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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
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Lund University, Malmö, Sweden.
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2013 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 1, p. 60-69Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer, 2013. Vol. 56, no 1, p. 60-69
Keywords [en]
family history, genetics, type 2 diabetes
National Category
Endocrinology and Diabetes Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:umu:diva-148531DOI: 10.1007/s00125-012-2715-xPubMedID: 23052052Scopus ID: 2-s2.0-84871612654OAI: oai:DiVA.org:umu-148531DiVA, id: diva2:1214805
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2018-06-07Bibliographically approved

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Franks, Paul W.Rolandsson, Olov
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