Background

We have shown that subjects with Laron syndrome (LS) due to growth hormone receptor deficiency (GHRD) and their relatives have comparable brain structure and function; moreover, the brain of individuals affected with GHRD appears like those of younger people. While the functionally absent growth hormone receptor and the diminished concentrations of the insulin-like growth factor-I have been associated to these findings, the role of the insulin-glucose axis is emerging as an unavoidable consideration when determining the aetiology of these observations. In consequence, we decided to search for the potential and discrete associations between the neurological findings and several parameters of carbohydrate metabolism that might exist in the subjects affected with GHRD.

Subjects and methods

Individuals affected with GHRD were compared to relative controls. Besides standard measures of anthropometry, body composition and brain characteristics, the elements of the carbohydrate metabolism (CHO), including glucose, insulin, triacylglycerol and the free insulin growth factor binding protein 1 (IGFBP1) concentrations were determined. In addition, the correlations existing between the parameters of CHO and brain characteristics were established.

Results

Besides the phenotypical characteristics of GHRD subjects, including those of brain structure and function, enhanced insulin sensitivity, and other minor, we observed that the insulin-regulated IGFBP1 had a consistent negative correlation with the main elements of the carbohydrate metabolism only in the individuals affected with the disease, and not in their relatives.

Conclusions

When compared to their relatives, subjects with GHRD who lack the counter-regulatory effects of GH on the insulin axis, despite their increased risk factor profile due to obesity and increased body fat percentage, have a healthy and younger looking brain associated to an enhanced and coordinated insulin sensitivity. Furthermore, it was observed that in the GHRD subjects IGFBP1 negatively correlates, in a constant and systematic manner, with the main elements of the CHO metabolism. These observations suggest a direct relationship between an efficient insulin sensitivity and a healthy brain.

中文翻译：

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人体中的生长激素受体缺乏症与肥胖症，体脂百分比增加，大脑健康和胰岛素敏感性协调相关

背景

我们已经表明，由于生长激素受体缺乏症（GHRD）而患有Laron综合征（LS）的受试者及其亲属具有相当的大脑结构和功能；而且，受GHRD影响的个体的大脑看起来像年轻人。尽管功能缺失的生长激素受体和胰岛素样生长因子-1的浓度降低与这些发现有关，但在确定这些发现的病因时，胰岛素-葡萄糖轴的作用已成为不可避免的考虑因素。因此，我们决定在神经病学发现与受GHRD影响的受试者中可能存在的碳水化合物代谢的几个参数之间寻找潜在的离散联系。

主题与方法

将受GHRD影响的个体与相对对照进行比较。除了人体测量，身体成分和大脑特征的标准测量方法外，还测定了碳水化合物代谢（CHO）的元素，包括葡萄糖，胰岛素，三酰甘油和游离胰岛素生长因子结合蛋白1（IGFBP1）的浓度。另外，建立了CHO参数与脑部特征之间的相关性。

结果

除了GHRD受试者的表型特征（包括脑结构和功能，胰岛素敏感性增强和其他轻微特征）外，我们还观察到胰岛素调节的IGFBP1与碳水化合物代谢的主要元素呈负相关，仅在受影响的个体中患有这种疾病，而不是亲戚。

结论

与他们的亲戚相比，尽管由于肥胖和体脂百分比增加而导致的危险因素增加，但缺乏GH对胰岛素轴的反调节作用的GHRD受试者的大脑健康而年轻，与协调胰岛素敏感性。此外，观察到在GHRD受试者中，IGFBP1以恒定和系统的方式与CHO代谢的主要元素负相关。这些观察结果表明有效的胰岛素敏感性和健康的大脑之间存在直接关系。