Serum cystatin C for risk stratification of prediabetes and diabetes populations

Background: The association between serum cystatin C level and vascular outcomes has not been fully elucidated in diabetes and is unclear in prediabetes. We aim to evaluate whether cystatin C level predicts future risk for mortality and vascular outcomes in prediabetes and diabetes.

Methods: A total of 85,371 participants with prediabetes and diabetes, and available baseline cystatin C in the UK biobank were included with a 14-year follow-up. Cox hazards models were used to calculate the associations between cystatin C level, mortality (all-cause, cause-specfic mortality) and vascular outcomes (myocardial infarction [MI], stroke, end-stage renal disease [ESRD] and diabetic retinopathy [DR]). The 1136 diabetes subjects in Guangzhou Diabetic Eye Study (GDES) were included for examing the impact of cystatin C on in vivo retinal degeneration and microvascular changes by using SS-OCT and OCTA.

Results: The highest cystatin C quartile had increased risks of all-cause (hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.86-2.19), cardiovascular (HR, 2.29; 95% CI 1.97-2.67), cancer (HR, 1.86; 95% CI 1.65-2.10) and other-cause mortality (HR, 2.24; 95% CI 1.90-2.64), MI (HR, 1.40; 95% CI 1.26-1.55), stroke (HR, 1.88; 95% CI, 1.57-2.26), ESRD (HR, 7.33; 95% CI, 5.02-10.71), DR (HR, 1.17; 95% CI 1.03-1.32) than those in the lowest quartile. Adding cystatin C to the conventional model improved C-statistic for all-cause (0.699-0.724), cardiovascular (0.762-0.789), cancer (0.661-0.674) and other-cause mortality (0.675-0.715), MI (0.748-0.750), stroke (0.712-0.718), and ESRD (0.808-0.827). The GDES analysis identified a strong association between increased cystatin C levels and diminished retinal neural layers, as well as microvascular rarefaction in both macular and optic disc regions (all P < 0.05).

Conclusions: Serum cystatin C refines the risk stratification for mortality and vascular outcomes among patients with prediabetes or diabetes.