HbA1c alone a weak predictor of diabetes and cardiovascular risk

NEW YORK (Reuters Health) - Don't rely on hemoglobin (Hb)A1c alone to identify patients at risk for diabetes and heart disease. It's far less precise than glucose tolerance or fasting plasma glucose tests, two new studies show.

"Hemoglobin A1c >6.5% and 5.7-6.4% cannot be used as the sole criteria for diagnosing diabetes and detecting at-risk individuals, respectively," lead author Dr. Carlos Lorenzo from University of Texas Health Science Center, San Antonio, told Reuters Health by e-mail. "Nevertheless, hemoglobin A1c >6.5% and 5.7-6.4% can be used along with categories based on fasting and 2-hour plasma glucose levels as proposed by the 2010 American Diabetes Association recommendations."

Dr. Lorenzo and colleagues analyzed HbA1c, fasting plasma glucose (FPG), and 2-hour plasma glucose concentrations (2-h PG) in 855 patients for their ability to identify individuals at risk of diabetes and for their association with insulin resistance and secretion.

The cohort included 136 diabetics. HbA1c of at least 6.5% identified 32.3%, FPG of at least 126 mg/dL identified 44.8%, and 2-h PG of at least 200 mg/dL identified 86.8%. The combination of elevated HbA1c and/or impaired fasting glucose (IFG, between 100 and 125 mg/dL) detected 52.2% of diabetics, whereas the combination of IFG and/or impaired glucose tolerance (IGT, 2-h PG between 140 and 199 mg/dL) detected 97.1%.

HbA1c between 5.7 and 6.4% identified only 23.6% of the 385 non-diabetic individuals at increased risk of diabetes, compared with 69.1% identified by IFG and 59.5% identified by IGT. The combination of HbA1c in this range and/or IGF detected 75.6%, while the combination of IFG and/or IGT detected 95.8%.

HbA1c between 5.7 and 6.4% was especially insensitive at detecting non-Hispanic whites at increased risk of diabetes, according to the study report published online June 23rd in Diabetes Care.

In linear regression models, HbA1c performed less well than FPG and 2-h PG for assessing insulin sensitivity and insulin secretion.

"Our results indicate that the recently proposed hemoglobin A1c categories (hemoglobin A1c >6.5% and 5.7-6.4%) may be inferior to previous recommendations based on fasting and 2-hour plasma glucose levels for both diagnosing diabetes and detecting at-risk individuals," Dr. Lorenzo concluded.

In the second report, Dr. Henna Cederberg from University of Oulu, Finland, and colleagues compared HbA1c, 2-h PG, and FPG as predictors of type 2 diabetes, cardiovascular disease, and cardiovascular disease mortality during a 10-year prospective study of 593 local residents.

Sixty-four individuals (17%) developed type 2 diabetes, including 37.8% of those with IFG, 27.1% of those with IGT, and 37.5% of those with HbA1c between 5.7% and 6.5%.

Sensitivity for predicting type 2 diabetes was 21.9% for IFG, 32.8% for elevated HbA1c, and 40.6% for IGT. Specificity ranged from 85.9% for IGT to 88.7% for elevated HbA1c and 92.6% for IFG.

HbA1c of 6.5% and above, as well as 2-h PG in the IGT and diabetic range, was significantly associated with the development of cardiovascular disease, but only in women.

The relationship of these markers to cardiovascular disease mortality could not be assessed due to the low mortality in this study.

"An intermediate range of HbA1c 5.7-6.4% may have a role in a non-diabetic population to identify those at an increased risk of type 2 diabetes, in addition to IGT and IFG," Dr. Cederberg told

"Further studies are required to compare 2-h glucose, fasting glucose, and HbA1c as predictors of type 2 diabetes and their association with different cardiovascular endpoints, in different populations and age groups," Dr. Cederberg added.

Diabetes Care 2010 July

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