Atrial Natriuretic Peptide in Diabetic and Nondiabetic Patients With and Without Heart Transplantation S. Benedini, R. Fiocchi, A. Battezzati, L. Serení Piceni, A. Gamba, C. Mammana, M. Bevilacqua, G. Perseghin, and L. Luzi ABSTRACT Background. Natriuretic peptides are useful markers for risk stratification of patients with heart disease. However, conflicting results have been reported about circulating atrial natriuretic peptide (ANP) concentration in heart transplant recipients. Methods. To ascertain the effects of diabetes and acute insulin administration on plasma ANP concentrations in a model of heart denervation, we studied 12 diabetic (D-OHT) and 6 nondiabetic heart-transplanted (OHT) patients using the euglycemic-hyperinsulinemic clamp and oral glucose tolerance tests. Five patients with type 2 diabetes without heart transplantation (D) and 9 healthy subjects (NOR) matched for anthropometric features served as the controls. Results. Means baseline plasma ANP concentration was higher in D-OHT (82  15 pg/mL) than in OHT or NOR (27  4 or 30  5; P  .01), but was not different than D (69  12; P = .82). During the clamp plasma ANP showed similar increases in all groups (49  4, 39  3, 59  4, and 49  3% in D-OHT, OHT, D, and NOR; P  .02 vs basal, P = NS among groups). Plasma osmolarity and catecholamines were also not different among groups and did not increase during the clamp. Fasting plasma ANP concentrations correlated with plasma glucose concentrations measured 120 minutes after oral glucose tolerance testing. Conclusions. Among heart transplantation recipients fasting plasma ANP concentra- tions were not different at 5 to 6 years after the surgical procedure than in nondiabetic controls. Increased ANP concentrations were observed among recipients with diabetes and among nontransplanted diabetic patients. Although the insulin-induced increment in ANP concentrations was not different among groups, circulating ANP was strongly associated with glucose tolerance status. A TRIAL NATRIURETIC PEPTIDE (ANP) is a hor- mone that plays a major role in fluid homeostasis, protecting the cardiovascular system against volume over- load. This polypeptide is released by the myocardium into the circulation in response to atrial distension. ANP release is enhanced during hypertonic saline infusion followed by spontaneous water drinking, owing to increased atrial pres- sure 1 and as a consequence of the atrial stretch during expansion of the intravascular fluid compartment. 2,3 Circu- lating natriuretic peptides concentration are useful tools for risk stratification of patients with heart diseases. 4 Among heart transplant recipients, high levels of ANP have been reported after the surgical procedure, 5,6 with a subsequent decrease to normal levels 7 or, according to some other reports, persistence of high values. 8 The reported variability may be secondary to other metabolic features affecting heart transplant recipients. In this respect, acute infusion of insulin or glucose 9 –12 have been shown to induce an increment in plasma ANP concentrations. Moreover, after From the Nutrition and Metabolism Unit, San Raffaele Scien- tific Institute, Milan, Italy; Department of Biomedical Technology, Università degli Studi di Milano, Milan Italy; Department of Cardiovascular Surgery, Ospedali Riuniti di Bergamo, Italy; and the Endocrinology Unit, Ospedale L. Sacco (Vialba) Milan, Italy. Address reprint requests to L. Luzi, MD, PhD, Nutrition and Metabolism Unit, S. Raffaele Scientific Institute, via Olgettina 60, Milano. 20132, Italy. E-mail: luzi.livio@hsr.it 0041-1345/07/$–see front matter © 2007 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2007.04.020 360 Park Avenue South, New York, NY 10010-1710 1580 Transplantation Proceedings, 39, 1580 –1585 (2007)