GH levels and insulin sensitivity are differently associated with biomarkers of cardiovascular disease in active acromegaly

Abstract

Context: Acromegaly is characterized by GH excess and insulin resistance. It is not known which of these disorders is responsible for the increased atherogenic risk in these patients. Objective: To analyse the associations of GH and homoeostasis model assessment (HOMA) with biomarkers of cardiovascular disease and to compare the above-mentioned variables between patients with active acromegaly and controls. Design and setting: This open cross-sectional study was conducted at a University Hospital. Patients: Twenty-two outpatients were compared with sex- and age-matched control subjects. Main outcomes: Included clinical features, hormonal status, markers of insulin resistance, lipoprotein profile and biomarkers of cardiovascular disease. Results: Patients presented higher triglyceride (median [IQR]) (1·2[1·1-1·6] vs 0·9[0·6-1·1] mm, P < 0·05), low-density lipoprotein-cholesterol (LDL-C) (mean ± SD) (3·5 ± 0·9 vs 3·0 ± 0·7mm, P < 0·05), apoB (0·98 ± 0·23 vs 0·77 ± 0·22 g/l, P < 0·05), free fatty acid (0·69 ± 0·2 vs 0·54 ± 0·2 mM, P < 0·05), oxidized-LDL (120 ± 22 vs 85 ± 19 U/l, P < 0·05) and endothelin-1 (0·90 ± 0·23 vs 0·72 ± 0·17 ng/l, P < 0·05) levels, increased cholesteryl ester transfer protein (CETP) activity (179 ± 27 vs 138 ± 30%/ml/h, P < 0·01) and lower C reactive protein (CRP) (0·25[0·1-0·9] vs 0·85[0·4-1·4] mg/l; P < 0·05) levels than control subjects. Vascular cell adhesion molecule (VCAM-1) concentration was not different. By multiple linear regression analyses, HOMA explained the variability of triglycerides (25%), high-density lipoprotein-cholesterol (HDL-C) (30%) and CETP activity (28%), while GH independently predicted LDL-C (18%), oxidized-LDL (40%) and endothelin-1 levels (19%). Conclusions: In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro-oxidative and pro-inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL-C, ox-LDL and endothelin-1.