title: The insulin sensitiser pioglitazone does not influence skin microcirculatory function in patients with type 2 diabetes treated with insulin.
abstract: OBJECTIVE
  Insulin resistance is associated with abnormal microvascular function. Treatment with insulin sensitisers may provoke oedema, suggesting microvascular effects. The mechanisms underlying the peripheral oedema observed during glucose-lowering treatment with thiazolidinediones are unclear. Therefore we examined the effect of pioglitazone on microvascular variables involved in oedema formation.
  
  
  METHODS
  Subjects (40-80 years) with type 2 diabetes and on insulin were randomised to 9 weeks of pioglitazone therapy (30 mg/day; n=14) or placebo (n=15). The following assessments were performed at baseline and 9 weeks: microvascular filtration capacity; isovolumetric venous pressure; capillary pressure; capillary recruitment following venous or arterial occlusion; postural vasoconstriction; and maximum blood flow. A number of haematological variables were also measured including vascular endothelium growth factor (VEGF), IL-6 and C-reactive protein (CRP).
  
  
  RESULTS
  Pioglitazone did not significantly influence any microcirculatory variable as compared with placebo (analysis of covariance [ANCOVA] for microvascular filtration capacity for the two groups, p=0.26). Mean VEGF increased with pioglitazone (61.1 pg/ml), but not significantly more than placebo (9.76 pg/ml, p=0.94). HbA(1c) levels and the inflammatory markers IL-6 and CRP decreased with pioglitazone compared with placebo (ANCOVA: p=0.009, p=0.001 and p=0.004, respectively).
  
  
  CONCLUSIONS
  Pioglitazone improved glycaemic control and inflammatory markers over 9 weeks but had no effect on microcirculatory variables associated with oedema or insulin resistance in type 2 diabetic patients treated with insulin.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, EX2 5AX, UK. john.tooke@pms.ac.uk
authors.forename: J E
authors.initials: JE
authors.lastname: Tooke
authors.forename: L M
authors.initials: LM
authors.lastname: Elston
authors.forename: K M
authors.initials: KM
authors.lastname: Gooding
authors.forename: C I
authors.initials: CI
authors.lastname: Ball
authors.forename: D M
authors.initials: DM
authors.lastname: Mawson
authors.forename: J
authors.initials: J
authors.lastname: Piper
authors.forename: R
authors.initials: R
authors.lastname: Sriraman
authors.forename: R
authors.initials: R
authors.lastname: Urquhart
authors.forename: A C
authors.initials: AC
authors.lastname: Shore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D010919:Placebos; D045162:Thiazolidinediones