Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
Surg Endosc. 2021 Jun;35(6):3104-3114. doi: 10.1007/s00464-020-07741-y. Epub 2020 Jun 30.
Metabolic surgery has beneficial metabolic effects, including remission of type 2 diabetes. We hypothesized that duodenojejunal bypass (DJB) surgery can protect against development of type 1 diabetes (T1D) by enhancing regulation of cellular and molecular pathways that control glucose homeostasis.
BBDP/Wor rats, which are prone to develop spontaneous autoimmune T1D, underwent loop DJB (n = 15) or sham (n = 15) surgery at a median age of 41 days, before development of diabetes. At T1D diagnosis, a subcutaneous insulin pellet was implanted, oral glucose tolerance test was performed 21 days later, and tissues were collected 25 days after onset of T1D. Pancreas and liver tissues were assessed by histology and RT-qPCR. Fecal microbiota composition was analyzed by 16S V4 sequencing.
Postoperatively, DJB rats weighed less than sham rats (287.8 vs 329.9 g, P = 0.04). In both groups, 14 of 15 rats developed T1D, at similar age of onset (87 days in DJB vs 81 days in sham, P = 0.17). There was no difference in oral glucose tolerance, fasting and stimulated plasma insulin and c-peptide levels, and immunohistochemical analysis of insulin-positive cells in the pancreas. DJB rats needed 1.3 ± 0.4 insulin implants vs 1.9 ± 0.5 in sham rats (P = 0.002). Fasting and glucose stimulated glucagon-like peptide 1 (GLP-1) secretion was elevated after DJB surgery. DJB rats had reduced markers of metabolic stress in liver. After DJB, the fecal microbiome changed significantly, including increases in Akkermansia and Ruminococcus, while the changes were minimal in sham rats.
DJB does not protect against autoimmune T1D in BBDP/Wor rats, but reduces the need for exogenous insulin and facilitates other metabolic benefits including weight loss, increased GLP-1 secretion, reduced hepatic stress, and altered gut microbiome.
代谢手术具有有益的代谢效应，包括 2 型糖尿病的缓解。我们假设十二指肠空肠旁路（DJB）手术可以通过增强控制葡萄糖稳态的细胞和分子途径的调节来预防 1 型糖尿病（T1D）的发展。
BBDP/Wor 大鼠易发生自发性自身免疫性 T1D，在糖尿病发生前，于 41 天大时接受环式 DJB（n=15）或假手术（n=15）。在 T1D 诊断时，植入皮下胰岛素丸，21 天后进行口服葡萄糖耐量试验，T1D 发病后 25 天收集组织。通过组织学和 RT-qPCR 评估胰腺和肝脏组织。通过 16S V4 测序分析粪便微生物组成。
手术后，DJB 大鼠的体重低于假手术组（287.8 克比 329.9 克，P=0.04）。在两组中，15 只大鼠中有 14 只发展为 T1D，发病年龄相似（DJB 组为 87 天，假手术组为 81 天，P=0.17）。口服葡萄糖耐量、空腹和刺激后血浆胰岛素和 C 肽水平以及胰腺中胰岛素阳性细胞的免疫组织化学分析均无差异。DJB 大鼠需要 1.3±0.4 个胰岛素植入物，而假手术组需要 1.9±0.5 个（P=0.002）。DJB 手术后空腹和葡萄糖刺激胰高血糖素样肽 1（GLP-1）分泌增加。DJB 大鼠肝脏的代谢应激标志物减少。DJB 后，粪便微生物组发生显著变化，包括阿克曼菌和真杆菌增加，而假手术组的变化最小。
DJB 不能预防 BBDP/Wor 大鼠的自身免疫性 T1D，但减少了对外源胰岛素的需求，并促进了其他代谢益处，包括体重减轻、GLP-1 分泌增加、肝应激减少和肠道微生物组改变。
