NCT01204216

Effect of Red Blood Cell Survival on a Commonly Used Diabetes Lab Test-HbA1c

Does Variation in Mean Red Cell Age Impact HbA1C Interpretation?

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Accepted

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

Conditions

• Diabetes Mellitus
• Impaired Fasting Glucose
• Prediabetes

Interventions

Type	Name	Description
BIOLOGICAL	re-infusion of biotin labeled cells	Subjects will participate in experiments involving re-infusion of biotin-labeled cells in which a small volume (\< 10 ml) of autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate. These experiments require a series of small, precisely timed post-infusion blood samples over a period of 4 months, with each subject undergoing the procedure twice separated by an interval of at least 8 month
BIOLOGICAL	Re-infusion of biotin labeled cells	Subjects will participate in experiments involving re-infusion of biotin-labeled cells in which a small volume (\< 10 ml) of autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate. These experiments require a series of small, precisely timed post-infusion blood samples over a period of 4 months, with each subject undergoing the procedure twice separated by an interval of at least 8 months. small volume (\< 10 ml) of autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate.
BEHAVIORAL	Diabetes education/diabetes medication adjustment	Between the initial 3-4 month trial period and the second infusion of biotin labeled cells approximately 8 months later,subjects will receive diabetes education from a CDE. In addition,if needed, diabetes medications may be adjusted by the study endocrinologist to improve subject's glycemic control.

Timeline

• Start date: 2010-09-01
• Primary completion: 2016-07-01
• Completion: 2016-09-01
• First posted: 2010-09-17
• Last updated: 2023-05-31
• Results posted: 2023-05-31

Locations

1 site across 1 country: United States