1130 HEPATIC REGULATION OF THE INSULIN-LIKE GROWTH FACTOR (IGF) SYSTEM BY ACUTE HYPOXIA IN CHILDREN

Abstract

Background and Aims: Adrenergic vascular hyper-responsiveness is a hallmark of different cardiometabolic disease, including essential hypertension, diabetes, obesity, metabolic syndrome, heart failure and chronic kidney disease. Previous studies have shown that sympathetic activation and insulin resistance are closely related each other, but the cause-and-effect relationship remains undefined. Iron overload impairs glucose metabolism in hemochromatosis patients by either insulin resistance or decreased insulin secretion. There are no data on the effect of iron overload on the adrenergic overdrive. Methods: The study groups consisted of 15 iron-loaded hemochromatosis male patients without iron-related organ damage, at diagnosis, and 10 age-matched healthy male controls. We measured, during a 30-minute resting period, beat-to-beat blood pressure (Finapres), heart rate (ECG) and postganglionic muscle sympathetic nerve traffic (MSNA) via microneurography into the peroneal nerve. Seven hemochromatosis patients were evaluated also after iron depletion. All patients underwent Magnetic Resonance for the assessment of hepatic iron concentration (HIC). Metabolic syndrome (defined according to the ATPIII criteria), essential hypertension, diabetes, obesity, heart and kidney failure, and cirrhosis were considered metabolic confounders and they represented the exclusion criteria. Insulin resistance was estimated by HOMA index (normal value <2.77). Results: In hemochromatosis patients at diagnosis, mean serum ferritin was 825±407mg/L, HIC 206±57mmol/g and HOMA index 1.7±0.82. MSNA values were significantly higher than in controls (63.53±10.93 vs 35.36±10.85 bursts/100 heart beats, p = 0.0001). In iron depleted patients sympathetic activation significantly decreased (68.24±12.26 vs 40.39±11.04 bursts/100 heart beats, p = 0.0156) reaching the normal range. Conclusions: The present study indicates that iron overloaded male patients with hemochromatosis are characterized by a hyperadrenergic state. Iron overload contributes to adrenergic hyper-responsiveness and could be directly involved in the overactivity of the autonomic nervous system also in the absence of an insulin resistance condition. Iron-dependent generation of reactive oxygen species might be involved in the pathogenesis of the adrenergic overdrive and more generally in cardiovascular damage.