Department of Molecular and Clinical Endocrinology and Oncology, Division of Endocrinology, Federico II University Medical School, Via S, Pansini 5-80131 Naples-Italy.
J Transl Med. 2011 Aug 16;9:136. doi: 10.1186/1479-5876-9-136.
Fat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS.
The study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound.
Metabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (β = -0.49; p = 0.001) and IGFBP-1 (β = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (β = -0.43; p = 0.004).
The present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.
超重/肥胖人群的脂肪量（FM）在决定低度慢性炎症方面起着主要作用，而低度慢性炎症反过来又会导致胰岛素抵抗（IR）和肝脏内异位脂质储存。肥胖、衰老和 FM 会影响生长激素/胰岛素样生长因子（IGF）-I 轴，而慢性炎症可能会降低 IGF-I 信号。在患有肝脂肪变性（HS）的患者中，经常观察到 IGF-I 轴发生改变。我们检验了以下假说，即 FM 或脾体积和 C 反应蛋白（CRP）——所有慢性炎症的指标——可能会影响超重/肥胖患者的 IGF-I 轴状态，而与 HS 无关。
该研究人群包括 48 名超重/肥胖女性（年龄 41±13 岁；BMI：35.8±5.8kg/m2；范围：25.3-53.7），她们接受了空腹血糖和胰岛素、稳态模型评估的胰岛素抵抗（HOMA）、胆固醇和甘油三酯、高密度脂蛋白胆固醇、转氨酶、高敏 CRP、尿酸、IGF-I、IGF 结合蛋白（BP）-1、IGFBP-3 和 IGF-I/IGFBP-3 比值的评估。还根据年龄计算了 IGF-I 的标准偏差评分（zSDS）。通过生物电阻抗分析确定 FM。通过超声评估 HS 严重程度分级（根据肝脏回声增强程度为 0-4 分）和脾长径（SLD）。
代谢综合征（MS）和 HS 的患病率分别为 33%和 85%。SLD 增加的患者中 MS 的患病率为 43%。与 HS 轻度患者相比，HS 严重患者的 IGF-I 值较低，而 IGF-I zSDS 和 IGF-I/IGFBP-3 比值较低，FM%、FPI、HOMA、ALT、CRP 较高。IGF-I zSDS（r=-0.42，r=-0.54，分别；p<0.05）和 IGFBP-1（r=-0.38，r=-0.42，分别；p<0.05）与 HS 严重程度和 FM%呈负相关。IGF-I/IGFBP-3 比值与 CRP、HS 严重程度和 SLD 呈负相关（r=-0.30，r=-0.33，r=-0.43，分别；p<0.05）。多元分析显示，FM%（β=-0.49；p=0.001）和 IGFBP-1（β=-0.32；p=0.05）是 IGF-I 的最佳决定因素，而 SLD 则是 IGF-I/IGFBP-3 比值的决定因素（β=-0.43；p=0.004）。
本研究表明，我们研究人群中 IGF-I 水平较低与较高的 FM、SLD、CRP 和更严重的 HS 有关。
