Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus
Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus
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DOI：
10.1046/j.1464-5491.1999.00067.x
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发表时间：
1999-05-01
影响因子：
3.5
通讯作者：
Rosmond, R
中科院分区：
文献类型：
--
作者：
Björntorp, P;Holm, G;Rosmond, R
目的当胰岛素抵抗超过代偿性胰岛素分泌能力时，发生2型糖尿病（DM）。胰岛素抵抗可能是通过精神神经内分泌途径引起的，这一可能性此前很少受到关注。方法我们使用唾液皮质醇测量来监测下丘脑-垂体-肾上腺（HPA）轴的活动，HPA轴是日常条件下参与调节外周胰岛素敏感性的激素的主要控制者。在随机选择的中年人群样本中，跟踪外部挑战的影响以及反馈调节的敏感性。结果健康状态下皮质醇分泌具有一定的节律性，具有较高的可塑性和有效的反馈控制。相比之下，一组受试者被确定为平坦、僵硬的日曲线和较差的反馈控制，他们表现出与压力相关的皮质醇分泌持续异常，包括性类固醇和生长激素的分泌受到抑制；胰岛素抵抗;腹部肥胖;瘦素水平升高；高血糖症;血脂异常和高血压伴心率升高。内分泌异常可能是人体测量和代谢异常的原因。循环紊乱似乎是由中枢交感神经系统的平行激活引起的，这表明一种“下丘脑觉醒综合征”，逐渐发展成为一种独立的疾病风险。已经确定了一系列相关的环境因素，包括社会心理和社会经济压力，抑郁和焦虑的特征，饮酒和吸烟，所有已知的激活下丘脑中心的因素。糖皮质激素受体基因的多态性，在瑞典男性人群中有13.7%的纯合子，与受体功能障碍相似，可能是相关胰岛素抵抗、中枢性肥胖和高血压的原因。结论：这是首次在人群基础上对自然环境中与躯体健康相关的心理神经内分泌过程进行详细检查。结果表明，下丘脑觉醒综合征与HPA轴和中枢交感神经系统并行激活，负责内分泌异常、胰岛素抵抗、中枢性肥胖、血脂异常和高血压的发展，导致包括2型糖尿病在内的直率疾病。我们认为，这种综合征可能是基于遗传易感个体的环境压力。
Aims Type 2 diabetes mellitus (DM) develops when insulin resistance overcomes the capacity of compensatory insulin secretion. Insulin resistance may be induced via psychoneuroendocrine pathways, a possibility which has received little previous attention.Methods We have used salivary cortisol measurements to monitor the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the major controller of hormones involved in the regulation of peripheral insulin sensitivity under everyday conditions. The influence of external challenges, as well as the sensitivity of feedback regulation, were followed in randomly selected middle-aged population samples.Results In health there is a rhythmicity of cortisol secretion, with a high plasticity and efficient feedback control. In contrast, a group of subjects were identified with a flat, rigid day curve and poor feedback control, who showed consistent abnormalities in stress-related cortisol secretion, including inhibited secretions of sex steroids and growth hormone; insulin resistance; abdominal obesity; elevated leptin levels; hyperglycaemia; dyslipidaemia and hypertension with elevated heart rate. The endocrine abnormalities are probably responsible for the anthropometric and metabolic abnormalities. The circulatory perturbations seem to be induced by a parallel activation of the central sympathetic nervous system suggesting an 'hypothalamic arousal syndrome', gradually developing into an independent risk for disease. An associated cluster of environmental factors, including psychosocial and socio-economic stress, traits of depression and anxiety, alcohol consumption and smoking, all factors known to activate hypothalamic centres, has been identified. A polymorphism of the glucocorticoid receptor gene, with 13.7% homozygotes in the male Swedish population, parallels receptor dysfunction, and may be responsible for the associated insulin resistance, central obesity and hypertension.Conclusions This is the first detailed examination of psychoneuroendocrinological processes in the natural environment on a population basis in relation to somatic health. The results suggest that an hypothalamic arousal syndrome, with parallel activation of the HPA axis and the central sympathetic nervous system, is responsible for development of endocrine abnormalities, insulin resistance, central obesity, dyslipidaemia and hypertension, leading to frank disease, including Type 2 DM. We suggest that this syndrome is probably based on environmental pressures in genetically susceptible individuals.