Serum Cystatin-C is linked to increased prevalence of diabetes and higher risk of mortality in diverse middle-aged and older adults

Type 2 Diabetes Mellitus (henceforth diabetes) affects roughly 35 million individuals in the US and is a major risk factor for cardiovascular and kidney disease. Serum Cystatin-C is used to monitor renal function and detect kidney damage. Recent research has focused on linking Cystatin-C to cardiovascular risk and disease, but most findings focus on small sample sizes and generalize poorly to diverse populations, thus limiting epidemiological inferences. The aim of this manuscript is to study the association between Cystatin-C, diabetes, and mortality and test for possible sex or racial/ethnic background modifications in these relationships. We analyzed 8-years of biennial panel data from Health and Retirement Study participants 50-years and older who self-identified as White (unweighted N (uN) = 5,595), Black (uN = 867), or Latino (uN = 565) for a total of uN = 7,027 individuals. We modeled diabetes and death over 8-years as function of baseline Cystatin-C (log transformed) adjusting for covariates and tested modifications in associations by race/ethnic background and sex. Mean log Cystatin-C at visit 1 was 0.03±0.32 standard deviation. A 10% increase in Cystatin-C levels was associated with 13% increased relative risk of diabetes at baseline (11% and 9% by years 4 and 8). A 10% increase in Cystatin-C was highly associated with increased relative risk of death (28% and 31% by years 4 and 8). These associations were present even after adjusting for possible confounders and were not modified by sex or racial/ethnic background. Despite differential risks for diabetes and mortality by racial/ethnic groups, Cystatin-C was equally predictive of these outcomes across groups. Cystatin-C dysregulations could be used as a risk indicator for diabetes and as a warning sign for accelerated risk of mortality.