Answer: (i)

The percentage of Hemoglobin A1c is the best indicator of the average levels of glucose in blood several weeks before the exam.

Hemoglobin A1c is formed through a non catalyzed reaction between glucose in blood and some amino groups in Hemoglobin A. This reaction is directly proportional to the concentration of glucose in blood. It means that hyperglycemic episodes in a  diabetic patient are registered in the blood as proportion of Hemoglobin A that becomes glycosylated. That is the connotation of the units used when this exam is reported: a report of  Hemoglobin A1c value equal  6 %, for example, means that 6 % of the Hemoglobin A of the patient is linked to glucose. The reference value of HbA1c for a non diabetic person is  4-6 %  .

An International study for a better standardization of the measurement and  report of HbA1c, including  the future use of  results as mmoles of Hb A1c per mol of Hemoglobin, is being developped in different countries. It also includes collecting and updating information to correlate the values of Hb A1c to the average values of glucose in blood for facilitating patient interpretation of HbA1c results.

In the following video, Dr. David M. Nathan summarize the presentation of the preliminary results of this ongoing investigation, in a recent American Diabetes Association meeting:

The value of Hb of HbA1c has shown a strong correlation to the average glucose level. Since the RBC has an average life span of 120 days, the proportion of glycosylated hemoglobin can reflect the glucose levels in previous months, but it mainly represents glycemia during the last month and is strongly influenced by glucose levels in the last two weeks.

This kind of glycosylation reaction is not exclusive of Hemoglobin, since other proteins also experiment it. As a consequence of repeated episodes of hyperglycemia over time, many proteins can become glycosylated with modification of their structure, functionality and solubility, producing complications seen in long term uncontrolled diabetes.  The concentration of glycosylated hemoglobin has shown a strong correlation with microvascular complications as retinopathies and nephropathies. 


Nowadays, the management plan of glycemic control for diabetic patients is based on Self Monitoring of Blood Glucose (SMBG) and measurement of Hemoglobin A1c. The American Diabetes Association (ADA) recommends to perform HbA1c determination twice a year in patients with controlled glycemia and every four months in patients that does not shows an appropriate glycemic control, or patients whose treatment have been changed.  (Standards of Medical Care in Diabetes, 2008)

The measurement of HbA1c is limited by the presence of concomitant conditions in the patient that affect the erythrocyte life, (like hemolytic anemias) or cases of Hemoglobin variants. Another limitation is related to the inability of this test to inform about hypoglycemic episodes in the patient.

 Recommended articles:


American Diabetes Association

Standards of Medical Care in Diabetes – 2008

Diabetes Care 31: S12-S54, 2008


Use of Glycated Hemoglobin and Microalbuminuria in the monitoring of Diabetes Mellitus.  Summary, Evidence Report/ Technology Assessment, Number 84. AHRQ Publication N o. 03-E048, July, 2003, Agency for healthcare, Research and Quality, Rockville, MD

American Diabetes Association: Care of Children and adolescent with Type I Diabetes. Diabetes Care, January 1, 2005 28 (sppl_1: S4-S36)

 Sacks, D. B. et al: Guidelines and recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Clin Chem 48: 436-472, 2002

American Diabetes Association: Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy  Diabetes Care:29, 1963-1972, 2006


Recommended Sites:


2 thoughts on “ANSWER TO I-01

  1. Pingback: Diabetes Mellitus (I-01) « The Biochemistry Questions Site

  2. Excellent blog you have got here.. It’s difficult to find good quality writing like yours these days. I truly appreciate people like you! Take care!!

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