Adiposity and Risks of Cardiovascular Disease Incidence and Mortality Among Chinese Adults with Type 2 Diabetes: A 9-Year Prospective Study

Background: Adiposity is a major risk factor for cardiovascular diseases (CVD). However, uncertainty remains about its relevance for mortality following incident CVD, particularly among individuals with diabetes. Methods: In 2004-08 the prospective China Kadoorie Biobank recruited 512,000 adults aged 30-79 years from 10 areas in China. After ~9 years’ follow-up, 3509 deaths (1431 from CVD) and 9940 incident CVD were recorded among 23,842 individuals with diabetes but without prior major diseases. Cox regression yielded adjusted hazard ratios (HRs) associating adiposity with disease outcomes. Findings: Among people with diabetes (mean baseline BMI 25.0 kg/m2), BMI was positively associated with CVD incidence (HR=1.19 [95% CI 1.15-1.22] per 5 kg/m2), but there was a U-shaped association with CVD mortality, with the lowest risk at 22.5-24.9 kg/m2. Case fatality following CVD onset (deaths occurring within 28 days, n=671) at lower BMI was particularly marked with HR of 3.32 (2.33-4.73) at <18.5 kg/m2 relative to 22.5-24.9 kg/m2, but a fairly constant HR at BMI ≥25.0 kg/m2. These associations were similar for different CVD types and other adiposity measures, and persisted after attempts to address reverse causality and confounding. For comparison, among individuals without diabetes (mean BMI 23.6 kg/m2; n=23,305 deaths), there were less extreme, albeit similar, excess mortality risks at BMI <22.5 kg/m2. Interpretation: Among relatively lean Chinese adults with diabetes, adiposity was positively associated with CVD incidence throughout the broad BMI range. The contrasting associations between CVD incidence and mortality may reflect adverse survival associated with low BMI after onset of CVD. Funding Statement: The baseline survey and the first re-survey were supported by a research grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term continuation of the project is supported by program grants from the UK Wellcome Trust (088158/Z/09/Z, 104085/Z/14/Z, 212946/Z/18/Z), the Chinese Ministry of Science and Technology (21BAI09B01, 2012-14), and the Chinese National Natural Science Foundation (81390540, 81390541, 81390544, 2014-18) and the National Key Research and Development Program of China (2016YFC0900500 / 2016YFC0900501 / 2016YFC0900504 / 2016YFC1303904, 2016-2021). The British Heart Foundation, Medical Research Council and Cancer Research UK provide core funding to the Oxford CTSU. Andri Iona acknowledges support from the Medical Research Council. Fiona Bragg acknowledges support from the BHF Centre of Research Excellence, Oxford (RE/13/1/30181). Declaration of Interests: None of the authors have any conflicts of interest in relation to this report. Ethics Approval Statement: Ethics approval was obtained from international, national and local ethics committees prior to commencing the study. All participants provided written informed consent.