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Epidemiology/Health Services Research
Characterizing the weight-glycemia phenotypes of type 1 diabetes in youth and young adulthood
  1. Anna R Kahkoska1,
  2. Crystal T Nguyen2,
  3. Xiaotong Jiang2,
  4. Linda A Adair1,
  5. Shivani Agarwal3,
  6. Allison E Aiello4,
  7. Kyle S Burger1,
  8. John B Buse5,
  9. Dana Dabelea6,7,
  10. Lawrence M Dolan8,
  11. Giuseppina Imperatore9,
  12. Jean Marie Lawrence10,
  13. Santica Marcovina11,
  14. Catherine Pihoker12,
  15. Beth A Reboussin13,
  16. Katherine A Sauder6,7,
  17. Michael R Kosorok2,14,
  18. Elizabeth J Mayer-Davis1,5
  1. 1Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  2. 2Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  3. 3Center for Diabetes Translational Research, Albert Einstein College of Medicine, Bronx, New York, USA
  4. 4Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  5. 5Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  6. 6Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA
  7. 7Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado, USA
  8. 8Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
  9. 9Division of Diabetes Translation, Centers of Disease Control and Prevention, Atlanta, Georgia
  10. 10Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, Southern California, USA
  11. 11Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, Washington, USA
  12. 12Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
  13. 13Department of Pediatrics, University of Washington, Seattle, Washington, USA
  14. 14Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  1. Correspondence to Dr Anna R Kahkoska; anna_kahkoska{at}med.unc.edu

Abstract

Introduction Individuals with type 1 diabetes (T1D) present with diverse body weight status and degrees of glycemic control, which may warrant different treatment approaches. We sought to identify subgroups sharing phenotypes based on both weight and glycemia and compare characteristics across subgroups.

Research design and methods Participants with T1D in the SEARCH study cohort (n=1817, 6.0–30.4 years) were seen at a follow-up visit >5 years after diagnosis. Hierarchical agglomerative clustering was used to group participants based on five measures summarizing the joint distribution of body mass index z-score (BMIz) and hemoglobin A1c (HbA1c) which were estimated by reinforcement learning tree predictions from 28 covariates. Interpretation of cluster weight status and glycemic control was based on mean BMIz and HbA1c, respectively.

Results The sample was 49.5% female and 55.5% non-Hispanic white (NHW); mean±SD age=17.6±4.5 years, T1D duration=7.8±1.9 years, BMIz=0.61±0.94, and HbA1c=76±21 mmol/mol (9.1±1.9)%. Six weight-glycemia clusters were identified, including four normal weight, one overweight, and one subgroup with obesity. No cluster had a mean HbA1c <58 mmol/mol (7.5%). Cluster 1 (34.0%) was normal weight with the lowest HbA1c and comprised 85% NHW participants with the highest socioeconomic position, insulin pump use, dietary quality, and physical activity. Subgroups with very poor glycemic control (ie, ≥108 mmol/mol (≥12.0%); cluster 4, 4.4%, and cluster 5, 7.5%) and obesity (cluster 6, 15.4%) had a lower proportion of NHW youth, lower socioeconomic position, and reported decreased pump use and poorer health behaviors (overall p<0.01). The overweight subgroup with very poor glycemic control (cluster 5) showed the highest lipids and blood pressure (p<0.01).

Conclusions There are distinct subgroups of youth and young adults with T1D that share weight-glycemia phenotypes. Subgroups may benefit from tailored interventions addressing differences in clinical care, health behaviors, and underlying health inequity.

  • pediatric Type 1 diabetes
  • obesity
  • clusters
  • phenotype
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-000886

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    Footnotes

    • MRK and EJM-D contributed equally.

    • Contributors ARK, CTN, XJ, MRK, and EJMD designed the analyses. ARK and CTN conducted the analyses. ARK and EJMD drafted the initial manuscript. LAA, SA, AEA, KSB, JBB, DD, LMD, GI, JML, SM, CP, BAR, and KAS reviewed all analyses and provided critical review of the manuscript. GI—a representative of one of the cosponsors—reviewed all analyses and provided critical review of the manuscript. ARK and EJMD had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. MRK and EJMD are cosenior authors.

    • Funding Grant support (SEARCH 4): The SEARCH for Diabetes in Youth cohort study (1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention. Grant support (SEARCH 3): The SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA numbers 00097, DP-05-069, and DP-10-001) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Site contract numbers: Kaiser Permanente Southern California (U18DP006133, U48/CCU919219, U01 DP000246, and U18DP002714), University of Colorado Denver (U18DP006139, U48/CCU819241-3, U01 DP000247, and U18DP000247-06A1), Cincinnati's Children's Hospital Medical Center (U18DP006134, U48/CCU519239, U01 DP000248, and 1U18DP002709), University of North Carolina at Chapel Hill (U18DP006138, U48/CCU419249, U01 DP000254, and U18DP002708), Seattle Children's Hospital (U18DP006136, U58/CCU019235-4, U01 DP000244, and U18DP002710-01), Wake Forest University School of Medicine (U18DP006131, U48/CCU919219, U01 DP000250, and 200-2010-35171). The authors wish to acknowledge the involvement of the Kaiser Permanente Southern California’s Clinical Research Center (funded by Kaiser Foundation Health Plan and supported in part by the Southern California Permanente Medical Group); the South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina, NIH/National Center for Advancing Translational Sciences (NCATS) grant numbers UL1 TR000062, UL1Tr001450; Seattle Children's Hospital and the University of Washington, NIH/NCATS grant number UL1 TR00423; University of Colorado Pediatric Clinical and Translational Research Center, NIH/NCATS grant number UL1 TR000154; the Barbara Davis Center at the University of Colorado at Denver (DERC NIH grant number P30 DK57516); the University of Cincinnati, NIH/NCATS grant numbers UL1 TR000077, UL1 TR001425; and the Children with Medical Handicaps program managed by the Ohio Department of Health. This study includes data provided by the Ohio Department of Health, which should not be considered an endorsement of this study or its conclusions. ARK is supported by the National Institute of Diabetes and Digestive and Kidney Disease of the National Institutes of Health under award number F30DK113728. MRK, CTN, XJ, and JBB are supported by funding from NC Tracs (the CTSA at UNC): UL1TR002489.

    • Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The study was approved by institutional review boards with jurisdiction, and the parent, adolescent or young adult, or both provided consent or assent for all participants, as appropriate.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data may be obtained from a third party and are not publicly available. The data that support the findings of this study are available from the SEARCH for Diabetes in Youth study, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the SEARCH for Diabetes in Youth study.