title: Insulin resistance in type 2 diabetes youth relates to serum free fatty acids and muscle mitochondrial dysfunction.
abstract: Insulin resistance (IR) correlates with mitochondrial dysfunction, free fatty acids (FFAs), and intramyocellular lipid (IMCL) in adults with type 2 diabetes (T2D). We hypothesized that muscle IR would relate to similar factors in T2D youth.
  
  
  
  Participants included 17 youth with T2D, 23 normal weight controls (LCs), and 26 obese controls (OBs) of similar pubertal stage and activity level.
  
  
  
  T2D and OB groups were of similar BMI. T2D youth were significantly more IR and had higher calf IMCL and serum FFA concentrations during hyperinsulinemia. ADP time constant (ADPTC), a blood-flow dependent mitochondrial function measure, was slowed and oxidative phosphorylation rates lower in T2D. In multiple linear regression of the entire cohort, lack of FFA suppression and longer ADPTC, but not IMCL or HbA1c, were independently associated with IR.
  
  
  
  We found that elevated FFAs and mitochondrial dysfunction are early abnormalities in relatively well-controlled youth with T2D. Further, post-exercise oxidative metabolism appears affected by reduced blood flow, and is not solely an inherent mitochondrial defect. Thus, lowering FFAs and improving mitochondrial function and blood flow may be potential treatment targets in youth with T2D.
authors.affiliation: Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045; Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045. Electronic address: Melanie.green@childrenscolorado.org.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cree-Green
authors.affiliation: Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Coe
authors.affiliation: Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Baumgartner
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, 80045.
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045; Division of Endocrinology, Metabolism and Diabetes, University to Colorado Anschutz Medical Campus, Aurora, CO, 80045; Veterans Affairs Medical Center, Aurora, CO, 80012.
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
authors.affiliation: Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brown
authors.affiliation: Honors Program, James Madison University, Harrisonburg, VA, 22807.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Newcomer
authors.affiliation: Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045; Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nadeau
mesh_terms: D000293:Adolescent; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D015444:Exercise / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology
chemical_list: D005230:Fatty Acids, Nonesterified
keywords: Adolescents; Free fatty acids; Insulin resistance; Mitochondrial function; Type 2 diabetes