Aims/hypothesis: We aimed to quantify changes in insulin action and insulin secretion associated with long-term gain, loss, regain, and maintenance of body weight in subjects with normal (NGT) or impaired (IGT) glucose tolerance.
Methods: Insulin action (hyperinsulinaemic clamp) and insulin secretion (intravenous glucose challenge) were measured longitudinally in 209 Pima Indians body weight 94.4 +/- 22.8 kg (means +/- SD) 89 women/120 men, 151 NGT/58 IGT[, who either lost (n = 110) or gained (n = 99) weight (-23% to +29%) over 2.6 +/- 2.0 years. Insulin action and insulin secretion were reassessed on a third occasion in 33 subjects who lost at least 5% body weight over 1.5 +/- 0.8 years and then either regained or maintained weight over the subsequent 1.8 +/- 1.1 years.
Results: There was a linear negative relation between changes in body weight and changes in insulin-stimulated glucose disposal in subjects with normal glucose tolerance (r = -0.51, p < 0.0001) and impaired glucose tolerance (r = -0.54, p < 0.0001). In contrast, changes in the acute insulin response were positively related to weight changes in subjects with normal glucose tolerance (r = +0.26, p < 0.005) but negatively in those with impaired glucose tolerance (r = -0.51, p < 0.0001). Improvements in insulin action after an average of 10% weight loss were lost with weight regain but largely preserved with weight maintenance.
Conclusion/interpretation: Improvements in insulin action are proportional to the amount of weight loss, similar in magnitude to the impairment in insulin action with weight gain, preserved with long-term weight maintenance and similar between subjects with normal and with impaired glucose tolerance. Weight gain could, however, have more detrimental effects in people with impaired glucose tolerance, in whom insulin secretion decreases rather than increases to compensate for the decreased insulin action.