Jain_Kantz_diet
tThe additional therapeutic effects of regular exercise during a dietary weight loss program in people with obesity and prediabetes are unclear. Here, we show whole-body (primarily muscle) insulin sensitivity (primary outcome) was two-fold greater (P=0.006) after 10% weight loss induced by calorie-restriction plus exercise training (Diet+EX; n=8, 4 women) than 10% weight loss induced by calorie restriction alone (Diet-ONLY; n=8, 6 women) in participants participating in two concurrent studies. The greater improvement in insulin sensitivity was accompanied by increased muscle expression of genes involved in mitochondrial biogenesis, energy metabolism and angiogenesis (secondary outcomes) in the Diet+EX group. There were no differences between groups in plasma branched-chain amino acids or markers of inflammation, and both interventions caused similar changes in the gut microbiome. Few adverse events were reported. These results demonstrate that regular exercise during a diet-induced weight loss program has profound additional metabolic benefits in people with obesity and prediabetes.