Journal Article

The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study

de Lauzon-Guillain, B, Ekelund, U, Bendinelli, B, Balkau, B, Rodriguez-Suarez, L, van der A, D L, Scott, R A, Nilsson, P M, Romieu, I, Boeing, H, Ardanaz, E, Barricarte, A, Rolandsson, O, Gonzalez, C, Griffin, S J, McCarthy, M I, Franks, P W, Barroso, I, Panico, S, Wark, P A, Kerrison, N D, van der Schouw, Y T, Krogh, V, Halkjaer, J, Groop, L C, Arriola, L, Wareham, N J, Huerta, J M, Overvad, K, Beulens, J W J, Deloukas, P, Riboli, E, Sacerdote, C, Drogan, D, Sharp, S J, Sánchez, M J, Tjonneland, A, Tumino, R, Fagherazzi, G, Khaw, K T, Kaaks, R, Norat, T, Romaguera, D, Langenberg, C, Spijkerman, A M W, Teucher, B

2013

Overview

Aims/hypothesis Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association. Methods A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created. Results A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history. Conclusions/interpretation Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Adult / Age / Aged / Aged, 80 and over / Biological and medical sciences / Body Mass Index / Case-Control Studies / Cohort analysis / Cohort Studies / Consortia / Cross-Sectional Studies / Diabetes / Diabetes Mellitus, Type 2 - epidemiology / Diabetes Mellitus, Type 2 - ethnology / Diabetes Mellitus, Type 2 - etiology / Diabetes Mellitus, Type 2 - genetics / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Europe - epidemiology / Families & family life / Family Health - ethnology / family history / Family medical history / Female / Follow-Up Studies / Genetic Predisposition to Disease / genetics / Human Physiology / Humans / Incidence / Internal Medicine / Investigations / Life Style - ethnology / Lifestyles / Male / Mediators / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Metabolism / Middle Aged / Mothers / Motor Activity / Questionnaires / Risk Factors / type 2 diabetes / Waist Circumference / Young Adult