Kristensen Peter Lommer, Høi-Hansen Thomas, Boomsma Frans, Pedersen-Bjergaard Ulrik, Thorsteinsson Birger
Endocrinology Section, Department of Cardiology and Endocrinology, Hillerød Hospital, DK-3400 Hillerød, Denmark.
Metabolism. 2009 Oct;58(10):1430-8. doi: 10.1016/j.metabol.2009.04.026. Epub 2009 Jul 1.
In healthy adults, levels of vascular endothelial growth factor (VEGF) increase in response to mild hypoglycemia. VEGF is implicated in glucose transport over the blood-brain barrier, and the increase during hypoglycemia has been positively correlated with preservation of cognitive function during hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased from 39 to 58 pg/L in the high-RAS group (P = .004) and from 76 to 109 pg/L in the low-RAS group (P = .01), with no difference between RAS groups (P = .9). A weak association between reduced preservation of cognitive function during hypoglycemia and low VEGF response was observed. Plasma VEGF levels increase during mild, short-term hypoglycemia in patients with type 1 diabetes mellitus. The VEGF response is not dependent on RAS activity and only weakly associated with preservation of cognitive function during hypoglycemia. Thus, the previously described association between low RAS activity and better cognitive performance during hypoglycemia does not seem to be mediated by VEGF.
在健康成年人中，血管内皮生长因子（VEGF）水平会因轻度低血糖而升高。VEGF与葡萄糖通过血脑屏障的转运有关，低血糖期间其水平升高与低血糖期间认知功能的保留呈正相关。肾素-血管紧张素系统（RAS）的高活性与1型糖尿病患者严重低血糖风险增加有关。肾素-血管紧张素系统可能通过VEGF在低血糖中发挥其作用机制。我们研究了轻度低血糖对1型糖尿病且RAS活性高或低的患者血浆VEGF的影响，并分析了VEGF水平与低血糖期间认知功能之间的关联。18例1型糖尿病患者——9例RAS活性高，9例RAS活性低——进行了一项单盲、安慰剂对照、交叉研究，分别经历轻度低血糖或血糖稳定状态。认知功能通过加利福尼亚认知评估套餐和阿尔茨海默快速测试进行评估。最低血浆葡萄糖水平为2.2（0.3）mmol/L。在对照研究期间，血浆VEGF没有变化。在低血糖期间，高RAS组血浆VEGF从39 pg/L增加到58 pg/L（P = 0.004），低RAS组从76 pg/L增加到109 pg/L（P = 0.01），RAS组之间无差异（P = 0.9）。观察到低血糖期间认知功能保留降低与低VEGF反应之间存在弱关联。在1型糖尿病患者轻度、短期低血糖期间，血浆VEGF水平会升高。VEGF反应不依赖于RAS活性，仅与低血糖期间认知功能的保留弱相关。因此，先前描述的低RAS活性与低血糖期间更好的认知表现之间的关联似乎不是由VEGF介导的。
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