Prognostic Implications of Single-Sample Confirmatory Testing for Undiagnosed Diabetes A Prospective Cohort Study

Background: Current clinical definitions of diabetes require repeated blood work to confirm elevated levels of glucose or hemoglobin A(1c) (HbA(1c)) to reduce the possibility of a false-positive diagnosis. Whether 2 different tests from a single blood sample provide adequate confirmation is uncertain. Objective: To examine the prognostic performance of a single-sample confirmatory definition of undiagnosed diabetes. Design: Prospective cohort study. Setting: The ARIC (Atherosclerosis Risk in Communities) study. Participants: 13 346 ARIC participants (12 268 without diagnosed diabetes) with 25 years of follow-up for incident diabetes, cardiovascular outcomes, kidney disease, and mortality. Measurements: Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (>= 7.0 mmol/L[>= 126 mg/dL]) and HbA(1c) (>= 6.5%) from a single blood sample. Results: Among 12268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA(1c) at baseline (1990 to 1992). Among these, 39% had both (confirmed undiagnosed diabetes), whereas 61% had only 1 elevated measure (unconfirmed undiagnosed diabetes). The confirmatory definition had moderate sensitivity (54.9%) but high specificity (98.1%) for identification of diabetes cases diagnosed during the first 5 years of follow-up, with specificity increasing to 99.6% by 15 years. The 15-year positive predictive value was 88.7% compared with 71.1% for unconfirmed cases. Confirmed undiagnosed diabetes was significantly associated with cardiovascular and kidney disease and mortality, with stronger associations than unconfirmed diabetes. Limitation: Lack of repeated measurements of fasting glucose and HbA(1c). Conclusion: A single-sample confirmatory definition of diabetes had a high positive predictive value for subsequent diagnosis and was strongly associated with clinical end points. Our results support the clinical utility of using a combination of elevated fasting glucose and HbA(1c) levels from a single blood sample to identify undiagnosed diabetes in the population. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.