Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study.
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).
Naoumova
Rossi P
RP
Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, United Kingdom.
Kindler
Heiko
H
Leccisotti
Lucia
L
Mongillo
Marco
M
Khan
Muhammad T
MT
Neuwirth
Clare
C
Seed
Mary
M
Holvoet
Paul
P
Betteridge
John
J
Camici
Paolo G
PG
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone