Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Endocrinol (Lausanne). 2021 Jun 16;12:671126. doi: 10.3389/fendo.2021.671126. eCollection 2021.
Adult growth hormone deficiency (AGHD) is a rare chronic inflammatory disease caused by damage to the pituitary gland and is accompanied by disorders of multiple metabolic pathways. By examining the correlation between the serum mesencephalic astrocyte-derived neurotrophic factor (MANF) levels of AGHD patients and those of normal controls, we hope to elucidate the close relationship among MANF, lipid metabolism and insulin resistance in AGHD and discuss the potential therapeutic value of MANF.
This study included 101 AGHD patients and 100 healthy subjects matched for sex, age, height, and weight. Anthropometric parameters and biochemical indicators such as body mass index, waist circumference, hip circumference, serum MANF level, blood lipids and insulin level were measured. The above patients were also divided into several subgroups for correlation analysis based on indicators such as insulin resistance and BMI.
The serum circulating MANF content of AGHD patients was significantly lower than that of the normal control group (5.235 (0.507-17.62) ng/ml (n=101) 10.30 (1.84-16.65) ng/ml (n=100); p<0.0001), and circulating MANF levels were linearly correlated with HOMA-IR in the AGHD population (R=0.481, P=0.0041). When MANF was at pathological concentrations (lower than the mean circulating MANF of normal controls), the lowest concentration tertile (OR=21.429 p<0.0001) had a significantly higher disease odds ratio, Framingham risk score and 10-year risk of atherosclerotic cardiovascular disease than the highest concentration tertile.
MANF has a significant correlation with insulin resistance in the AGHD state. There is a strong correlation with abnormal glucose and lipid metabolism in the obese AGHD population. MANF is also a good assessment factor for the risk of cardiovascular disease in AGHD patients and has excellent therapeutic potential.
成人生长激素缺乏症（AGHD）是一种罕见的慢性炎症性疾病，由垂体损伤引起，并伴有多种代谢途径的紊乱。通过检查 AGHD 患者和正常对照者血清中脑星形胶质细胞衍生神经营养因子（MANF）水平的相关性，我们希望阐明 AGHD 中 MANF、脂代谢和胰岛素抵抗之间的密切关系，并探讨 MANF 的潜在治疗价值。
本研究纳入了 101 例 AGHD 患者和 100 例性别、年龄、身高和体重相匹配的健康对照者。测量了人体测量学参数和生化指标，如体重指数、腰围、臀围、血清 MANF 水平、血脂和胰岛素水平。以上患者还根据胰岛素抵抗和 BMI 等指标进一步分为多个亚组进行相关性分析。
AGHD 患者的血清循环 MANF 含量明显低于正常对照组（5.235（0.507-17.62）ng/ml（n=101）vs. 10.30（1.84-16.65）ng/ml（n=100）；p<0.0001），并且 AGHD 人群中循环 MANF 水平与 HOMA-IR 呈线性相关（R=0.481，P=0.0041）。当 MANF 处于病理浓度（低于正常对照者的平均循环 MANF）时，最低浓度三分位（OR=21.429，p<0.0001）的疾病比值比、弗雷明汉风险评分和 10 年动脉粥样硬化性心血管疾病风险明显高于最高浓度三分位。
MANF 在 AGHD 状态下与胰岛素抵抗具有显著相关性。在肥胖的 AGHD 人群中，与异常的糖脂代谢也具有很强的相关性。MANF 也是评估 AGHD 患者心血管疾病风险的良好指标，具有很好的治疗潜力。
