Associations of 1,5-Anhydroglucitol and 2-Hour Glucose with Major Clinical Outcomes in the Atherosclerosis Risk in Communities (ARIC) Study

Bethany Warren, Alexandra K. Lee, Christie M. Ballantyne, Ron C. Hoogeveen, James S. Pankow, Morgan E. Grams, Anna Köttgen, Elizabeth Selvin

Research output: Contribution to journalArticlepeer-review


BACKGROUND: 1,5-Anhydroglucitol (1,5-AG) is a novel biomarker of glycemic control proposed to monitor recent hyperglycemic excursions in persons with diabetes. The clinical utility of 1,5-AG outside of diagnosed diabetes is unclear, but it may identify people at high risk for diabetes and its complications. We compared associations of 1,5-AG with 2-h glucose for risk of major clinical complications. RESEARCH DESIGN AND METHODS: We prospectively followed 6644 Atherosclerosis Risk in Communities (ARIC) Study participants without diagnosed diabetes for incident diagnosed diabetes, chronic kidney disease, cardiovascular disease, and all-cause mortality for ∼20 years. We assessed associations of 1,5-AG and 2-h glucose (modeled categorically and continuously with restricted cubic splines) with adverse outcomes using Cox models and evaluated improvement in risk discrimination using Harrell's c-statistic. RESULTS: 1,5-AG <10 µg/mL was statistically significantly associated with incident diabetes (HR: 2.70, 95% CI 2.31, 3.15), and showed suggestion of association with the other outcomes compared to 1,5-AG ≥10 µg/mL. Continuous associations of 1,5-AG with outcomes displayed a clear threshold effect, with risk associations generally observed only <10 µg/mL. Comparing associations of 1,5-AG and 2-h glucose with outcomes resulted in larger c-statistics for 2-h glucose than 1,5-AG for all outcomes (difference in c-statistic [2-h glucose -1,5-AG] for diagnosed diabetes: 0.17 [95%CI, 0.15, 0.19]; chronic kidney disease 0.02 [95%CI 0.00, 0.05]; cardiovascular disease 0.03 [95%CI, 0.00, 0.06]; and all-cause mortality 0.04 [95%CI, 0.02, 0.06]). CONCLUSIONS: In this community-based population without diagnosed diabetes, low 1,5-AG was modestly associated with major clinical outcomes and did not outperform 2-h glucose.

Original languageEnglish (US)
Pages (from-to)1296-1306
Number of pages11
JournalThe journal of applied laboratory medicine
Issue number6
StatePublished - Nov 1 2020

Bibliographical note

Publisher Copyright:
© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email:

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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