Association of Diabetic Retinopathy and Diabetic Kidney Disease With All-Cause and Cardiovascular Mortality in a Multiethnic Asian Population

IMPORTANCE The association of diabetic microvascular complications such as diabetic retinopathy (DR) and diabetic kidney disease (DKD) with mortality in populations is not clear. OBJECTIVE To examine the association of DR and DKD separately and jointly with all-cause and cardiovascular disease (CVD) mortality in a multiethnic Asian population. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort study was conducted including 2964 adults between the ages of 40 and 80 years with diabetes who participated in the Singapore Epidemiology of Eye Diseases study (baseline, 2004-2011). Data analysis was performed from January to May 2018. EXPOSURES Diabetic retinopathy ascertained from retinal photographs and DKD from estimated glomerular filtration rate. MAIN OUTCOMES AND MEASURES All-cause and CVD mortality obtained by linkage with the National Registry of Births and Deaths until May 2017. RESULTS Of the 2964 adults (mean [SD] age, 61.8 [10.0] years; 1464 [49.4%] female; 592 Chinese, 1052 Malay, and 1320 Indian), 29.9% of the participants had DR, while 20.7% had DKD. Over a median (interquartile range) follow-up of 8.8 (7.2-11.0) years, 610 deaths occurred (20.6%), of which 267 (9.0%) were due to CVD. In separate models, the multivariable hazard ratios for all-cause and CVD mortality were 1.54 (95% CI, 1.24-1.91) and 1.74 (95% CI, 1.27-2.40), respectively, for DR and 2.04 (95% CI, 1.64-2.56) and 2.29 (95% CI, 1.64-3.19), respectively, for DKD. In models including both DR and DKD, the subgroup with DKD alone (27.1% and 12.6%) followed by DR alone (6.5% and 5.2%) contributed substantially to the excess risk of all-cause and CVD mortality. Compared with those with no DR and DKD, the hazard ratios of all-cause and CVD mortality were 1.89 (95% CI, 1.40-2.57) and 2.26 (95% CI, 1.42-3.61), respectively, for DKD alone and 1.38 (95% CI, 1.03-1.86) and 1.64 (95% CI, 1.06-2.56), respectively, for DR alone. Hazard ratios for all-cause and CVD mortality were 2.76 (95% CI, 2.05-3.72) and 3.41 (95% CI, 2.19-5.32), respectively, for those with both DKD and DR. The relative excess risk associated with the interaction was 0.49 (95% CI,-0.29 to 1.27; P=.20) for all-cause mortality and 0.51 (95% CI,-0.83 to 1.85; P=.50) for CVD mortality. CONCLUSIONS AND RELEVANCE These results suggest that risks of all-cause and CVD mortality were significantly higher in those with DKD and DR, but DKD was more strongly associated with excess risk. The findings underscore the importance of early identification and close monitoring and management of patients with DR and DKD to reduce the risk of death.