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Pioglitazone improves insulin sensitivity, heart function in diabetes
Pioglitazone improved insulin sensitivity and left ventricular diastolic function in patients with type 2 diabetes, according to findings recently published in Diabetes Care.
“Diastolic dysfunction is a common abnormality in [type 2 diabetes] found on echocardiography, yet most patients … are asymptomatic,” Ralph A. DeFronzo, MD, of the diabetes division at the University of Texas Health Science Center, San Antonio, and colleagues wrote. “The effect of pioglitazone on myocardial insulin sensitivity in [type 2 diabetes] is of considerable clinical importance because myocardial insulin resistance has been implicated in the development of myocardial dysfunction and accelerated coronary atherosclerosis.”
The researchers administered a euglycemic insulin clamp to 12 patients with type 2 diabetes and 12 with normal glucose tolerance. They measured myocardial glucose uptake and myocardial perfusion in all patients before and after 24 weeks of treatment with pioglitazone, and used MRI to evaluate myocardial function and transmitral early diastolic relation/atrial contraction flow ratio.
Treatment with pioglitazone reduced HbA1c by 0.9%, while systolic and diastolic blood pressure both fell by 7 mm Hg, the researchers reported (P < .05 for both).
Among patients with diabetes, pioglitazone also increased whole-body insulin-stimulated glucose uptake by 71%, from a mean 3.4 mg/kg per minute to 5.8 mg/kg per minute (P < .01), DeFronzo and colleagues wrote. Myocardial glucose uptake rose by 75%, from a mean 0.24 µmol/min per g to 0.42 µmol/min (P < .01), and myocardial perfusion rose by 16%, from a mean 0.95 mL/min per g to 1.10 mL/min (P < .05).
The researchers also reported increases in transmitral early diastolic function/atrial contraction flow ratio (1.04 to 1.25; P <.01) and peak left ventricular filling rate (349 to 433 mL/min; P < .01). End systolic and diastolic BP both increased, as did peak left ventricular ejection rate and cardiac output, but changes did not reach statistical significance. Ejection fraction increased significantly, however, from 61% to 66% (P < .05), while stroke volume increased from 71 L/min to 80 L/min (P < .05).
Based on their findings, DeFronzo and colleagues wrote that in patients with type 2 diabetes, there is a close association between left ventricular diastolic dysfunction and myocardial insulin resistance. Additionally, they wrote that “pioglitazone exerts no negative effects on myocardial function and can be used safely in patients with [type 2 diabetes] without clinically evident CV disease.” – by Andy Polhamus
Disclosures: DeFronzo reports advisory roles with AstraZeneca, Boehringer Ingelheim, Elcelyx and Intarcia; research support from AstraZeneca, Boehringer Ingelheim, Janssen and Takeda Pharmaceuticals; and speaking fees from AstraZeneca and Novo Nordisk. Please see the study for all other authors’ relevant financial disclosures.