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Relation of glomerular filtration to insulin resistance and related risk factors in obese children

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Abstract

Background and objective

Childhood obesity is associated with later development of significant renal morbidity. We evaluated the impact of the degree of insulin sensitivity on estimated glomerular filtration rate (eGFR) and determined the factors associated with eGFR in obese children. We further tested the relation of eGFR to clinical outcomes such as blood pressure and microalbuminuria.

Materials and methods

We evaluated the relation of whole body insulin sensitivity and estimated glomerular filtration rate (eGFR) across the spectrum of obesity in children and adolescents. eGFR was calculated using the iCARE formula, which has been validated in obese children with varying glucose tolerance.

Results

1080 children and adolescents with overweight and obesity (701 females and 379 males) participated. Insulin sensitivity was a strongly negatively associated with (B = −2.72, p < 0.001) eGFR), even after adjustment for potential confounders. Male sex emerged to be significantly associated with eGFR with boys having greater values than girls (B = 18.82, p < 0.001). Age was a positively associated (B = 2.86, p < 0.001) with eGFR. Whole body and hepatic insulin sensitivity decreased across eGFR quartiles. Adjusted eGFR was tightly positively associated with systolic blood pressure (B = 0.09, p = 0.003) and negatively associated with the presence of microalbuminuria (B = −2.18, p = 0.04).

Conclusions

eGFR tends to increase with greater degrees of insulin resistance in children and adolescents representing hyperfiltration and is associated with cardiovascular risk factors. Longitudinal studies are needed to determine the natural history of childhood insulin resistance related hyperfiltration in regards to future kidney disease.

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Fig. 1: eGFR (iCARE) by degree of obesity and insulin sensitivity quartiles.
Fig. 2: eGFR (iCARE) levels by sex and degree of obesity.
Fig. 3: Metabolic parameters across eGFR (iCARE) quartiles.

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Acknowledgements

This paper is in loving memory of Bridget Pierpont, the research coordinator of the Yale Pathophysiology of Type 2 Diabetes in Youth Study cohort, who passed away unexpectedly during the preparation of this paper. We wish to thank the participants and their families for their willingness and cooperation. This study was supported by the National Institutes of Health, National Institute of Child Health and Human Development (grants R01-HD-40787, R01DK111038, R01-HD-28016, and K24-HD-01464 to S.C.), the National Center for Research Resources (Clinical and Translational Science Award [grant UL1-RR-0249139] to SC), the American Diabetes Association (Distinguished Clinical Scientist Award to SC), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01-DK-111038 to SC; grant R01-DK-114504-01A1)

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Author notes

  1. These authors contributed equally: Daniella Magen, Rana Halloun.

Authors and Affiliations

  1. Department of Pediatrics, Ruth Children’s Hospital, Rambam Medical Center, Haifa, Israel

    Daniella Magen, Rana Halloun & Ram Weiss

  2. The Department of Pediatrics, Yale University, New-Haven, CT, USA

    Daniella Magen, Rana Halloun, Sonia Caprio & Ram Weiss

  3. Department of Woman and Child’s Health, University of Padova, Padova, Italy

    Alfonso Galderisi

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  1. Daniella Magen
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Contributions

DM and RN performed the analysis and wrote the paper, AG took part in the clinical care and added to the discussion; SC and RW designed the study, took part in the clinical care and the analysis and added to the discussion. All authors read, edited and approved the paper. RW is the guarantor of this analysis.

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Correspondence to Ram Weiss.

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Magen, D., Halloun, R., Galderisi, A. et al. Relation of glomerular filtration to insulin resistance and related risk factors in obese children. Int J Obes 46, 374–380 (2022). https://doi.org/10.1038/s41366-021-01001-2

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