Continuous Glucose Monitoring and Use of Alternative Markers To Assess Glycemia in Chronic Kidney Disease

Abstract

Objective: In chronic kidney disease, glycated albumin and fructosamine have been postulated to be better biomarkers of glycemic control than HbA_1c. We evaluated the accuracy, variability, and covariate bias of three biomarkers (HbA_1c, glycated albumin, and fructosamine) compared with continuous glucose monitoring (CGM)-derived measurement of glycemia across estimated glomerular filtration rate (eGFR) in type 2 diabetes.

Research design and methods: A prospective cohort study was conducted of 104 participants with type 2 diabetes, 80 with eGFR <60 mL/min/1.73 m² (not treated with dialysis) and 24 frequency-matched control subjects with eGFR ≥60 mL/min/1.73 m². Participants wore a blinded CGM for two 6-day periods separated by 2 weeks, with blood and urine collected at the end of each CGM period. HbA_1c, glycated albumin, and fructosamine were measured by high-performance liquid chromatographic, enzymatic, and colorimetric nitroblue tetrazolium methods, respectively.

Results: Within-person biomarker values were strongly correlated between the two CGM periods (r = 0.92-0.95), although no marker fully captured the within-person variability of mean CGM glucose. All markers were similarly correlated with mean CGM glucose (r = 0.71-77). Compared with mean CGM glucose, glycated albumin and fructosamine were significantly biased by age, BMI, serum iron concentration, transferrin saturation, and albuminuria; HbA_1c was underestimated in those with albuminuria.

Conclusions: Glycated albumin and fructosamine were not less variable than HbA_1c at a given mean CGM glucose level, with several additional sources of bias. These results support measuring HbA_1c to monitor trends in glycemia among patients with eGFR <60 mL/min/1.73 m². Direct measurements of glucose are necessary to capture short-term variability.