Continuous Glucose Monitoring in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes

Twenty participants with end stage kidney disease (ESKD) and burnt-out diabetes, and 20 non-diabetic participants with ESKD will wear a continuous glucose monitoring (CGM) device for 10 days to see if the use of CGM is a better tool to assess glycemic control than glycosylated hemoglobin (HbA1c) in patients with ESKD on dialysis.

Study Overview

• Status: Completed
• Conditions: End Stage Kidney Disease
• Intervention / Treatment: Device: Continuous glucose monitoring (CGM)

Detailed Description

More than 37 million adults, or 14.7% of all Americans aged 18 and older, are living with diabetes. Controlling hyperglycemia is foundational to diabetes management and is necessary to reduce the risks of chronic diabetes complications and death. Diabetic nephropathy accounts for great morbidity, as diabetes is the number one cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the United States. It is estimated that diabetes affects up to 40% of patients with ESKD.

Assessment of glucose control in patients with advanced CKD/ESKD is complex due to changes in glucose homeostasis, potential effects on assays of glycemia, and altered pharmacokinetics of diabetes medications. Glycosylated hemoglobin (HbA1c) has been the gold standard to assess glycemic control in patients with diabetes. HbA1c reflects the average glycemic value over approximately 3 months. Although HbA1c is associated with chronic complications of diabetes in patients with normal kidney function, its predictive value is uncertain in patients with ESKD or estimated glomerular filtration rate (eGFR) <30 ml/min. HbA1c reliability in ESKD is reduced because of anemia, shortened erythrocyte lifespan, protein-energy wasting, and malnutrition-inflammation cachexia syndrome, among others. To overcome the limitations of HbA1c, alternative methods to assess long-term glycemic control have been proposed including fructosamine and glycated albumin. Fructosamine measures ketoamines formed by non-enzymatic glycation of serum proteins. It is a useful index for glycemic control over the prior 2 to 4 weeks, and some studies have reported that fructosamine more accurately reflects blood glucose control than HbA1c in anemic patients with ESKD on dialysis. However, there may be falsely low readings in the presence of hypoalbuminemia due to protein-energy wasting and in peritoneal dialysis due to dialysate protein loss. Glycated albumin is a useful marker reflecting glycemic control over the prior 2 to 4 weeks. In patients with ESKD, glycated albumin more rapidly reflects the status of blood glucose control than HbA1c. Like fructosamine, there is potential for falsely low readings in patients with peritoneal dialysis with dialysate protein losses and hypoalbuminemia.

Continuous glucose monitoring (CGM) technology in the outpatient setting has transformed glucose monitoring for diabetes self-management, providing more comprehensive glycemic control data than intermittent point-of-care capillary blood glucose monitoring and HbA1c.

Once progressed to ESKD, up to one fourth of patients experience resolution of their hyperglycemia, as defined by an HbA1c level of less than 6.5%, and consequently are no longer on antidiabetic agents and insulin. This phenomenon is known as "burnt-out diabetes" which is likely due to various underlying factors, including but not limited to, malnutrition, reduced clearance and degradation of insulin, decreased kidney gluconeogenesis, and accumulation of uremic toxins. These patients are likely at a greater risk of morbidity and mortality and an increased risk of hypoglycemic episodes. There is a need for further research in patients with ESKD to establish what is the most appropriate tool to assess glycemic control in those with 'burnt-out diabetes'.

This study will use CGM to measure patients' glucose with real-time levels as opposed to relying on surrogate markers like HbA1c. These results can give insight into the reality of glycemic control in these patients and can impact the best monitoring and treatment for patients with burnt-out diabetes. It is not known if patients with burnt-out diabetes have complete normoglycemia or if they may have episodes of (untreated) hyperglycemia, which may be associated with poor outcomes. The researchers of this study will compare glycemic control by CGM in patients with burnt-out diabetes and non-diabetic patients with ESKD.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Atlanta, Georgia, United States, 30318
      • Emory Dialysis at Northside
    • Atlanta, Georgia, United States, 30331
      • Emory Dialysis at Greenbriar
    • Decatur, Georgia, United States, 30034
      • Emory Dialysis at Candler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Dialysis treatment for more than 3 months
• HbA1c less than 6.5% at the first clinic visit
• Willing to wear a CGM for 10 days

Exclusion Criteria:

• Have used insulin or any diabetes treatment during the last 3 months
• Be pregnant or plan to become pregnant during the study
• Known allergy to medical-grade adhesives
• Taking acetaminophen (more than 1 gram every six hours) or hydroxyurea (may interfere with sensor membrane)
• Current or anticipated use of stress steroid doses (prednisone </= 5 mg or its equivalent is allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ESKD with Burnt-out Diabetes; Participants with ESKD and burnt-out diabetes wearing a CGM for 10 days.	Device: Continuous glucose monitoring (CGM); The Dexcom G6 CGM system is a compact, light-weight glucose testing device that measures glucose every 5 minutes. Participants will wear the CGM with the display off for 10 days while continuing their routine dialysis sessions.; Other Names: Dexcom G6 CGM
Experimental: ESKD without Diabetes; Non-diabetic participants with ESKD wearing a CGM for 10 days.	Device: Continuous glucose monitoring (CGM); The Dexcom G6 CGM system is a compact, light-weight glucose testing device that measures glucose every 5 minutes. Participants will wear the CGM with the display off for 10 days while continuing their routine dialysis sessions.; Other Names: Dexcom G6 CGM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemia Event Rate	Hypoglycemia is defined as blood glucose < 70 mg/dL and is assessed by Dexcom G6 CGM. The hypoglycemic event rate is defined as the number of hypoglycemic events per patient per day.	Up to Day 10
Nocturnal Hypoglycemia Event Rate	Hypoglycemia is defined as blood glucose < 70 mg/dL and is assessed by Dexcom G6 CGM. A nocturnal hypoglycemia episode is defined as an episode occurring during the time interval of 10:00 Post Meridiem (PM) to 6:00 Ante Meridiem (AM). The hypoglycemic event rate is defined as the number of hypoglycemic events per patient per day.	Up to Day 10
Percent of Time in Range (TIR) Between 70-180 mg/dL	Glycemic control is measured as the percentage of time that blood glucose levels are in the range of 70 and 180 mg/dL, as measured by CGM.	Up to 10 days
Percent of Time Above Range (Blood Glucose >180 mg/dL)	Glycemic control is assessed a the percentage of time in hyperglycemia, defined as the time above range (TAR) with blood glucose measurements >180 mg/dL, as measured by CGM.	Up to 10 days
Percent of Time Above Range (Blood Glucose >250 mg/dL)	Glycemic control is assessed a the percentage of time in hyperglycemia, defined as the time above range (TAR) with blood glucose measurements >250 mg/dL, as measured by CGM.	Up to 10 days
Duration of Hyperglycemia (Blood Glucose >180 mg/dL)	Glycemic control is assessed as the duration of hyperglycemia with blood glucose measurements >180 mg/dL, as measured by CGM for hyperglycemia time periods of greater than 15 minutes.	Up to 10 days
Duration of Hyperglycemia (Blood Glucose >250 mg/dL)	Glycemic control is assessed as the duration of hyperglycemia with blood glucose measurements >250 mg/dL, as measured by CGM for hyperglycemia time periods of greater than 15 minutes.	Up to 10 days
Number of Participants With Hyperglycemic Episodes With Blood Glucose >250 mg/dL	The number of participants experiencing hyperglycemia with blood glucose levels > 250 mg/dL as measured by CGM.	Up to Day 10
Percent of Time Below Range (Blood Glucose <70 mg/dL)	Glycemic control is assessed a the percentage of time in hypoglycemia, defined as the time below range (TBR) with blood glucose measurements < 70 mg/dL, as measured by CGM.	Up to 10 days
Percent of Time Below Range (Blood Glucose <54 mg/dL)	Glycemic control is assessed a the percentage of time in severe hypoglycemia, defined as the time below range (TBR) with blood glucose measurements < 54 mg/dL, as measured by CGM.	Up to 10 days
Number of Participants With Hypoglycemic Episodes	The number of participants experiencing hypoglycemia with blood glucose levels < 70 mg/dL as measured by CGM.	Up to Day 10
Number of Participants With Nocturnal Hypoglycemic Episodes	The number of participants experiencing nocturnal hypoglycemia with blood glucose levels < 70 mg/dL as measured by CGM. A nocturnal hypoglycemia episode is defined as an episode occurring during the time interval of 10:00 Post Meridiem (PM) to 6:00 Ante Meridiem (AM).	Up to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Daily Blood Glucose Concentration	Glycemic control is assessed as mean daily glucose concentration, measured by Dexcom G6 CGM.	Up to Day 10
Glycemic Variability Calculated by Mean Amplitude of Glycemic Excursions (MAGE)	Mean amplitude of glycemic excursions (MAGE) is the parameter for assessing glycemic variability and is calculated based on the arithmetic mean of differences between consecutive peaks and nadirs of differences greater than one standard deviation (SD) of mean glucose values. It is designated to assess major glucose swings and exclude minor ones.	Up to 10 Days

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Guillermo Umpierrez, MD, Emory University

Publications and helpful links

General Publications

• Kaminski CY, Galindo RJ, Navarrete JE, Zabala Z, Moazzami B, Gerges A, McCoy RG, Fayfman M, Vellanki P, Idrees T, Peng L, Umpierrez GE. Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes. Diabetes Care. 2024 Feb 1;47(2):267-271. doi: 10.2337/dc23-1276.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2022
• Primary Completion (Actual): March 9, 2023
• Study Completion (Actual): March 9, 2023

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: End stage renal disease; Dialysis; Kidney failure; Burnt-out diabetes
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: STUDY00004617

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes