BackgroundEvidence suggests that the PPARγ-agonist insulin sensitizer pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC) number is associated with impaired glucose tolerance (IGT) or diabetes, conditions characterised by increased CV risk.AimTo evaluate whether pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects.Materials and MethodsEarly and late-outgrowth EPCs were obtained from peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of pioglitazone (10 µM) with/without PPARγ-antagonist GW9662 (1 µM) was assessed on EPC viability, apoptosis, ability to form tubular-like structures and pro-inflammatory molecule expression.ResultsPioglitazone increased early and late-outgrowth EPC viability, with negligible effects on apoptosis. The capacity of EPCs to form tubular-like structures was improved by pioglitazone in early (mean increase 28%; p = 0.005) and late-outgrowth (mean increase 30%; p = 0.037) EPCs. Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early (p = 0.001 and p = 0.012 respectively) and late-outgrowth (p = 0.047 and p = 0.048, respectively) EPCs. Similarly, pioglitazone reduced TNFα gene and protein expression in both early (p = 0.034;p = 0.022) and late-outgrowth (p = 0.026;p = 0.017) EPCs compared to control. These effects were prevented by incubation with the PPARγ-antagonist GW9662.ConclusionPioglitazone exerts beneficial effects in vitro on EPCs isolated from IGT subjects, supporting the potential implication of pioglitazone as a CV protective agents.

The liver plays a central role in the regulation of nutrition by trafficking the metabolism of nutrients, their distribution and appropriate use. Accordingly, protein-energy malnutrition is common in patients with advanced liver disease, and it is a significant prognostic factor, affecting survival, the success of liver transplantation and quality of life. Clinical guidelines for the assessment and treatment of malnutrition have been issued by International societies, suggesting that nutritional therapy should be instituted in all patients where requirements are not adequately met by diet. The supplementation of the diet with amino acids (mainly branched-chain amino acids) and trace elements may improve nutritional status, liver function and hepatic encephalopathy. Nutritional issues should be carefully considered in Liver Units treating patients with advanced cirrhosis, and long-term, carefully controlled studies are needed to better define the type of nutritional support and the amount and timing of administration.

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Diabetes and chronic heart failure are interrelated conditions with major medical and economic impact that have to be treated as a distinct entity. Several pathological mechanisms have been investigated and proposed to explain the structural and functional changes associated with diabetic cardiomyopathy. These mechanisms are likely to act synergically and may potentiate one the other. This review outlines recent advances in the pathophysiological mechanisms implicated in the development and progression of diabetic cardiomyopathy and in current therapeutic strategies.

Our findings support the case of a beneficiary role played by n-3 PUFA in EPC function and bioavailability.