Clinical trial NCT05741489: Continuous Glucose Monitoring in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes
Official title: Continuous Glucose Monitoring in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Kidney Disease
Keywords: Burnt-out diabetes
Dialysis
End stage renal disease
Kidney failure
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2023-02-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percent of Time in Range (TIR) Between 70-180 mg/dL
timeFrame: Up to 10 days
measure: Percent of Time Above Range (Blood Glucose >180 mg/dL)
timeFrame: Up to 10 days
measure: Percent of Time Above Range (Blood Glucose >250 mg/dL)
timeFrame: Up to 10 days
measure: Duration of Hyperglycemia (Blood Glucose >180 mg/dL)
timeFrame: Up to 10 days
measure: Duration of Hyperglycemia (Blood Glucose >250 mg/dL)
timeFrame: Up to 10 days
measure: Number of Participants With Hyperglycemic Episodes With Blood Glucose >250 mg/dL
timeFrame: Up to Day 10
measure: Percent of Time Below Range (Blood Glucose <70 mg/dL)
timeFrame: Up to 10 days
measure: Percent of Time Below Range (Blood Glucose <54 mg/dL)
timeFrame: Up to 10 days
measure: Hypoglycemia Event Rate
timeFrame: Up to Day 10
measure: Number of Participants With Hypoglycemic Episodes
timeFrame: Up to Day 10
measure: Nocturnal Hypoglycemia Event Rate
timeFrame: Up to Day 10
measure: Number of Participants With Nocturnal Hypoglycemic Episodes
timeFrame: Up to Day 10
Secondary outcomes:
measure: Mean Daily Blood Glucose Concentration
timeFrame: Up to Day 10
measure: Glycemic Variability Calculated by Mean Amplitude of Glycemic Excursions (MAGE)
timeFrame: Up to 10 Days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory Dialysis at Northside
state: Georgia
city: Atlanta
country: United States
facility: Emory Dialysis at Greenbriar
state: Georgia
city: Decatur
country: United States
facility: Emory Dialysis at Candler
state: Georgia
Study officials:
affiliation: Emory University
name: Guillermo Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.