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

Not Applicable
Completed
Conditions
End Stage Kidney Disease
Interventions
Device: Continuous glucose monitoring (CGM)
Registration Number
NCT05741489
Lead Sponsor
Emory University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ESKD without DiabetesContinuous glucose monitoring (CGM)Non-diabetic participants with ESKD wearing a CGM for 10 days.
ESKD with Burnt-out DiabetesContinuous glucose monitoring (CGM)Participants with ESKD and burnt-out diabetes wearing a CGM for 10 days.
Primary Outcome Measures
NameTimeMethod
Percent of Time in Range (TIR) Between 70-180 mg/dLUp to 10 days

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.

Percent of Time Below Range (Blood Glucose <70 mg/dL)Up to 10 days

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.

Percent of Time Below Range (Blood Glucose <54 mg/dL)Up to 10 days

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.

Percent of Time Above Range (Blood Glucose >180 mg/dL)Up to 10 days

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.

Duration of Hyperglycemia (Blood Glucose >180 mg/dL)Up to 10 days

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.

Duration of Hyperglycemia (Blood Glucose >250 mg/dL)Up to 10 days

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.

Number of Participants With Hyperglycemic Episodes With Blood Glucose >250 mg/dLUp to Day 10

The number of participants experiencing hyperglycemia with blood glucose levels \> 250 mg/dL as measured by CGM.

Number of Participants With Nocturnal Hypoglycemic EpisodesUp to Day 10

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).

Percent of Time Above Range (Blood Glucose >250 mg/dL)Up to 10 days

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.

Nocturnal Hypoglycemia Event RateUp to Day 10

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.

Hypoglycemia Event RateUp to Day 10

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.

Number of Participants With Hypoglycemic EpisodesUp to Day 10

The number of participants experiencing hypoglycemia with blood glucose levels \< 70 mg/dL as measured by CGM.

Secondary Outcome Measures
NameTimeMethod
Mean Daily Blood Glucose ConcentrationUp to Day 10

Glycemic control is assessed as mean daily glucose concentration, measured by Dexcom G6 CGM.

Glycemic Variability Calculated by Mean Amplitude of Glycemic Excursions (MAGE)Up to 10 Days

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.

Trial Locations

Locations (4)

Emory Dialysis at Northside

🇺🇸

Atlanta, Georgia, United States

Emory Dialysis at Greenbriar

🇺🇸

Atlanta, Georgia, United States

Grady Memorial Hospital

🇺🇸

Atlanta, Georgia, United States

Emory Dialysis at Candler

🇺🇸

Decatur, Georgia, United States

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