Adherence to a healthier lifestyle was associated with lower type 1 diabetes mellitus (T1DM) incidence across all genetic risk groups in a large UK Biobank analysis published in Diabetes-Metabolism Research and Reviews.

T1DM is strongly influenced by inherited susceptibility, but the extent to which modifiable lifestyle factors alter this risk remains less clearly defined. The study evaluated the joint contribution of genetic predisposition and lifestyle behaviors using both cross-sectional and longitudinal analyses.

Using UK Biobank data, investigators assessed 403,778 participants for cross-sectional analyses and 402,005 participants for longitudinal follow-up. A polygenic risk score (PRS) quantified inherited susceptibility to T1DM. A composite lifestyle index incorporated six domains: adiposity, smoking status, alcohol intake, physical activity, diet quality, and sleep duration.

Over a 15-year study period with a median follow-up of 12.3 years, 1,474 incident T1DM cases were identified. Compared with the lowest genetic risk group, participants in the intermediate-risk group had higher incident T1D risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.00-1.37), while the highest-risk group had markedly higher risk (HR, 2.89; 95% CI, 2.46-3.39).

Compared with the unhealthy lifestyle group, intermediate lifestyle patterns were associated with lower T1DM risk (HR, 0.61; 95% CI, 0.52-0.71), and healthy lifestyle patterns were associated with further reductions (HR, 0.43; 95% CI, 0.37-0.52), independent of genetic predisposition. Significant interaction between genetic risk and lifestyle was observed in both cross-sectional and longitudinal analyses (P<0.001).

The findings suggest lifestyle modification may significantly reduce T1DM susceptibility, including among individuals with elevated inherited risk.