Energy metabolism in diabetic and nondiabetic heart transplant recipients.
OBJECTIVE
This study examined the metabolic effects of heart transplantation in patients in end-stage cardiac failure.


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/m(2); 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 beta-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.
Benedini
Stefano
S
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.
Fiocchi
Roberto
R
Battezzati
Alberto
A
Scifo
Paola
P
Sereni
Lucia Piceni
LP
Gamba
Amando
A
Mammana
Carmelo
C
Del Maschio
Alessandro
A
Perseghin
Gianluca
G
Luzi
Livio
L
D000328:Adult; D000419:Albuminuria / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000453:epidemiology; D004734:Energy Metabolism; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D008055:Lipids; D005934:Glucagon; D002784:Cholesterol