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Impact of exercise training on insulin sensitivity, physical fitness, and muscle oxidative capacity in first-degree relatives of type 2 diabetic patients

¹Department of Endocrinology and Diabetes M, Aarhus University Hospital, Aarhus Sygehus, and Department of Clinical Pharmacology, University of Aarhus, Aarhus; ²Copenhagen Muscle Research Center, Rigshospitalet, Copenhagen, Denmark; and ³Division of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota

Submitted 11 January 2005 ; accepted in final form 12 December 2005

First-degree relatives of type 2 diabetic patients (offspring) are often characterized by insulin resistance and reduced physical fitness (O_{2 max}). We determined the response of healthy first-degree relatives to a standardized 10-wk exercise program compared with an age-, sex-, and body mass index-matched control group. Improvements in O_{2 max} (14.1 ± 11.3 and 16.1 ± 14.2%; both P < 0.001) and insulin sensitivity (0.6 ± 1.4 and 1.0 ± 2.1 mg·kg^–1·min^–1; both P < 0.05) were comparable in offspring and control subjects. However, O_{2 max} and insulin sensitivity in offspring were not related at baseline as in the controls (r = 0.009, P = 0.96 vs. r = 0.67, P = 0.002). Likewise, in offspring, exercise-induced changes in O_{2 max} did not correlate with changes in insulin sensitivity as opposed to controls (r = 0.06, P = 0.76 vs. r = 0.57, P = 0.01). Skeletal muscle oxidative capacity tended to be lower in offspring at baseline but improved equally in both offspring and controls in response to exercise training (citrate synthase enzyme activity 26 vs. 20%, and cyclooxygenase enzyme activity 25 vs. 23%. Skeletal muscle fiber morphology and capillary density were comparable between groups at baseline and did not change significantly with exercise training. In conclusion, this study shows that first-degree relatives of type 2 diabetic patients respond normally to endurance exercise in terms of changes in O_{2 max} and insulin sensitivity. However, the lack of a correlation between the O_{2 max} and insulin sensitivity in the first-degree relatives of type 2 diabetic patients indicates that skeletal muscle adaptations are dissociated from the improvement in O_{2 max}. This could indicate that, in first-degree relatives, improvement of insulin sensitivity is dissociated from muscle mitochondrial functions.

insulin resistance; exercise; skeletal muscle; oxidative capacity

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