Annelise M Poss1, Benjamin Krick2, J Alan Maschek3, Benjamin Haaland4, James E Cox5, Prasoona Karra6, Anna R Ibele7, Steven C Hunt8, Ted D Adams9, William L Holland1, Mary C Playdon6, Scott A Summers10. 1. 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. 2. Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA. 3. Department of Biochemistry, University of Utah College of Medicine, Salt Lake City, UT, USA; Metabolomics Core Research Facility, University of Utah, Salt Lake City, UT, USA; Proteomics Core Research Facility, University of Utah, Salt Lake City, UT, USA. 4. Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA; Huntsman Cancer Institute, Salt Lake City, UT, USA. 5. Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA; Department of Biochemistry, University of Utah College of Medicine, Salt Lake City, UT, USA; Metabolomics Core Research Facility, University of Utah, Salt Lake City, UT, USA. 6. 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. 7. Department of Surgery, University of Utah, Salt Lake City, UT, USA. 8. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar. 9. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Intermountain Live Well Center Salt Lake, Intermountain Healthcare, Salt Lake City, UT, USA. 10. 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. Electronic address: scott.a.summers@health.utah.edu.
Abstract
BACKGROUND: 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). METHODS: 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. FINDINGS: 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. CONCLUSIONS: Ceramide decreases may explain the insulin sensitization and diabetes resolution observed in most RYGB surgery patients. FUNDING: Funded by the National Institutes of health (NIH), The Juvenile Diabetes Research Foundation, and the American Heart Association.
BACKGROUND: 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). METHODS: 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. FINDINGS: 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. CONCLUSIONS: Ceramide decreases may explain the insulin sensitization and diabetes resolution observed in most RYGB surgery patients. FUNDING: Funded by the National Institutes of health (NIH), The Juvenile Diabetes Research Foundation, and the American Heart Association.
Authors: Helen M Heneghan; Hazel Huang; Sangeeta R Kashyap; Heather L Gornik; Arthur J McCullough; Philip R Schauer; Stacy A Brethauer; John P Kirwan; Takhar Kasumov Journal: Surg Obes Relat Dis Date: 2011-12-20 Impact factor: 4.734
Authors: Annelise M Poss; J Alan Maschek; James E Cox; Benedikt J Hauner; Paul N Hopkins; Steven C Hunt; William L Holland; Scott A Summers; Mary C Playdon Journal: J Clin Invest Date: 2020-03-02 Impact factor: 14.808
Authors: William L Holland; Joseph T Brozinick; Li-Ping Wang; Eric D Hawkins; Katherine M Sargent; Yanqi Liu; Krishna Narra; Kyle L Hoehn; Trina A Knotts; Angela Siesky; Don H Nelson; Sotirios K Karathanasis; Greg K Fontenot; Morris J Birnbaum; Scott A Summers Journal: Cell Metab Date: 2007-03 Impact factor: 27.287
Authors: Rozenn N Lemaitre; Chaoyu Yu; Andrew Hoofnagle; Nair Hari; Paul N Jensen; Amanda M Fretts; Jason G Umans; Barbara V Howard; Colleen M Sitlani; David S Siscovick; Irena B King; Nona Sotoodehnia; Barbara McKnight Journal: Diabetes Date: 2018-03-27 Impact factor: 9.461
Authors: Amanda M Fretts; Paul N Jensen; Andrew N Hoofnagle; Barbara McKnight; Barbara V Howard; Jason Umans; Colleen M Sitlani; David S Siscovick; Irena B King; Luc Djousse; Nona Sotoodehnia; Rozenn N Lemaitre Journal: J Lipid Res Date: 2021-09-20 Impact factor: 5.922