biostudies-literatureFretts AMNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNIA NIH HHSNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNational Institute on Aging100119https://www.ebi.ac.uk/biostudies/studies/S-EPMC8517199biostudies-literatureUnknown62Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences the biological activity of those sphingolipids. However, it is unknown whether associations of sphingolipids with diabetes may differ by the identity of bound lipid species. Here, we investigated associations of 15 ceramide (Cer) and SM species (i.e., all sphingolipids, measured with coefficient of variation less than 20%) with incident type 2 diabetes in the Cardiovascular Health Study (n = 3,645), a large cohort study of cardiovascular disease among elderly adults who were followed from 1989 to 2015. Diabetes incidence was defined as fasting glucose ≥126 mg/dl or nonfasting glucose ≥200 mg/dl; reported use of insulin or oral hypoglycemic medication; or documentation of diabetes diagnosis through the Centers for Medicare and Medicaid Services records. Associations of each sphingolipid with incident diabetes were assessed using a Cox proportional hazards regression model. We found that higher circulating levels of Cer with acylated palmitic acid (Cer-16), stearic acid containing Cer (Cer-18), arachidic acid containing Cer (Cer-20), and behenic acid containing Cer (Cer-22) were each associated with a higher risk of diabetes. The hazard ratios for incident diabetes per 1 SD higher log levels of each Cer species were as follows: 1.21 (95% CI: 1.09-1.34) for Cer-16, 1.23 (95% CI: 1.10-1.37) for Cer-18, 1.14 (95% CI: 1.02-1.26) for Cer-20, and 1.18 (95% CI: 1.06-1.32) for Cer-22. In conclusion, higher levels of Cer-16, Cer-18, Cer-20, and Cer-22 were associated with a higher risk of diabetes.Journal of lipid researchPlasma ceramides containing saturated fatty acids are associated with risk of type 2 diabetes.PMC8517199P30-DK035816R01AG023629R01 HL12857575N92021D00006U01 HL080295HHSN268200800007CN01HC55222N01HC85081U01HL080295N01HC85082HHSN268201800001CR01 AG023629N01HC85080HHSN268201200036CN01HC85086N01HC85083N01HC85079R01 DK103657P30 DK035816U01HL130114U01 HL130114Howard BVSitlani CMHoofnagle ANUmans JSiscovick DSLemaitre RNFretts AMMcKnight BDjousse LSotoodehnia NJensen PNKing IBfalsePlasma ceramides containing saturated fatty acids are associated with risk of type 2 diabetes.Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences the biological activity of those sphingolipids. However, it is unknown whether associations of sphingolipids with diabetes may differ by the identity of bound lipid species. Here, we investigated associations of 15 ceramide (Cer) and SM species (i.e., all sphingolipids, measured with coefficient of variation less than 20%) with incident type 2 diabetes in the Cardiovascular Health Study (n = 3,645), a large cohort study of cardiovascular disease among elderly adults who were followed from 1989 to 2015. Diabetes incidence was defined as fasting glucose ≥126 mg/dl or nonfasting glucose ≥200 mg/dl; reported use of insulin or oral hypoglycemic medication; or documentation of diabetes diagnosis through the Centers for Medicare and Medicaid Services records. Associations of each sphingolipid with incident diabetes were assessed using a Cox proportional hazards regression model. We found that higher circulating levels of Cer with acylated palmitic acid (Cer-16), stearic acid containing Cer (Cer-18), arachidic acid containing Cer (Cer-20), and behenic acid containing Cer (Cer-22) were each associated with a higher risk of diabetes. The hazard ratios for incident diabetes per 1 SD higher log levels of each Cer species were as follows: 1.21 (95% CI: 1.09-1.34) for Cer-16, 1.23 (95% CI: 1.10-1.37) for Cer-18, 1.14 (95% CI: 1.02-1.26) for Cer-20, and 1.18 (95% CI: 1.06-1.32) for Cer-22. In conclusion, higher levels of Cer-16, Cer-18, Cer-20, and Cer-22 were associated with a higher risk of diabetes.2021-01-01T00:00:00Z20212024-11-12T04:33:11.254Z2024-11-12T04:33:11.254ZS-EPMC85171993455537110.1016/j.jlr.2021.100119