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Prediabetes, intervening diabetes and subsequent risk of dementia: the Atherosclerosis Risk in Communities (ARIC) study

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Abstract

Aims/hypothesis

The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes.

Methods

Among participants of the Atherosclerosis Risk in Communities (ARIC) study we defined baseline prediabetes as HbA1c 39–46 mmol/mol (5.7–6.4%) and subsequent incident diabetes as a self-reported physician diagnosis or use of diabetes medication. Incident dementia was ascertained via active surveillance and adjudicated. We quantified the association of prediabetes with dementia risk before and after accounting for the subsequent development of diabetes among ARIC participants without diabetes at baseline (1990–1992; participants aged 46–70 years). We also evaluated whether age at diabetes diagnosis modified the risk of dementia.

Results

Among 11,656 participants without diabetes at baseline, 2330 (20.0%) had prediabetes. Before accounting for incident diabetes, prediabetes was significantly associated with the risk of dementia (HR 1.12 [95% CI 1.01, 1.24]). After accounting for incident diabetes, the association was attenuated and non-significant (HR 1.05 [95% CI 0.94, 1.16]). Earlier age of onset of diabetes had the strongest association with dementia: HR 2.92 (95% CI 2.06, 4.14) for onset before 60 years; HR 1.73 (95% CI 1.47, 2.04) for onset at 60–69 years; and HR 1.23 (95% CI 1.08, 1.40) for onset at 70–79 years.

Conclusions/interpretation

Prediabetes is associated with dementia risk but this risk is explained by the subsequent development of diabetes. Earlier age of onset of diabetes substantially increases dementia risk. Preventing or delaying progression of prediabetes to diabetes will reduce dementia burden.

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Abbreviations

ARIC:

Atherosclerosis Risk in Communities

FG:

Fasting glucose

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Jiaqi Hu, Michael Fang, A. Richey Sharrett, Josef Coresh & Elizabeth Selvin

  2. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA

    Jiaqi Hu, Michael Fang, A. Richey Sharrett, Josef Coresh & Elizabeth Selvin

  3. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    James R. Pike

  4. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    Pamela L. Lutsey

  5. Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Lynne E. Wagenknecht

  6. Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Timothy M. Hughes

  7. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Jesse C. Seegmiller

  8. Stroke Branch, National Institute of Neurological Disorders and Stroke, Baltimore, MD, USA

    Rebecca F. Gottesman

  9. The MIND Center, University of Mississippi School of Medicine, Jackson, MS, USA

    Thomas H. Mosley

Authors
  1. Jiaqi Hu
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Corresponding author

Correspondence to Elizabeth Selvin.

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Acknowledgements

The authors thank the staff and participants of the ARIC study for their important contributions.

Data availability

The ARIC data are not publicly available due to confidentiality issues. Investigators can access data from the ARIC study by submitting a manuscript proposal to aricpub@unc.edu.

Funding

The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I and HHSN268201700004I. Collection of neurocognitive data was funded by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902 and 2U01HL096917 from the NIH (NHLBI, National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA] and National Institute on Deafness and Other Communications Disorders [NIDCD]); previous brain MRI examinations were funded by R01-HL70825 and biomarkers by R01-HL134320 from the NHLBI. PLL was supported NIH/NHLBI grant K24 HL159246. RFG was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program. ES was supported by NIH/NHLBI grants K24 HL152440 and R01 HL158022, NIH/NIDDK grants R01 DK089174 and R01 DK128837, and NIH/NIA grant RF1 AG074044.

Authors’ relationships and activities

ES is on the advisory board for Diabetologia and had no role in peer-review of the manuscript. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Contribution statement

JH, MF, JC and ES designed the study, researched the data and contributed to discussion. JH conducted the analyses and wrote the initial manuscript. All authors provided substantial contributions to the interpretation of data, made critical revisions to the manuscript and approved the final manuscript. JH is the guarantor of this work and, as such, had full access to all the data in the study, controlled the decision to publish and takes responsibility for the integrity of the data and the accuracy of the data analysis. The corresponding author, ES, attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

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Hu, J., Fang, M., Pike, J.R. et al. Prediabetes, intervening diabetes and subsequent risk of dementia: the Atherosclerosis Risk in Communities (ARIC) study. Diabetologia 66, 1442–1449 (2023). https://doi.org/10.1007/s00125-023-05930-7

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