Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jan;56(1):60-9.
doi: 10.1007/s00125-012-2715-x. Epub 2012 Sep 28.

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

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, J W J Beulens, 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, N J Wareham

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

InterAct Consortium et al. Diabetologia. 2013 Jan.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Association of degrees of family history with risk of T2D in men, women and overall: The EPIC-InterAct study
Referent groups were individuals with no reported family history of diabetes. *Only UK and Netherlands had sufficient data available on age of diagnosis of parental diabetes and these analyses are restricted to those two countries.
Figure 2
Figure 2. Association of family history with T2D risk after adjustment for potential mediators in individuals with full availability of mediators
All analyses were adjusted for sex and centre. Models were then individually adjusted for each specified risk factor, and all mediators where specified. The proportion of the family-history effect explained by each mediator was calculated as (1-(lnHRadjusted model/ lnHRcrude model)
See this image and copyright information in PMC

References

    1. Groop L, Forsblom C, Lehtovirta M, et al. Metabolic consequences of a family history of NIDDM (the Botnia study): evidence for sex-specific parental effects. Diabetes. 1996;45:1585–1593. - PubMed
    1. Meigs JB, Cupples LA, Wilson PW. Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes. 2000;49:2201–2207. - PubMed
    1. van ’t Riet E, Dekker JM, Sun Q, Nijpels G, Hu FB, van Dam RM. Role of adiposity and lifestyle in the relationship between family history of diabetes and 20-year incidence of type 2 diabetes in U.S. women. Diabetes Care. 2010;33:763–767. - PMC - PubMed
    1. Harrison TA, Hindorff LA, Kim H, et al. Family history of diabetes as a potential public health tool. Am.J.Prev.Med. 2003;24:152–159. - PubMed
    1. Manson JE, Rimm EB, Stampfer MJ, et al. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet. 1991;338:774–778. - PubMed

Publication types

MeSH terms