Citation: Diabetes. 2018 Mar 27.Journal: Diabetes.Published: 2018ISSN: 0012-1797.Full author list: Lemaitre RN; Yu C; Hoofnagle A; Hari N; Jensen P; Fretts AM; Umans JG; Howard BV; Sitlani CM; Siscovick DS; King IB; Sotoodehnia N; McKnight B.UI/PMID: 29588286.Subject(s): IN PROCESS -- NOT YET INDEXEDInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.2337/db17-1449 (Click here)Abbreviated citation: Diabetes. 2018 Mar 27.Local Holdings: Available online from MWHC library: 1995 - present (after 3 months), Available in print through MWHC library: 1999 - 2006.Abstract: Experimental studies suggest ceramides may play a role in insulin resistance. However, the relationships of circulating ceramides and related sphingolipids with plasma insulin have been underexplored in humans. We measured 15 ceramide and sphingomyelin species in fasting baseline samples from the Strong Heart Family Study, a prospective cohort of American Indians. We examined sphingolipid associations with both baseline and follow-up measures of plasma insulin, Homeostatic Model Assessment of Insulin Resistance (HOMAIR) and Homeostatic Model Assessment of beta-cell function (HOMAB) after adjustment for risk factors. Among 2086 participants without diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0 (16 carbons, 0 double bond), 18:0, 20:0 or 22:0 were associated with higher plasma insulin and higher HOMAIR at baseline and at follow-up an average of 5.4 years later. For example, a two-fold higher baseline concentration of ceramide-16:0 was associated with 14% higher baseline insulin (p<0.0001). Associations between sphingomyelin species carrying 18:0, 20:0, 22:0 or 24:0 and insulin were modified by BMI (p<0.003): higher levels were associated with lower fasting insulin, HOMAIR and HOMAB among those with normal BMI. Our study suggests lowering circulating ceramides might be a target in pre-diabetes, and targeting circulating sphingomyelins should take into account BMI.Abstract: Copyright (c) 2018 by the American Diabetes Association.