In insulin-dependent diabetes mellitus, hyperglycaemia has a profound effect on renal and systemic haemodynamic function. The mechanism for this is unknown. 2. We conducted a study in 11 males with insulin-dependent diabetes mellitus, within 6 years of diagnosis. We examined the neurohumoral, haemodynamic and renal variables during euglycaemia (4.0-6.0 mmol/l) and after a 12 h period of hyperglycaemia (8.5-10.5 mmol/l). Subjects were examined in a sodium-replete state during supine rest and during simulated orthostatic stress induced by lower body negative pressure at -15 mmHg. 3. Variations in glycaemia markedly influenced plasma renin activity, which was increased at baseline during hyperglycaemia (3.82 +/- 0.66 pmol of angiotensin I h-1 ml-1 compared with 2.13 +/- 0.33 pmol of angiotensin I h-1 ml-1 during euglycaemia, P = 0.009), and rose further during simulated orthostatic stress. Mean arterial pressure was also elevated during hyperglycaemia (89 +/- 2 mmHg compared with 81 +/- 3 mmHg during euglycaemia, P = 0.03), both at rest and during orthostatic stress. 4. The renal haemodynamic effects of hyperglycaemia included maintenance of glomerular filtration rate in the face of significant declines in renal blood flow, and a probable increase in filtration fraction (0.21 +/- 0.01 compared with 0.18 +/- 0.01 during euglycaemia, P = 0.06). The responses of mean arterial pressure and renal blood flow to simulated orthostatic stress were not affected by hyperglycaemia, but the forearm vascular response was significantly augmented. 5. These data suggest that sustained hyperglycaemia activates the renin-angiotensin system, thereby increasing systemic and renal vasomotor tone. Over time such changes may have deleterious microvascular consequences.
摘要
在胰岛素依赖型糖尿病中，高血糖对肾脏和全身血流动力学功能有深远影响。其机制尚不清楚。2. 我们对11名诊断后6年内的胰岛素依赖型糖尿病男性患者进行了一项研究。我们在血糖正常（4.0 - 6.0 mmol/l）期间以及12小时高血糖（8.5 - 10.5 mmol/l）后检查了神经体液、血流动力学和肾脏变量。受试者在仰卧休息时处于钠充足状态，并在 - 15 mmHg下半身负压诱导的模拟直立应激期间接受检查。3. 血糖变化显著影响血浆肾素活性，高血糖期间基线时肾素活性增加（高血糖时为3.82±0.66 pmol血管紧张素I h - 1 ml - 1，而血糖正常时为2.13±0.33 pmol血管紧张素I h - 1 ml - 1，P = 0.009），在模拟直立应激期间进一步升高。高血糖期间平均动脉压也升高（高血糖时为89±2 mmHg，血糖正常时为81±3 mmHg，P = 0.03），无论是在休息时还是直立应激期间。4. 高血糖对肾脏血流动力学的影响包括在肾血流量显著下降的情况下维持肾小球滤过率，以及滤过分数可能增加（高血糖时为0.21±0.01，血糖正常时为0.18±0.01，P = 0.06）。平均动脉压和肾血流量对模拟直立应激的反应不受高血糖影响，但前臂血管反应显著增强。5. 这些数据表明，持续性高血糖激活肾素 - 血管紧张素系统，从而增加全身和肾脏血管运动张力。随着时间的推移，这种变化可能会产生有害的微血管后果。
