The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations: the EPIC-InterAct Study

Objective: To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.

Research Design And Methods: The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.

Results: In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes.

Conclusions: Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.

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References

Rubilar M, Jara C, Poo Y, Acevedo F, Gutierrez C, Sineiro J . Extracts of Maqui ( Aristotelia chilensis ) and Murta ( Ugni molinae Turcz.): sources of antioxidant compounds and α-Glucosidase/α-Amylase inhibitors. J Agric Food Chem. 2011; 59(5):1630-7. DOI: 10.1021/jf103461k. View

Beulens J, van der Schouw Y, Bergmann M, Rohrmann S, Schulze M, Buijsse B . Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size The EPIC-InterAct study. J Intern Med. 2012; 272(4):358-70. DOI: 10.1111/j.1365-2796.2012.02532.x. View

Neveu V, Perez-Jimenez J, Vos F, Crespy V, du Chaffaut L, Mennen L . Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). 2010; 2010:bap024. PMC: 2860900. DOI: 10.1093/database/bap024. View

Cooper A, Forouhi N, Ye Z, Buijsse B, Arriola L, Balkau B . Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis. Eur J Clin Nutr. 2012; 66(10):1082-92. PMC: 3652306. DOI: 10.1038/ejcn.2012.85. View

Barlow W, Ichikawa L, ROSNER D, Izumi S . Analysis of case-cohort designs. J Clin Epidemiol. 1999; 52(12):1165-72. DOI: 10.1016/s0895-4356(99)00102-x. View

Slimani N, Deharveng G, Unwin I, Southgate D, Vignat J, Skeie G . The EPIC nutrient database project (ENDB): a first attempt to standardize nutrient databases across the 10 European countries participating in the EPIC study. Eur J Clin Nutr. 2007; 61(9):1037-56. DOI: 10.1038/sj.ejcn.1602679. View

Whiting D, Guariguata L, Weil C, Shaw J . IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011; 94(3):311-21. DOI: 10.1016/j.diabres.2011.10.029. View

Riboli E, Hunt K, Slimani N, Ferrari P, Norat T, Fahey M . European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr. 2003; 5(6B):1113-24. DOI: 10.1079/PHN2002394. View

Wedick N, Pan A, Cassidy A, Rimm E, Sampson L, Rosner B . Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr. 2012; 95(4):925-33. PMC: 3302366. DOI: 10.3945/ajcn.111.028894. View

10.

Ward H, Kuhnle G, Mulligan A, Lentjes M, Luben R, Khaw K . Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database. Am J Clin Nutr. 2009; 91(2):440-8. DOI: 10.3945/ajcn.2009.28282. View

11.

van Woudenbergh G, Kuijsten A, Drogan D, van der A D, Romaguera D, Ardanaz E . Tea consumption and incidence of type 2 diabetes in Europe: the EPIC-InterAct case-cohort study. PLoS One. 2012; 7(5):e36910. PMC: 3364250. DOI: 10.1371/journal.pone.0036910. View

12.

Matsuda T, Ferreri K, Todorov I, Kuroda Y, Smith C, Kandeel F . Silymarin protects pancreatic beta-cells against cytokine-mediated toxicity: implication of c-Jun NH2-terminal kinase and janus kinase/signal transducer and activator of transcription pathways. Endocrinology. 2004; 146(1):175-85. DOI: 10.1210/en.2004-0850. View

13.

Song Y, Manson J, Buring J, Sesso H, Liu S . Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. J Am Coll Nutr. 2005; 24(5):376-84. DOI: 10.1080/07315724.2005.10719488. View

14.

van der Schouw Y, Sampson L, Willett W, Rimm E . The usual intake of lignans but not that of isoflavones may be related to cardiovascular risk factors in U.S. men. J Nutr. 2005; 135(2):260-6. DOI: 10.1093/jn/135.2.260. View

15.

Lee S, Wen W, Xiang Y, Barnes S, Liu D, Cai Q . Assessment of dietary isoflavone intake among middle-aged Chinese men. J Nutr. 2007; 137(4):1011-6. PMC: 2040062. DOI: 10.1093/jn/137.4.1011. View

16.

Margetts B, Pietinen P . European Prospective Investigation into Cancer and Nutrition: validity studies on dietary assessment methods. Int J Epidemiol. 1997; 26 Suppl 1:S1-5. DOI: 10.1093/ije/26.suppl_1.s1. View

17.

Hanhineva K, Torronen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkanen H . Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci. 2010; 11(4):1365-402. PMC: 2871121. DOI: 10.3390/ijms11041365. View

18.

Zamora-Ros R, Rabassa M, Llorach R, Gonzalez C, Andres-Lacueva C . Application of dietary phenolic biomarkers in epidemiology: past, present, and future. J Agric Food Chem. 2012; 60(27):6648-57. DOI: 10.1021/jf204742e. View

19.

Han M . Epigallocatechin gallate, a constituent of green tea, suppresses cytokine-induced pancreatic beta-cell damage. Exp Mol Med. 2003; 35(2):136-9. DOI: 10.1038/emm.2003.19. View

20.

Kwon O, Eck P, Chen S, Corpe C, Lee J, Kruhlak M . Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J. 2006; 21(2):366-77. DOI: 10.1096/fj.06-6620com. View