Value of risk stratification to increase the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population

BACKGROUND: Opportunistic screening using hemoglobin A1c (HbA1c) may improve detection of undiagnosed diabetes but remains controversial. OBJECTIVE: To evaluate the predictive validity of HbA1c as a screening test for undiagnosed diabetes in a risk-stratified sample of the US population. DESIGN: Weighted cross-sectional analysis of diabetes risk factors, HbA1c, and fasting plasma glucose (FPG) in National Health and Nutrition Examination Survey (NHANES), 1999-2004. SUBJECTS: Six thousand seven hundred and twenty-three NHANES participants from morning examination session, aged >= 18 years and without prior physician-diagnosed diabetes. MEASUREMENTS: HbA1c and undiagnosed diabetes defined by FPG >= 7.0 mmol/l (126 mg/dl). RESULTS: The estimated prevalence of undiagnosed diabetes in the US population was 2.8% (5.5 million people). HbA1c had strong correlation with undiagnosed diabetes, with an area under the receiver-operating characteristic curve of 0.93. Independent predictors of undiagnosed diabetes were older age, male sex, black race, hypertension, elevated waist circumference, elevated triglycerides, and low high-density lipoprotein cholesterol. We derived a risk score for undiagnosed diabetes and stratified participants into low (0.44% prevalence), moderate (4.1% prevalence), and high (11.1% prevalence) risk subgroups. In moderate and high risk groups, a threshold HbA1c value >= 6.1% identified patients requiring confirmatory FPG; HbA1c <= 5.4% identified patients for whom diabetes could be reliably excluded. Intermediate HbA1c (5.5-6.0%) may exclude diabetes in moderate, but not high risk groups). CONCLUSIONS: Risk stratification improves the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population. Although opportunistic screening with HbA1c would improve detection of undiagnosed diabetes, cost-effectiveness studies are needed before implementation of specific screening strategies using HbA1c.