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Higher glucose and insulin responses to a mixed meal are associated with increased risk of diabetic retinopathy in Indigenous Americans

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Abstract

Purpose

Prior research has focused on glucose/insulin responses to meal challenges to create personalized diets to improve health, though it is unclear if these responses predict chronic diseases. We aimed to identify glucose and insulin responses to a mixed meal tolerance test (MMTT) that predict the development of diabetic retinopathy (DR) and compare the predictive abilities with the oral glucose tolerance test (OGTT).

Methods

Indigenous American adults without diabetes (n = 168) underwent a 4-h MMTT, body composition assessment, and a 3-h OGTT at baseline. During follow-up (median 13.4 years), DR was diagnosed by direct ophthalmoscopy (n = 28) after onset of type 2 diabetes. Total and incremental area under the curve (AUC and iAUC) were calculated from glucose/insulin responses after the MMTT and OGTT.

Results

In separate Cox proportional hazards models adjusted for age, sex, and body fat (%), MMTT glucose AUCs (180-min and 240-min) and iAUC (180-min) predicted DR (HR 1.50, 95% CI 1.06, 2.12; HR 1.50, 95% CI 1.05, 2.14; HR 1.58, 95% CI 1.01, 2.46). The predictive abilities were better than the fasting OGTT glucose (p < 0.01) but similar to the 120-min OGTT glucose (p = 0.53). MMTT insulin AUCs (180-min and 240-min) and iAUC (180-min) also predicted DR (HR 1.65, 95% CI 1.09, 2.51; HR 1.58, 95% CI 1.00, 2.35; HR 1.53 95% CI 1.06, 2.22) while insulin AUC and iAUC from the OGTT did not (p > 0.05).

Conclusions

Higher MMTT glucose and insulin responses predicted DR and were comparable to the OGTT, supporting the use of a meal challenge for precision nutrition.

Trial registrations: Clinical Trial Registry: ClinicalTrials.gov identifier: NCT00340132, NCT00339482.

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Data availability

Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval.

Abbreviations

AUC:

Area under the curve

DR:

Diabetic retinopathy

DXA:

Dual-energy X-ray absorptiometry

iAUC:

Incremental area under the curve

MMTT:

Mixed meal tolerance test

OGTT:

Oral glucose tolerance test

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Acknowledgements

We thank the participants and the research staff of the Phoenix Epidemiology and Clinical Research Branch.

Funding

This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (Grant No. DK069015-36).

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Author notes

  1. E. J. Stinson and C. M. Mitchell contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 N. 16th Street, Phoenix, AZ, 85016, USA

    E. J. Stinson, C. M. Mitchell, H. C. Looker, J. Krakoff & D. C. Chang

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  2. C. M. Mitchell
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  3. H. C. Looker
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Contributions

This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. E.J.S. and C.M.M. analyzed the data, contributed to discussion, and wrote, reviewed, and edited the manuscript. H.C.L., J.K, and D.C.C. contributed to discussion, and reviewed and edited the manuscript. All authors approved the final version of the manuscript. D.C.C. is the guarantor and therefore takes full responsibility for the work as a whole, including access to data, and the decision to submit and publish the manuscript.

Corresponding author

Correspondence to D. C. Chang.

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Conflict of interests

On behalf of all authors, the corresponding author states that there is no conflict of interest. The study was previously approved by the NIDDK Institutional Review Board. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all participants.

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Stinson, E.J., Mitchell, C.M., Looker, H.C. et al. Higher glucose and insulin responses to a mixed meal are associated with increased risk of diabetic retinopathy in Indigenous Americans. J Endocrinol Invest 47, 699–707 (2024). https://doi.org/10.1007/s40618-023-02187-0

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  • DOI: https://doi.org/10.1007/s40618-023-02187-0

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