Longitudinal associations of serum fatty acid composition with type 2 diabetes risk and markers of insulin secretion and sensitivity in the Finnish Diabetes Prevention Study
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To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes, insulin secretion and insulin sensitivity over several years.
We conducted a prospective cohort study derived from the randomized Finnish Diabetes Prevention Study. Total serum fatty acid composition was measured using gas chromatography in 407 overweight, middle-aged people with impaired glucose tolerance at baseline (1993–1998) and annually during the intervention period (1994–2000). Longitudinal associations of 20 fatty acids and three desaturase activities (Δ5 (20:4n-6/20:3n-6, D5D), Δ6 (18:3n-6/18:2n-6, D6D), stearoyl-CoA desaturase-1 (16:1n-7/16:0, SCD-1)) with type 2 diabetes incidence, and estimates of insulin sensitivity (Matsuda), secretion (ratio of insulin and glucose concentrations) and β-cell function (disposition index) by an oral glucose tolerance test were analyzed using Cox regression and linear mixed models. We validated estimated D5D and D6D using a known FADS1 gene variant, rs174550.
The baseline proportions of 20:5n-3, 22:5n-3 and 22:6n-3, and D5D were associated with lower incidence of type 2 diabetes during a median follow-up of 11 years (HR per 1SD: 0.72, 0.74, 0.73, 0.78, respectively, P ≤ 0.01). These long-chain omega-3 fatty acids and D5D were associated with higher insulin sensitivity in subsequent years but not with disposition index. Saturated, monounsaturated and trans fatty acids and 18:3n-3, 18:2n-6, SCD-1 and D6D were inconsistently associated with type 2 diabetes or related traits.
Serum long-chain omega-3 fatty acids and D5D predicted lower type 2 diabetes incidence in people at a high risk of diabetes attending to an intervention study; a putative mechanism behind these associations was higher insulin sensitivity.
KeywordsType 2 diabetes Biomarkers Serum fatty acids Fatty acid desaturases Omega-3 fatty acids Cohort study
Alpha-linolenic acid (18:3n-3)
Arachidonic acid (20:4n-6)
Docosahexaenoic acid (22:6n-3)
Docosapentaenoic acid (22:5n-3)
Finnish Diabetes Prevention Study
Delta 5 desaturase
Delta 6 desaturase
Eicosapentaenoic acid (20:5n-3)
Insulin secretion index
Impaired glucose tolerance
Linoleic acid (18:2n-6)
- Matsuda ISI0,30,120
Matsuda insulin sensitivity index
Oral glucose tolerance test
Stearoyl-coenzyme A desaturase-1
We thank TETHYS Bioscience Inc. for carrying out the fatty acid composition measurements. We thank the FUSION researchers Michael Boehnke, Francis Collins, Karen Mohlke and Heather Stringham who contributed to the genetic analyses. The DPS study has been financially supported by the Academy of Finland (128315, 129330, 131593), Ministry of Education, Novo Nordisk Foundation, Yrjö Jahnsson Foundation, Juho Vainio Foundation, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, Unilever, and Competitive Research Funding from Tampere, Kuopio and Oulu University Hospitals.
Conflict of interest
The authors state no conflict of interest.
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