Haffner S M, D'Agostino R, Mykkänen L, Hales C N, Savage P J, Bergman R N, O'Leary D, Rewers M, Selby J, Tracy R, Saad M F
Department of Medicine, University of Texas Health Science Center at San Antonio, 78284-7873, USA.
Stroke. 1998 Aug;29(8):1498-503. doi: 10.1161/01.str.29.8.1498.
Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis.
We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis.
In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (r=0.07, P=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispanic whites and Hispanics, significant correlations between CCA and proinsulin (r=0.087) and between ICA and proinsulin (r=0.101), split proinsulin (r = 0.092), and fasting insulin (r = 0.087) were observed. The significant correlations became more attenuated (and nonsignificant) after adjustment for cardiovascular risk factors, especially plasminogen activator inhibitor-1 (PAI-1).
The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin and IMT. Adjustment for PAI-1 markedly attenuated the association between proinsulin and IMT, suggesting a possible mediating role for PAI-1 in this association. It is possible that proinsulin may represent a marker of atherosclerosis rather than a causal factor for atherosclerosis. Studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays as well as determination of proinsulin concentrations.
胰岛素抵抗和高胰岛素血症与动脉粥样硬化有关。最近的关注焦点在于胰岛素原的可能作用，因为大多数胰岛素放射免疫测定法会与胰岛素原发生交叉反应。因此，尚不清楚二者之中胰岛素本身还是胰岛素原与动脉粥样硬化的关系更为密切。
我们在胰岛素抵抗动脉粥样硬化研究中，对985名非糖尿病受试者的空腹胰岛素原、空腹裂解胰岛素原、空腹及口服葡萄糖负荷后2小时胰岛素水平，与颈总动脉（CCA）和颈内动脉（ICA）的内膜中层厚度（IMT）之间的关系进行了研究。该研究是一项关于胰岛素抵抗和动脉粥样硬化的多民族研究。
在总体人群中，观察到胰岛素原与CCA的IMT之间存在微弱但显著的关系（r = 0.07，P = 0.029）。然而，西班牙裔和非西班牙裔白人中胰岛素原与IMT的关系比非裔美国人更强。在非西班牙裔白人和西班牙裔中，观察到CCA与胰岛素原（r = 0.087）、ICA与胰岛素原（r = 0.101）、裂解胰岛素原（r = 0.092）以及空腹胰岛素（r = 0.087）之间存在显著相关性。在调整心血管危险因素，尤其是纤溶酶原激活物抑制剂-1（PAI-1）后，这些显著相关性变得更弱（且无统计学意义）。
胰岛素原与IMT之间的关联虽然微弱，但似乎比胰岛素与IMT之间的关联更强。对PAI-1进行调整显著减弱了胰岛素原与IMT之间的关联，提示PAI-1在这种关联中可能起中介作用。胰岛素原有可能代表动脉粥样硬化的一个标志物，而非动脉粥样硬化的致病因素。在胰岛素抵抗综合征和动脉粥样硬化研究中，如果使用胰岛素作为胰岛素抵抗的替代指标，应考虑使用特定的胰岛素测定方法以及测定胰岛素原浓度。
