Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes
Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes
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DOI：
10.2337/diabetes.48.9.1856
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发表时间：
1999-09-01
期刊：
影响因子：
7.7
通讯作者：
Veves, A
中科院分区：
文献类型：
--
作者：
Caballero, AE;Arora, S;Veves, A
2型糖尿病患者的微循环和大循环血管反应性明显降低。然而，很少有人知道血管反应性的变化，在发展为2型糖尿病的风险。为了解决这种情况，在四个年龄和性别相当的组中研究了微循环和大循环中的血管反应性：30例血糖正常、一级亲属无2型糖尿病史的健康受试者（对照组），39名父母一方或双方有2型糖尿病史的血糖正常的健康受试者（亲属）、32名葡萄糖耐量受损（IGT）受试者和42名无血管并发症的2型糖尿病患者（糖尿病）。激光多普勒灌注成像用于测量前臂皮肤对1%氯化乙酰胆碱（Ach）（内皮依赖性）和1%硝普钠（SNP）（内皮非依赖性）的血管舒张反应，而高分辨率超声图像用于测量反应性充血期间肱动脉直径的变化。内皮素-1（ET-1）、血管性血友病因子（vWF）、可溶性细胞间粘附分子（sICAM）和可溶性血管细胞粘附分子（sVCAM）的血浆浓度也被测量为内皮细胞活化的指标。与对照组（126 +/- 67）相比，亲属组（98 +/- 48，平均值+/- SD）、IGT组（94 +/- 52）和糖尿病组（74 +/- 45）对Ach的血管舒张反应（以血流量较基线增加的百分比表示）降低（对照组与亲属组、IGT组和糖尿病组相比P < 0.001）。对SNP的反应也同样降低：（123 +/- 46），亲属（85 +/- 46），IGT（83 +/- 48）和糖尿病（65 +/- 31）（对照组与亲属、IGT和糖尿病组相比P < 0.001），反应性充血期间肱动脉直径的反应也是如此：对照组（13.7 ± 6.1）、亲属组（10.5 ± 6.7）、IGT组（9.8 ± 4.5）和糖尿病组（8.4 ± 5.0）（对照组与亲属组、IGT组和糖尿病组相比P < 0.01）。女性在微血管和大血管循环试验中的反应比男性更大，但随着葡萄糖耐受不良程度的增加，在两种性别中观察到类似的进行性降低。微血管反应性与收缩压、空腹血糖、高密度脂蛋白胆固醇、空腹血浆胰岛素和稳态模型评估（HOMA）值（胰岛素抵抗指数）呈显著负相关。BMI和舒张压仅与内皮依赖性血管舒张功能呈显著负相关。在大循环中，收缩压、HbA（1c）、HDL胆固醇和HOMA与肱动脉直径变化显著相关。与对照组比较，各组ET-1均显著升高，vWF仅在糖尿病组升高，sICAM在IGT组和糖尿病组均升高，而sVCAM在亲属组和糖尿病组均升高（P < 0.05）。多因素逐步回归分析显示，年龄、性别、空腹血糖和BMI是影响血管反应性的重要因素。所有临床和生化指标的增加仅解释了血管反应性变化的32-37%。这些结果表明，血管反应性和内皮细胞活化的生化标志物的异常是目前早期在个人的风险发展为2型糖尿病，甚至在一个阶段，当正常的葡萄糖耐量存在，以及除了胰岛素抵抗的因素可能是可操作的。
Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to ioatophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), vonWillebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent; vasodilation. In the macrocirculation, systolic blood pressure, HbA(1c), HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose and BMI were the most important; contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at; a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.