Metabolic and hormonal changes in diabetic patients after bariatric surgery

Abstract

Background: The prevalence of obesity inducing type 2 diabetes is increasing worldwide. Bariatric surgery is gaining acceptance as a weight loss surgical intervention for obesity and associated comorbidities .Type 2 diabetes remission has been shown to occur after surgical intervention, and before significant weight loss has taken place. Therefore, researchers are interested in investigating the underlying mechanisms for diabetes remission. Moreover, the impact of surgery induced weight loss on body composition parameters has been an area of interest. Compared to non-surgical interventions, weight loss after bariatric surgery appears to be better maintained. This result may to some degree be because resting energy expenditure per unit fat-free mass is raised following the surgery. It has been suggested that the gut plays an important role and focus has been directed at the gut hormones, such as the incretin, to understand the beneficial effects of bariatric surgery. The objective of this study was to examine the effects of bariatric surgery on insulin, glucose homeostasis and gut hormones and on body composition and resting energy expenditure. Method: Twenty participants who were enrolled in a double-blind, randomised trial comparing laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy were studied. Entry to this trial required that patients were obese and diagnosed with type 2 diabetes. The study will not be unblinded until five years of follow-up has been completed. Body composition and bone mineral density, measured using dual-energy X-ray absorptiometry (DEXA), and glucose tolerance, measured with an oral glucose tolerance test (OGTT), were evaluated immediately preoperatively and 12 months following surgery. Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP), pancreatic polypeptide YY, leptin and ghrelin were performed during the OGTT at the preoperative and postoperative times. Area under the curve (AUC) was examined at 30 and 60 minutes. Lipid profiles were measured in the fasting state pre- and postoperatively. Resting energy expenditure was measured by indirect calorimetry in the fasted state before the OGTT. Result: Of the 20 patients, 6 did not achieve diabetes remission at one year after bariatric surgery. At follow up the study showed reduction in the body weight by 29.1 ± 2.8 kg, body mass index by 10.1 ± 2.8 kg/m2 and total body fat by 23.7±2.7 kg. The weight loss was composed of 79 ± 2% fat. The visceral and subcutaneous fat in the abdominal region, as assessed by DEXA, are also decreased by similar amounts. In addition to the significant improvement in glucose control (HbA1c: 7.9±0.2% vs 5.8±0.2%, P˂0.0001), HOMA-IR reduced significantly (P=0.0002). In addition there was a significant increase in the insulin area under the curve (AUC30, P=0.001, AUC60, P=0.005).There was also marked increases in the postprandial GLP-1 (AUC30 and AUC60, P˂0.0001), GIP (AUC30, P=0.005), Cpeptide (AUC30, P=0.0004, AUC60 P=0.005), and PYY (AUC30 and AUC60, P˂0.0001).The high density lipoprotein increased from 1.13±0.06 to 1.65±1.27 mmol/L (P=0.0001). The total body, femoral neck and spine bone mineral density reduced by 0.038±0.010, 0.059±0.007, and 0.039 ±0.012 gm/cm2. All these changes were statistically significant. Resting energy expenditure per unit fat free mass declined from 28.4±0.8 kcal/kg/d to 26.3± 0.7 kcal/kg/d (P=0.0003). Conclusion: The improvement in insulin response and restoration of incretin hormone and glucose responses at one year after surgery might explain the reversal of type 2 diabetes after bariatric surgery. The reduction in resting energy expenditure adjusted for fat-free mass may, however, predispose these patients to weight regain.