American Association for Clinical Chemistry
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NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By William E. Winter, MD, FACB

A recent article in Diabetes Care (1) found that hemoglobin A1c did not perform as well for the detection of risk for diabetes as fasting plasma glucose or the 2-h glucose on an OGTT. Do you agree or disagree? Is this the only interpretation of the data? What else might be studied?


My comments: The study group was composed of 1625 subjects from the Insulin Resistance Atherosclerosis Study (IRAS). At follow-up [after an average of 5.2 years (range 4.5– 6.6 years)], fasting plasma glucose (FPG), 2-h glucose following a 75 g glucose challenge (2-h Glu) and hemoglobin A1c were measured. In the absence of diabetes, increased risk for diabetes was defined as a FPG of 100-125 mg/dL (i.e., impaired fasting glucose; IFG), a 2-h Glu of 140-199 mg/dL (impaired glucose tolerance; IGT) or an A1c of 5.7-6.4%. Based upon this definition, IFG was present in 69% of the "at risk subjects", IGT was present in 60% of "at risk" individuals and A1c between 5.7 and 6.4% was present in only 31% of the "at risk" individuals.


A concern is that the rates of eventual conversion to full-fledged diabetes were not reported. It is possible that a borderline elevated A1c is more predictive of diabetes that either IFG or IGT. In the natural history of type 2 diabetes, it is known that IGT precedes IFG and a borderline elevation in A1c may be a later event. To this end, the authors reference the literature that an A1c of =>6.5% only recognized one third of people with diabetes. IFG, IGT and a borderline A1c do not describe equivalent stages in the transition from non-diabetic to diabetic. Is this article prematurely critical of A1c for diabetes risk detection?  While A1c is more expensive than a plasma glucose measurement, it is more reproducible and does not require a fasting specimen.



  1. Lorenzo C, Wagenknecht LE, Hanley AJ, Rewers MJ, Karter AJ, Haffner SM. A1C between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care. 2010 Sep;33(9):2104-9.

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Posted by
On 3/27/2011

The treatment of choice on individuals diagnosed with diabetes is change in lifestyle and the use of Metformin for glycemic control. In fact, Metformin is the most widely used drug in the world for diabetes treatment. Metformin is know to reduce A1c levels to even undetectable levels. However, fasting blood glucose could still be elevated. What can we conclude from an A1c from diabetic patients using Metformin ? Cristian Saez, PhD CoreMedica Laboratoties

Posted by
On 3/2/2011

with the recent GDM guidelines, is it recommended that the fasting glucose be tested prior to administering the glucola? If the Fasting is greater than or equal to 92, the diagnosis of GDM is made. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!

Posted by
On 2/13/2011

As per my experience fasting and postprandial blood sugar estimation will be helpful in detecting diabetes. The HbA1c may be helpful in monitoring the blood sugar. I found in most of the cases that the person with fasting sugar 250 mg showed HbA1c of above 9.0 %. Therefore, I strongly feel that HbA1c can be used to monitor the sugar than detecting. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!

Posted by
On 2/7/2011

I would also be concerned about falsely normal HbA1c values in this patient population, thus under-identifying at-risk patients. This test is more sensitive to pre-analytical errors than the other two. Specifically, if the patients have any condition (e.g. certain chronic anemias or hemglobinopathies) that shortens RBC lifetimes, it will depress the HbA1c (which labels the older fraction of the RBC mass). I would hope that these considerations were part of the study performance, but I am often surprised by how often pre-analytical sources of error are not adequately addressed. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!

Posted by
On 2/4/2011

Is the goal to detect transient states of hyperglycemia or longer periods of hyperglycemia and associated pathologies? The tests are not mutually exclusive and knowing both answers may help grade risk. An IGT test is difficult to perform, but an IFG and HbA1c can be easily done at the same time, unless the patient was not fasting. The IFG can be done inexpensively on repeat occasions and, while the HbA1c is more expensive, it would not be done more than 3-4 times per year at a reasonble cost. If an FPG was above 100, what would be the course of action? It is not known how long a patient has had an IFG, so is there a need to determine the HbA1c also? How does the advice to the patient change if the FPG is above 100 and the HbA1c is 6.3% vs 6.7%?

About the Author
William E. Winter, MD, FACB
William E. Winter, MD, FACB 
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