Following Roux-en-Y gastric bypass surgery, serum ceramides demarcate patients that will fail to achieve normoglycemia and diabetes remission

• Published in: Med (New York, N.Y. : Online) Vol. 3; no. 7; pp. 452 - 467.e4
• Main Authors: Poss, Annelise M, Krick, Benjamin, Maschek, J Alan, Haaland, Benjamin, Cox, James E, Karra, Prasoona, Ibele, Anna R, Hunt, Steven C, Adams, Ted D, Holland, William L, Playdon, Mary C, Summers, Scott A
• Format: Journal Article
• Language: English
• Published: United States 08.07.2022
• Subjects: Ceramides; Diabetes Mellitus, Type 2 - complications; Female; Gastric Bypass; Humans; Male; Obesity - complications; Prospective Studies; United States; Weight Loss; United States; lipids; bariatric surgery; sphingolipids; diabetes remission; Translation to patients; diabetes; ceramides
• ISSN: 2666-6340; 2666-6359; 2666-6340
• DOI: 10.1016/j.medj.2022.05.011

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.