ATHEROSCLEROSIS IN DIABETES - THE ROLE OF HYPERINSULINEMIA
ATHEROSCLEROSIS IN DIABETES - THE ROLE OF HYPERINSULINEMIA
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DOI：
10.1016/0026-0495(88)90180-1
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发表时间：
1988-02-01
影响因子：
9.8
通讯作者：
STOLAR, MW
中科院分区：
文献类型：
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作者：
STOLAR, MW
非胰岛素依赖型糖尿病(NIDDM)是成人过早发病和死亡的主要原因。冠状动脉和外周血管的大血管疾病是这些患者的主要死亡原因。大量的实验和流行病学研究表明，高胰岛素血症加速了动脉粥样硬化的发展。在实验模型中，胰岛素促进饮食诱导的病变发展，并推翻病变消退和雌激素对动脉粥样硬化的保护作用。选择性动脉输注引起的局部高胰岛素血症加速了灌流动脉的动脉粥样硬化。胰岛素已被证明能刺激培养的内膜下平滑肌和成纤维细胞，并增加这些细胞对脂质的摄取和局部合成。胰岛素也可能导致纤溶抑制。对非糖尿病患者进行的几项前瞻性研究表明，空腹或餐后胰岛素水平是独立于其他危险因素的冠状动脉疾病发展的敏感预测因子。最近对NIDDM患者的两项研究证实了这一发现，并表明血糖控制可能不是大血管疾病发展的重要因素。碳水化合物耐量疾病，如NIDDM、糖耐量受损、肥胖，经常与循环胰岛素水平升高有关，无论是生理上的还是治疗后的。鉴于心血管疾病在这些人群中的高患病率，改进治疗以最大限度地减少高胰岛素血症应该是治疗方案中的一个重要考虑因素。与传统的口服药物或胰岛素治疗相比，使用格列吡嗪或格列齐特等口服药物可能更有利，因为它们引起的昼夜高胰岛素血症较少。
Non-insulin-dependent diabetes (NIDDM) is a major cause of premature morbidity and mortality among adults. Macrovascular disease of coronary and peripheral vessels is the primary cause of death in these patients. Numerous experimental and epidemiologic studies have suggested that hyperinsulinemia accelerates the development of atherosclerosis. In experimental models, insulin promotes diet-induced lesion development and overrides lesion regression and estrogen protection against atherosclerosis. Local hyperinsulinemia induced by selected arterial infusion accelerates atherosclerosis in the perfused artery. Insulin has been shown to stimulate subintimal smooth muscle and fibroblast cells in culture, and to increase the uptake and local synthesis of lipid by these cells. Insulin may also induce inhibition of fibrinolysis. Several prospective studies performed on nondiabetic patients show that either fasting or postprandial insulin levels are a sensitive predictor of the development of coronary disease independent of other risk factors. Two recent studies in NIDDM patients confirm this finding and suggest that glycemic control may not be a significant factor in the development of macrovascular disease. Diseases of carbohydrate tolerance, ie, NIDDM, impaired glucose tolerance, obesity, are frequently associated with elevated circulating insulin levels, either physiologically or secondary to treatment. Given the high prevalence of cardiovascular disease in these populations, modifying therapy to minimize hyperinsulinemia should be an important consideration in a treatment program. Use of oral agents such as glipizide or gliclazide, which induce less diurnal hyperinsulinemia, may be advantageous when compared to traditional oral agent or insulin therapy.