Suppression of insulin secretion by protein deprivation in obesity.

The effect of low protein diets on insulin levels was studied in 17 obese, nondiabetic hyperinsulinemic subjects. Their mean weight was 271% of ideal weight. Nine patients were fed a weight-maintaining 3700-calorie diet for 14 days; this diet contained 398 g carbohydrate and 170 g protein. The patients were then fed an isocaloric diet containing only 6 g protein and 587 g carbohydrate for 14 more days. Mean basal insulin levels decreased from 50.4 to 34.7 μU/ml. This decrease was accompanied by a significant decrease in mean plasma glucose. In seven patients who were fed the low-protein diet after a 4-day period of total fast, the low-protein diet prevented the recovery of basal insulin levels decreased during fasting. These findings were in contrast to the apparent recovery of basal insulin levels observed when the control rather than the low-protein diet was refed in 4 patients following a fast. The suppression of basal insulin levels by protein deprivation was not correlated with changes in plasma glucose, glucagon, urinary 17-hydroxycorticoids, or body weight. Although urinary 17-hydroxycorticoids and free cortisol decreased significantly on protein-restricted diets, treatment with cortisol did not prevent the effect of protein deprivation on basal insulin and glucose levels. Plasma levels of branched chain amino acids (valine, leucine, and isoleucine) decreased in parallel to insulin levels on the isocaloric low-protein diets. We conclude that protein-restricted diets can decrease basal plasma insulin levels in obesity even in the presence of sufficient calories to maintain weight and high carbohydrate content. Of the factors investigated that may account for this phenomenon, it is unlikely that glucagon, glucose, or cortisol play a direct role. It is possible that protein as well as carbohydrate plays a role in the development of hyperinsulinemia and insulin resistance in obesity.