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

Current clinical definitions of diabetes require repeated blood work to confirm elevated levels of glucose or hemoglobin A1c (HbA1c) to reduce the possibility of a false-positive diagnosis. Whether 2 different tests from a single blood sample provide adequate confirmation is uncertain.

To examine the prognostic performance of a single-sample confirmatory definition of undiagnosed diabetes.

Prospective cohort study.

The ARIC (Atherosclerosis Risk in Communities) study.

13 346 ARIC participants (12 268 without diagnosed diabetes) with 25 years of follow-up for incident diabetes, cardiovascular outcomes, kidney disease, and mortality.

Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (≥7.0 mmol/L [≥126 mg/dL]) and HbA1c (≥6.5%) from a single blood sample.

Among 12 268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA1c 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.

Lack of repeated measurements of fasting glucose and HbA1c.

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 HbA1c levels from a single blood sample to identify undiagnosed diabetes in the population.

National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.