Effect of pioglitazone on heart function and N-terminal pro-brain natriuretic peptide levels of patients with type 2 diabetes

Abstract

We assessed the effect of the addition of pioglitazone on metabolic control and heart function of patients with type 2 diabetes already receiving sulfonylurea plus metformin. Forty-four patients were given 30 mg of pioglitazone for 3 months. Physical examination, laboratory tests including N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography, were performed at baseline and at study completion. Target HbA(1c) levels were achieved by 44.2% of the patients. Pioglitazone ameliorated lipid profile and lowered liver enzymes and C-reactive protein. Significant increases in NT-proBNP by 39% (P < 0.005) were noticed, but echocardiographic parameters were not altered, even in high-risk subgroups (patients older than 60 years, with diabetes for more than 10 years, with hypertension, with elevated baseline NT-proBNP levels, with left ventricular hypertrophy). In patients with a greater than 60% increase in NT-proBNP levels, a significant increase in left ventricular ejection fraction (P < 0.05) and in fractional shortening (P < 0.05) was found. None of the patients developed edema or signs or symptoms of heart failure. Triple oral combination antidiabetic treatment is an effective therapeutic strategy and weight gain does not abrogate its beneficial actions. Pioglitazone does not affect heart function and even though it increases NT-proBNP, this appears to represent a reaction to volume overload.

Thiazolidinediones and the Promise of Insulin Sensitization in Type 2 Diabetes

“…The cardiotoxic effects of high doses of rosiglitazone were recently shown to be largely PPARγ-independent and involve mitochondrial dysfunction (He et al, 2014). In human studies, TZDs are associated with lipid accumulation in cardiomyocytes (Marfella et al, 2009), but pioglitazone showed no effect or even beneficial effects on echocardiographic measures of cardiac function (Horio et al, 2005; Sambanis et al, 2008). TZDs are not generally thought to cause cardiomyopathy directly, but rather to exacerbate heart failure via fluid retention in susceptible patients.…”

Lack of effects of pioglitazone on cardiac function in patients with type 2 diabetes and evidence of left ventricular diastolic dysfunction: a tissue doppler imaging study

“…On the other hand, clinical studies have demonstrated a neutral effect of pioglitazone on cardiac structure and systolic function in DM2 patients with normal [15] or impaired systolic function [16] using conventional echocardiography. The effects of pioglitazone on echocardiographic indices in patients with DM2 and LVDD have not been largely studied, while Tissue Doppler Imaging (TDI) echocardiography that allows more direct quantification of LV diastolic function [17] has been very little used in this context [18].…”

Serum A-FABP Is Increased and Closely Associated with Elevated NT-proBNP Levels in Type 2 Diabetic Patients Treated with Rosiglitazone

“…One probable explanation is the result of increased cardiac wall stretch caused by volume retention which is considered as the main adverse event of TZD therapy. Christos Sambanis et al reported that pioglitazone does not alter echocardiographic parameters even though it increases NT-proBNP after a 3 month treatment period in 44 patients with T2DM, and speculated that it may represent a reaction to volume overload [27]. It has been suggested that serial monitoring changes in BNP levels over time is beneficial to potentially enable the detection of volume overload secondary to TZD use and the onset of cardiac dysfunction before echocardiographic changes [28].…”