Use of Continuous Glucose Monitoring in the Assessment and Management of Patients With Diabetes and Chronic Kidney Disease

Abstract

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA_1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to 'burnt-out' beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.

Keywords: continuous glucose monitoring; diabetes; diabetic kidney disease; diabetic nephropathy; dialysis; end stage kidney disease (ESKD); type 2 (non-insulin-dependent) diabetes mellitus.

Figure 1

Potential enzymatic and electrochemical interference by substances commonly encountered in patients with chronic kidney disease using continuous glucose monitoring (CGM) systems. In the presence of oxygen (O₂), energy in glucose (G) is gradually released in the form of electrons in a series of electrochemical chains catalyzed by Glucose oxidase (GO), an enzyme with Flavin Adenine Dinucleotide (FAD) as cofactor. Released electron is captured by the electrode membrane to generate electric current between platinum electrode and silver electrode. Platinum and silver are chosen for their excellent biocompatibility, electro-conductivity and non-toxicity. Blue arrows indicate normal substrate for electrochemical chain. Red arrows indicate potential interference of CGM sensors by for example galactose, maltose from peritoneal dialysis fluids. Enzymatic interference includes competitive inhibition on active site of GOx by inhibitors. Electrochemical interference includes interaction between the electrode and interfering chemicals that pass through the semi-permeable membrane. GOx, glucose oxidase; FAD, Flavin Adenine Dinucleotide; H₂O₂, hydrogen peroxide; Pt, platinum; Ag, Silver. Adapted from Boehm et al. (35).

Figure 2

Glycemic disarray showing marked variability in patients during haemodialysis (HD) and post-HD period. 24-hour CGM glucose profile in a 58-year-old man with type 2 diabetes on HD using glucose- free dialysate. He was treated with insulin glargine 24 units in the morning and alogliptin 6.25mg daily with HbA_1c of 8.2%. The HD period is indicated by red arrow, showing an acute drop in sensor glucose, followed by post HD-associated hyperglycemia (orange arrow) up to 20 mmol/l at midnight. Green lines indicates target range (3.9 mmol/L to 10 mmol/L).

Figure 3

An illustrative 24-hour ambulatory glucose profile in a patient with type 2 diabetes on continuous ambulatory peritoneal dialysis (CAPD). He is on three 1.5% dextrose exchanges daily and basal-bolus insulin regimen. Laboratory measures of glycemic control were HbA_1c 7.5% and Fructosamine 224 µmol/L. Based on CGM metrics, glucose management indicator (GMI) was 6.9%, coefficient variation (CV) 36.9%. Blue arrow on bottom indicates times of insulin injection and meal intake. Vertical blue arrow on top indicate PD exchange timing, and horizontal blue arrow on top indicate PD exchange period. Green lines indicates target CGM glucose range (3.9 mmol/L to 10 mmol/L).