Katz R J, Ratner R E, Cohen R M, Eisenhower E, Verme D
Department of Medicine, Division of Cardiology, George Washington University School of Medicine, Washington, DC 20037, USA.
Diabetes. 1996 Jun;45(6):736-41. doi: 10.2337/diab.45.6.736.
Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin levels with the likelihood of a patient having or not having CAD disappears after adjustment for BMI, suggesting that insulin and proinsulin are not independent risk markers but are primarily dependent on obesity.
关于高胰岛素血症和高胰岛素原血症是否为冠状动脉粥样硬化的独立风险标志物，目前仍存在争议。以往大多数研究的一个共同局限在于，对正常组和冠状动脉疾病（CAD）组疾病状态的分类不够精确。在一项病例对照研究中，我们评估了胰腺β细胞分泌产物与早发CAD之间的关系。该研究纳入了134名年龄≤55岁的非糖尿病受试者，通过心导管检查和/或铊应激试验仔细确定其CAD状态。病例组包括66例早发CAD患者，对照组（非CAD组）包括68例无CAD但有传统CAD危险因素、胸痛和/或心电图异常但心导管检查和/或铊应激试验正常的患者。除了CAD组与非CAD组的比较外，两组还与由27名瘦胖混合的对照志愿者组成的参考组进行了比较。所有CAD和非CAD患者均进行了3小时75克口服葡萄糖耐量试验，测量空腹及葡萄糖负荷后免疫反应性胰岛素（IRI）、特异性胰岛素（INS）、胰岛素原样物质（PI）和C肽。在多分类逻辑回归模型中，与参考组相比，空腹胰岛素和空腹胰岛素原水平升高均与早发CAD组和非CAD组的较高患病几率在统计学上显著相关（两种比较中，每种β细胞分泌产物增加20%时，优势比至少为1.20，P<0.05）。然而，与非CAD组相比，胰腺β细胞分泌激素水平升高在早发CAD组中并未显示出统计学上显著的相对风险。在调整体重指数（BMI）后，当比较CAD组和非CAD组与参考组的优势比时，IRI、INS和PI的所有统计学显著关联均消失。此外，与参考组相比，早发CAD组和非CAD组的患病几率与PI与胰岛素及C肽的比值无显著关联。因此，尽管与参考组相比，早发CAD的患病几率与胰岛素和胰岛素原水平升高之间存在统计学显著关联，但这些发现同样常见于有传统CAD危险因素但未检测出CAD的受试者中。此外，在调整BMI后，较高的胰岛素和胰岛素原水平与患者患CAD与否的可能性之间的关联消失，这表明胰岛素和胰岛素原不是独立的风险标志物，而是主要依赖于肥胖。
