Associations of Combined Genetic and Lifestyle Risks with Incident Type 2 Diabetes in the UK Biobank

Résumé fourni par la source

Type 2 diabetes results from the interplay of genetic susceptibility and unhealthy lifestyle but their combined effects are not well studied. We examined whether unhealthy modifiable behaviors were associated with similar increases in the risk of incident type 2 diabetes among individuals with different levels of genetic risk. Among 332,251 non-diabetic UK Biobank participants, we constructed a multi-ancestry genetic risk score (GRS) based on 783 type 2 diabetes-associated variants, categorized into tertiles. Lifestyle was classified as healthy, intermediate, or unhealthy based on baseline self-reported smoking, BMI, physical activity, and diet quality. Cox proportional hazards regression models were used to generate adjusted hazards ratios (HR) for type 2 diabetes and associated 95% CI. During follow-up (median 13.6 years), 13,128 (4.0%) participants developed type 2 diabetes. GRS (P < 0.001) and lifestyle classification (P < 0.001) were independently associated with increased risk for type 2 diabetes. Compared with healthy lifestyle, unhealthy lifestyle was associated with increased risk in all genetic risk strata, with adjusted HR ranging from 7.11 to 16.33. High genetic risk and unhealthy lifestyle were the most significant contributors to type 2 diabetes development. Individuals at all levels of genetic risk can greatly mitigate their type 2 diabetes risk through lifestyle modifications.

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