Blood glucose and diabetes mellitus as risk factors for cardiovascular disease in the China Kadoorie Biobank of 0.5 million people

Background: In China, the incidence of diabetes is rising, but little is known about its impact on cardiovascular diseases (CVD). Moreover, substantial uncertainty remains, both in China and elsewhere, about the relevance to CVD of blood glucose levels below the glycaemic threshold for diabetes. This thesis assessed these associations in Chinese adults. Methods: In 2004-08, the China Kadoorie Biobank recruited 0.5 million adults aged 30-79 years from 10 diverse regions, recording 25 488 deaths by 1st January 2014. Logistic and Cox regression yielded adjusted odds (ORs) and hazard ratios (HRs), respectively, relating self-reported diabetes and, among people without self-reported diabetes, random plasma glucose (RPG) levels to prevalent and incident CVD. Results: At baseline, 5.9% of participants had self-reported (3.2%) or screen-detected (2.8%) diabetes. Self-reported diabetes was associated with approximately 2-fold increased odds of prevalent ischaemic heart disease (IHD) (n=14 771, OR 2.16, 95% CI 2.05-2.28) and stroke/transient ischaemic attack (n=8430, 1.88, 1.75-2.02). There were also significant excess risks of CVD mortality (n=6916, HR 2.07, 95% CI 1.90-2.26) and incident IHD (n=3465, 2.44, 2.18-2.73), ischaemic stroke (n=19 778, 1.68, 1.60-1.77) and intra-cerebral haemorrhage (ICH) (n=4423, 1.24, 1.07-1.44). These risks increased with longer diabetes duration and number of other presenting risk factors. Screen-detected diabetes was also associated with significant, though more modest, excess incident CVD risks. Among participants without self-reported diabetes, there was a positive log-linear association of RPG with prevalent and incident CVDs. In prospective analyses the association continued down to baseline RPG of ~4.0 mmol/L. After adjusting for regression dilution bias, each 1 mmol/L higher usual RPG was associated with ~10% increased risks of incident ischaemic CVDs and CVD mortality, and ~5% increased risks of incident ICH. In ~89 000 genotyped individuals, a RPG-related genetic risk score was associated significantly with RPG. It showed no significant association with ischaemic CVD risks, but power to detect such an association was low. Conclusions: Among adult Chinese, diabetes is associated with significantly increased risks of major CVDs. In individuals without diabetes, there is a positive log-linear association between RPG and CVDs, with no evidence of a threshold.