Assessment of Glycemic Control in Patients With Type 2 Diabetes Mellitus and Late Stage Chronic Kidney Disease

Diabetes control is often assessed by tests of glucose levels over time, such as the glycosylated hemoglobin A1c (HbA1c) and fructosamine. In the later stages of chronic kidney disease (CKD) there is limited data available on the utility of these tests. There are reasons to believe that the tests may be less accurate in this population. Continuous glucose monitoring (CGM) offers an effective method for understanding the totality of glucose exposure and incidence of both hyperglycemic and hypoglycemic excursions.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Diabetes
• Intervention / Treatment: Device: Continuous Glucose Monitoring

Detailed Description

In the proposed study Investigator plan to utilize CGM in patients with late stage CKD stages 3b-5 to 1) determine accuracy of HbA1c and serum fructosamine testing as measures of glucose control in patients with Type 2 Diabetes Mellitus (T2DM), 2) Better understand test characteristics in the late stage CKD population (correlation, linear equation, slope, Y intercept, average glucose at different HbA1c levels), 3) Develop a preliminary understanding of how test characteristics differ in late stage CKD compared to other patients with diabetes, 4) quantify time burden and number of episodes of hypoglycemia, 4) study hyperglycemic burden and 5) analyze glucose variability. The research staff will explain the study to patients that meet all inclusion criteria. Patients will get time to understand the study, review the consent document, ask questions to the PI, and then provide their consent to participate in the study. On Day 1 of the study, a CGM (Freestyle Libre) device will be placed on patients with CKD 3b-5 which will be worn for 14 consecutive days. Patients will return on Day 14 to remove the CGM device. HbA1c and fructosamine values will be drawn on Day 14 and these results will be compared with average glucose monitoring values as recorded on the CGM device. Incidence, duration, and severity of both hypoglycemic and hyperglycemic events will be analyzed. Investigators hypothesis that there will be significant variability in the serum HbA1c values when compared with calculated HbA1c from CGM readings. Investigators also hypothesize that the results will reflect a greater incidence of hypoglycemia in this population by CGM analysis.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health (Division Endocrinology and Nephrology)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years and older with ability to speak and understand English
• Established diagnosis of type 2 Diabetes Mellitus
• Chronic Kidney Disease (stages 3b, 4 or 5, eGFR (Glomerular Filtration Rate) < 45 ml/min, and not on dialysis) documented within 3 months of enrollment

Exclusion Criteria:

• Type 2 Diabetes Mellitus.
• Patient with End stage kidney disease on Dialysis.
• Presence of Hemoglobinopathies.
• Red blood cell transfusion in the last 12 weeks.
• Hb < 9 g/dL documented within 3 months of enrollment - Dosing with an erythropoiesis stimulating agent is acceptable but dose must be stable for two months.
• Use of acetaminophen on a daily basis.
• Systemic steroid treatment in the past 12 weeks.
• Greater than 50% dose change in diabetes medications or new diabetes medications started in the previous 8 weeks.
• Currently pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Continuous glucose monitoring; If subjects meet inclusion criteria then they will return to the research site on Day 1 to place Freestyle Libre Pro device by the research staff for 14-day monitoring.; Subjects will be advised to return to the research site on Day 14 to remove the CGM device for analysis. On Day 14, blood will be drawn for HbA1c and fructosamine, The blood drawn for this research will be approximately 10-15 milliliters.; There are no drug washout periods. Subjects will continue to take all their medications and/or insulins as prescribed by their doctor.; Baseline data including age, race, ethnicity, past medical history, home medication list, and diabetes related laboratory data will be collected.

Device: Continuous Glucose Monitoring; The FreeStyle Libre Pro Flash Glucose Monitoring System is a professional continuous glucose monitoring (CGM) device indicated for detecting trends and tracking patterns in persons (age 18 and older) with diabetes. The Freestyle Libre Pro device is FDA approved (PMA# P150021). Participants will use the FreeStyle Libre Pro Flash Glucose Monitoring device according to its approved use, on the back of the arm.; CGM monitoring will be performed on Day 1 by placing the Freestyle Libre Pro on research subjects for intended use of 14 days.; Subjects will be advised to return to the research site on Day 14 to remove the CGM device for analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Glucose Concentration Measured by CGM	Mean glucose concentration (mg/dL) will be measured using measurements taken by CGM device.	14 Days
Number of Participants With Hypoglycemic Events	Hypoglycemic event will be considered when blood sugar level is <=70 mg/dl. Detail information like time of event, number of subjects with an event, duration of event will be analyzed.	14 Days
Mean Number of Hypoglycemic Events Per Participant.	Total number of hypoglycemic events per subject will be calculated during the study period. Mean number of events per subject will be analyzed.	14 Days
Duration Hypoglycemic Events	As monitoring device measures blood glucose level numerous time, duration of hypoglycemic event will be calculated in percent time per subject based on total duration of time subject wore CGM device.	14 Days
Mean HbA1c	HbA1c collected at end of the participation.	14 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Serum Fructosamine Concentration	Serum fructosamine (µmol/L) collected at the end of participation.	14 Days
Determination of Serum Fructosamine	Using blood glucose information measured with continuous blood glucose monitoring device, probable level of serum fructosamine (µmol/L) will be measured for each participant and mean will be analyzed.	14 days

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Lubaina Presswala, DO, Northwell Health

Publications and helpful links

General Publications

• Miedema K. Standardization of HbA1c and Optimal Range of Monitoring. Scand J Clin Lab Invest Suppl. 2005;240:61-72. doi: 10.1080/00365510500236143.
• Rabkin R, Ryan MP, Duckworth WC. The renal metabolism of insulin. Diabetologia. 1984 Sep;27(3):351-7. doi: 10.1007/BF00304849.
• Castellino P, DeFronzo RA. Glucose metabolism and the kidney. Semin Nephrol. 1990 Sep;10(5):458-63.
• Dolscheid-Pommerich RC, Kirchner S, Weigel C, Eichhorn L, Conrad R, Stoffel-Wagner B, Zur B. Impact of carbamylation on three different methods, HPLC, capillary electrophoresis and TINIA of measuring HbA1c levels in patients with kidney disease. Diabetes Res Clin Pract. 2015 Apr;108(1):15-22. doi: 10.1016/j.diabres.2015.01.034. Epub 2015 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2017
• Primary Completion (Actual): August 21, 2018
• Study Completion (Actual): August 21, 2018

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 17-0531

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Access to study data will be limited to Institutional Review Board (IRB) approved personnel only.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No