| Summary: | 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.
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