For many years, the diagnosis of diabetes has been based on plasma glucose criteria, either FPG or 2-h 75-g OGTT values. In 1997, the first Expert Committee on the Diagnosis and Classification of Diabetes Mellitus revised the diagnostic criteria using the observed association between glucose levels and presence of retinopathy as the key factor to identify threshold FPG and 2-h PG levels. The committee examined data from three cross-sectional epidemiologic studies that assessed retinopathy and measured glycemia as FPG, 2-h PG and HbA1C (AIC). The studies demonstrated glycemic levels below which there was little prevalent retinopathy and above which the prevelance of retinopathy increased in apparently linear fashion. The analysis helped to inform a then-new diagnostic cut point greater than or equal to 126 mg/dl (7.0 mmol/l) for FPG and confirmed the diagnostic 2-h PG value of greater than or equal to 200 mg/dl (11.1 mmol/l).

The ADA has not previously recommended the use of A1C for diagnosing diabetes. This was in part due to the lack of standardization of the assay. However, A1C assays are now highly standardized in the US and their results can be uniformly applied both temporally and across populations. In a recent report (Diabetes Care 32: 1327-1334, 2009), an international expert committee recommended the use of the A1C test to diagnose diabetes with a threshold of greater than or equal to 6.5% which was subsequently affirmed by the ADA. They recommended that the diagnostic test be performed using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the DCCT reference assay. Point-of-care A1C assays are not considered accurate at this time to use for diagnostic purposes.

Data from epidemiologic studies show a relationship between A1C and the risk of retinopathy similar to that which has been shown for corresponding FPG and 2-h PG thresholds.

The A1C has several advantages, to include greater convenience, since fasting is not required. Also, there is evidence to suggest greater pre-analytical stability and less day to day perturbations during periods of stress and illness. Disadvantages of AIC include greater cost, limited availability of A1C testing in certain regions of the developing world and incomplete correlation between A1C and average glucose in certain individuals. Also, the A1C can be misleading in patients with certain forms of anemia and hemoglobinopathies.

The established glucose criteria for the diagnosis of diabetes (FPG and 2-h PG) remain valid. Patients with severe hyperglycemia like those with severe classic hyperglycemic symptoms or hyperglycemic crisis can continue to be diagnosed when a random or causal PG of greater than or equal to 200 mg/dl is found.

A test result diagnostic of diabetes should be repeated to rule out laboratory error, unless the diagnosis is clear on clinical grounds, as in the case of a patient with classic symptoms of hyperglycemia or hyperglycemic crisis. It is recommended that the same test be repeated for confirmation because there will be a greater likelihood of concurrence in this case.

The criteria for the diagnosis of diabetes as recommended by the ADA can be summarized as follows:

1. A1C > 6.5%. The test should be preformed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.
OR
2. FPG > 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours.
OR
3. Two-hour plasma glucose > 200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
OR
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose > 200 mg/dl (11.1 mmol/l).

In the absence of unequivocal hyperglycemia, criteria 1-3 should be confirmed with repeat testing.

The ADA has also recommended the use of A1C to identify patients at increased risk of developing diabetes. The categories of increased risk for diabetes are as follows:

1. FPG 100-125 mg/dl (5.6-6.9 mmol/l) [IFG] 2. 2-h PG on the 75-g OGTT 140-199 mg/dl (7.8-11.0 mmol/l) [IGT] 3. A1C 5.7-6.4%

For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher ends of the range.

The introduction of A1C is a diagnostic test for diabetes is indeed a welcome development because it is more convenient to use since fasting is not required. However, there is one task that we need to accomplish before we can use A1C as diagnostic test for diabetes in our country. We need to standardize our A1C assays using a method certified by NGSP and standardized to the DCCT reference assay. Only then can we confidently use A1C as a diagnostic test for diabetes. A tough job indeed, but something that must be done on a national level.

References:

1. Standards of Medical Care in Diabetes – 2010. American Diabetes Association. Diabetes Care 33 (Suppl 1): S11-S61, 2010.
2. Diagnosis and Classification of Diabetes Mellitus. American Diabetes Association. Diabetes Care 33 (Suppl 1): S62-S69, 2010.
3. International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care 32: 1327-1334, 2009.