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Published on: June 2, 2023
Longitudinal Associations of Phospholipid and Cholesteryl Ester Fatty Acids With Disorders Underlying Diabetes
Luke W Johnston1, Stewart B Harris1, Ravi Retnakaran1
1Department of Nutritional Sciences (L.W.J., Z.L., R.P.B., A.J.H.), University of Toronto, Toronto, ON M5S 3E2, Canada; Centre for Studies in Family Medicine (S.B.H.), University of Western Ontario, London, ON N6G 2M1, Canada; Division of Endocrinology (R.R., B.Z.), University of Toronto, Toronto, ON M5S 1A8, Canada; Lunenfeld Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Department of Physiology (A.G.), University of Toronto, Toronto, ON M5S 1A8, Canada; and Dalla Lana School of Public Health (A.J.H.), University of Toronto, Toronto, ON M5T 3M7, Canada.
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 β-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 γ-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-γ-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.
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