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Original Investigation
February 8, 2021

Risk of Progression to Diabetes Among Older Adults With Prediabetes

Author Affiliations
  • 1Welch Center for Prevention, Epidemiology, and Clinical Research, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 2Kaiser Permanente Center for Health Research, Portland, Oregon
  • 3Division of Epidemiology and Community Health, University of Minnesota, Minneapolis
  • 4Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, Maryland
JAMA Intern Med. 2021;181(4):511-519. doi:10.1001/jamainternmed.2020.8774
Key Points

Question  What is the risk of progression to diabetes among older adults with prediabetes (based on glycated hemoglobin level of 5.7%-6.4%, fasting glucose levels of 100-125 mg/dL, either, or both) in a community-based population?

Findings  In this cohort study of 3412 older adults, the prevalence of prediabetes (mean [SD] age, 75.6 [5.2] years) was high and differed substantially depending on the definition used, with estimates ranging from 29% for glycated hemoglobin levels of 5.7% to 6.4% and fasting glucose levels of 100 to 125 mg/dL to 73% for either glycated hemoglobin levels of 5.7% to 6.4% or fasting glucose levels of 100 to 125 mg/dL. During the 6 years of follow-up, death or regression to normoglycemia from prediabetes was more frequent than progression to diabetes.

Meaning  Prediabetes may not be a robust diagnostic entity in older age.


Importance  The term prediabetes is used to identify individuals at increased risk for diabetes. However, the natural history of prediabetes in older age is not well characterized.

Objectives  To compare different prediabetes definitions and characterize the risks of prediabetes and diabetes among older adults in a community-based setting.

Design, Setting, and Participants  In this prospective cohort analysis of 3412 older adults without diabetes from the Atherosclerosis Risk in Communities Study (baseline, 2011-2013), participants were contacted semiannually through December 31, 2017, and attended a follow-up visit between January 1, 2016, and December 31, 2017 (median [range] follow-up, 5.0 [0.1-6.5] years).

Exposures  Prediabetes defined by a glycated hemoglobin (HbA1c) level of 5.7% to 6.4%, impaired fasting glucose (IFG) level (FG level of 100-125 mg/dL), either, or both.

Main Outcomes and Measures  Incident total diabetes (physician diagnosis, glucose-lowering medication use, HbA1c level ≥6.5%, or FG level ≥126 mg/dL).

Results  A total of 3412 participants without diabetes (mean [SD] age, 75.6 [5.2] years; 2040 [60%] female; and 572 [17%] Black) attended visit 5 (2011-2013, baseline). Of the 3412 participants at baseline, a total of 2497 participants attended the follow-up visit or died. During the 6.5-year follow-up period, there were 156 incident total diabetes cases (118 diagnosed) and 434 deaths. A total of 1490 participants (44%) had HbA1c levels of 5.7% to 6.4%, 1996 (59%) had IFG, 2482 (73%) met the HbA1c or IFG criteria, and 1004 (29%) met both the HbA1c and IFG criteria. Among participants with HbA1c levels of 5.7% to 6.4% at baseline, 97 (9%) progressed to diabetes, 148 (13%) regressed to normoglycemia (HbA1c, <5.7%), and 207 (19%) died. Of those with IFG at baseline, 112 (8%) progressed to diabetes, 647 (44%) regressed to normoglycemia (FG, <100 mg/dL), and 236 (16%) died. Of those with baseline HbA1c levels less than 5.7%, 239 (17%) progressed to HbA1c levels of 5.7% to 6.4% and 41 (3%) developed diabetes. Of those with baseline FG levels less than 100 mg/dL, 80 (8%) progressed to IFG (FG, 100-125 mg/dL) and 26 (3%) developed diabetes.

Conclusions and Relevance  In this community-based cohort study of older adults, the prevalence of prediabetes was high; however, during the study period, regression to normoglycemia or death was more frequent than progression to diabetes. These findings suggest that prediabetes may not be a robust diagnostic entity in older age.

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    3 Comments for this article
    Patient-centric diagnosis of pre-diabetes in older adults: a missing part of the puzzle
    Saeid Shahraz, MD PhD | University
    Using a risk factor tool, we have previously shown that 8 of 10 people aged at least 60 years are at risk of prediabetes in the United States(1). The newly published article by Rooney et al. (2) indicated that roughly between 3 to 7 of 10 people ( depending on the definition) in their large sample had prediabetes. These numbers make us think that it is time to ask older adults what they think of prediabetes as a medical diagnosis? With the recent advancement in patient-centric medicine, we can understand the actual needs of elderly patients and quantify their preferences. The patient gaze is becoming increasingly important in medical diagnosis and treatment. Relevant medical associations can incorporate patient experience and preferences into an approach to defining new cutoffs for any pre-diagnosis like prediabetes in older adults.

    1.Shahraz S, Pittas AG, Kent DM. Prediabetes Risk in Adult Americans According to a Risk Test. JAMA Intern Med. 2016;176(12):1861–1863. doi:10.1001/jamainternmed.2016.5919

    2. Rooney MR, Rawlings AM, Pankow JS, et al. Risk of Progression to Diabetes Among Older Adults With Prediabetes. JAMA Intern Med. Published online February 08, 2021. doi:10.1001/jamainternmed.2020.8774
    "pre-diabetes," more context
    Daniel Krell, M.D. | Retired family physician
    Charles Piller (Science Magazine, 3/8/19, Vol. 363, Issue 6431) addressed this issue and came to the same conclusion. Larger context about and history of this diagnosis were discussed. Given this JAMA Network article and related references, it appears to be time, if not already being done, to include "unlearning" of this diagnosis in current and future medical education programs.

    Daniel Krell, M.D.
    RE: Risk of progression to diabetes among older adults with prediabetes
    Tomoyuki Kawada, MD | Nippon Medical School
    Rooney et al. conducted a 6.5-year follow-up study to evaluate the risk of diabetes among older adults with prediabetes (1). Among older adults with impaired fasting glucose at baseline, 8% progressed to diabetes, 16% died, 44% regressed to normoglycemia, and others remained prediabetes. I have two comments about their study.

    Shang et al. reported that one-third of older adults with prediabetes developed diabetes or died, and others remained stable or reverted to normoglycemia during a 12-year follow-up (2). They also specified that lower SBP, no heart diseases and good weight management were effective for reversion to normoglycemia. This means
    that preventive strategies are important to improve prognosis in patients with prediabetes.

    Recently, Wagner et al. classified prediabetes into 6 clusters by using oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content and genetic risk for specifying the risk of type 2 diabetes and complications (3). Pathophysiological heterogeneity existed in each cluster before diagnosis of type 2 diabetes, and one cluster presented an increased risk of complications without progression to type 2 diabetes in patients with prediabetes. Definition of prediabetes should be re-evaluated with special reference to prognosis and health outcomes.

    1. Rooney MR, Rawlings AM, Pankow JS, et al. Risk of progression to diabetes among older adults with prediabetes. JAMA Intern Med 2021 doi: 10.1001/jamainternmed.2020.8774
    2. Shang Y, Marseglia A, Fratiglioni L, et al. Natural history of prediabetes in older adults from a population-based longitudinal study. J Intern Med 2019;286(3):326-340.
    3. Wagner R, Heni M, Tabák AG, et al. Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes. Nat Med 2021;27(1):49-57.