High-Normal HbA1c Is a Strong Predictor of Type 2 Diabetes

HbA_1c is an independent risk factor for Type 2 diabetes. Subjects with high-normal levels deserve particular attention because they have a strong risk of developing diabetes….

Glycosylated hemoglobin (HbA_1c) recently has been recommended for the diagnosis of diabetes by the American Diabetes Association, but its value in the prediction of Type 2 diabetes is poorly understood. This study evaluated how high-normal HbA_1c levels predict Type 2 diabetes.

HbA_1c was measured in 919 Caucasian subjects, aged 40–79 years, and recorded new cases of Type 2 diabetes in the following 15 years. Diabetes was diagnosed with HbA_1c.

Subjects were stratified according to baseline HbA_1c (<5.0, 5.00–5.49 [reference], 5.50–5.99, and 6.00–6.49%). Sex- and age-adjusted hazard ratios (95% CI) for Type 2 diabetes were 1.11 (0.30–4.41), 1.00, 3.79 (1.79–8.06), and 12.50 (5.51–28.34), respectively. Results did not change after adjusting for several putative confounding factors and were confirmed when models with updated variables were used.

It is well known that HbA1c captures chronic hyperglycemia in the prior 2–3 months, is well correlated to chronic diabetes complications, and has less pre-analytical problems and biological variability than plasma glucose. For such reasons, HbA1c was recommended for diabetes diagnosis and risk stratification.

The findings of the current study confirm a progressively increased risk of Type 2 diabetes across categories of HbA1c and clearly document that subjects with high-normal HbA1c have a strong risk of developing Type 2 diabetes, even after adjusting for several putative risk factors (e.g., BMI) and potentially confounding variables (e.g., anemia). Remarkably, diabetes risk in subjects with high-normal HbA1c is higher than in subjects with IFG.

The study population was entirely Caucasian, and subjects were aged 40 years. Therefore, the findings cannot be necessarily extrapolated to other ethnicities and/or to younger subjects.

This study is the first to examine how baseline HbA1c predicts HbA1c-diagnosed diabetes. The findings, consistent with those of studies based on self-reported diagnosis of diabetes, more strongly support the ADA recommendations of using HbA1c for diabetes risk stratification and including subjects with high-normal levels in an effective prevention strategy.

These subjects, indeed, have a high rate of progression to diabetes and deserve particular attention in order to prevent or delay the disease. Specific intervention trials, however, are needed to confirm such a conclusion because those conducted so far, based on lifestyle changes and/or drug use, recruited subjects at risk according to their plasma glucose levels and not HbA1c.

Diabetes Care February 9, 2011 DC_101180