The Use of HbA1c, Glycated Albumin and Continuous Glucose Monitoring to Assess Glucose Control in the Chronic Kidney Disease Population Including Dialysis

Abstract

<b><i>Background:</i></b> Glycated haemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) has limitations as a glycemic marker for patients with diabetes and CKD and for those receiving dialysis. Glycated albumin is an alternative glycemic marker, and some studies have found that glycated albumin more accurately reflects glycemic control than HbA<sub>1c</sub> in these groups. However, several factors are known to influence the value of glycated albumin including proteinuria. Continuous glucose monitoring (CGM) is another alternative to HbA<sub>1c</sub>. CGM allows one to assess mean glucose, glucose variability, and the time spent in hypo-, normo-, and hyperglycemia. Currently, several different CGM models are approved for use in patients receiving dialysis; CKD (not on dialysis) is not a contraindication in any of these models. Some devices are for blind recording, while others provide real-time data to patients. Small studies suggest that CGM could improve glycemic control in hemodialysis patients, but this has not been studied for individual CKD stages. <b><i>Summary:</i></b> Glycated albumin and CGM avoid the pitfalls of HbA<sub>1c</sub> in CKD and dialysis populations. However, the value of glycated albumin may be affected by several factors. CGM provides a precise estimation of the mean glucose. Here, we discuss the strengths and limitations for using HbA1c, glycated albumin, or CGM in CKD and dialysis population. <b><i>Key Messages:</i></b> Glycated albumin is an alternative glycemic marker but is affected by proteinuria. CGM provides a precise estimation of mean glucose and glucose variability. It remains unclear if CGM improves glycemic control in the CKD and dialysis populations.

Use of continuous glucose monitoring system in patients with type 2 mellitus diabetic during hemodialysis treatment

“…Patients undergoing dialysis treatment have erythrocytes with a reduced shelf life and often use erythropoiesis-stimulating agents to treat nephrogenic anemia. These agents, when increasing erythropoiesis, increase the proportion of young non-glycated erythrocytes, underestimating the calculated mean glycemia [ 3 ]. It also contributes to this underestimating the reduction in lifespan of erythrocytes.…”

Continuous glucose monitoring in an end‐stage renal disease patient with diabetes receiving hemodialysis

“…A CGM device uses a small subcutaneous sensor that is inserted for a period of 6–14 days to measure interstitial glucose levels 8,9 . Most available sensors measure glucose enzymatically (via glucose oxidase) and provide an indirect measurement of blood glucose as interstitial and blood glucose equilibrate 10 . Real‐time CGM devices automatically transmit interstitial glucose values to a patient's receiver or smartphone as frequently as every 5 min, and in addition to presenting a continuous display of glucose levels can also show (1) directional glucose trends and rates of change (allowing patients to pre‐emptively adjust their medications and dietary intake) and additional metrics such as (2) glucose variability (i.e., fluctuations in glucose with values ≥ 36% signal hypoglycemia‐risk 10,11 ), and (3) time‐in‐range (i.e., proportion of time spent in the target glucose range, time above range, and time below range) 8–10 .…”

“…Most available sensors measure glucose enzymatically (via glucose oxidase) and provide an indirect measurement of blood glucose as interstitial and blood glucose equilibrate 10 . Real‐time CGM devices automatically transmit interstitial glucose values to a patient's receiver or smartphone as frequently as every 5 min, and in addition to presenting a continuous display of glucose levels can also show (1) directional glucose trends and rates of change (allowing patients to pre‐emptively adjust their medications and dietary intake) and additional metrics such as (2) glucose variability (i.e., fluctuations in glucose with values ≥ 36% signal hypoglycemia‐risk 10,11 ), and (3) time‐in‐range (i.e., proportion of time spent in the target glucose range, time above range, and time below range) 8–10 . The Dexcom G6 CGM model used by this patient also allows users to tailor low‐ and high‐glucose thresholds and anticipatory low glucose alerts, and these CGM data and alerts can be remotely shared with others (i.e., care‐partners and healthcare providers) via smartphone and data/cloud‐based technology 12…”

“…Glycated albumin and fructosamine are produced from the non‐enzymatic glycation of serum proteins and albumin, respectively, and correspond to mean glycemic control over a 7‐ to 14‐day period. While glycated albumin and fructosamine may also be confounded by non‐glycemic factors, including conditions leading to altered serum protein states such as malnutrition, hepatic disease, thyroid dysfunction, pregnancy, hyperuricemia, smoking, and steroid use, 4,9 some data suggest that glycated albumin and fructosamine are more accurate than HbA1c in assessing glycemic status in dialysis patients 10,26 . In addition, there is lack of consensus on standardized measurement methods and universally accepted reference intervals for these metrics 10 …”

“…While the Dexcom G6 device is not yet approved in dialysis patients, 10,12 there is ongoing research studying the agreement between this CGM technology versus “gold‐standard” blood glucose measurements that aim to confirm the former metric's accuracy in diabetic ESRD patients (ClinicalTrials.gov #NCT04217161) 32 . To date, two small pilot studies of diabetic ESRD patients receiving hemodialysis in France have shown that CGM regimens improve short‐term glycemic control without increasing hypoglycemia 33,34 .…”