Insulin-like growth factor-1 deficiency determines increased intima–media thickness at common carotid arteries in adult patients with growth hormone deficiency

Authors


Dr Annamaria Colao, Department of Molecular and Clinical Endocrinology and Oncology, ‘Federico II’ University of Naples, via S. Pansini, 5, 80131 Naples, Italy. Tel.: + 39 081 7462132; Fax: + 39 081 5465443; E-mail: colao@unina.it

Summary

objective  To investigate the role of IGF-1 on intima–media thickness (IMT) at common carotid arteries by Doppler ultrasonography.

subjects  Thirty-nine patients (17 women, 22 men, aged 25–70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF-1 levels, and 39 sex-, age- and body mass index (BMI)-matched healthy controls.

results  Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0·88 ± 0·26 vs. 0·69 ± 0·14 mm, P < 0·001), and systolic and diastolic peak velocity (P < 0·001) compared to controls. Eight patients (18%) and one control (2·1%, P = 0·04) had well-defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0·78, P < 0·001). In both controls (r = −0·82; P < 0·0001) and patients with GHD (r = −0·84, P < 0·0001), serum IGF-1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH-deficient patients were total cholesterol levels (t = 5·2, P < 0·001), followed by disease duration (t = 2·4, P = 0·02), while in controls the variables most significantly related to IMT were IGF-1 levels (t = −9·9, P < 0·001), followed by low density lipoprotein (LDL)-cholesterol levels (t = −2·3, P = 0·02). Compared to patients with normal IGF-1 levels, those with low IGF-1 levels had lower high density lipoprotein (HDL)-cholesterol levels (1·0 ± 0·2 vs. 1·3 ± 0·2 mmol/l, P = 0·0002), and higher glucose (54·3 ± 6·1 vs. 48·9 ± 5·9 mmol/l, P = 0·008), insulin (25·2 ± 6·8 vs. 18·8 ± 6·0 mUl/l, P = 0·004), total cholesterol (7·1 ± 1·1 vs. 4·9 ± 0·6 mmol/l, P < 0·0001), total/HDL-cholesterol ratio (7·2 ± 1·8 vs. 3·9 ± 0·7, P < 0·0001), fibrinogen levels (319·8 ± 56·9 vs. 241·8 ± 53·0 mg/dl, P < 0·0001) and mean IMT at common carotid arteries (1·05 ± 0·25 vs. 0·69 ± 0·07 mm, P < 0·0001). Atherosclerotic plaques were found only in GH-deficient patients with low IGF-1 levels.

conclusions  GH-deficient patients have alterations in lipid profile with an increase in the total/HDL-cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF-1 deficiency have increased IMT.

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