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Energy Metabolism in Diabetic and Nondiabetic Heart Transplant Recipients

¹ Division of Internal Medicine I, Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Department of Biomedical Technology, Università degli Studi di Milano, Milan, Italy
² Divisione di Cardiochirurgia, Ospedali Riuniti di Bergamo, Bergamo, Italy
³ Division of Diagnostic Radiology, Division of Nuclear Medicine, Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Università degli Studi di Milano, Milan, Italy

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 ß-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.

Abbreviations: AU, arbitrary units • ß-OHB, ß-O-hydroxybutyrate • CON, control subjects • D-Tx, patients with type 2 diabetes • FFA, free fatty acid • IMCL, intramyocellular triglyceride • KIC, -ketoisocaproic • OGTT, oral glucose tolerance test • Tx, patients without type 2 diabetes

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				G. Lattuada, L. P. Sereni, D. Ruggieri, A. Scollo, S. Benedini, F. Ragogna, F. Costantino, A. Battezzati, L. Luzi, and G. Perseghin Postabsorptive and Insulin-Stimulated Energy Homeostasis and Leucine Turnover in Offspring of Type 2 Diabetic Patients Diabetes Care, November 1, 2004; 27(11): 2716 - 2722. [Abstract] [Full Text] [PDF]