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.
OBJECTIVE
To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes, insulin secretion and insulin sensitivity over several years.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. markust@student.uef.fi.
Markus J
MJ
Takkunen
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.|Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland.
Ursula S
US
Schwab
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.
Vanessa D F
VD
de Mello
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.|Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.|Folkhälsan Research Centre, Helsingfors Universitet, Helsinki, Finland.|Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
Johan G
JG
Eriksson
Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
Jaana
J
Lindström
Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.|Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.|Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ), Madrid, Spain.|Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
Jaakko
J
Tuomilehto
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.|Research Unit, Kuopio University Hospital, Kuopio, Finland.
Matti I J
MI
Uusitupa
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage / Q000032:analysis; D004043:Dietary Fiber / Q000008:administration & dosage / Q000032:analysis; D002149:Energy Intake; D015444:Exercise; D044943:Fatty Acid Desaturases / Q000097:blood / Q000235:genetics; D005227:Fatty Acids / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000097:blood; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013230:Stearoyl-CoA Desaturase / Q000097:blood
D015415:Biomarkers; D000090943:Delta-5 Fatty Acid Desaturase; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004043:Dietary Fiber; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D007328:Insulin; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C000716847:FADS1 protein, human
Biomarkers; Cohort study; Fatty acid desaturases; Omega-3 fatty acids; Serum fatty acids; Type 2 diabetes