This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is one of the most serious health problems in the US. Over 45% of adult Americans are obese and of these, between 3 and 7 million are morbidly obese. This condition substantially raises the risk of morbidity from hypertension, type II diabetes mellitus, coronary artery disease, gallbladder disease and osteoarthritis. The gravest consequence of severe obesity is type II diabetes mellitus. The etiology of the relationship between obesity and diabetes, a relationship recognized for centuries, is not clear, but appears to be due to insulin resistance and eventual failure of the pancreas to meet the ever-higher demand for insulin production. Bariatric surgery is a well-proven and effective therapy for morbid obesity. When morbid obesity is treated successfully with surgery, the diabetes usually improves along with the amelioration of a number of other comorbidities associated with obesity. The gastric bypass (GB), a form of bariatric surgery, is remarkably effective in controlling type II diabetes mellitus as shown by the rapid (within days) correction of the abnormal concentrations of fasting glucose, fasting hyperinsulinemia, glycosylated hemoglobin, and oral glucose tolerance test. Functionally, the operation limits food intake with the creation of a small reservoir, delays emptying with the small gastrojejunostomy, bypasses the endocrine mechanisms of the foregut, and frequently produces dumping when high-carbohydrate fluids flow directly into the jejunum. Weight loss has generally been cited as explanation for GB providing such excellent and durable control of type II diabetes. However, it has been shown that the return to euglycemia and normal insulin levels occur within days after surgery, before any significant weight loss has occurred. This normalization is independent of either weight loss or regaining of weight provided the bypass of the stomach is maintained as the major physiologic alteration. Furthermore, it has been noted that many patients are still obese after the operation, e.g., a 400-lb woman may loose 150-lb with a successful procedure, but at 250-lb is still obese; her diabetes is nevertheless controlled. The mechanism for this improvement is not clear, but may be explained in part by the bypass of neuroendocrine mechanisms inherent to the antrum and duodenum. In support of this theory is the finding that vertical banded gastroplasty, a form of bariatric surgery in which the proximal small intestine is not bypassed, produces lesser reductions of hyperglycemia and hyperinsulinemia.
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