucose metabolism was 73%. It is concluded that adolescents with IDDM are insulin resistant compared with healthy control subjects, and this resistance is attributable to the state of diabetes control. However, the level of physical fitness explains a major part of interindividual variation in insulin action in both control subjects and adolescents with IDDM.

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