Clinical trial NCT01204216: Effect of Red Blood Cell Survival on a Commonly Used Diabetes Lab Test-HbA1c
Official title: Does Variation in Mean Red Cell Age Impact HbA1C Interpretation?
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus
Impaired Fasting Glucose
Prediabetes
Keywords: Hemoglobin A1c
HbA1c
glycated serum proteins
fructosamine
glycated albumin
glycation gap
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of Cincinnati
First posted: 2010-09-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Prevention of complications in veterans with diabetes depends heavily on assessment of blood glucose and HbA1c. The HbA1c is a blood test that measures the exposure of hemoglobin (Hb) to a person's average blood glucose over the lifespan of a red blood cell (RBC). The test is heavily relied upon as a measure of blood glucose control. It is normally assumed that all people (those with and without diabetes) have a narrow range of red blood cell survival. It has been recently shown that this is not a valid assumption.

A more precise test of red blood cell survival, using a biotin label method, demonstrated a substantial difference of red blood cell survival among otherwise normal people. There is sufficient difference in red blood cell survival to alter the estimate of glycemic control from the HbA1c test by as much as 30 per cent. This introduces concern that HbA1c values do not mean the same thing in a significant number of people.

Although the evidence is clear that there is variation in RBC survival among people, attributing this variation to differences between individuals depends on answering several simple questions which surprisingly remain unanswered: whether RBC survival is stable over time within an individual and whether blood glucose control affects its stability. Therefore, the goal of the proposed studies is to define these characteristics.

Detailed description: The first Specific Aim tests the hypothesis that mean RBC age is stable in subjects without diabetes and in subjects with diabetes at stable glycemic control. The second Specific Aim tests the hypothesis that mean RBC age will not change in subjects with diabetes studied initially in poor glycemic control, and again after being treated to stable, improved glycemic control for \>8 months. To accomplish the two aims, RBC survival and mean blood glucose will be determined at two times separated by at least eight months in 10 subjects without diabetes, 10 subjects with diabetes and stable glycemic control, and up to 15 subjects with diabetes in initial poor glycemic control in order to re-study 10 subjects subsequently in improved glycemic control. The RBC survival will be measured using the same novel biotin RBC label in conjunction with mean glucose determination by continuous glucose monitoring. Mean blood glucose will be assessed using blood glucose testing meter , continuous glucose monitoring equipment, HbA1c, fructosamine and glycated albumin determinations HbA1c is the most highly valued clinical test for long term monitoring of glycemic control and the prediction of diabetes complications risk is relied upon for hundreds of thousands of clinical decisions made every year in veterans with diabetes. The proposed studies, by further defining RBC survival stability necessary to develop a new approach to HbA1c interpretation, therefore has the potential to dramatically support the Department of Veterans Affairs in its mission to reduce the burden of diabetes and its complications

Eligibility criteria: Inclusion Criteria:

* Subjects will be between ages 18 and 85 for Aim 1 and between 18 and 80 years for Aim 2 and non-pregnant
* Subjects with both types 1 and 2 diabetes
* Subjects without diabetes (as determined by an OGTT test at screening)
* veterans receiving care at VAMC will be given preference but open to both veterans and non-veterans.

Exclusion Criteria:

* known hemoglobinopathy or RBC disorder
* positive pregnancy test (in women of child-bearing potential or are breast feeding or planning pregnancy during the course of the study;
* baseline serum creatinine \>1.5 mg/dl
* CBC outside the normal range
* history of GI blood loss or coagulopathy
* urine microalbumin \>100 mcg/mg creatinine (spot collection);
* transaminases \>3 X the upper limit of normal
* presence of serum antibodies to biotinylated proteins (which could interfere with the biotin RBC labeling protocol)
* greater than or equal to NYHA stage 3 heart failure;
* active infection;
* known rheumatologic disease
* uncontrolled hypo-or hyperthyroidism or an underlying illness known to be associated with either body wasting or changes in serum proteins
* plans to move out of the area within the time frame of the Aim for which they are recruited
* unwillingness to perform self monitoring of blood glucose

Primary outcomes:
measure: Specific Aim 1: To Determine the Stability of MRBC (Mean RBC Age)Over Time at Stable Glycemia. The Hypothesis is MRBC Will be Stable in Subjects Without Diabetes and in Subjects With Diabetes at Stable Glycemic Control.
timeFrame: Baseline and 8 months later
Secondary outcomes:
measure: Specific Aim 2: To Determine the Impact of Glycemic Control on MRBC.
timeFrame: Baseline and 8 months later
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center, Cincinnati, OH
state: Ohio
Study officials:
affiliation: Cincinnati VA Medical Center, Cincinnati, OH
name: Robert M Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cohen RM, Franco RS, Khera PK, Smith EP, Lindsell CJ, Ciraolo PJ, Palascak MB, Joiner CH. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood. 2008 Nov 15;112(10):4284-91. doi: 10.1182/blood-2008-04-154112. Epub 2008 Aug 11.
citation: Cohen RM, Lindsell CJ. When the blood glucose and the HbA(1c) don't match: turning uncertainty into opportunity. Diabetes Care. 2012 Dec;35(12):2421-3. doi: 10.2337/dc12-1479. No abstract available.