title: Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration.
abstract: To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth.
  
  
  
  Case-control study.
  
  
  
  Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2-5, 25 youth with IR (IR+) and 50 without IR (IR-) who were enrolled in the Pediatric HIV/AIDS Cohort Study. IR was defined as a homeostatic model of assessment for IR value at least 4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells. Unadjusted and adjusted differences in mitochondrial respiration markers between IR+ and IR- were evaluated, as were correlations between mitochondrial respiration markers and biochemical measurements.
  
  
  
  IR+ and IR- youth were similar on age, sex, and race/ethnicity. Mean age was 16.5 and 15.6 years in IR+ and IR-, respectively. The IR+ group had significantly higher mean BMI and metabolic analytes (fasting glucose, insulin, cholesterol, triglycerides, and venous lactate and pyruvate) compared with the IR-. Mitochondrial respiration markers were, on average, lower in the IR+ compared with IR-, including basal respiration (417.5 vs. 597.5 pmol, P = 0.074), ATP production (11 513 vs. 15 202 pmol, P = 0.078), proton leak (584.6 vs. 790.0 pmol, P = 0.033), maximal respiration (1815 vs. 2399 pmol, P = 0.025), and spare respiration capacity (1162 vs. 2017 pmol, P = 0.032). Nonmitochondrial respiration did not differ by IR status. The results did not change when adjusted for age.
  
  
  
  HIV-infected youth with IR have lower mitochondrial respiration markers when compared to youth without IR. Disordered mitochondrial respiration may be a potential mechanism for IR in this population.
authors.affiliation: aDepartment of Pharmaceutical Sciences, Ben and Maytee Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, Texas bDepartment of Pediatrics, University of Miami, Miller School of Medicine, Miami, Florida cCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts dThe Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California eTulane University School of Medicine, New Orleans, Louisiana fDepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
authors.forename: Jody K
authors.initials: JK
authors.lastname: Takemoto
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Miller
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacobson
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Geffner
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: Mariana
authors.initials: M
authors.lastname: Gerschenson
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D019069:Cell Respiration; D002648:Child; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007333:Insulin Resistance; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*