Abstract 6247: Effects of Angiotensin Receptor Inhibition and Lipoic Acid on Myocardial Glucose Uptake and Fatty Acid Oxidation in Patients with the Metabolic Syndrome
Background: A pro-inflammatory and pro-oxidative vascular environment appears to be a hallmark in the initiation and progression of the metabolic syndrome. We studied the role of angiotensin receptor blockers and lipoic acid on myocardial glucose uptake and fatty acid oxidation in patients with the metabolic syndrome.
Methods: We investigated 24 normotensive (systolic BP < 140 mm Hg) patients that met the Adult Treatment III criteria for the metabolic syndrome. Patients were randomized in a double blinded manner to placebo or daily irbesartan/lipoic acid (IRB/LA, 150/600 mg) for a 24 week period. Using positron emission tomography (PET), measurement of myocardial glucose uptake and myocardial fatty acid oxidation was made under euglycemic hyperinsulinemic clamp conditions using C-11 glucose and C-11 palmitate, respectively.
Results: There were no significant changes in systolic BP, plasma glucose, or plasma insulin in either the IRB/LA or placebo groups. In comparison to placebo (pre: 34.6±7.0, post: 35.1±5.9 umol/100g/min, NS), treatment with IRB/LA significantly increased myocardial glucose uptake (pre: 35.3±5.9, post: 53.6±8.4 umol/100g/min, p=0.006). Myocardial glucose uptake for the left ventricle was significantly improved in the IRB/LA group (pre: 149.9±34.5, post: 198.7±41.2 umol/min, p=0.011) and unchanged in placebo (pre: 158.5±40.0, post: 155.5±33.9 umol/min, NS). In comparison to placebo (pre: 28.3±8.0, post: 26.9±8.6 umol/100g/min, NS), myocardial fatty acid oxidation was significantly reduced in the IRB/LA group (pre: 30.1±7.3, post: 20.3±6.3 umol/100g/min, p=0.021). Treatment with IRB/LA was well tolerated in all patients throughout the study period.
Conclusion: A combination of angiotensin receptor inhibitor therapy and lipoic acid increases glucose uptake and reduces fatty acid oxidation in the myocardium, suggesting improved cardiovascular efficiency and performance in the metabolic syndrome.