Guevara-Aguirre Jaime, Mishra Amrendra, Canepa Marco, Guevara Carolina, Villacres Álvaro, Guevara Alexandra, Peña Gabriela, Lescano Daniela, Kopchick John J, Balasubramanian Priya, Longo Valter D
College of Medicine, Universidad San Francisco de Quito, Quito, Ecuador; Instituto de Endocrinología IEMYR, Quito, Ecuador; Maastricht University, Maastricht, the Netherlands.
Longevity Institute, Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Department of Life Sciences, GITAM (Deemed to be University), Bengaluru, India.
Med. 2024 Jul 12;5(7):816-825.e4. doi: 10.1016/j.medj.2024.03.022. Epub 2024 Apr 26.
Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives.
We measured markers of CVD in two phases: one in a cohort of 30 individuals (GHRD = 16, control relatives = 14) brought to USC (in Los Angeles, CA) and one in a cohort including additional individuals examined in Ecuador (where the subjects live) for a total of 44 individuals (GHRD = 21, control relatives = 23). Data were collected on GHRD and control groups living in similar geographical locations and sharing comparable environmental and socio-economic circumstances.
Compared to controls, GHRD subjects displayed lower serum glucose, insulin, blood pressure, smaller cardiac dimensions, similar pulse wave velocity, lower carotid artery intima-media thickness, lower creatinine, and a non-significant but major reduction in the portion of subjects with carotid atherosclerotic plaques (7% GHRDs vs. 36%, Controls p = 0.1333) despite elevated low-density lipoprotein cholesterol levels.
The current study indicates that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors as compared to their relatives.
This study was funded in part by NIH/NIA grant P01 AG034906 to V.D.L.
由于生长激素受体缺乏（GHRD）/拉龙综合征导致全身性生长激素（GH）不敏感的人类受试者，胰岛素抵抗、糖尿病和癌症的发病率极低，且与年龄相关的认知衰退延迟。然而，这些受试者患心血管疾病（CVD）的风险尚不清楚。在此，我们评估了GHRD受试者及其亲属的心血管功能、损伤和风险因素。
我们分两个阶段测量CVD标志物：一个阶段是在30名个体（GHRD = 16名，对照亲属 = 14名）的队列中进行，这些个体被带到南加州大学（位于加利福尼亚州洛杉矶）；另一个阶段是在一个队列中进行，该队列包括在厄瓜多尔（受试者居住的地方）检查的其他个体，总共44名个体（GHRD = 21名，对照亲属 = 23名）。收集了生活在相似地理位置、具有可比环境和社会经济状况的GHRD组和对照组的数据。
与对照组相比，GHRD受试者的血清葡萄糖、胰岛素、血压较低，心脏尺寸较小，脉搏波速度相似，颈动脉内膜中层厚度较低，肌酐较低，尽管低密度脂蛋白胆固醇水平升高，但有颈动脉粥样硬化斑块的受试者比例有非显著性但较大幅度的降低（GHRD组为7%，对照组为36%，p = 0.1333）。
当前研究表明，与亲属相比，GHRD个体的心血管疾病风险因素水平正常或有所改善。
本研究部分由美国国立卫生研究院/国家老龄问题研究所授予V.D.L.的P01 AG034906资助。
