title: Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness.
abstract: OBJECTIVE
  Our aim was to examine the possible direct relationship of interleukin-6 and TNFalpha with insulin sensitivity in humans.
  
  
  METHODS
  We carried out two series of euglycaemic-hyperinsulinaemic clamp experiments. In the first (CLAMP1), skeletal muscle mRNA expression and plasma concentrations of IL-6 and TNFalpha were examined in patients with Type 2 diabetes ( n=6), subjects matched for age (n=6), and young healthy (n=11) control subjects during a 120-min supra-physiological hyperinsulinaemic (40 mU.m(-2).min(-1)) euglycaemic clamp. In the second series of experiments (CLAMP2), patients with Type 2 diabetes (n=6) and subjects matched for age (n=7) were studied during a 240-min high-physiological hyperinsulinaemic (7 mU.m(-2).min(-1)) euglycaemic clamp, during which arterial and venous (femoral and subclavian) blood samples were measured for IL-6 and TNFalpha flux.
  
  
  RESULTS
  In both experiments the glucose infusion rate in the patients was markedly lower than that in the other groups. In CLAMP1, basal skeletal muscle IL-6 and TNFalpha mRNA were the same in all groups. They were not affected by insulin and they were not related to the glucose infusion rate. In CLAMP2, neither cytokine was released from the arm or leg during insulin stimulation in either group. In both experiments plasma concentrations of these cytokines were similar in the patients and in the control subjects, although in CLAMP1 the young healthy control group had lower (p<0.05) plasma IL-6 concentrations. Using data from all subjects, a strong positive correlation (r=0.85; p<0.00001) was observed between basal plasma IL-6 and BMI. Conversely, a negative relationship (r=-0.345; p<0.05) was found between basal plasma TNFalpha and BMI, although this was not significant when corrected for BMI. When corrected for BMI, no relationship was observed between either basal plasma IL-6 or TNFalpha and GIR.
  
  
  CONCLUSIONS
  These data show that the increased circulating IL-6 concentrations seen in patients with Type 2 diabetes are strongly related to fat mass and not insulin responsiveness, and suggest that neither IL-6 nor TNFalpha are indicative of insulin resistance.
authors.affiliation: Skeletal Muscle Research Laboratory, School of Medical Sciences, RMIT University, PO Box 71, Bundoora 3083, Victoria, Australia.
authors.forename: A L
authors.initials: AL
authors.lastname: Carey
authors.forename: C R
authors.initials: CR
authors.lastname: Bruce
authors.forename: M
authors.initials: M
authors.lastname: Sacchetti
authors.forename: M J
authors.initials: MJ
authors.lastname: Anderson
authors.forename: D B
authors.initials: DB
authors.lastname: Olsen
authors.forename: B
authors.initials: B
authors.lastname: Saltin
authors.forename: J A
authors.initials: JA
authors.lastname: Hawley
authors.forename: M A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001315:Australia; D015992:Body Mass Index; D003627:Data Interpretation, Statistical; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique / Q000295:instrumentation / Q000379:methods; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications; D007262:Infusions, Intravenous; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose