Endothelial function and biochemical vascular markers in first-degree relatives of type 2 diabetic patients: the effect of exercise training

Endothelial dysfunction (ED) is associated with the presence of atherosclerosis. However, ED is also considered a sign of the early vascular changes preceding atherosclerosis. By measuring flow-mediated vasodilation (FMD) and circulating markers of endothelial function we sought to explore whether impaired endothelial function is already present in healthy subjects at increased risk of developing type 2 diabetes mellitus. Furthermore, we aimed to assess the impact of short-term lifestyle intervention (10 weeks endurance exercise) on the potentially primary defects of endothelial function. Twenty-nine healthy but insulin-resistant first-degree relatives of patients diagnosed with type 2 diabetes mellitus (33 ± 5 years; body mass index, 26.3 ± 1.6 kg/m2) were compared with 19 control subjects without a family history of diabetes mellitus (31 ± 5 years; body mass index, 25.8 ± 3.0 kg/m2). At baseline the von Willebrand factor was significantly increased in the relatives (P < .05). Furthermore, mannose-binding lectin (P = .06), soluble intercellular adhesion molecule 1 (P = .08), and osteoprotegerin (P = .08) tended to be increased in relatives. The following markers of endothelial function were comparable at baseline: FMD, C-reactive protein, plasminogen activator inhibitor 1, and soluble vascular cell adhesion molecule 1. Exercise training resulted in a decrease in mannose-binding lectin (P = .02) and osteoprotegerin (P < .01) in relatives only, whereas other biochemical markers were unaffected in both groups. Moreover, the relatively high-intensity exercise training tended weakly to reduce FMD in the relatives (P = .15). In conclusion, healthy subjects predisposed for type 2 diabetes mellitus show only minor signs of endothelial dysfunction. Under these almost normal vascular conditions, exercise training has little effect on endothelial function.