A1C versus Glucose Testing: A Comparison

From Diabetes Care

David B. Sacks, MB; CHB; FRCPATH

Posted: 03/02/2011; Diabetes Care. 2011;34(2) © 2011 American Diabetes Association, Inc.

Introduction

Diabetes was originally identified by the presence of glucose in the urine.
Almost 2,500 years ago it was noticed that ants were attracted to the urine of some individuals. In the 18th and 19th centuries the sweet taste of urine was used for diagnosis before chemical methods became available to detect sugars in the urine. Tests to measure glucose in the blood were developed over 100 years ago, and hyperglycemia subsequently became the sole criterion recommended for the diagnosis of diabetes.
Initial diagnostic criteria relied on the response to an oral glucose challenge, while later measurement of blood glucose in an individual who was fasting also became acceptable.
The most widely accepted glucose-based criteria for diagnosis are fasting plasma glucose (FPG) ≥126 mg/dL or a 2-h plasma glucose ≥200 mg/dL during an oral glucose tolerance test (OGTT) on more than one occasion.[1,2]
In a patient with classic symptoms of diabetes, a single random plasma glucose ≥200 mg/dL is considered diagnostic.
Before 2010 virtually all diabetes societies recommended blood glucose analysis as the exclusive method to diagnose diabetes.
Notwithstanding these guidelines, over the last few years many physicians have been using hemoglobin A1C to screen for and diagnose diabetes.
Although considered the "gold standard" for diagnosis, measurement of glucose in the blood is subject to several limitations, many of which are not widely appreciated. Measurement of A1C for diagnosis is appealing but has some inherent limitations. These issues have become the focus of considerable attention with the recent publication of the Report of the International Expert Committee that recommended the use of A1C for diagnosis of diabetes, a position that has been endorsed (at the time of writing) by the American Diabetes Association (ADA), the Endocrine Society, and in a more limited fashion by American Association of Clinical Endocrinologists/American College of Endocrinology. This review will provide an overview of the factors that influence glucose and A1C testing.

Perspective

Notwithstanding the use of glucose (FPG and/or the OGTT) as the "gold standard" for the diagnosis of diabetes for many years, glucose testing suffers from several deficiencies. The requirement that the subject be fasting at the time the blood is drawn is a considerable inconvenience. While our ability to measure glucose has improved, inherent biological variability can produce very large differences within and among individuals. In conjunction with lack of sample stability, which is difficult to overcome in clinical practice, these factors results in lack of reproducibility of glucose testing.

A1C, which reflects chronic blood glucose values, is routinely used in monitoring glycemic control and guiding therapy. The significant reduction in microvascular complications with lower A1C and the absence of sample lability, combined with several other advantages (Table 3), have led to the recommendation by some organizations that A1C be used for screening and diagnosis of diabetes.
Accumulating evidence suggests that racial differences in A1C values may be present, and the possible clinical significance of this needs to be determined. Importantly, A1C cannot be measured in certain conditions. Despite these caveats, A1C can be measured accurately in the vast majority of people. A comprehension of the factors that influence A1C values and the conditions where it should not be used will produce accurate and clinically meaningful results.
The convenience of sampling at any time without regard to food ingestion makes it likely that measurement of A1C will result in the detection of many of the millions of people with diabetes who are currently undiagnosed.