title: Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus.
abstract: BACKGROUND
  Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycemic control subjects.
  
  
  METHODS
  49 non-insulin dependent male T2D patients and 54 male control subjects were enrolled, and a hyperinsulinemic-euglycemic clamp and indirect calorimetry were performed. A muscle biopsy was taken and intramyocellular lipid (IMCL) was measured. In vivo mitochondrial function was measured by PCr recovery in 30 T2D patients and 31 control subjects.
  
  
  RESULTS
  Fasting NEFA levels were significantly elevated in T2D patients compared with controls, but IMCL was not different. Mitochondrial function in T2D patients was compromised by 12.5% (p<0.01). Whole body glucose disposal (WGD) was higher at baseline and lower after insulin stimulation. Metabolic flexibility (ΔRER) was lower in the type 2 diabetic patients (0.050±0.033 vs. 0.093±0.050, p<0.01). Mitochondrial function was the sole predictor of basal respiratory exchange ratio (RER) (R(2) = 0.18, p<0.05); whereas WGD predicted both insulin-stimulated RER (R(2) = 0.29, p<0.001) and metabolic flexibility (R(2) = 0.40, p<0.001).
  
  
  CONCLUSIONS
  These results indicate that defects in skeletal muscle in vivo mitochondrial function in type 2 diabetic patients are only reflected in basal substrate oxidation and highlight the importance of glucose disposal rate as a determinant of substrate utilization in response to insulin.
authors: Department of Human Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Tineke
authors: T
authors: van de Weijer
authors: Lauren Marie
authors: LM
authors: Sparks
authors: Esther
authors: E
authors: Phielix
authors: Ruth Carla
authors: RC
authors: Meex
authors: Noud Antonius
authors: NA
authors: van Herpen
authors: Matthijs Karel C
authors: MK
authors: Hesselink
authors: Patrick
authors: P
authors: Schrauwen
authors: Vera Bettina
authors: VB
authors: Schrauwen-Hinderling
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin