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.