Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young-adults with Barth syndrome

作者：Cade W Todd^*; Spencer Carolyn T; Reeds Dominic N; Waggoner Alan D; O' Connor Robert; Maisenbacher Melissa; Crowley Jan R; Byrne Barry J; Peterson Linda R

来源：Journal of Inherited Metabolic Disease, 2013, 36(1): 91-101.

DOI：10.1007/s10545-012-9486-x

Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high mortality rates. It is currently unknown if BTHS related mitochondrial dysfunction results in substrate metabolism abnormalities and thereby contributes to cardioskeletal myopathy in patients with BTHS. %26lt;br%26gt;Adolescents and young adults with BTHS (n = 5, 20 +/- 4 yrs) and age and activity matched healthy controls (n = 5, 18 +/- 4 yrs) underwent an hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of body composition and 2-D and strain echocardiography for measurement of left ventricular function. %26lt;br%26gt;Participants with BTHS had lower fat-free mass (FFM) (BTHS: 31.4 +/- 6.9 vs. Control: 46.7 +/- 5.3 kg, p %26lt; 0.005), lower systolic strain, BTHS: -15.2 +/- 2.4 vs. Control: -19.0 +/- 2.4 %, p %26lt; 0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5 +/- 16.3 vs. Control: 67.4 +/- 17.6 mu mol/kgFFM/min, p %26lt; 0.05), lower basal (BTHS: 4.6 +/- 2.7 vs. Control: 11.9 +/- 4.4 mu mol/kgFM/min, p %26lt; 0.05) and hyperinsulinemic (BTHS: 1.6 +/- 0.4 vs. Control: 3.6 +/- 1.6 mu mol/kgFM/min, p %26lt; 0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal leucine rate of appearance per kg FFM (BTHS: 271.4 +/- 69.3 vs. Control: 193.1 +/- 28.7 mu mol/kgFFM/hr, p = 0.07) compared to controls. Higher basal leucine rate of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be associated with lower left ventricular systolic strain (r = -0.57, p = 0.09). %26lt;br%26gt;Whole-body fatty acid, glucose and amino acid metabolism kinetics when expressed per unit of body composition are altered and appear to be related to cardioskeletal myopathy in humans with BTHS. Further studies examining myocardial substrate metabolism and whole-body substrate metabolism during increased energy demands (e.g., exercise) and their relationships to skeletal and cardiac function are recommended.

• 出版日期2013-1