title: Asian Indians have enhanced skeletal muscle mitochondrial capacity to produce ATP in association with severe insulin resistance.
abstract: OBJECTIVE
  Type 2 diabetes has become a global epidemic, and Asian Indians have a higher susceptibility to diabetes than Europeans. We investigated whether Indians had any metabolic differences compared with Northern European Americans that may render them more susceptible to diabetes.
  
  
  METHODS
  We studied 13 diabetic Indians, 13 nondiabetic Indians, and 13 nondiabetic Northern European Americans who were matched for age, BMI, and sex. The primary comparisons were insulin sensitivity by hyperinsulinemic-euglycemic clamp and skeletal muscle mitochondrial capacity for oxidative phosphorylation (OXPHOS) by measuring mitochondrial DNA copy number (mtDNA), OXPHOS gene transcripts, citrate synthase activity, and maximal mitochondrial ATP production rate (MAPR). Other factors that may cause insulin resistance were also measured.
  
  
  RESULTS
  The glucose infusion rates required to maintain identical glucose levels during the similar insulin infusion rates were substantially lower in diabetic Indians than in the nondiabetic participants (P < 0.001), and they were lower in nondiabetic Indians than in nondiabetic Northern European Americans (P < 0.002). mtDNA (P < 0.02), OXPHOS gene transcripts (P < 0.01), citrate synthase, and MAPR (P < 0.03) were higher in Indians irrespective of their diabetic status. Intramuscular triglyceride, C-reactive protein, interleukin-6, and tumor necrosis factor-alpha concentrations were higher, whereas adiponectin concentrations were lower in diabetic Indians.
  
  
  CONCLUSIONS
  Despite being more insulin resistant, diabetic Indians had similar muscle OXPHOS capacity as nondiabetic Indians, demonstrating that diabetes per se does not cause mitochondrial dysfunction. Indians irrespective of their diabetic status had higher OXPHOS capacity than Northern European Americans, although Indians were substantially more insulin resistant, indicating a dissociation between mitochondrial dysfunction and insulin resistance.
authors.affiliation: Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. nair.sree@mayo.edu
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Maureen L
authors.initials: ML
authors.lastname: Bigelow
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Chow
authors.forename: Jill M
authors.initials: JM
authors.lastname: Coenen-Schimke
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Klaus
authors.forename: Zeng-Kui
authors.initials: ZK
authors.lastname: Guo
authors.forename: Raghavakaimal
authors.initials: R
authors.lastname: Sreekumar
authors.forename: Brian A
authors.initials: BA
authors.lastname: Irving
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007194:India / Q000208:ethnology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009656:North America; D010085:Oxidative Phosphorylation; D012016:Reference Values; D044465:White People
chemical_list: D001786:Blood Glucose; D000255:Adenosine Triphosphate