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

Abstract

INTRODUCTION: Observational studies have shown that the association between type 2 diabetes and cardiovascular disease (CVD) is stronger in females than in males. It remains unclear whether the causal effects of diabetes and glycaemic traits on CVD are also different between females and males. METHODS: We performed sex-stratified observational and Mendelian randomisation (MR) analyses in the UK Biobank to investigate the sex-specific associations of type 2 diabetes and HbA1c with CVD outcomes (combined CVD, coronary heart disease [CHD], myocardial infarction, stroke, ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage). As secondary analyses, we performed sex-stratified MR for the association of genetically proxied fasting glucose and insulin with CVD outcomes. RESULTS: In observational analysis, diabetes was associated with a greater excess risk for CHD in females than in males (female-to-male ratio of hazard ratios 1.11 [95% CI 1.03, 1.21]). The association of HbA1c with CVD outcomes was similar in both sexes. In MR, the relationship between genetic liability to diabetes and CHD was similar in females and males (female-to-male ratio of odds ratios 0.98 [95% CI 0.91, 1.05]). No sex differences were found for the association between diabetes and stroke in both observational and MR analyses. Moreover, MR results on HbA1c, fasting glucose and fasting insulin were similar for females and males. CONCLUSION: This study suggests that causal effects of diabetes and glycaemic traits on CVD are similar in females and males.