Effects of chronic elevation of atrial natriuretic peptide and free fatty acid levels in the induction of type 2 diabetes mellitus and insulin resistance in patients with mitral valve disease

BACKGROUND AND AIMS: The relationship between atrial natriuretic peptide (ANP), increased free fatty acid (FFA) and insulin resistance in patients with mitral valve disease (MVD), a group characterised by elevated atrial pressure and increased ANP levels, is not defined. The present study was performed to evaluate, in MVD patients, the relationship between increased ANP and FFA levels and insulin resistance and the role of mitral valve replacement/repair in ameliorating these metabolic alterations. Conversely, coronary heart disease (CHD) patients were evaluated before and after coronary artery bypass grafting (CABG), since they are known to be insulin resistant in the presence of chronic FFA increase. METHODS AND RESULTS: Fifty MVD patients and 55 CHD patients were studied before and 2 months after surgery and compared with 166 normal subjects. Before surgery, 56% of MVD patients had impaired glucose tolerance or newly diagnosed type 2 diabetes after a standard oral glucose load and this percentage decreased to 46% after surgery. In CHD, impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetic patients were 67% of patients before and after CABG. In MVD, left atrial (LA) volume, ANP, FFA incremental area and insulin levels were higher and Insulin Sensitivity (IS) index significantly reduced while after surgery, LA volume, ANP and FFA significantly decreased and IS index significantly improved. In CHD, insulin resistance and hyperinsulinaemia were present both before and after surgery with increased tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels. CONCLUSION: In MVD, a higher degree of abnormal glucose tolerance and insulin resistance are associated to increased levels of ANP and FFA, while these metabolic alterations are improved by mitral valve replacement/repair surgery. Clinical Trial.gov registration number NCT 00520962.