Glycaemic Markers in Persons With Type 2 Diabetes on Haemodialysis

NCT ID: NCT03909269

Last Updated: 2020-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

88 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-04-01

Study Completion Date

2020-04-01

Brief Summary

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To investigate the correlation between the mean glucose concentration measured by continuous glucose monitoring (CGM) and the estimated mean blood glucose from glycated haemoglobin A1c (HbA1c) in persons with type 2 diabetes and on chronic haemodialysis. Furthermore, the aim is to compare CGM and HbA1c with glycated albumin and fructosamine.

Detailed Description

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Background:

In persons with diabetes, glycated haemoglobin A1c (HbA1c) is used as a retrospective measurement of the patient's estimated mean blood glucose over the past 3 months. HbA1c forms in a non-enzymatic pathway when haemoglobin is exposed to blood glucose. The normal range of HbA1c and the correlation to the estimated mean blood glucose is determined from studies in persons with normal erythrocyte turnover of approximately 120 days and without severe chronic kidney disease (CKD). Several smaller studies have shown that HbA1c in persons with type 2 diabetes and CKD, especially on chronic haemodialysis, is an uncertain marker of the mean blood glucose. Generally, studies show that HbA1c underestimate the actual mean blood glucose. The reason for a false low HbA1c in persons with type 2 diabetes and with CKD has yet to be established. However, it is known that erythropoietin treatment and iron infusion increases the erythropoiesis, which results in new non-glycated erythrocytes, and this is likely to lower HbA1c. The erythrocyte life span is found to be reduced in persons on dialysis, which in combination with blood loss from the dialysis also contributes to a reduction in HbA1c. The shorter erythrocyte life span is thought to be due to the toxic uraemic environment as well as mechanical damage caused by haemodialysis.

Objective:

To investigate the correlation between the mean glucose concentration measured by CGM and the estimated mean blood glucose from HbA1c in persons with type 2 diabetes and on chronic haemodialysis compared to a control groups of persons with type 2 diabetes and normal renal function.

Method:

Prospective case-control study over 17 weeks with 40 persons in each group. The case group consist of 40 persons with type 2 diabetes and on chronic haemodialysis. The control group consists of persons with type 2 diabetes and normal renal function (defined as and estimated glomerular filtration rate (eGFR) above 60 ml/min). CGM is performed for a maximum of seven days on week 0, 4, 8, 12 and 16 of the study period with simultaneous analysis of glycaemic markers (HbA1c, glycated albumine and fructosamine). Each of the first five visit was conducted with 3 to 5 weeks interval and the final visit not more than two weeks after the final visit. The erythrocyte life span will be measured with an isotope (Crom-51) method in both the dialysis group and the control group, to establish if diminished erythrocyte life span and falsely low HbA1c is correlated.

Statistical methods:

The null hypothesis is that there is no difference between the ratio of total mean glucose from CGM and estimated mean blood glucose from HbA1c at week 17 when measured in type 2 diabetic persons on chronic haemodialysis compared to type 2 diabetic persons with normal renal function.

The alternative hypothesis is that there is a difference in the ratio between the groups which in a pilot study of persons with diabetes on chronic haemodialysis was found to be 0.16 (mean glucose from CGM/mean blood glucose from HbA1c) when compared to persons with diabetes with out nephropathy.

From one of the pilot arms ώ = 0.148 and σ = 0.128 were extracted. The following scenarios were considered; β(0) = 0 and β (1) = 0, 0.01, ..., 0.2 and n = 40. For each scenario, 5000 data sets were simulated in accordance with the above specifications. Each data set was analyzed by a mixed linear model with treatment arm as fixed effect and person as random effect. The hypothesis β(0) = β(1) was tested at a significance of 5%. The simulated effect in each scenario was calculated as the fraction of rejections in the 5000 tests. Datasets were simulated in the statistical programming language R (www.r-project.org). The smallest difference in the ratio of mean glucose from CGM and mean blood glucose from HbA1c that could be detected with a power of 80% based on the likelihood ratio test described above and using a 5% significance level was 0.1 for n=40 per arm.

Conditions

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Diabetic Nephropathy Type 2 Type2 Diabetes

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Haemodialysis and type 2 diabetes

On chronic haemodialysis and type 2 diabetes

Continuous glucose monitoring

Intervention Type DEVICE

Continuous glucose monitoring five times over 17 weeks

Glycaemic markers

Intervention Type DIAGNOSTIC_TEST

Measurement of HbA1c by immunoassay (Roche) and chromatography (TOSOH), including glycated albumin and fructosamine.

Erythrocyte life span

Intervention Type RADIATION

Erythrocyte life span measured by Crom-51 labelling over 4 weeks

Carbon monoxide (CO)-rebreathing method

Intervention Type DEVICE

Measurement of total blood volume, plasma volume and erythrocyte volume

Control group

Type 2 diabetes and with eGFR above 60ml/min

Continuous glucose monitoring

Intervention Type DEVICE

Continuous glucose monitoring five times over 17 weeks

Glycaemic markers

Intervention Type DIAGNOSTIC_TEST

Measurement of HbA1c by immunoassay (Roche) and chromatography (TOSOH), including glycated albumin and fructosamine.

Erythrocyte life span

Intervention Type RADIATION

Erythrocyte life span measured by Crom-51 labelling over 4 weeks

Interventions

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Continuous glucose monitoring

Continuous glucose monitoring five times over 17 weeks

Intervention Type DEVICE

Glycaemic markers

Measurement of HbA1c by immunoassay (Roche) and chromatography (TOSOH), including glycated albumin and fructosamine.

Intervention Type DIAGNOSTIC_TEST

Erythrocyte life span

Erythrocyte life span measured by Crom-51 labelling over 4 weeks

Intervention Type RADIATION

Carbon monoxide (CO)-rebreathing method

Measurement of total blood volume, plasma volume and erythrocyte volume

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Type 2 diabetes\*
* BMI 17.5-50 kg/m2
* Receiving antidiabetic treatment
* Chronic haemodialysis treatment for a minimum of 3 months
* 24 hour urinary protein excretion of less than 10.0 g/day at screening or within the last 6 months


* Type 2 diabetes\*
* BMI 17.5-50 kg / m2
* Receiving antidiabetic treatment
* Plasma creatinine in the normal range (men: 60-105 μmol/l, women: 45-90 μmol/l)
* eGFR \> 60 ml/min/1.73m2
* Urinary Albumin-to-Creatinine Ratio \< 300mg/g or 24h urinary protein excretion \<0.3g at screening or within the last 6 months

Exclusion Criteria

* Type 1 diabetes
* Acute or chronic pancreatitis
* Intermittent treatment with steroid during study period (defined as more than two days)
* Haemoglobin \< 6.0 mmol / l (day of screening)
* Hypertriglyceridemia (≥ 10mmol / L)
* Hyperbilirubinemia (≥ 35 μmol / L)
* Pregnant or breast-feeding
* Blood transfusion within the last 3 months
* Blood transfusion during the investigation period
* Splenectomy
* High alcohol consumption (defined as more than 21 units per week)
* Vitamin E supplement
* Ribavirin treatment
* Interferon Alpha treatment
* Positive for haemoglobinopathy (examined for haemoglobinopathy if patients come from Africa, Mediterranean, Middle East, Iran, Iraq, India, Pakistan or Southeast Asia)
* Severe infections


* Type 1 diabetes
* Acute or chronic pancreatitis
* Intermittent treatment with steroid during study period (defined as more than two days)
* Haemoglobin \<7.3 mmol / l for women
* Haemoglobin \<8.3 mmol / l for men
* Hypertriglyceridemia (≥ 10mmol / L)
* Hyperbilirubinemia (≥ 35 μmol / L)
* Pregnant or breast-feeding
* Blood transfusion within the last 3 months
* Blood transfusion during the investigation period
* Splenectomy
* Intermittent treatment with steroid during study period (defined as more than two days)
* High alcohol consumption (defined as more than 21 units per week)
* Vitamin E supplement
* Ribavirin
* Interferon Alpha treatment
* Positive for haemoglobinopathy (examined for haemoglobinopathy if patients come from Africa, Mediterranean, Middle East, Iran, Iraq, India, Pakistan or Southeast Asia)
* Severe infections

\*Inclusion with diagnosis of type 2 diabetes was defined as ongoing antidiabetic treatment and previously diagnosed with type 2 diabetes according to the following criteria:
* A random venous plasma glucose concentration ≥ 11.1 mmol/l or
* A fasting plasma glucose concentration ≥ 7.0 mmol/l (whole blood ≥ 6.1 mmol/l) or
* Two hour plasma glucose concentration ≥ 11.1 mmol/l two hours after 75g anhydrous glucose in an oral glucose tolerance test or
* HbA1c above 48 mmol/mol
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Steno Diabetes Center Copenhagen

OTHER

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Bo Feldt-Rasmussen

Professor, DMSc, Head of Nephrology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Rigshospitalet

København Ø, , Denmark

Site Status

Countries

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Denmark

Other Identifiers

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GLYCOHEMO

Identifier Type: -

Identifier Source: org_study_id

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