title: Insulin Resistance in Youth Without Diabetes Is Not Related to Muscle Mitochondrial Dysfunction.
abstract: Obesity, insulin resistance (IR), and diabetes are increasing in youth, especially in girls. IR is associated with muscle mitochondrial dysfunction in youth and adults with diabetes. However, it is unknown whether this relationship is present in youth prior to development of diabetes.
  
  
  
  Assess IR and mitochondrial function, including sex differences, in nondiabetic youth.
  
  
  
  Cross-sectional study of youth in the Exploring Perinatal Outcomes among Children, Resistance to InSulin in Type 1 And Type 2 diabetes, and Androgens and Insulin Resistance Study cohorts.
  
  
  
  Academic medical university.
  
  
  
  Two hundred seventy-five youth, 13 to 19 years old [43% males: 17.1 (16.52, 17.63) years, body mass index z-score (BMI-Z) 0.36, 64.7% Tanner 5; 57% females: 17.2 (16.43, 17.67) years, BMI-Z 0.72, 78.9% Tanner 5].
  
  
  
  Fasting laboratories, oral glucose tolerance test, and 31P magnetic resonance spectroscopy.
  
  
  
  IR [triglyceride:high-density lipoprotein (HDL) ratio, Matsuda index, and homeostasis model for insulin resistance (HOMA-IR)] and muscle mitochondrial function (adenosine 5'-diphosphate time constant and oxidative phosphorylation rate).
  
  
  
  Compared with males, females were more insulin resistant, with higher triglyceride:HDL ratio [1.95 (1.30, 2.79) vs 1.69 (1.21, 2.23), P = 0.042], HOMA-IR [3.18 (2.42, 4.39) vs 2.76 (2.02, 4.08), P = 0.035], and fasting free fatty acids (FFAs) and lower Matsuda score [3.98 (2.71, 5.96) vs 5.39 (3.43, 7.57), P < 0.001]. After adjustment for the higher BMI and Tanner stage and lower physical activity levels seen in females, there were no sex differences in mitochondrial function nor in any IR measure except FFAs. We did not find an association between measures of IR and mitochondrial function.
  
  
  
  The greater IR seen in adolescent girls vs boys is mostly explained by differences in BMI and physical activity. Mitochondrial function does not appear to be related to IR in a large cohort of nondiabetic youth.
authors.affiliation: Pediatric Endocrinology, University of Colorado Anschutz and Children's Hospital Colorado, Aurora, Colorado 80045.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cree-Green
authors.affiliation: Pediatric Endocrinology, University of Colorado Anschutz and Children's Hospital Colorado, Aurora, Colorado 80045.
authors.forename: Ninghe
authors.initials: N
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado 80045.|Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado 80045.
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado 80045.
authors.forename: Brandy
authors.initials: B
authors.lastname: Ringham
authors.affiliation: Radiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brown
authors.affiliation: Department of Physics, James Madison University, Harrisonburg, Virginia 22807.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Newcomer
authors.affiliation: Pediatric Endocrinology, University of Colorado Anschutz and Children's Hospital Colorado, Aurora, Colorado 80045.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nadeau
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado 80045.|Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado 80045.
authors.forename: Dana
authors.initials: D
authors.lastname: Dabelea
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000293:Adolescent; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015444:Exercise / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010759:Phosphorus Isotopes; D012737:Sex Factors; D014280:Triglycerides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D008075:Lipoproteins, HDL; D010759:Phosphorus Isotopes; D014280:Triglycerides; D000244:Adenosine Diphosphate