Weight-adjusted-waist index, estimated glucose disposal rate, C-reactive protein, and mortality risks among individuals with type 2 diabetes: 2 prospective cohort studies in China and the United Kingdom

Weight-adjusted-waist index (WWI) is an anthropometric index for reflecting fat mass and muscle mass, both of which are important factors influencing insulin resistance and inflammation. We aimed to examine the associations of WWI with all-cause, cardiovascular, and non-cardiovascular mortality among individuals with type 2 diabetes (T2D), and to further investigate whether insulin resistance and inflammation, measured by estimated glucose disposal rate (eGDR) and C-reactive protein (CRP) respectively, can mediate these associations. Participants with T2D were included from two prospective cohorts of the China Changshu Cohort Type 2 Diabetes (CT2D) (N=10,157) and UK Biobank (UKB) (N=25,019), respectively. WWI was calculated as waist circumference divided by the square root of body weight. In CT2D, participants in the highest WWI quartile had higher risks of all-cause mortality (HR: 1.64, 95% CI: 1.44-1.86), cardiovascular mortality (HR: 1.51, 95% CI: 1.20-1.89), and non-cardiovascular mortality (HR: 1.71, 95% CI: 1.47-2.00) compared with those in the lowest quartile. In UKB, the corresponding HRs (95% CIs) were 1.55 (1.42-1.70), 1.80 (1.52-2.13) and 1.46 (1.31-1.62), respectively. WWI also showed better predictive ability than many current obesity indicators in both cohorts. Furthermore, eGDR mediated the relation between WWI and all-cause, cardiovascular, and non-cardiovascular mortality by 16.20% (6.77%-27.63%), 57.92% (33.52%-115.98%) and 1.03% (-9.96%-11.95%) in CT2D, and by 23.70% (15.60%-34.57%), 38.02% (23.89%-59.19%) and 16.06% (5.51%-29.55%) in UKB. In UKB, the mediation proportions of CRP for all-cause, cardiovascular, and non-cardiovascular mortality were 8.75% (6.23%-12.18%), 7.64% (4.40%-12.73%) and 9.38% (6.20%-13.91%), respectively. High WWI levels were associated with increased risks of all-cause, cardiovascular, and non-cardiovascular mortality among individuals with T2D, and eGDR and CRP mediated their associations. Our study highlights the value of WWI in identifying high-risk individuals and the potential of monitoring and intervening in eGDR and CRP to prevent mortality in people with T2D.