• InterAct Consortium, R A Scott, C Langenberg, S J Sharp, P W Franks, O Rolandsson, D Drogan, Y T van der Schouw, U Ekelund, N D Kerrison, E Ardanaz, L Arriola, B Balkau, A Barricarte, I Barroso, B Bendinelli, BeulensJ W JJW, H Boeing, B de Lauzon-Guillain, P Deloukas, G Fagherazzi, C Gonzalez, S J Griffin, L C Groop, J Halkjaer, J M Huerta, R Kaaks, K T Khaw, V Krogh, P M Nilsson, T Norat, K Overvad, S Panico, L Rodriguez-Suarez, D Romaguera, I Romieu, C Sacerdote, M J Sánchez, A M W Spijkerman, B Teucher, A Tjonneland, R Tumino, D L van der A, P A Wark, M I McCarthy, E Riboli, and N J Wareham.
• Diabetologia. 2013 Jan 1; 56 (1): 60-9.

Aims/HypothesisAlthough 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.MethodsA 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.ResultsA 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/InterpretationProminent 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.

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