Lifestyle modifies the associations of early-life smoking behaviors and genetic susceptibility with type 2 diabetes: A prospective cohort study involving 433,872 individuals from UK Biobank

Abstract

BackgroundTo investigate whether and what lifestyle factors in later life modify the associations of early-life smoking behaviors and genetic susceptibility with type 2 diabetes (T2D). MethodsIn the UK Biobank, in utero tobacco exposure (n=354,493) and age of smoking initiation (n=353,557) were self-reported. A composite lifestyle score was calculated based on diet, physical activity, nicotine exposure, sleep duration, and BMI. Hazard ratio (HR) and absolute risk difference (ARD) were used to estimate the associations of early-life smoking behaviors and genetic risk with incident T2D, as well as the effect modification of the lifestyle score. ResultsDuring a median follow-up of 14.6 years, the HRs (95% CIs) of T2D for in utero tobacco exposure, and smoking initiation in adulthood, adolescence, and childhood, compared with no smoking behavior, were 1.19 (1.16-1.23), 1.34 (1.29-1.39), 1.58 (1.53-1.64), 2.22 (2.11-2.32), respectively (P for trend<0.001). Early-life smoking behaviors and high genetic risk (vs no smoking behavior and low genetic risk) were associated with a 302%-593% higher T2D risk (P for additive interaction<0.05). Compared to participants with early-life smoking behaviors, high genetic risk, and an unfavorable lifestyle, those who adhered to a favorable lifestyle had a lower T2D risk in all subgroups (HRs from 0.05 to 0.36 and ARD from -14.97% to -9.51%), with the highest ARD attributable to lifestyle in participants with early-life smoking behaviors and high genetic risk. ConclusionsThe T2D risk associated with early-life smoking behaviors and genetic risk was modified by a favorable lifestyle.