European Journal of Nutrition

, Volume 55, Issue 3, pp 967–979 | Cite as

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

  • Markus J. TakkunenEmail author
  • Ursula S. Schwab
  • Vanessa D. F. de Mello
  • Johan G. Eriksson
  • Jaana Lindström
  • Jaakko Tuomilehto
  • Matti I. J. Uusitupa
  • the DPS Study Group
Original Contribution



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.


Type 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)


Disposition index


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.

Supplementary material

394_2015_911_MOESM1_ESM.pdf (161 kb)
Supplementary material 1 (PDF 160 kb)


  1. 1.
    Tuomilehto J, Lindström J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350. doi: 10.1056/NEJM200105033441801 CrossRefGoogle Scholar
  2. 2.
    Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, Diabetes Prevention Program Research Group (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403. doi: 10.1056/NEJMoa012512 CrossRefGoogle Scholar
  3. 3.
    Ley SH, Hamdy O, Mohan V, Hu FB (2014) Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 383:1999–2007CrossRefGoogle Scholar
  4. 4.
    Rivellese AA, Lilli S (2003) Quality of dietary fatty acids, insulin sensitivity and type 2 diabetes. Biomed Pharmacother 57:84–87CrossRefGoogle Scholar
  5. 5.
    Zhang M, Picard-Deland E, Marette A (2013) Fish and marine omega-3 polyunsaturated fatty acid consumption and incidence of type 2 diabetes: a systematic review and meta-analysis. Int J Endocrinol 2013:501015. doi: 10.1155/2013/501015 Google Scholar
  6. 6.
    Schwab U, Lauritzen L, Tholstrup T, Haldorssoni T, Riserus U, Uusitupa M, Becker W (2014) Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review. Food Nutr Res. doi: 10.3402/fnr.v58.25145 (eCollection 2014)Google Scholar
  7. 7.
    Krachler B, Norberg M, Eriksson JW, Hallmans G, Johansson I, Vessby B, Weinehall L, Lindahl B (2008) Fatty acid profile of the erythrocyte membrane preceding development of type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 18:503–510. doi: 10.1016/j.numecd.2007.04.005 CrossRefGoogle Scholar
  8. 8.
    Fumeron F, Lamri A, Abi Khalil C et al (2011) Dairy consumption and the incidence of hyperglycemia and the metabolic syndrome: results from a French prospective study, Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 34:813–817. doi: 10.2337/dc10-1772 CrossRefGoogle Scholar
  9. 9.
    Sampath H, Ntambi JM (2005) Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 25:317–340. doi: 10.1146/annurev.nutr.25.051804.101917 CrossRefGoogle Scholar
  10. 10.
    Gehrmann W, Elsner M, Lenzen S (2010) Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic beta-cells. Diabetes Obes Metab 12(Suppl 2):149–158. doi: 10.1111/j.1463-1326.2010.01265.x CrossRefGoogle Scholar
  11. 11.
    Hodson L, Skeaff CM, Fielding BA (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res 47:348–380. doi: 10.1016/j.plipres.2008.03.003 CrossRefGoogle Scholar
  12. 12.
    Sampath H, Ntambi JM (2011) The role of stearoyl-CoA desaturase in obesity, insulin resistance, and inflammation. Ann N Y Acad Sci 1243:47–53. doi: 10.1111/j.1749-6632.2011.06303.x CrossRefGoogle Scholar
  13. 13.
    Warensjo E, Ingelsson E, Lundmark P, Lannfelt L, Syvanen AC, Vessby B, Riserus U (2007) Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity. Obesity (Silver Spring) 15:1732–1740CrossRefGoogle Scholar
  14. 14.
    Kröger J, Schulze MB (2012) Recent insights into the relation of Delta5 desaturase and Delta6 desaturase activity to the development of type 2 diabetes. Curr Opin Lipidol 23:4–10. doi: 10.1097/MOL.0b013e32834d2dc5 CrossRefGoogle Scholar
  15. 15.
    Vessby B, Aro A, Skarfors E, Berglund L, Salminen I, Lithell H (1994) The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters. Diabetes 43:1353–1357CrossRefGoogle Scholar
  16. 16.
    Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH, ARIC Study Investigators (2003) Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 78:91–98Google Scholar
  17. 17.
    Kröger J, Zietemann V, Enzenbach C et al (2011) Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European prospective investigation into cancer and nutrition (EPIC)–potsdam study. Am J Clin Nutr 93:127–142. doi: 10.3945/ajcn.110.005447 CrossRefGoogle Scholar
  18. 18.
    Djousse L, Biggs ML, Lemaitre RN et al (2011) Plasma omega-3 fatty acids and incident diabetes in older adults. Am J Clin Nutr 94:527–533. doi: 10.3945/ajcn.111.013334 CrossRefGoogle Scholar
  19. 19.
    Mahendran Y, Agren J, Uusitupa M et al (2014) Association of erythrocyte membrane fatty acids with changes in glycemia and risk of type 2 diabetes. Am J Clin Nutr 99:79–85. doi: 10.3945/ajcn.113.069740 CrossRefGoogle Scholar
  20. 20.
    Virtanen JK, Mursu J, Voutilainen S, Uusitupa M, Tuomainen TP (2014) Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio ischemic heart disease risk factor study. Diabetes Care 37:189–196. doi: 10.2337/dc13-1504 CrossRefGoogle Scholar
  21. 21.
    Eriksson J, Lindström J, Valle T et al (1999) Prevention of Type II diabetes in subjects with impaired glucose tolerance: the diabetes prevention study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme. Diabetologia 42:793–801CrossRefGoogle Scholar
  22. 22.
    Lindström J, Peltonen M, Eriksson JG et al (2013) Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS). Diabetologia 56:284–293. doi: 10.1007/s00125-012-2752-5 CrossRefGoogle Scholar
  23. 23.
    Lindström J, Louheranta A, Mannelin M et al (2003) The Finnish Diabetes Prevention Study (DPS): lifestyle intervention and 3-year results on diet and physical activity. Diabetes Care 26:3230–3236CrossRefGoogle Scholar
  24. 24.
    Voight BF, Kang HM, Ding J et al (2012) The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits. PLoS Genet 8:e1002793. doi: 10.1371/journal.pgen.1002793 CrossRefGoogle Scholar
  25. 25.
    Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509Google Scholar
  26. 26.
    de Mello VD, Lindström J, Eriksson J et al (2012) Insulin secretion and its determinants in the progression of impaired glucose tolerance to type 2 diabetes in impaired glucose-tolerant individuals: the Finnish Diabetes Prevention Study. Diabetes Care 35:211–217. doi: 10.2337/dc11-1272 CrossRefGoogle Scholar
  27. 27.
    Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470CrossRefGoogle Scholar
  28. 28.
    Stancakova A, Javorsky M, Kuulasmaa T, Haffner SM, Kuusisto J, Laakso M (2009) Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6,414 Finnish men. Diabetes 58:1212–1221. doi: 10.2337/db08-1607 CrossRefGoogle Scholar
  29. 29.
    Zhu J, Sun Q, Zong G et al (2013) Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans. J Lipid Res 54:1477–1483. doi: 10.1194/jlr.P027516 CrossRefGoogle Scholar
  30. 30.
    Dupuis J, Langenberg C, Prokopenko I et al (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42:105–116. doi: 10.1038/ng.520 CrossRefGoogle Scholar
  31. 31.
    Wu JH, Micha R, Imamura F et al (2012) Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Br J Nutr 107(Suppl 2):S214–S227. doi: 10.1017/S0007114512001602 CrossRefGoogle Scholar
  32. 32.
    Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M et al (2013) N-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 368:1800–1808. doi: 10.1056/NEJMoa1205409 CrossRefGoogle Scholar
  33. 33.
    ORIGIN Trial Investigators, Bosch J, Gerstein HC et al (2012) N-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 367:309–318. doi: 10.1056/NEJMoa1203859 CrossRefGoogle Scholar
  34. 34.
    Akinkuolie AO, Ngwa JS, Meigs JB, Djousse L (2011) Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of randomized controlled trials. Clin Nutr 30:702–707. doi: 10.1016/j.clnu.2011.08.013 CrossRefGoogle Scholar
  35. 35.
    Forouhi NG, Koulman A, Sharp SJ et al (2014) Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-interact case–cohort study. Lancet Diabetes Endocrinol 2:810–818. doi: 10.1016/S2213-8587(14)70146-9 CrossRefGoogle Scholar
  36. 36.
    Peter A, Cegan A, Wagner S et al (2011) Relationships between hepatic stearoyl-CoA desaturase-1 activity and mRNA expression with liver fat content in humans. Am J Physiol Endocrinol Metab 300:E321–E326. doi: 10.1152/ajpendo.00306.2010 CrossRefGoogle Scholar
  37. 37.
    Vessby B, Uusitupa M, Hermansen K et al (2001) Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU study. Diabetologia 44:312–319CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Markus J. Takkunen
    • 1
    Email author
  • Ursula S. Schwab
    • 1
    • 2
  • Vanessa D. F. de Mello
    • 1
  • Johan G. Eriksson
    • 3
    • 4
    • 5
    • 6
  • Jaana Lindström
    • 7
  • Jaakko Tuomilehto
    • 7
    • 8
    • 9
    • 10
  • Matti I. J. Uusitupa
    • 1
    • 11
  • the DPS Study Group
  1. 1.Institute of Public Health and Clinical NutritionUniversity of Eastern FinlandKuopioFinland
  2. 2.Institute of Clinical Medicine, Internal MedicineKuopio University HospitalKuopioFinland
  3. 3.Department of Chronic Disease PreventionNational Institute for Health and WelfareHelsinkiFinland
  4. 4.Department of General Practice and Primary Health CareUniversity of HelsinkiHelsinkiFinland
  5. 5.Folkhälsan Research CentreHelsingfors UniversitetHelsinkiFinland
  6. 6.Unit of General PracticeHelsinki University Central HospitalHelsinkiFinland
  7. 7.Diabetes Prevention UnitNational Institute for Health and WelfareHelsinkiFinland
  8. 8.Centre for Vascular PreventionDanube-University KremsKremsAustria
  9. 9.Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ)MadridSpain
  10. 10.Diabetes Research GroupKing Abdulaziz UniversityJeddahSaudi Arabia
  11. 11.Research UnitKuopio University HospitalKuopioFinland

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