Previti Elena, Salinari Serenella, Bertuzzi Alessandro, Capristo Esmeralda, Bornstein Stephan, Mingrone Geltrude
Department of Computer, Control, and Management Engineering "Antonio Ruberti," Sapienza University of Rome, Rome, Italy.
Institute for System Analysis and Computer Science "Antonio Ruberti," Consiglio Nazionale delle Ricerche, Rome, Italy.
Am J Physiol Endocrinol Metab. 2017 Nov 1;313(5):E622-E630. doi: 10.1152/ajpendo.00042.2017. Epub 2017 Jul 11.
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.
本研究的目的是探讨非酯化脂肪酸（NEFA）和肠促胰岛素在导致脂肪泻的吸收不良代谢手术后对胰岛素抵抗和糖尿病改善的作用。事实上，输注NEFA会降低葡萄糖刺激的胰岛素分泌，而高脂饮食可预测糖尿病的发生。对6名健康对照者、11名肥胖受试者和10名2型糖尿病（T2D）受试者在胆胰分流术（BPD）前及术后1个月进行了研究。获取了24小时血浆葡萄糖、NEFA、胰岛素、C肽、胰高血糖素样肽-1（GLP-1）和胃抑制多肽（GIP）的时间进程，并通过格兰杰因果关系和图形分析进行了分析。通过口服葡萄糖最小模型计算胰岛素敏感性和分泌。在代谢手术前，NEFA水平对肥胖和T2D受试者的其他变量影响最强。手术后，GLP-1和C肽水平在肥胖和T2D受试者中控制着该系统。BPD后24小时GIP水平显著降低。最后，不仅GLP-1水平发挥了核心作用，胰岛素和C肽水平在健康对照者的网络中也具有相当的相关性。BPD后，肥胖和T2D个体的胰岛素敏感性均完全恢复正常。24小时循环GLP-1水平升高对接受吸收不良减肥手术的肥胖和T2D受试者的葡萄糖稳态产生了积极影响。在后者中，血浆GIP水平的降低也有助于改善糖代谢。降低GIP并提高GLP-1血浆水平的药物联合应用可能有助于更好地控制T2D患者的血糖。格兰杰因果关系和图形分析的应用为代谢手术的病理生理学提供了新的见解。
