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In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome

Stephanie Cung, Laura Pyle, Kristin Nadeau, Dana Dabelea, Melanie Cree-Green, Shanlee M Davis
DOI: 10.1136/jim-2021-001966 Published 23 December 2021
Stephanie Cung
1 University of Colorado Denver School of Medicine, Aurora, Colorado, USA
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Laura Pyle
2 Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
3 Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA
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Kristin Nadeau
2 Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
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Dana Dabelea
4 Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA
5 Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, Colorado, USA
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Melanie Cree-Green
2 Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
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Shanlee M Davis
2 Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
6 eXtraordinarY Kids Clinic and Research Program, Children’s Hospital Colorado, Aurora, Colorado, USA
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Abstract

Klinefelter syndrome (XXY) occurs in 1 in 600 males, resulting in testosterone deficiency and a high prevalence of insulin resistance. Testosterone deficiency in men is a known cause of insulin resistance, and mitochondrial dysfunction is hypothesized to mediate this relationship. The aim of this cross-sectional study was to evaluate muscle mitochondrial function in XXY compared with male controls. Twenty-seven boys with XXY (age 14.7±1.8 years) were compared with 87 controls (age 16.9±0.9). In-vivo calf muscle mitochondrial function was assessed via phosphorus magnetic resonance spectroscopy (31P-MRS) following 90 s of isometric 70% maximal exercise. Multiple linear regression was used to compare 31P-MRS outcomes (ADP and phosphocreatine (PCr) time constants, rate of oxidative phosphorylation (Oxphos), and Qmax or the maximal mitochondrial function relative to mitochondrial density) between groups after adjusting for age differences. There were no statistically significant differences in the mitochondrial outcomes of ADP, Oxphos, PCr, and Qmax between the groups. There were also no differences in a sensitivity analysis within the XXY group by testosterone treatment status. In this study, in-vivo postexercise skeletal muscle mitochondrial function does not appear to be impaired in adolescents with XXY compared with controls and is not significantly different by testosterone treatment status in XXY.

Footnotes

  • MC-G and SMD are joint senior authors.

  • Contributors SC and DD drafted the initial manuscript, interpreted the data, and critically reviewed and revised the manuscript. DD conceptualized and designed the study and worked with MC-G and KN to finalize the methods to conduct the study as well as contribute to the control data. SMD conducted the EPOCH study, which contributed to the control data. LP supervised the analysis and critically reviewed and revised the manuscript.

  • Funding SMD: Child Maternal Health CCTSI Pilot Award (UL1TR002535), Pediatric Endocrine Society Clinical Scholar Award, and NICHD K23HD092588; MC-G: NIDDK T32 DK063687; KN: NIDDK 1R56DK088971, NIDDK K23 RR020038, JDRF 11-2010-343, JT 1S10OD018435. Institution: supported by NIH/NCATS Colorado CTSA Grant Number UL1 TR002535.

  • Competing interests None declared.

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

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Journal of Investigative Medicine: 70 (1)
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In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome
Stephanie Cung, Laura Pyle, Kristin Nadeau, Dana Dabelea, Melanie Cree-Green, Shanlee M Davis
Journal of Investigative Medicine Jan 2022, 70 (1) 104-107; DOI: 10.1136/jim-2021-001966

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In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome
Stephanie Cung, Laura Pyle, Kristin Nadeau, Dana Dabelea, Melanie Cree-Green, Shanlee M Davis
Journal of Investigative Medicine Jan 2022, 70 (1) 104-107; DOI: 10.1136/jim-2021-001966
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In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome
Stephanie Cung, Laura Pyle, Kristin Nadeau, Dana Dabelea, Melanie Cree-Green, Shanlee M Davis
Journal of Investigative Medicine Jan 2022, 70 (1) 104-107; DOI: 10.1136/jim-2021-001966
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