Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study.

Abstract

OBJECTIVES:

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: Rossi P Naoumova, Heiko Kindler, Lucia Leccisotti, Marco Mongillo, Muhammad T Khan, Clare Neuwirth, Mary Seed, Paul Holvoet, John Betteridge, Paolo G Camici
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 50 Issue 21 Pg. 2051-8 (Nov 20 2007) ISSN: 1558-3597 [Electronic] United States
• PMID: 18021872 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Hypolipidemic Agents
• Thiazolidinediones
• Glucose
• Pioglitazone

Topics

• Blood Glucose (analysis)
• Coronary Circulation (drug effects)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glucose (analysis, metabolism)
• Heart (drug effects)
• Humans
• Hyperlipidemia, Familial Combined (drug therapy)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Hypolipidemic Agents (therapeutic use)
• Male
• Middle Aged
• Pioglitazone
• Positron-Emission Tomography
• Thiazolidinediones (pharmacology, therapeutic use)
• Treatment Outcome