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The dose–response effect of insulin sensitivity on albuminuria in children according to diabetes type

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Abstract

Background

Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose–response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases.

Methods

These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model.

Results

There was an association between IS and UACR in type 2 diabetes only (beta = −0.39; p < 0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta = 0.40; p < 0.001) but not type 1 diabetes (p = 0.3).

Conclusions

In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.

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Acknowledgments

The SEARCH for Diabetes in Youth Study is indebted to the many youth and their families, and their health care providers, whose participation made this study possible.

Grant Support: 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 (U48/CCU919219, U01 DP000246, and U18DP002714), University of Colorado Denver (U48/CCU819241-3, U01 DP000247, and U18DP000247-06A1), Children’s Hospital Medical Center (Cincinnati) (U48/CCU519239, U01 DP000248, and 1U18DP002709), University of North Carolina at Chapel Hill (U48/CCU419249, U01 DP000254, and U18DP002708), University of Washington School of Medicine (U58/CCU019235-4, U01 DP000244, and U18DP002710-01), Wake Forest University School of Medicine (U48/CCU919219, U01 DP000250, and 200-2010-35171).

The authors wish to acknowledge the involvement of General Clinical Research Centers (GCRC) at the South Carolina Clinical & Translational Research (SCTR) Institute, at the Medical University of South Carolina (NIH/NCRR Grant number UL1RR029882); Seattle Children’s Hospital (NIH CTSA Grant UL1 TR00423 of the University of Washington); University of Colorado Pediatric Clinical and Translational Research Center (CTRC) (Grant Number UL1 TR000154) and the Barbara Davis Center at the University of Colorado at Denver (DERC NIH P30 DK57516); and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8 UL1 TR000077; and the Children with Medical Handicaps program managed by the Ohio Department of Health.

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 Disease

Author information

Authors and Affiliations

  1. UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Amy K. Mottl

  2. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Jasmin Divers

  3. Department of Epidemiology, School of Public Health, University of Colorado Denver, Aurora, CO, USA

    Dana Dabelea

  4. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA

    David M. Maahs

  5. Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Lawrence Dolan

  6. Santa Barbara, CA, USA

    David Pettitt

  7. Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, WA, USA

    Santica Marcovina

  8. Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Giuseppina Imperatore

  9. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Catherine Pihoker

  10. Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA

    Michael Mauer

  11. Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA

    Michael Mauer

  12. Department of Nutrition, University of North Carolina School of Public Health, Chapel Hill, NC, USA

    Elizabeth J. Mayer-Davis

  13. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Elizabeth J. Mayer-Davis

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  1. Amy K. Mottl
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  2. Jasmin Divers
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  3. Dana Dabelea
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  4. David M. Maahs
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  5. Lawrence Dolan
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  7. Santica Marcovina
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  8. Giuseppina Imperatore
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  9. Catherine Pihoker
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  10. Michael Mauer
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  11. Elizabeth J. Mayer-Davis
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for the SEARCH for Diabetes in Youth Study

Corresponding author

Correspondence to Amy K. Mottl.

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The study protocol was reviewed and approved by local institutional review boards (IRB) that had jurisdiction over the local study populations. Consent was obtained from parents of all participants under age 18 years and assent from participants according to the specific age requirement deemed by the local IRB.

Conflict of interest

The authors declare no conflict of interest.

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Mottl, A.K., Divers, J., Dabelea, D. et al. The dose–response effect of insulin sensitivity on albuminuria in children according to diabetes type. Pediatr Nephrol 31, 933–940 (2016). https://doi.org/10.1007/s00467-015-3276-2

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  • DOI: https://doi.org/10.1007/s00467-015-3276-2

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