Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

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.

References

  1. Lind, M. et al. Glycemic control and excess mortality in type 1 diabetes. N. Engl. J. Med. 371, 1972–1982 (2014).

    PubMed  Article  CAS  Google Scholar 

  2. Corbin, K. D. et al. Obesity in type 1 diabetes: pathophysiology, clinical impact, and mechanisms. Endocr. Rev. 39, 629–663 (2018).

    PubMed  Article  Google Scholar 

  3. Polsky, S. & Ellis, S. L. Obesity, insulin resistance, and type 1 diabetes mellitus. Curr. Opin. Endocrinol. Diabetes Obes. 22, 277–282 (2015).

    CAS  PubMed  Article  Google Scholar 

  4. Purnell, J. Q., Zinman, B. & Brunzell, J. D. The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (Dcct/Edic) Study. Circulation 127, 180–187 (2013).

    CAS  PubMed  Article  Google Scholar 

  5. Miller, K. M. et al. Current state of type 1 diabetes treatment in the US: updated data from the T1d Exchange Clinic Registry. Diabetes Care 38, 971–978 (2015).

    PubMed  Article  Google Scholar 

  6. Liu, L. L. et al. Prevalence of overweight and obesity in youth with diabetes in USA: the search for diabetes in youth study. Pediatr. Diabetes 11, 4–11 (2010).

    PubMed  Article  Google Scholar 

  7. DuBose, S. N. et al. Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. J. Pediatr. 167, 627–632.e624 (2015) .

    PubMed  Article  Google Scholar 

  8. Craigie, A. M., Lake, A. A., Kelly, S. A., Adamson, A. J. & Mathers, J. C. Tracking of obesity-related behaviours from childhood to adulthood: a systematic review. Maturitas 70, 266–284 (2011).

    PubMed  Article  Google Scholar 

  9. Driscoll, K. A. et al. Biopsychosocial aspects of weight management in type 1 diabetes: a review and next steps. Curr. Diabetes Rep. 17, 58 (2017).

    Article  CAS  Google Scholar 

  10. Minges, K. E. et al. Correlates of overweight and obesity in 5529 adolescents with type 1 diabetes: the T1d Exchange Clinic Registry. Diabetes Res. Clin. Pract. 126, 68–78 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  11. Hu, F. Obesity Epidemiology (Oxford University Press, 2008).

  12. Kahkoska, A. R. et al. Sociodemographic associations of longitudinal adiposity in youth with type 1 diabetes. Pediatr. Diabetes 19, 1429–1440 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Purnell, J. Q. et al. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. JAMA 280, 140–146 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Jacob, A., Salinas, K., Adams‐Huet, B. & Raskin, P. Potential causes of weight gain in type 1 diabetes mellitus. Diabetes Obes. Metab. 8, 404–411 (2006).

    CAS  PubMed  Article  Google Scholar 

  15. Russell‐Jones, D. & Khan, R. Insulin‐associated weight gain in diabetes–causes, effects and coping strategies. Diabetes Obes. Metab. 9, 799–812 (2007).

    PubMed  Article  CAS  Google Scholar 

  16. Mehta, S. N. et al. Emphasis on carbohydrates may negatively influence dietary patterns in youth with type 1 diabetes. Diabetes Care 32, 2174–2176 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  17. Ibfelt, E. et al. Association between glycaemic outcome and BMI in Danish children with type 1 diabetes in 2000–2018: a nationwide population‐based study. Diabet. Med. 38, e14401 (2020).

  18. Nansel, T., Lipsky, L. & Iannotti, R. Cross-sectional and longitudinal relationships of body mass index with glycemic control in children and adolescents with type 1 diabetes mellitus. Diabetes Res. Clin. Pract. 100, 126–132 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Pasco, J. A. et al. Body mass index and measures of body fat for defining obesity and underweight: a cross-sectional, population-based study. BMC Obes. 1, 1–7 (2014).

    Article  Google Scholar 

  20. Siervogel, R. M. et al. Annual changes in total body fat and fat‐free mass in children from 8 to 18 years in relation to changes in body mass index: the Fels Longitudinal Study. Ann. N. Y. Acad. Sci. 904, 420–423 (2000).

    CAS  PubMed  Article  Google Scholar 

  21. Sørensen, K. & Juul, A. BMI percentile-for-age overestimates adiposity in early compared with late maturing pubertal children. Eur. J. Endocrinol. 173, 227–235 (2015).

    PubMed  Article  CAS  Google Scholar 

  22. Stevens, J., Ou, F.-S., Cai, J., Heymsfield, S. & Truesdale, K. Prediction of percent body fat measurements in americans 8 years and older. Int. J. Obes. 40, 587–594 (2016).

    CAS  Article  Google Scholar 

  23. Kichler, J. C. et al. The Flexible Lifestyle Empowering Change (FLEX) intervention for self-management in adolescents with type 1 diabetes: trial design and baseline characteristics. Contemp. Clin. Trials 66, 64–73 (2018).

    PubMed  Article  Google Scholar 

  24. Patry-Parisien, J., Shields, M. & Bryan, S. Comparison of waist circumference using the World Health Organization and National Institutes of Health protocols. Health Rep. 23, 53–60 (2012).

    PubMed  Google Scholar 

  25. Vanderwall, C., Clark, R. R., Eickhoff, J. & Carrel, A. L. BMI is a poor predictor of adiposity in young overweight and obese children. BMC Pediatr. 17, 1–6 (2017).

    Article  Google Scholar 

  26. Vanderwall, C., Eickhoff, J., Clark, R. R. & Carrel, A. L. BMI Z-score in obese children is a poor predictor of adiposity changes over time. BMC Pediatr. 18, 1–6 (2018).

    Article  Google Scholar 

  27. Bridge, P. et al. Validation of longitudinal DXA changes in body composition from pre-to mid-adolescence using MRI as reference. J. Clin. Densitom. 14, 340–347 (2011).

    PubMed  Article  Google Scholar 

  28. Nagin, D. S. Analyzing developmental trajectories: a semiparametric, group-based approach. Psychol. Methods 4, 139 (1999).

    Article  Google Scholar 

  29. Loomba-Albrecht, L. A. & Styne, D. M. Effect of puberty on body composition. Curr. Opin. Endocrinol. Diabetes Obes. 16, 10–15 (2009).

    CAS  PubMed  Article  Google Scholar 

  30. Nagin, D. Group-based Modeling of Development. 4159, 9780674041318 (Harvard University Press, Cambridge, Mass, 2005).

  31. Nagin, D. S. & Odgers, C. L. Group-based trajectory modeling in clinical research. Annu. Rev. Clin. Psychol. 6, 109–138 (2010).

    PubMed  Article  Google Scholar 

  32. Kahkoska, A. R. et al. Dysglycemia among youth with type 1 diabetes and suboptimal glycemic control in the Flexible Lifestyle Empowering Change trial. Pediatr. Diabetes 20, 180–188 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Abraham, M. B. et al. Ispad Clinical Practice Consensus Guidelines 2018: assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr. Diabetes 19, 178–192 (2018).

    PubMed  Article  Google Scholar 

  34. Bumbu, A. et al. Non‐severe hypoglycaemia is associated with weight gain in patients with type 1 diabetes: results from the Diabetes Control and Complication Trial. Diabetes Obes. Metab. 20, 1289–1292 (2018).

    CAS  PubMed  Article  Google Scholar 

  35. Williams, D. P. et al. Body fatness and risk for elevated blood pressure, total cholesterol, and serum lipoprotein ratios in children and adolescents. Am. J. Public Health 82, 358–363 (1992).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. Going, S. B. et al. Percent body fat and chronic disease risk factors in US children and youth. Am. J. Preventive Med. 41, S77–S86 (2011).

    Article  Google Scholar 

  37. Mueller, W. H., Harrist, R. B., Doyle, S. R. & Labarthe, D. R. Percentiles of body composition from bioelectrical impedance and body measurements in US adolescents 8–17 years old: Project Heartbeat! Am. J. Hum. Biol. 16, 135–150 (2004).

    PubMed  Article  Google Scholar 

  38. Neovius, M. G., Linné, Y. M., Barkeling, B. S. & Rossner, S. O. Sensitivity and specificity of classification systems for fatness in adolescents. Am. J. Clin. Nutr. 80, 597–603 (2004).

    CAS  PubMed  Article  Google Scholar 

  39. Sardinha, L. B., Going, S. B., Teixeira, P. J. & Lohman, T. G. Receiver operating characteristic analysis of body mass index, triceps skinfold thickness, and arm girth for obesity screening in children and adolescents. Am. J. Clin. Nutr. 70, 1090–1095 (1999).

    CAS  PubMed  Article  Google Scholar 

  40. Taylor, R., Falorni, A., Jones, I. & Goulding, A. Identifying adolescents with high percentage body fat: a comparison of bmi cutoffs using age and stage of pubertal development compared with bmi cutoffs using age alone. Eur. J. Clin. Nutr. 57, 764–769 (2003).

    CAS  PubMed  Article  Google Scholar 

  41. Willett, W. Nutritional Epidemiology, Vol. 40 (Oxford University Press, 2012).

  42. Igudesman, D. et al. Dietary intake on days with and without hypoglycemia in youth with type 1 diabetes: the Flexible Lifestyle Empowering Change Trial. Pediatr. Diabetes 21, 1475–1484 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. Hanna, K. M. & Guthrie, D. Adolescents’ behavioral autonomy related to diabetes management and adolescent activities/rules. Diabetes Educator. 29, 283–291 (2003).

    PubMed  Article  Google Scholar 

  44. Amiel, S. A., Sherwin, R. S., Simonson, D. C., Lauritano, A. A. & Tamborlane, W. V. Impaired insulin action in puberty. N. Engl. J. Med. 315, 215–219 (1986).

    CAS  PubMed  Article  Google Scholar 

  45. Mayer-Davis, E. J. et al. The Flexible Lifestyles Empowering Change (FLEX) intervention for adolescents with type 1 diabetes: randomized clinical trial results for effect on metabolic status, diabetes related behaviors, and quality of life. Lancet Child Adolesc. Health 2, 635 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

Download references

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

Authors

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.

Ethics declarations

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.

Consent for publication

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.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

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

Search

Quick links