Genetic susceptibility, obesity and lifetime risk of type 2 diabetes: The ARIC study and Rotterdam Study.

TitleGenetic susceptibility, obesity and lifetime risk of type 2 diabetes: The ARIC study and Rotterdam Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsLigthart, S, Hasbani, NR, Ahmadizar, F, van Herpt, TTW, Leening, MJG, Uitterlinden, AG, Sijbrands, EJG, Morrison, AC, Boerwinkle, E, Pankow, JS, Selvin, E, M Ikram, A, Kavousi, M, de Vries, PS, Dehghan, A
JournalDiabet Med
Date Published2021 Oct
KeywordsAged, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Life Style, Male, Middle Aged, Multifactorial Inheritance, Obesity, Risk, White People

AIMS: Both lifestyle factors and genetic background contribute to the development of type 2 diabetes. Estimation of the lifetime risk of diabetes based on genetic information has not been presented, and the extent to which a normal body weight can offset a high lifetime genetic risk is unknown.

METHODS: We used data from 15,671 diabetes-free participants of European ancestry aged 45 years and older from the prospective population-based ARIC study and Rotterdam Study (RS). We quantified the remaining lifetime risk of diabetes stratified by genetic risk and quantified the effect of normal weight in terms of relative and lifetime risks in low, intermediate and high genetic risk.

RESULTS: At age 45 years, the lifetime risk of type 2 diabetes in ARIC in the low, intermediate and high genetic risk category was 33.2%, 41.3% and 47.2%, and in RS 22.8%, 30.6% and 35.5% respectively. The absolute lifetime risk for individuals with normal weight compared to individuals with obesity was 24% lower in ARIC and 8.6% lower in RS in the low genetic risk group, 36.3% lower in ARIC and 31.3% lower in RS in the intermediate genetic risk group, and 25.0% lower in ARIC and 29.4% lower in RS in the high genetic risk group.

CONCLUSIONS: Genetic variants for type 2 diabetes have value in estimating the lifetime risk of type 2 diabetes. Normal weight mitigates partly the deleterious effect of high genetic risk.

Alternate JournalDiabet Med
PubMed ID34245042
PubMed Central IDPMC8429251
Grant ListUL1 RR025005 / RR / NCRR NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
P30 ES030285 / ES / NIEHS NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
UL1 TR003098 / TR / NCATS NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States

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