The purpose of this study was to examine the contribution of nonesterified fatty acids (NEFA) and incretin to insulin resistance and diabetes amelioration after malabsorptive metabolic surgery that induces steatorrhea. In fact, NEFA infusion reduces glucose-stimulated insulin secretion, and high-fat diets predict diabetes development. Six healthy controls, 11 obese subjects, and 10 type 2 diabetic (T2D) subjects were studied before and 1 mo after biliopancreatic diversion (BPD). Twenty-four-hour plasma glucose, NEFA, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) time courses were obtained and analyzed by Granger causality and graph analyses. Insulin sensitivity and secretion were computed by the oral glucose minimal model. Before metabolic surgery, NEFA levels had the strongest influence on the other variables in both obese and T2D subjects. After surgery, GLP-1 and C-peptide levels controlled the system in obese and T2D subjects. Twenty-four-hour GIP levels were markedly reduced after BPD. Finally, not only did GLP-1 levels play a central role, but also insulin and C-peptide levels had a comparable relevance in the network of healthy controls. After BPD, insulin sensitivity was completely normalized in both obese and T2D individuals. Increased 24-h GLP-1 circulating levels positively influenced glucose homeostasis in both obese and T2D subjects who underwent a malabsorptive bariatric operation. In the latter, the reduction of plasma GIP levels also contributed to the improvement of glucose metabolism. It is possible that the combination of a pharmaceutical treatment reducing GIP and increasing GLP-1 plasma levels will contribute to better glycemic control in T2D. The application of Granger causality and graph analyses sheds new light on the pathophysiology of metabolic surgery.
Keywords: Granger causality; graph theory; insulin secretion; insulin sensitivity; metabolic surgery.
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