Objective: To examine the association between the cardiovascular-kidney-metabolic (CKM) syndrome and macrovascular and microvascular complications in people with type 2 diabetes (T2D), and to evaluate whether CKM modifies the efficacy of randomized blood glucose and blood pressure (BP) lowering treatments, and whether these treatments influence CKM progression. Design and method: Post hoc analyses of 10,934 participants with T2D in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial who were categorized into three groups based on baseline CKM syndrome stages. Multivariable Cox regression models were used to determine associations of baseline CKM syndrome with vascular events and all-cause mortality. Tests of homogeneity of the randomized treatment effects on outcomes according to baseline CKM syndrome stages were conducted by adding interaction terms in the Cox regression models. Results: There were 2195 (20.1%) participants with stage 2, 5508 (50.4%) stage 3, and 3231 (29.5%) stage 4 CKM syndrome at baseline. Compared to participants with stage 2 CKM, hazard ratios for those with stage 4 CKM were 1.18 (95% confidence interval CI 1.24-1.63) for the composite of major macrovascular or microvascular events, 2.13 (1.66-2.73) for major macrovascular events, and 2.24 (1.66-3.02) for all-cause mortality during a mean follow-up of 5 years. There was no heterogeneity in the effect of intensive blood glucose control (all P for interaction >0.09) or BP lowering (all P for interaction >0.22) treatments on any outcomes by baseline CKM stages. Overall, 27.8% of participants experienced CKM syndrome progression, defined as an increase in CKM stage or death, from baseline to the last follow-up (median 5 years). The incidence of CKM progression was similar between the standard and intensive glucose control groups (28.3% vs. 27.2%), as well as between the placebo and active BP lowering treatment groups (27.9% vs. 27.6%). Conclusions: Advanced CKM syndromes are associated with higher risks of major macrovascular events and death in high-risk adults with T2D. Baseline CKM syndrome did not alter the effects of intensive blood glucose control or BP lowering on any outcomes, and CKM progression rates were similar between treatment groups.
You et al. (Fri,) studied this question.