End Stage Kidney Disease
Conditions
Keywords
Burnt-out diabetes, Dialysis, End stage renal disease, Kidney failure
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.
Interventions
DEVICEContinuous 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.
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Nocturnal Hypoglycemic Episodes | Up 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). |
| Number of Participants With Hypoglycemic Episodes | Up to Day 10 | The number of participants experiencing hypoglycemia with blood glucose levels \< 70 mg/dL as measured by CGM. |
| Nocturnal Hypoglycemia Event Rate | Up 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. |
| Percent of Time in Range (TIR) Between 70-180 mg/dL | Up 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 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. |
| 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. |
| 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/dL | Up to Day 10 | The number of participants experiencing hyperglycemia with blood glucose levels \> 250 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. |
| Hypoglycemia Event Rate | Up 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Mean Daily Blood Glucose Concentration | Up to Day 10 | Glycemic control is assessed as mean daily glucose concentration, measured by Dexcom G6 CGM. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Emory Dialysis centers in Atlanta, Georgia, USA. Participant enrollment began August 10, 2022 and all follow-up assessments were completed by March 9, 2023.
Participants by arm
| Arm | Count |
|---|---|
| ESKD With Burnt-out Diabetes Participants with ESKD and burnt-out diabetes wearing a CGM for 10 days. The Dexcom G6 CGM system is a compact, light-weight glucose testing device that measures glucose every 5 minutes. Participants wore the CGM with the display off for 10 days while continuing their routine dialysis sessions. | 20 |
| ESKD Without Diabetes Non-diabetic participants with ESKD wearing a CGM for 10 days. The Dexcom G6 CGM system is a compact, light-weight glucose testing device that measures glucose every 5 minutes. Participants wore the CGM with the display off for 10 days while continuing their routine dialysis sessions. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | ESKD With Burnt-out Diabetes | ESKD Without Diabetes |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.9 | 62.7 years STANDARD_DEVIATION 8.3 | 60.1 years STANDARD_DEVIATION 9.5 |
| Coronary artery disease | 10 Participants | 7 Participants | 3 Participants |
| Fructosamine level (mmol/L) greater than or equal to 285 | 28 Participants | 15 Participants | 13 Participants |
| Fructosamine level (mmol/L) less than 285 | 8 Participants | 3 Participants | 5 Participants |
| Fructosamine level (mmol/L) not assessed | 4 Participants | 2 Participants | 2 Participants |
| Glycated albumin level 13.6% to < 16% | 9 Participants | 4 Participants | 5 Participants |
| Glycated albumin level greater than or equal to 16% | 18 Participants | 12 Participants | 6 Participants |
| Glycated albumin level less than 13.6% | 9 Participants | 2 Participants | 7 Participants |
| Glycated albumin level not assessed | 4 Participants | 2 Participants | 2 Participants |
| Heart failure | 29 Participants | 14 Participants | 15 Participants |
| Hemoglobin A1c (HbA1c) < 5.7% | 23 Participants | 10 Participants | 13 Participants |
| Hemoglobin A1c (HbA1c) 5.7 to < 6.5% | 17 Participants | 10 Participants | 7 Participants |
| Hypertension | 38 Participants | 20 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 20 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 40 Participants | 20 Participants | 20 Participants |
| Sex: Female, Male Female | 18 Participants | 10 Participants | 8 Participants |
| Sex: Female, Male Male | 22 Participants | 10 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Duration of Hyperglycemia (Blood Glucose >180 mg/dL) | 4.1 hours per day | Standard Deviation 3.4 |
| ESKD Without Diabetes | Duration of Hyperglycemia (Blood Glucose >180 mg/dL) | 1.1 hours per day | Standard Deviation 1.3 |
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Duration of Hyperglycemia (Blood Glucose >250 mg/dL) | 0.5 hours per day | Standard Deviation 0.7 |
| ESKD Without Diabetes | Duration of Hyperglycemia (Blood Glucose >250 mg/dL) | 0.1 hours per day | Standard Deviation 0.1 |
Primary
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.
Time frame: Up to Day 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Hypoglycemia Event Rate | 3.60 events per patient per day | Standard Deviation 7.37 |
| ESKD Without Diabetes | Hypoglycemia Event Rate | 3.44 events per patient per day | Standard Deviation 10.43 |
Primary
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.
Time frame: Up to Day 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Nocturnal Hypoglycemia Event Rate | 1.30 events per patient per day | Standard Deviation 3.05 |
| ESKD Without Diabetes | Nocturnal Hypoglycemia Event Rate | 0.94 events per patient per day | Standard Deviation 2.86 |
Primary
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.
Time frame: Up to Day 10
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ESKD With Burnt-out Diabetes | Number of Participants With Hyperglycemic Episodes With Blood Glucose >250 mg/dL | 11 Participants |
| ESKD Without Diabetes | Number of Participants With Hyperglycemic Episodes With Blood Glucose >250 mg/dL | 3 Participants |
Primary
Number of Participants With Hypoglycemic Episodes
The number of participants experiencing hypoglycemia with blood glucose levels \< 70 mg/dL as measured by CGM.
Time frame: Up to Day 10
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ESKD With Burnt-out Diabetes | Number of Participants With Hypoglycemic Episodes | 10 Participants |
| ESKD Without Diabetes | Number of Participants With Hypoglycemic Episodes | 11 Participants |
Primary
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).
Time frame: Up to Day 10
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ESKD With Burnt-out Diabetes | Number of Participants With Nocturnal Hypoglycemic Episodes | 7 Participants |
| ESKD Without Diabetes | Number of Participants With Nocturnal Hypoglycemic Episodes | 4 Participants |
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Percent of Time Above Range (Blood Glucose >180 mg/dL) | 17.2 percentage of time | Standard Deviation 14.1 |
| ESKD Without Diabetes | Percent of Time Above Range (Blood Glucose >180 mg/dL) | 4.6 percentage of time | Standard Deviation 5.3 |
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Percent of Time Above Range (Blood Glucose >250 mg/dL) | 2.0 percentage of time | Standard Deviation 3 |
| ESKD Without Diabetes | Percent of Time Above Range (Blood Glucose >250 mg/dL) | 0.1 percentage of time | Standard Deviation 0.4 |
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Percent of Time Below Range (Blood Glucose <54 mg/dL) | 1.3 percentage of time | Standard Deviation 3.5 |
| ESKD Without Diabetes | Percent of Time Below Range (Blood Glucose <54 mg/dL) | 0.4 percentage of time | Standard Deviation 1.7 |
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Percent of Time Below Range (Blood Glucose <70 mg/dL) | 2.5 percentage of time | Standard Deviation 5.8 |
| ESKD Without Diabetes | Percent of Time Below Range (Blood Glucose <70 mg/dL) | 1.5 percentage of time | Standard Deviation 5 |
Primary
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.
Time frame: Up to 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Percent of Time in Range (TIR) Between 70-180 mg/dL | 80.4 percentage of time | Standard Deviation 14 |
| ESKD Without Diabetes | Percent of Time in Range (TIR) Between 70-180 mg/dL | 94.0 percentage of time | Standard Deviation 6.4 |
Secondary
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.
Time frame: Up to 10 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Glycemic Variability Calculated by Mean Amplitude of Glycemic Excursions (MAGE) | 54.9 mg/dL | Standard Deviation 18.2 |
| ESKD Without Diabetes | Glycemic Variability Calculated by Mean Amplitude of Glycemic Excursions (MAGE) | 42.4 mg/dL | Standard Deviation 9.4 |
Secondary
Mean Daily Blood Glucose Concentration
Glycemic control is assessed as mean daily glucose concentration, measured by Dexcom G6 CGM.
Time frame: Up to Day 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESKD With Burnt-out Diabetes | Mean Daily Blood Glucose Concentration | 141.7 mg/dL | Standard Deviation 22.2 |
| ESKD Without Diabetes | Mean Daily Blood Glucose Concentration | 125.7 mg/dL | Standard Deviation 13.7 |