Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT 84112, USA; Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.
Med. 2022 Jul 8;3(7):452-467.e4. doi: 10.1016/j.medj.2022.05.011. Epub 2022 Jun 15.
Obesity is a prevalent health threat and risk factor for type 2 diabetes. In this study, we evaluate the relationship between ceramides, which inhibit insulin secretion and sensitivity, and markers of glucose homeostasis and diabetes remission or recursion in patients who have undergone a Roux-en-Y gastric bypass (RYGB).
The Utah Obesity Study is a prospective cohort study, with targeted ceramide and dihydroceramide measurements performed on banked serum samples. The Utah Obesity Study consists of 1,156 participants in three groups: a RYGB surgery group, a non-surgery group denied insurance coverage, and severely obese population controls. Clinical examinations and ceramide assessments were performed at baseline and 2 and 12 years after RYGB surgery.
Surgery patients (84% female, 42.2 ± 10.6 years of age at baseline) displayed lower levels of several serum dihydroceramides and ceramides at 2 and 12 years after RYGB. By contrast, neither the control group (77% female, 48.7± 6.4 years of age at baseline) nor the non-surgery group (95% female, 43.0± 11.4 years of age at baseline) experienced significant decreases in any species. Using a linear mixed effect model, we found that multiple dihydroceramides and ceramides positively associated with the glycemic control measures HOMA-IR and HbA1c. In surgery group participants with prevalent diabetes, ceramides inversely predict diabetes remission, independent of changes in weight.
Ceramide decreases may explain the insulin sensitization and diabetes resolution observed in most RYGB surgery patients.
Funded by the National Institutes of health (NIH), The Juvenile Diabetes Research Foundation, and the American Heart Association.
肥胖是一种普遍存在的健康威胁，也是 2 型糖尿病的风险因素。在这项研究中，我们评估了神经酰胺（一种抑制胰岛素分泌和敏感性的物质）与葡萄糖稳态标志物之间的关系，以及在接受 Roux-en-Y 胃旁路手术（RYGB）的患者中糖尿病缓解或复发的关系。
犹他州肥胖研究是一项前瞻性队列研究，对银行存储的血清样本进行靶向神经酰胺和二氢神经酰胺测量。犹他州肥胖研究包括三组参与者：一组接受 RYGB 手术，一组因保险原因未接受手术，以及一组严重肥胖的人群对照组。在基线和 RYGB 手术后 2 年和 12 年进行临床检查和神经酰胺评估。
手术患者（84%为女性，基线时年龄为 42.2±10.6 岁）在 RYGB 手术后 2 年和 12 年均显示出几种血清二氢神经酰胺和神经酰胺水平降低。相比之下，对照组（77%为女性，基线时年龄为 48.7±6.4 岁）和非手术组（95%为女性，基线时年龄为 43.0±11.4 岁）均未出现任何物种的显著减少。使用线性混合效应模型，我们发现多种二氢神经酰胺和神经酰胺与血糖控制指标 HOMA-IR 和 HbA1c 呈正相关。在有糖尿病的手术组参与者中，神经酰胺与糖尿病缓解呈负相关，与体重变化无关。
神经酰胺的减少可能解释了大多数 RYGB 手术患者中观察到的胰岛素敏感性增强和糖尿病缓解。
美国国立卫生研究院（NIH）、青少年糖尿病研究基金会和美国心脏协会资助。
