Improved beta-cell function after standardized weight reduction in severely obese subjects.

Islet function was examined in 13 severely obese women [body mass index 46.4 +/- 5.5 (SD) kg/m(2)] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR(1)), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37-50% after 15 and 25% WR (P <or= 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps (r = 0.74, P < 0.001) and a hyperbolic relation to AIR(1) (r = -0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 +/- 182% after 15% (P = 0.004) and by 489 +/- 276% after 25% WR (P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR(1) x M/I). Thus DI increased by 95 +/- 24% after 15% (P = 0.018) and by 176 +/- 35% after 25% WR (P = 0.011). This improved beta-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved beta-cell function when related to insulin sensitivity.