Insulin sensitivity improvement with exercise training is mediated by body weight loss in subjects with metabolic...

To determine whether exercise training improves insulin actions through concomitant body weight loss (BWL).

Subjects (aged 55±8 years) with metabolic syndrome (MetS), prediabetes (fasting blood glucose: 111±2mg·dL^-1, HbA1c: 5.85±0.05%) and abdominal obesity (waist circumference: 104±7.9cm) were randomly allocated to either a group performing aerobic interval training (EXER; n=76) or a sedentary group receiving lifestyle counselling (CONT; n=20) for 16 weeks.

At baseline, insulin sensitivity (according to HOMA2 and intravenous glucose tolerance test; CS_I), body composition and VO_2max were similar between the groups. After the intervention, both groups had similar BWL (1-2%), but only the EXER group showed decreased [mean (95% CI)] trunk fat mass [from 18.2 (17.4-18.9) to 17.3kg (16.6-17.9); P<0.001] and HOMA2 scores [from 1.6 (1.5-1.7) to 1.4 (1.3-1.5); P=0.001], and increased VO_2max [from 2.07 (1.92-2.21) to 2.28 (2.11-2.45) LO₂·min^-1; P<0.001]. However, CS_I did not improve in any group. Within-group subdivision by BWL (≤0%, 0-3%, ≥3%) revealed higher CS_I in those with BWL≥3% in both groups. Trunk fat mass reductions were closely associated with CS_I and HOMA-IR improvement (r=-0.452-0.349; P<0.001).

In obese MetS subjects with prediabetes, 3% BWL is required for consistent improvement in insulin sensitivity. Thus, exercise-training programmes should be combined with calorie restriction to achieve BWL levels that prevent the development of diabetes.