Muscle mitochondrial function is impaired in patients with prior acromegaly

Julia Szendrödi; Elisabeth Zwettler; Albrecht Ingo Schmid; Marek Chmelik; Giovanni Pacini; Gertrud Kacerovsky; Christoph Schnack; Guntram Schernthaner; Oswald Wagner; Klaus Klaushofer; Michael Roden

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Endocrine Abstracts (2007) 14 P171

ECE2007 Poster Presentations (1) (659 abstracts)

Muscle mitochondrial function is impaired in patients with prior acromegaly

Julia Szendrödi ¹ , Elisabeth Zwettler ² , Albrecht Ingo Schmid ³ , Marek Chmelik ³ , Giovanni Pacini ⁴ , Gertrud Kacerovsky ⁵ , Christoph Schnack ⁶ , Guntram Schernthaner ⁶ , Oswald Wagner ⁷ , Klaus Klaushofer ² & Michael Roden ⁵

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¹Karl-Landsteiner Institute for Endocrinology and Metabolism, Vienna, Austria; ²Dept. Intern. Med. 4 and Ludwig Boltzmann Institute for Osteology, Hanusch Hospital, Vienna, Austria; ³MR Centre of Excellence, Med. Univ. Vienna, Vienna, Austria; ⁴National Research Council, Padova, Italy; ⁵Dept. Intern. Med. 1 and Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria; ⁶Dept. Intern. Med. I, Rudolfstiftung Hospital, Vienna, Austria; ⁷Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria.

Acromegaly is amongst other symptoms associated with myopathy, alterations of energy expenditure and insulin action which are mediated by growth hormone (GH) and insulin-like growth factors (IGFs). It is unclear to which extent these abnormalities remain after treatment. Thus, we examined glucose metabolism, intracellular fat deposition and mitochondrial function in patients with prior acromegaly (AM).

Six AM (4f/2 m, age: 49±10 years, body mass index, BMI: 27±3 kg/m²) with an at least 7-years history of successful treatment and age-/BMI-matched healthy volunteers (CON: 3f/3 m, 43±12 years, 26±4 kg/m²) were studied. Insulin sensitivity (OGIS) and first-phase insulin secretion were assessed from the frequently sampled OGTT (insulinogenic index, ISEC). Mitochondrial function was assessed from ATP synthetic flux (fATP) during fasting using ³¹P magnetic resonance spectroscopy (MRS) of calf muscle. Intracellular lipid contents of tibialis anterior (IMCLt) and soleus muscles (IMCLs) as well as liver (HCL) were measured with ¹H MRS. The protocol was approved by the local institutional ethics board.

IGF-1 did not differ between groups (AM: 177±88 ng/ml; CON: 145±51 ng/l). Fasting plasma glucose was ∼16% higher in AM (99±8, CON: 85±6 mg/dl, P<0.05), OGIS was comparable (395±74, CON: 415±14), but ISEC was ∼87% lower in AM (0.9±0.9, CON: 6.7±4.3, P<0.05). fATP was ∼22% lower in AM (10.1±1.5 vs. 12.9±2.4 mmol.l⁻¹.min⁻¹, P<0.05) and related positively to ISEC (r=0.687, P<0.01). IMCLt and IMCLs and HCL were not different different between groups. IMCLs related negatively to insulin sensitivity (r=−0.745, P=0.005).

Successfully treated acromegaly patients exhibit reduced insulin secretion and muscle ATP synthesis despite normal insulin sensitivity. The impairment of mitochondrial function could be explained by previous long-term GH/IGF exposure and/or chronically increased plasma glucose concentrations resulting from impaired ß cell function.