A NEW PARADIGM FOR TYPE-2 DIABETES-MELLITUS - COULD IT BE A DISEASE OF THE FOREGUT

Summ. Background Data We previously reported, in a study of 608 patien ts, that the gastric bypass operation (GB) controls type 2 diabetes me llitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible t o reduce the mortality from diabetes; GB reduced the chance of dying f rom 4.5% per year to 1 % per year. This control of diabetes has been a scribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss w as really the important factor. Methods Fasting plasma insulin, fastin g plasma glucose. minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 mont hs after surgery Versus a control group of six women who did not under go surgery and were similarly weight-stable. The two groups were match ed in age, percentage of fat, body mass index, waist circumference, an d aerobic capacity. Results Even though the two groups of patients wer e closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgica l group demonstrated significantly lower levels of serum leptin, fasti ng plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was signif icantly higher in the surgical group. Finally, self-reported food inta ke was significantly lower in the surgical group. Conclusions Weight l oss is not the reason why GB controls diabetes mellitus. Instead, bypa ssing the foregut and reducing food intake produce the profound long-t erm alterations in glucose metabolism and insulin action. These findin gs suggest that our current paradigms of type 2 diabetes mellitus dese rve review. The critical lesion may lie in abnormal signals from the g ut.