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Cited by 73Diabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and ResearchDiabetes and associated disorders

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

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Selvin, Elizabeth, Wang, Dan, Matsushita, Kunihiro, Grams, Morgan E., Coresh, Josef·2018·Annals of Internal Medicine
DOI 10.7326/m18-0091PMC PMC6082697
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Abstract

Background: 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. 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 HbA1c (≥6.5%) from a single blood sample. Results: 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. Limitation: Lack of repeated measurements of fasting glucose and HbA1c. 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 HbA1c 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.

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  • Because the concordance among diagnostic tests is imperfect, diagnosis of DM requires two abnormal test results unless hyperglycemic symptoms accompany a glucose level of at least 200 mg/dL.

    “The concordance between FPG, 2-hour PG, and A1C is not perfect; thus, the diagnosis of DM requires 2 different (fasting glucose and A1C) abnormal test results, either from the same sample or 2 abnormal results on samples drawn on different days.”

    From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [3]

    The paper’s introductory passage says diabetes diagnosis requires confirmation of an elevated glucose or HbA1c result and that two different tests above diagnostic thresholds can provide confirmation. It also says repeating the same test on a later sample is preferred, so two different tests are not required. The Discussion says guidelines were unclear about using two tests from one sample; our copy does not address the quoted exception for symptoms with glucose of at least 200 mg/dL or concordance involving 2-hour PG. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The concordance among fasting plasma glucose, 2-hour plasma glucose, and A1C is imperfect.

    “The concordance between FPG, 2-hour PG, and A1C is not perfect”

    From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [3]

    The Results report 95% overall agreement between fasting glucose and HbA1c diagnostic categories, with isolated elevations of each, supporting imperfect concordance between those two tests. The Discussion says the study lacked contemporaneous 2-hour glucose measurements, so it does not establish concordance among all three tests. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • In the absence of classic hyperglycemic symptoms, repeat testing is required to confirm the diagnosis regardless of the test used.

    “In the absence of classic hyperglycemic symptoms, repeat testing is required to con fi rm the diagnosis regardless of the test used (see CONFIRMING THE DIAGNOSIS, below).”

    From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [29]

    The Background and Discussion state that clinical definitions call for confirmation of elevated glucose or HbA1c. The paper does not specify the absence of classic symptoms, and it says two different tests may provide confirmation while examining whether both can be done on one sample. It therefore does not establish an unqualified requirement for repeat testing regardless of the test used. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • An HbA1c value of 6.5% (48 mmol/mol) or greater is considered diagnostic of diabetes.

    “An HbA 1c value of 6.5% (48 mmol/mol) or greater is considered diagnostic.”

    From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [319]

  • Unless there is a clear clinical diagnosis, diagnosis requires two abnormal screening test results, measured either at the same time or at two different time points.

    “Unless there is a clear clinical diagnosis (e.g., individual with classic symptoms of hyperglycemia or hyperglycemic crisis and random plasma glucose $ 200 mg/dL [ $ 11.1 mmol/L]), diagnosis requires two abnormal screening test results, measured either at the same time (29) or at two different time points.”

    From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [29]

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Authors
Selvin, E., Wang, D., Matsushita, K., Grams, M. E., & Coresh, J.
Affiliations
Johns Hopkins University (US)
ORCID
Venue
Annals of Internal Medicine
Publisher
American College of Physicians
Published
2018-08-07
Volume
169
Issue
3
Pages
156-164
ISSN
  • 0003-4819 (ISSN-L)
  • 1539-3704
DOI
10.7326/m18-0091
PMC
PMC6082697
OpenAlex
W2809391967
Semantic Scholar
5f841d964abc371a8a46a3fc06730a001d7d93e1
Cited by
73
References
22
Citations by year
2026: 5 · 2025: 8 · 2024: 6 · 2023: 14 · 2022: 7 · 2021: 8 · 2020: 14 · 2019: 5 · 2018: 6
FWCI
6.56
Type
journal article
Language
en
Open access
Licence
www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations
  • Annals of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R21HL133694)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K24DK106414, R01DK089174)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
undiagnosed diabetes, diabetes diagnosis, fasting blood glucose, HbA1c, positive predictive value, new-onset diabetes, cardiovascular outcomes, kidney disease, mortality, sensitivity and specificity, Atherosclerosis Risk in Communities Study
MeSH terms
Blood Glucose, Diabetes Mellitus, Female, Glycated Hemoglobin, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Sensitivity and Specificity

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