Investigating whether smoking and alcohol behaviours influence risk of type 2 diabetes using a Mendelian...

Previous studies suggest that smoking and higher alcohol consumption are associated with greater type 2 diabetes (T2D) risk. However, studies examining whether this reflects causal relationships are limited and often do not consider continuous glycaemic traits. We conducted both two-sample and one-sample Mendelian randomisation (MR), using publicly available GWAS data and UK Biobank data, respectively, to examine the potential causal effects of lifetime smoking index (LSI) and alcoholic drinks per week (DPW) on T2D and continuous traits (fasting glucose, fasting insulin and glycated haemoglobin, HbA1c). Two-sample MR results suggested possible causal effects of higher LSI on T2D risk (OR per 1SD higher LSI: 1.42, 95% CI 1.22 to 1.64); however, sensitivity analyses did not consistently support this finding. There was no robust evidence that higher DPW influenced T2D risk (OR per 1 SD higher log-transformed DPW: 1.04, 95% CI 0.40 to 2.65). There was evidence of a potential causal effect on higher fasting glucose (difference in mean fasting glucose in mmol/l per 1SD higher log-transformed DPW: 0.34, 95% CI 0.09 to 0.59), though, this was attenuated when accounting for body mass index (BMI), suggesting BMI confounding might explain the potential effect. One-sample MR results suggested a possible causal effect of higher DPW on T2D risk (OR per 1 SD higher log-transformed DPW: 1.71, 95% CI 1.24 to 2.36), but lower HbA1c levels (difference in mean SD of log transformed HbA1c (mmol/mol) per 1 SD higher log-transformed DPW: -0.07, 95% CI -0.11 to -0.02). Our results suggest effective public health interventions to prevent and/or reduce smoking and alcohol consumption are unlikely to reduce T2D prevalence.