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IGF-I/IGFBP3/ALS 在肌肉减少症中的缺乏:低 GHBP 提示老年患者亚组存在 GH 抵抗。

IGF-I/IGFBP3/ALS Deficiency in Sarcopenia: Low GHBP Suggests GH Resistance in a Subgroup of Geriatric Patients.

机构信息

Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.

Friedrich-Baur-Institute, Department of Neurology, University Hospital, LMU Munich, Munich, Germany.

出版信息

J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1698-e1707. doi: 10.1210/clinem/dgaa972.

Abstract

CONTEXT

Definition of etiological subgroups of sarcopenia may help to develop targeted treatments. insulin like growth factor-I (IGF-I), Insulinlike growth factor binding protein 3 (IGFBP3), and acid labile subunit (ALS) build a ternary complex that mediates growth hormone (GH) effects on peripheral organs, such as muscle. Low GH binding protein (GHBP) as a marker of GH receptor number would hint toward GH resistance.

OBJECTIVE

We aimed to analyze the association of IGF-I, IGFBP3, and ALS with sarcopenia.

STUDY PARTICIPANTS AND SETTING

A total of 131 consecutively recruited patients of a geriatric ward were included in a single-center cross-sectional analysis; the nonsarcopenic patients served as controls.

METHODS

Measures included sarcopenia status by hand-grip strength measurement and Skeletal Muscle Index (SMI); IGF-I, IGFBP3, ALS, GH, GHBP; body mass index (BMI); Activity of Daily Living (ADL); Mini-Mental State Examination (MMSE); routine laboratory parameters; and statistical regression modeling.

RESULTS

Compared with controls, sarcopenic patients did not differ regarding age, sex, ADL, MMSE, C-reactive protein, glomerular filtration rate, and albumin serum concentrations. However, sarcopenic patients had significantly lower IGF-I, IGFBP3, and ALS. IGF-I and ALS associated significantly with sarcopenia and low hand-grip strength, even after adjustment for age, sex, BMI, and albumin, but not with low SMI. GHBP serum was low in sarcopenic patients, but normal in geriatric patients without sarcopenia. Over 60% of patients with IGF-I/ALS deficiency patients showed GH resistance.

CONCLUSIONS

Our data suggest that in geriatric patients, low IGF-I/IGFBP3/ALS could be evaluated for causative connection of the sarcopenia spectrum. Low GHBP points toward potential GH resistance as one possible explanation of this deficiency.

摘要

背景

肌少症病因亚组的定义可能有助于制定针对性治疗方法。胰岛素样生长因子-I(IGF-I)、胰岛素样生长因子结合蛋白 3(IGFBP3)和酸不稳定亚基(ALS)形成三元复合物,介导生长激素(GH)对周围器官(如肌肉)的作用。低 GH 结合蛋白(GHBP)作为 GH 受体数量的标志物提示 GH 抵抗。

目的

我们旨在分析 IGF-I、IGFBP3 和 ALS 与肌少症的关系。

研究参与者和设置

一项单中心横断面分析共纳入 131 名连续招募的老年病房患者;非肌少症患者作为对照组。

方法

通过握力测量和骨骼肌指数(SMI)评估肌少症状态;IGF-I、IGFBP3、ALS、GH、GHBP;体重指数(BMI);日常生活活动(ADL);简易精神状态检查(MMSE);常规实验室参数;和统计回归建模。

结果

与对照组相比,肌少症患者的年龄、性别、ADL、MMSE、C 反应蛋白、肾小球滤过率和白蛋白血清浓度无差异。然而,肌少症患者的 IGF-I、IGFBP3 和 ALS 显著降低。IGF-I 和 ALS 与肌少症和握力降低显著相关,即使在调整年龄、性别、BMI 和白蛋白后也是如此,但与低 SMI 无关。肌少症患者的 GHBP 血清水平较低,但无肌少症的老年患者正常。超过 60%的 IGF-I/ALS 缺乏患者表现出 GH 抵抗。

结论

我们的数据表明,在老年患者中,IGF-I/IGFBP3/ALS 降低可评估肌少症谱的因果关系。GHBP 降低提示潜在的 GH 抵抗可能是这种缺乏的一个解释。

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