Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals.
Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals.
复制标题
DOI：
10.2337/dc09-0354
复制
发表时间：
2010-07
期刊：
影响因子：
16.2
通讯作者：
Davis SN
中科院分区：
文献类型：
--
作者：
Gogitidze Joy N;Hedrington MS;Briscoe VJ;Tate DB;Ertl AC;Davis SN
最近的大型随机试验将不良心脑血管事件与低血糖联系起来。然而，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 小时的中度钳制低血糖是否会降低 1 型糖尿病患者和健康个体的纤溶平衡并激活促动脉粥样硬化机制。 35 名健康志愿者（19 名男性和 16 名女性受试者，年龄 32 ± 2 岁，BMI 26 ± 2 kg/m2，A1C 5.1 ± 0.1%）和 24 名 1 型糖尿病患者（12 名男性和 12 名女性受试者，年龄 33 ± 3 岁，BMI 24 ± 2 kg/m2，A1C 7.7 ± 0.2%）在任一研究期间进行了研究。 2 小时高胰岛素 (9 pmol·kg−1·min−1) 正常血糖或低血糖 (2.9 ± 0.1 mmol/l) 钳夹或两种方案。在每次研究之前，1 型糖尿病受试者的血浆葡萄糖水平过夜标准化。所有四种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 型糖尿病受试者和健康对照受试者的低血糖水平也相当（2.9 ± 0.1 mmol/l）。通过重复方差分析，发现高胰岛素低血糖2小时内纤溶酶原激活剂抑制剂（PAI-1）、血管细胞粘附分子（VCAM）、细胞间粘附分子（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）和脂联素反应均显着增加（P < 0.05）。健康对照受试者的血糖正常。与 1 型糖尿病正常血糖相比，低血糖期间除 PAI-1 外的所有指标均有所增加。总之，中度低血糖会急剧增加 1 型糖尿病患者和健康个体中 PAI-1、VEGF、血管粘附分子（VCAM、ICAM、E-选择素）、IL-6 和血小板活化标志物（P-选择素）的循环水平。我们的结论是，急性低血糖可导致复杂的血管效应，包括激活 1 型糖尿病患者和健康个体的促血栓形成、促炎症和促动脉粥样硬化机制。
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/m2, 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/m2, A1C 7.7 ± 0.2%) were studied during either a 2-h hyperinsulinemic (9 pmol · kg−1 · 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.