Association of Glucose Variability with Coronary Artery Calcium Score in Patients with Nondialysis-Dependent CKD: Findings from KNOW-CKD

Background: Coronary artery calcification (CAC) is common in patients with chronic kidney disease (CKD) and predicts the risk of cardiovascular disease. Glucose variability has been implicated as an independent risk factor for adverse cardiovascular outcomes in various populations. We investigated whether glucose variability is associated with CAC prevalence and progression in patients with non-dialysis CKD. Methods: We used a prospective cohort of Korean patients with CKD. CAC score was measured at baseline and 4-year with Agatston units and fasting blood glucose was measured at baseline, 6-month, and 1-year. Glucose variability was defined as the standard deviation of three fasting blood glucose measurements. CAC prevalence was defined as a baseline CAC score greater than zero and CAC progression was defined as an annual CAC percentage change of 15% or greater. Results: Of the total of 1,518 patients, mean age was 53.5 years and 39.9% were men. According to four glucose variability group stratified by quartile, the prevalence of CAC was 37.6%, 38.9%, 52.0% and 76.3% for each group (Q1 vs Q4, prevalence ratio 1.35, 95% CI 1.08−1.69, p=0.009). In overall patients, higher glucose variability was associated with a higher risk of CAC progression (Q1 vs Q4, relative risk 1.85, 95% CI 1.20−2.87, p=0.005). In a subgroup analysis stratified according to the presence of diabetes, association was only observed in non-diabetic CKD patients (non-diabetic Q1 vs Q4, relative risk 2.01, 95% CI 1.12−3.62, p=0.02; diabetic CKD Q1 vs Q4, relative risk 1.31 (0.37−4.64), p=0.68). Conclusion: In non-dialysis CKD patients, higher glucose variability was associated with a higher prevalence of CAC, and in non-diabetic CKD patients, higher glucose variability was associated with CAC progression. Funding: Government Support – Non-U.S. - Prevalence of Coronary artery calcification (N=1518) Progression of Coronary artery calcification (N=959) Glucose variability group No. of events (%) Prevalence ratio (95% CI) P value No. of events (%) Odds ratio (95% CI) P value Q1 143 (37.6%) 1.0 − 71 (29.6%) 1.0 − Q2 148 (38.9%) 0.97 (0.77-1.22) 0.807 82 (34.2%) 1.15 (0.77-1.72) 0.496 Q3 197 (52.0%) 1.08 (0.87-1.35) 0.486 94 (39.2%) 1.32 (0.88-1.98) 0.186 Q4 289 (76.3%) 1.35 (1.08-1.69) 0.009 127 (53.1%) 1.85 (1.20-2.87) 0.005 Model was adjusted for age, sex, educational level, smoking status, charlson's comorbidity index, body mass index, systolic BP, statin use, eGFR category, and natural log-transformed urinary protein-to-creatinine ratio.