Pioglitazone Improves Left Ventricular Diastolic Function and Decreases Collagen Accumulation in Prediabetic Stage of a Type II Diabetic Rat

Abstract

This study investigated the effect of pioglitazone, an insulin sensitizer, on metabolic abnormalities and oxidative stress as a cause of myocardial collagen accumulation in prediabetic rat hearts. Twenty male diabetic rats and 9 male nondiabetic age-matched rats were used. The diabetic rats were divided into two groups: diabetic treated and untreated. Pioglitazone was mixed in rat chow fed to the diabetic treated group (0.01%). Treatment duration was 5 weeks. At baseline (15 weeks) and 20 weeks of age, blood glucose, lipid, insulin, and plasma malondialdehyde-thiobarbituric acid (MDA) levels were measured and Doppler echocardiography was tracked. At 20 weeks of age, left ventricular collagen content was studied. Blood glucose, plasma insulin, and triglyceride levels in the diabetic treated group were significantly lower than those in the untreated diabetic group. Deceleration time (ms) of early diastolic inflow in the treated diabetic group decreased significantly compared with the untreated diabetic group (65 +/- 8 vs. 77 +/- 8, p < 0.01). Ratio of left ventricular weight to body weight (mg/g) and ratio of left ventricular collagen content to dry weight (mg/100 mg) were decreased in the treated diabetic group (1.5 +/- 0.1, 1.3 +/- 0.3) compared with the untreated diabetic group (1.7 +/- 0.2, p < 0.01; 1.7 +/- 0.3, p < 0.05). Plasma MDA concentration (nmol/ml) significantly decreased (2.9 +/- 0.3 at baseline to 2.3 +/- 0.3 at 20 weeks, p = 0.001) in the treated diabetic group, and was lower than that in the untreated diabetic group (3.2 +/- 0.7 at 20 weeks, p < 0.05). Pioglitazone improved glucose and lipid metabolism and reduced oxidative stress in the left ventricle, which decreased left ventricular collagen accumulation and improved left ventricular diastolic function of prediabetic rat hearts.

Determinants of subclinical diabetic heart disease

“…An insulin sensitiser (troglitazone) has been shown to protect against relaxation abnormalities caused by hyperglycaemia [27] and pioglitazone decreased LV collagen accumulation and improved LV diastolic function of prediabetic rat hearts [28]. Similarly, regular insulin treatment in type I diabetics is associated with normal or nearly normal diastolic function in young patients with diabetes of short duration [29] or less severe diastolic dysfunction in type 1 diabetic patients with a relatively higher HbA 1 c value or longer duration of the known disease compared with type 2 diabetic patients [30].…”

Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease

“…[17][18][19][20] In animals, thiazolidinediones have been shown to improve cardiac contractile function directly or indirectly by enhancing insulin sensitivity and reducing inflammation and oxidative stress. [1][2][3]19 The action of thiazolidinediones on diastolic myocardial function in relation to these factors has not yet been demonstrated in man, however.Given the high occurrence of diastolic myocardial dysfunction in patients with T2DM and its prognostic relevance, [20][21][22] we tested the hypothesis that the thiazolidinedione rosiglitazone, versus the sulfonylurea glimepiride, may improve diastolic myocardial function in these patients by simultaneously reducing oxidative stress and/or inflammation. Accordingly, the primary objective was to evaluate the change of diastolic myocardial function, measured as early diastolic myocardial velocity by pulsed tissue Doppler, after 16 weeks of oral treatment with rosiglitazone compared with glimepiride in patients with type 2 diabetes but without overt heart disease.…”

Thiazolidinediones and risk for atherosclerosis: pleiotropic effects of PPARγ agonism

“…In animal models, PPARγ agonists improve contractility and systolic performance, [78][79][80][81] enhance diastolic performance, [79][80][81][82] and decrease cardiac hypertrophy independent of loading conditions. [83][84][85] Similarly, randomised controlled trials of patients with DM have demonstrated no untoward effects on cardiac performance, assessed using echocardiography, and some trends toward improved function associated with longer-term TZD therapy. 78,86 The mechanism contributing to peripheral oedema and incremental risk for CHF is most likely to be alteration of sodium handling resulting in net volume retention.…”