Tobacco exposure in adulthood is a well-established risk factor for type 2 diabetes (T2D), but how early-life tobacco exposure implicates in the development of T2D as well as whether this association varies by different genetic predisposition to T2D are unclear. Addressing these gaps may provide novel insights into early interventions of T2D.
Hypothesis We hypothesized that tobacco exposure in utero and childhood/adolescence stages was significantly associated with incident T2D in adulthood and there were significant interactions and joint effects between early-life tobacco exposure and genetic risk for T2D in relation to risk of T2D.
Methods This prospective cohort study used data from the UK Biobank. In utero tobacco exposure and age of smoking initiation [never smoking, childhood (5-14 years), adolescence (15-17 years), and adulthood (≥18 years)] were assessed through self-reported questionnaires. Multivariable Cox proportional hazard models, adjusted for demographics and early-life factors, were used to estimate the associations of tobacco exposure in utero and childhood/adolescence stages with incident T2D. A polygenic risk score (PRS) for T2D divided into tertiles was used to assess the interactions and joint effects between early-life tobacco exposure and genetic susceptibility on the development of T2D.
Results A total of 475,957 participants without T2D at baseline were included. During a median follow-up time of 14.6 years (IQR, 13.7-15.3), 23,480 incident T2D events occurred. Tobacco exposure in utero vs no exposure was significantly associated with incident T2D (hazard ratio [HR], 1.22 [95% CI, 1.18-1.26]). Compared with never smoking, smoking initiation in childhood (HR, 2.19 [95% CI, 2.08-2.29]), adolescence (HR, 1.57 [95% CI, 1.51-1.62]), and adulthood (HR, 1.33 [95% CI, 1.28-1.38]) were significantly associated with incident T2D (P for trend <0.001). Additive interactions were observed between tobacco exposure in utero or childhood/adolescence stages and PRS for T2D (relative excess risk due to interaction >0, P interaction <0.001). Compared with participants having no early-life tobacco exposure and a low PRS, those with a high PRS had a 330% higher risk of developing T2D when exposed to tobacco in utero (HR, 4.30 [95% CI, 4.07-4.54]), a 639% higher risk of developing T2D when starting smoking in childhood (HR, 7.39 [95% CI, 6.84-7.99]), and a 427% higher risk when starting smoking in adolescence (HR, 5.27 [95% CI, 4.95-5.62]).
Conclusions In utero tobacco exposure was significantly associated with incident T2D. Earlier smoking initiation was more strongly associated with incident T2D than later initiation. Early-life tobacco exposure and genetic predisposition to T2D interacted and jointly determined risk of T2D.
https://www.abstractsonline.com/pp8/#!/20343/presentation/114
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