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More hypoglycemia not associated with increasing estimated adiposity in youth with type 1 diabetes

Pediatric Research (2022)Cite this article

Abstract

Background

Despite the widespread clinical perception that hypoglycemia may drive weight gain in youth with type 1 diabetes (T1D), there is an absence of published evidence supporting this hypothesis.

Methods

We estimated the body fat percentage (eBFP) of 211 youth (HbA1c 8.0–13.0%, age 13–16) at baseline, 6, and 18 months of the Flexible Lifestyles Empowering Change trial using validated equations. Group-based trajectory modeling assigned adolescents to sex-specific eBFP groups. Using baseline 7-day blinded continuous glucose monitoring data, “more” vs. “less” percent time spent in hypoglycemia was defined by cut-points using sample median split and clinical guidelines. Adjusted logistic regression estimated the odds of membership in an increasing eBFP group comparing youth with more vs. less baseline hypoglycemia.

Results

More time spent in clinical hypoglycemia (defined by median split) was associated with 0.29 the odds of increasing eBFP in females (95% CI: 0.12, 0.69; p = 0.005), and 0.33 the odds of stable/increasing eBFP in males (95% CI: 0.14, 0.78; p = 0.01).

Conclusions

Hypoglycemia may not be a major driver of weight gain in US youth with T1D and HbA1c ≥8.0. Further studies in different sub-groups are needed to clarify for whom hypoglycemia may drive weight gain and focus future etiological studies and interventions.

Impact

  • We contribute epidemiological evidence that hypoglycemia may not be a major driver of weight gain in US youth with type 1 diabetes and HbA1c ≥8.0% and highlight the need for studies to prospectively test this hypothesis rooted in clinical perception.

  • Future research should examine the relationship between hypoglycemia and adiposity together with psychosocial, behavioral, and other clinical factors among sub-groups of youth with type 1 diabetes (i.e., who meet glycemic targets or experience a frequency/severity of hypoglycemia above a threshold) to further clarify for whom hypoglycemia may drive weight gain and progress etiological understanding of and interventions for healthy weight maintenance.

Overweight and obesity compound the elevated cardiovascular disease risk faced by individuals with type 1 diabetes, underscoring the need to understand the reasons for weight gain in this population and develop strategies for healthy weight maintenance.1,2 Overweight is associated with hypertension, dyslipidemia, inflammation, oxidative stress, and further challenges to glycemic levels through disruptions in insulin sensitivity as well as fat and carbohydrate metabolism.2,3 Critically, there are data to suggest that the cardiometabolic risks associated with being overweight or obese may offset the protective effects of intensive insulin therapy for cardiovascular health.4

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Fig. 1: Change in estimated body fat percentage (eBFP) among male (n = 104) and female (n = 107) FLEX trial participants over 18 months.

Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The FLEX trial is indebted to the many youths and their families whose participation made this study possible.

Funding

This analysis used data from the Flexible Lifestyles Empowering Change (FLEX) trial, which was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (1UC4DK101132) and the Helmsley Charitable Trust.

Author information

Authors and Affiliations

  1. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Angelica Cristello Sarteau, Anna R. Kahkoska, Daria Igudesman, Frank Muntis & Elizabeth Mayer-Davis

  2. School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Jamie Crandell

  3. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Jamie Crandell

  4. Translational Research Institute, AdventHealth Orlando, Orlando, FL, USA

    Karen D. Corbin & Richard Pratley

  5. Department of Psychology, University of Windsor, Windsor, ON, Canada

    Jessica C. Kichler

  6. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    David M. Maahs

  7. Stanford Diabetes Research Center and Health Research and Policy (Epidemiology), Stanford, CA, USA

    David M. Maahs & Dessi Zaharieva

  8. Cincinnati Children’s Hospital Medical Center, University of Cincinnati Medical School, Cincinnati, OH, USA

    Michael Seid

  9. School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Elizabeth Mayer-Davis

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  1. Angelica Cristello Sarteau
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Contributions

E.M.-D., D.M.M., J.C.K., M.S., A.R.K., and A.C.S. designed the analysis. A.C.S conducted the analysis and interpreted the data. A.C.S. drafted the initial manuscript. All authors reviewed analyses and approved the manuscript.

Corresponding author

Correspondence to Angelica Cristello Sarteau.

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Competing interests

A.R.K. received financial support for travel from Novo Nordisk A/S to present work unrelated to this analysis in 2019. For work unrelated to the present analysis, D.M.M. reports research support from the NIH, JDRF, NSF, and the Helmsley Charitable Trust, and his institution has had research support from Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem, and Roche. D.M.M. has consulted for Abbott, Aditxt, the Helmsley Charitable Trust, Sanofi, Novo Nordisk, Eli Lilly, Medtronic, Insulet, and Dompe. All other authors have nothing to disclose. For work unrelated to the present analysis, D.Z. reports fellowship funding from ISPAD-JDRF, grants from the Helmsley Charitable Trust, and Medtronic Diabetes, Ascensia Diabetes Care, and Insulet Canada speaker bureau participation. R.P. reports consulting fees from AstraZeneca; consulting fees from Glytec, LLC; grants from Hanmi Pharmaceutical Co.; grants and consulting fees from Janssen; consulting fees from Merck; grants from Metavention; consulting fees from Mundipharma; grants, speaker fees, and consulting fees from Novo Nordisk; consulting fees from Pfizer; grants from Poxel SA; grants and consulting fees from Sanofi; consulting fees from Scohia Pharma Inc.; consulting fees from Sun Pharmaceutical Industries; personal consulting fees from Sanofi US Services, Inc. Except for consulting fees in February 2018 and June 2018 from Sanofi US Services, Inc., R.P. services were paid for directly to AdventHealth, a nonprofit organization. All other authors report no financial ties to products used in the study or perceived/potential conflicts of interest.

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Written informed consent and assent were provided by parent and adolescent, respectively, at the first in-person baseline measurement visit of the Flexible Lifestyles Empowering Change (FLEX) trial.

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Sarteau, A.C., Kahkoska, A.R., Crandell, J. et al. More hypoglycemia not associated with increasing estimated adiposity in youth with type 1 diabetes. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02129-1

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  • DOI: https://doi.org/10.1038/s41390-022-02129-1

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