Elizabeth Selvin, PhD, MPH; Dan Wang, MS; Kunihiro Matsushita, MD, PhD; Morgan E. Grams, MD, PhD, MHS; Josef Coresh, MD, PhD, MHS
Acknowledgment: The authors thank the staff and participants of the ARIC study for their important contributions.
Financial Support: The ARIC study has received federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services, under contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. Dr. Selvin was supported by grants K24DK106414 and R01DK089174 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Matsushita was supported by grant R21HL133694 from the National Heart, Lung, and Blood Institute.
Disclosures: Dr. Matsushita reports grants and personal fees from Fukuda Denshi and Kyowa Hakko Kirin outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0091.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Selvin (e-mail, firstname.lastname@example.org).
Corresponding Author: Elizabeth Selvin, PhD, MPH, Professor of Epidemiology & Medicine, Welch Center for Prevention, Epidemiology and Clinical Research and the Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21287; e-mail, email@example.com.
Current Author Addresses: Drs. Selvin, Matsushita, Grams, and Coresh and Ms. Wang: Welch Center for Prevention, Epidemiology and Clinical Research and the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21287.
Author Contributions: Conception and design: E. Selvin.
Analysis and interpretation of the data: E. Selvin, D. Wang, K. Matsushita, M. Grams, J. Coresh.
Drafting of the article: E. Selvin.
Critical revision of the article for important intellectual content: E. Selvin, D. Wang, K. Matsushita, M. Grams, J. Coresh.
Final approval of the article: E. Selvin, D. Wang, K. Matsushita, M. Grams, J. Coresh.
Statistical expertise: E. Selvin, D. Wang, J. Coresh.
Obtaining of funding: E. Selvin.
Collection and assembly of data: E. Selvin, K. Matsushita, M. Grams, J. Coresh.
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.
Selvin E, Wang D, Matsushita K, Grams ME, Coresh J. Prognostic Implications of Single-Sample Confirmatory Testing for Undiagnosed Diabetes: A Prospective Cohort Study. Ann Intern Med. [Epub ahead of print 19 June 2018]169:156–164. doi: 10.7326/M18-0091
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Published: Ann Intern Med. 2018;169(3):156-164.
Published at www.annals.org on 19 June 2018
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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