Diabetes, glycaemic traits and cardiovascular disease in females and males: Observational and Mendelian randomisation analyses in the UK Biobank

FIGURE 1. Cox regression estimates and Mendelian randomisation estimates of the association between type 2 diabetes and cardiovascular disease outcomes in females and males. MR estimates are from inverse‐variance weighted MR, and ORs can be interpreted as the effect per unit increase in log odds of genetic liability to diabetes. MR analyses were performed in 337 386 UK Biobank participants. Cox regressions were performed in 468 838 UK Biobank participants and were adjusted for sex, Townsend deprivation index (an area‐based measure of socioeconomic status), systolic blood pressure, total cholesterol levels, smoking status, body mass index, use of lipid‐lowering medication and use of antihypertensives, including an interaction term between each of these adjustment variables and sex. RHRs present the female‐to‐male ratios of HRs as obtained from an interaction term of diabetes with sex, and RORs present the female‐to‐male ratios of ORs as obtained from two separate MR analyses. CI, confidence interval; HR, hazard ratio; MR, Mendelian randomisation; OR, odds ratio; RHR, ratio of hazard ratios; ROR, ratio of odds ratios.

FIGURE 2. Cox regression estimates and Mendelian randomisation estimates of the association between HbA1c and cardiovascular disease outcomes in females and males. MR estimates are from inverse‐variance weighted MR and odds ratios (ORs) can be interpreted as the effect per 1% increase in genetically predicted HbA1c level. MR analyses were performed in 337 386 UK Biobank participants. Cox regressions were performed in 468 838 UK Biobank participants and adjusted for sex, type 2 diabetes status, Townsend deprivation index (an area‐based measure of socioeconomic status), systolic blood pressure, total cholesterol levels, smoking status, body mass index, use of lipid‐lowering medication and use of antihypertensives, including an interaction term between each of these adjustment variables and sex. RHRs present the female‐to‐male ratios of HRs as obtained from an interaction term of HbA1c and sex, and RORs present the female‐to‐male ratios of ORs as obtained from two separate MR analyses. CI, confidence interval; HR, hazard ratio; MR, Mendelian randomisation; OR, odds ratio; RHR, ratio of hazard ratios; ROR, ratio of odds ratios.

FIGURE 3. Mendelian randomisation estimates of the association between fasting glucose and cardiovascular disease outcomes in females and males. Estimates are from inverse‐variance weighted MR. The odds ratios (ORs) can be interpreted as the effect per 1 mmol/L increase in genetically predicted fasting glucose levels. MR analyses were performed in 337 386 UK Biobank participants. RORs present the female‐to‐male ratios of ORs as obtained from two separate MR analyses. CI, confidence interval; OR, odds ratio; ROR, ratio of odds ratios.

FIGURE 4. Mendelian randomisation estimates of the association between fasting insulin and cardiovascular disease outcomes in females and males. Estimates are from inverse‐variance weighted MR. The odds ratios (ORs) can be interpreted as the effect per one log unit increase in genetically predicted fasting insulin level. MR analyses were performed in 337 386 UK Biobank participants. RORs present the female‐to‐male ratios of ORs as obtained from two separate MR analyses. CI, confidence interval; OR, odds ratio; ROR, ratio of odds ratios.