title: Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  This study's aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL).
  
  
  BACKGROUND
  Thiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance.
  
  
  METHODS
  We undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment.
  
  
  RESULTS
  Whereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 +/- 1.59 mg/kg/min to 5.24 +/- 1.65 mg/kg/min; p = 0.004) and MGU (0.62 +/- 0.26 micromol/g/min to 0.81 +/- 0.14 micromol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 +/- 0.20 ml/min/g to 1.25 +/- 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (-35%; p = 0.017) was reduced.
  
  
  CONCLUSIONS
  In patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlled-trials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659).
authors.affiliation: Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Rossi P
authors.initials: RP
authors.lastname: Naoumova
authors.forename: Heiko
authors.initials: H
authors.lastname: Kindler
authors.forename: Lucia
authors.initials: L
authors.lastname: Leccisotti
authors.forename: Marco
authors.initials: M
authors.lastname: Mongillo
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Khan
authors.forename: Clare
authors.initials: C
authors.lastname: Neuwirth
authors.forename: Mary
authors.initials: M
authors.lastname: Seed
authors.forename: Paul
authors.initials: P
authors.lastname: Holvoet
authors.forename: John
authors.initials: J
authors.lastname: Betteridge
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003326:Coronary Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone