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Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults.Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency.Improved insulin sensitivity was significantly related to exercise dose in a graded dose–response relationship. No evidence of threshold or maximal dose–response effect was observed. Age and gender did not influence this dose–response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not.This study identifies a graded dose–response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations.