Longitudinal associations of phospholipid and cholesteryl ester fatty acids with disorders underlying diabetes

Abstract

Context: Specific serum fatty acid (FA) profiles predict the development of incident type 2 diabetes; however, limited longitudinal data exist exploring their role in the progression of insulin sensitivity (IS) and β-cell function. Objective: To examine the longitudinal associations of the FA composition of serum phospholipid (PL) and cholesteryl ester (CE) fractions with IS and β-cell function over 6 years. Design: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort is a longitudinal observational study, with clinic visits occurring every 3 years. Three visits have been completed, totaling 6 years of follow-up. Setting: Individuals (n=477) at risk for diabetes recruited from the general population in London and Toronto, Canada. Main Outcome Measures: Values from an oral glucose tolerance test were used to compute 1/HOMA-IR and the Matsuda index for IS, the insulinogenic index over HOMA-IR, and the insulin secretion-sensitivity index-2 for-cell function. Thin-layer chromatograph and gas chromatograph quantified FA. Generalized estimating equations were used for the analysis. Results: IS and β-cell function declined by 8.3-19.4% over 6 years. In fully adjusted generalized estimating equation models, PL cis-vaccenate (18:1n-7) was positively associated with all outcomes, whereas β-linolenate (GLA; 18:3n-6) and stearate (18:0) were negatively associated with IS. Tests for time interactions revealed that PL eicosadienoate (20:2n-6) and palmitate (16:0) and CE dihomo-β-linolenate (20:3n-6), GLA, and palmitate had stronger associations with the outcomes after longer follow-up. Conclusions: In a Canadian population at risk for diabetes, we found that higher PL stearate and GLA and lower cis-vaccenic acid predicted consistently lower IS and β-cell function over 6 years.