title: Metabolic flexibility and oxidative capacity independently associate with insulin sensitivity in individuals with newly diagnosed type 2 diabetes.
abstract: Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake ([Formula: see text]) and/or metabolic flexibility (as given by ΔRQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that [Formula: see text] and ΔRQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships.
  
  
  
  Near-normoglycaemic individuals with type 2 diabetes mellitus (n = 136) with a short known disease duration (<12 months) underwent cycling spiroergometry, indirect calorimetry and hyperinsulinaemic-euglycaemic clamp tests.
  
  
  
  Both [Formula: see text] (r = 0.39, p < 0.0001) and ΔRQ (r = 0.32, p < 0.0001) correlated positively with whole-body insulin sensitivity, even after adjusting for anthropometric variables, glycaemia and glucose-lowering medication, but not after adjusting for NEFA. [Formula: see text] further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, [Formula: see text] did not relate to ΔRQ, even after adjusting for whole-body insulin sensitivity.
  
  
  
  Oxidative capacity and metabolic flexibility are independent determinants of insulin sensitivity but are influenced by circulating NEFA in recent-onset type 2 diabetes. ClinicalTrial.gov registration no: NCT01055093.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Apostolopoulou
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strassburger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Knebel
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzka
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, c/o German Diabetes Center at Heinrich-Heine University, Auf dem Hennekamp 65, 40225, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany. michael.roden@ddz.uni-duesseldorf.de.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, c/o German Diabetes Center at Heinrich-Heine University, Auf dem Hennekamp 65, 40225, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000378:metabolism; D050177:Overweight / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002097:C-Reactive Protein
keywords: Energy metabolism; Inflammation; Insulin sensitivity; Mitochondria; Muscle