Energy metabolism in diabetic and nondiabetic heart transplant recipients

Abstract

OBJECTIVE - This study examined the metabolic effects of heart transplantation in patients in end-stage cardiac failure. RESEARCH DESIGN AND METHODS - A total of 18 patients after heart transplantation for end-stage heart disease (age 47 ± 3 years; transplant age 5.5 ± 1.5 years; BMI 25.8 ± 0.8 kg/m2; cyclosporin A 4.2 ± 0.6 mg/[kg·day]; azathioprine 0.87 ± 0.31 mg/[kg·day]), 12 patients with type 2 diabetes (D-Tx), and 6 patients without type 2 diabetes (Tx) were studied by means of 1) an oral glucose tolerance test (OGTT) to assess the β-cell secretory response, 2) a euglycemic-hyperinsulinemic (1 mU/[kg·min]) clamp combined with indirect calorimetry and a primed continuous infusion of [6,6-2H2]glucose and [1- 13C]leucine to measure postabsorptive and insulin-stimulated carbohydrate and protein metabolism, and 3) 1H-NMR spectroscopy of the calf muscles to measure intramyocellular triglyceride (IMCL) content. The patients were selected from 480 transplant patients in whom there was a 6% prevalence of type 2 diabetes. Five healthy subjects matched for anthropometric parameters served as control subjects (CON). RESULTS - Tx had postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism, as well as IMCL content, similar to that of CON. D-Tx were characterized by a reduced secretory response during the OGTT and peripheral insulin resistance with respect to glucose metabolism, which was paralleled by increased plasma free fatty acid concentrations and IMCL content. A defective insulin-dependent suppression of the endogenous leucine flux (index of proteolysis) was also evident during the clamp in D-Tx. CONCLUSIONS - Heart transplantation, notwithstanding the immunosuppressive therapy, was characterized by a normal postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism in Tx. In contrast, insulin resistance with respect to glucose, free fatty acids, and protein metabolism was present in D-Tx regardless of whether diabetes was preexisting or consequent to heart transplantation.