Document Detail

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.
MedLine Citation:
PMID:  23052052     Owner:  NLM     Status:  MEDLINE    
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.
; 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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-28
Journal Detail:
Title:  Diabetologia     Volume:  56     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-18     Completed Date:  2013-05-28     Revised Date:  2014-10-07    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  60-9     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Body Mass Index
Case-Control Studies
Cohort Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 2 / epidemiology*,  ethnology,  etiology,  genetics
Europe / epidemiology
Family Health* / ethnology
Follow-Up Studies
Genetic Predisposition to Disease
Life Style* / ethnology
Middle Aged
Motor Activity*
Risk Factors
Waist Circumference
Young Adult
Grant Support
083270/Z/07/Z//Wellcome Trust; 098051//Wellcome Trust; G0601261//Medical Research Council; G1000143//Medical Research Council; MC_U106179473//Medical Research Council; MC_U106179474//Medical Research Council; MC_UU_12015/1//Medical Research Council; //Cancer Research UK

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