University of Maryland School of Medicine, Baltimore, Maryland, USA.
Diabetes Care. 2010 Jul;33(7):1529-35. doi: 10.2337/dc09-0354.
Recent large randomized trials have linked adverse cardiovascular and cerebrovascular events with hypoglycemia. However, the integrated physiological and vascular biological mechanisms occurring during hypoglycemia have not been extensively examined. Therefore, the aim of this study was to determine whether 2 h of moderate clamped hypoglycemia could decrease fibrinolytic balance and activate pro-atherothrombotic mechanisms in individuals with type 1 diabetes and healthy individuals.
Thirty-five healthy volunteers (19 male and 16 female subjects age 32 +/- 2 years, BMI 26 +/- 2 kg/m(2), A1C 5.1 +/- 0.1%) and twenty-four with type 1 diabetes (12 male and 12 female subjects age 33 +/- 3 years, BMI 24 +/- 2 kg/m(2), A1C 7.7 +/- 0.2%) were studied during either a 2-h hyperinsulinemic (9 pmol x kg(-1) x min(-1)) euglycemic or hypoglycemic (2.9 +/- 0.1 mmol/l) clamp or both protocols. Plasma glucose levels were normalized overnight in type 1 diabetic subjects prior to each study.
Insulin levels were similar (602 +/- 44 pmol/l) in all four protocols. Glycemia was equivalent in both euglycemic protocols (5.2 +/- 0.1 mmol/l), and the level of hypoglycemia was also equivalent in both type 1 diabetic subjects and healthy control subjects (2.9 +/- 0.1 mmol/l). Using repeated ANOVA, it was determined that plasminogen activator inhibitor (PAI-1), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), E-selectin, P-selectin, interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and adiponectin responses were all significantly increased (P < 0.05) during the 2 h of hyperinsulinemic hypoglycemia as compared with euglycemia in healthy control subjects. All measures except PAI-1 were also found to be increased during hypoglycemia compared with euglycemia in type 1 diabetes.
In summary, moderate hypoglycemia acutely increases circulating levels of PAI-1, VEGF, vascular adhesion molecules (VCAM, ICAM, E-selectin), IL-6, and markers of platelet activation (P-selectin) in individuals with type 1 diabetes and healthy individuals. We conclude that acute hypoglycemia can result in complex vascular effects including activation of prothrombotic, proinflammatory, and pro-atherogenic mechanisms in individuals with type 1 diabetes and healthy individuals.
最近的大型随机试验将不良心血管和脑血管事件与低血糖联系起来。然而，在低血糖期间发生的综合生理和血管生物学机制尚未得到广泛研究。因此，本研究的目的是确定 2 小时的中度钳夹性低血糖是否会降低 1 型糖尿病患者和健康个体的纤溶平衡并激活促动脉血栓形成机制。
研究了 35 名健康志愿者（19 名男性和 16 名女性，年龄 32 +/- 2 岁，BMI 26 +/- 2 kg/m(2)，A1C 5.1 +/- 0.1%）和 24 名 1 型糖尿病患者（12 名男性和 12 名女性，年龄 33 +/- 3 岁，BMI 24 +/- 2 kg/m(2)，A1C 7.7 +/- 0.2%）在 2 小时高胰岛素（9 pmol x kg(-1) x min(-1)）正常血糖或低血糖（2.9 +/- 0.1 mmol/l）钳夹或两者方案期间进行研究。在每项研究之前，1 型糖尿病患者会在夜间使血糖水平正常化。
所有四个方案中的胰岛素水平相似（602 +/- 44 pmol/l）。两种正常血糖方案中的血糖水平相当（5.2 +/- 0.1 mmol/l），1 型糖尿病患者和健康对照组中的低血糖水平也相当（2.9 +/- 0.1 mmol/l）。使用重复方差分析，确定纤溶酶原激活物抑制剂（PAI-1）、血管细胞黏附分子（VCAM）、细胞间黏附分子（ICAM）、E-选择素、P-选择素、白细胞介素-6（IL-6）、血管内皮生长因子（VEGF）和脂联素的反应在健康对照组中，与正常血糖相比，在 2 小时高胰岛素低血糖期间均显着增加（P < 0.05）。在 1 型糖尿病中，与正常血糖相比，除 PAI-1 外，所有指标均发现低血糖期间均升高。
总之，中度低血糖会在 1 型糖尿病患者和健康个体中急性增加循环中的 PAI-1、VEGF、血管黏附分子（VCAM、ICAM、E-选择素）、IL-6 和血小板活化标志物（P-选择素）水平。我们得出结论，急性低血糖会导致复杂的血管效应，包括在 1 型糖尿病患者和健康个体中激活促血栓形成、促炎和促动脉粥样硬化机制。
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