Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls

C. Ekman, T. Elgzyri, K. Ström, P. Almgren, H. Parikh, Marloes Dekker Nitert, T. Rönn, Fiona Manderson Koivula, C. Ling, Å. B. Tornberg, P. Wollmer, K. F. Eriksson, L. Groop, O. Hansson

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility when compared to subjects without heredity for diabetes (FH-). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared to FH-. 16 FH+ and 19 FH- insulin sensitive men similar in age, VO2peak and BMI completed an exercise intervention with heart rate monitoration during exercise for 7 months. Before and after the exercise intervention, the participants underwent a physical examination, tests for glucose tolerance and exercise capacity and muscle biopsies were taken for expression analysis. The participants attended on average 39 training sessions during the intervention and spent 18.8 MJ on exercise. VO2peak/kg increased by 14% and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH+ group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH- groups separately. Exercise volume had a significant effect on VO2peak, weight and waist circumference in the FH- group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation and cellular respiration increased more in the FH-, compared to the FH+ group. This suggests that healthy, insulin sensitive FH+ and FH- participants with similar age, VO2peak and BMI may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.