PHILADELPHIA – A sub-study of the original STAMPEDE trial found that although both obesity treatment surgical techniques had similar weight loss outcomes, a greater proportion of patients with greater abdominal fat loss achieved relief from diabetes symptoms. Sangeeta R. Kashyap, M.D., of the Cleveland Clinic, and colleagues reported that patients with moderately obese uncontrolled diabetes who underwent gastric bypass with biliopancreatic anastomosis or tubular gastrostomy had similar weight loss outcomes (27.4 and 28.2 kg/m2, respectively), as measured by body mass index at 2 years after surgery. This means that the change in BMI does not explain why patients who underwent bypass had 33.3% remission of diabetic symptoms compared with 10.5% for the other procedure, Kashyap said in a recent study presented at the American Diabetes Association meeting. The answer, she said, is the amount of abdominal fat loss in the patients. The difference was statistically significant in the amount of abdominal fat reduction in patients who underwent bypass (15.9 percent) compared with the reduction in patients who underwent tubular gastrectomy (10.1 percent). The 1-year results of this original STAMPEDE trial were presented at the 2012 American College of Cardiology meeting; the results showed that the combination of either of the two procedures involved in the trial with the best drug therapy was better than the best drug therapy alone in controlling type II diabetes. At 12 months into the study, a higher percentage of patients in the surgery group had hemoglobin A1c levels at or below 6 percent compared to the drug therapy group. In this sub-study, the researchers analyzed data from 20 patients. Previously, these 20 patients were randomly assigned to groups (10% stopped the trial halfway through). The average body mass index (BMI) of these patients, who were in their 40s, was 36. The average duration of their diabetes was 7 to 10 years, Kashyap explained. Many of them were taking three or more medications and had metabolic syndrome, and about half had started taking insulin. The researchers determined glucose metabolism capacity with a mixed dietary glucose tolerance test. Before starting the trial, the initial glucose level in the surgical group was 150 mg/dL and 250 mg/dL at the end; however, at two years into the trial, the bypass patients’ glucose levels were at 85 to 90 mg/dL and had reached normal levels. Kashyap told MedPage Today, “It was remarkable; it brought no less a shock than seeing brain-dead patients reappear with normal ECGs. For endocrinologists, it’s very surprising.” Even though the tubular gastrostomy patients had similar weight loss results to the bypass patients, the glycemic changes were worse (150 mg/dL). Interestingly, both surgical groups had a positive effect on insulin secretion, although insulin sensitivity in the bypass group increased to 3.5 times its original value, changing from 1.5 mg/min at the beginning of the experiment to 5.2 mg/min at 2 years (P<0.001, indicating a statistically significant change in insulin sensitivity). The effect of improved insulin sensitivity in patients in the tubular stomach group was not very significant (from 3.9 to 5.7 mg/min, P=0.05). Islet β-cell function was measured by oral glucose disposition index. Beta cell function increased 5.3-fold in the bypass group (P<0.001, indicating a statistically significant increase); in the tubular gastric group, it increased only 2-fold, similar to the effect of the drug treatment group. The researchers also found that patients in the bypass group had a better response to glucagon-like peptide-1 (GLP-1) and gastroinhibitory polypeptide (GIP). These two hormones are responsible for the secretion of insulin after diet. The latter two findings are particularly important because insulin secretion leads to a return to normal blood sugar levels, Kashyap said. "It's more than just intestinal hypoglycemia, though, because we've seen that the percentage of diabetes symptoms remitted in the tubular stomach group is not so high. We think that body composition is the key. The fact that the removal of fat from the trunk area led to increased insulin sensitivity and increased insulin secretion; this is all restoring the patient to normal glucose metabolism one step at a time."