Roussel Ronan, Natali Andrea, Balkau Beverley, Højlund Kurt, Sánchez Gabriel, Nolan John J, Mari Andrea, Kozakova Michaela, Bonnet Fabrice
aINSERM, U1138, Centre de Recherche des Cordeliers bUniversité Paris Diderot cDiabétologie, AP-HP, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France dDepartment of Experimental and Clinical Medicine, University of Pisa, Italy eInserm U-1018, CESP, Team 5 (EpReC, Renal and cardiovascular Epidemiology), UVSQ-UPS, Villejuif, France fDepartment of Endocrinology, Odense University Hospital, Odense, Denmark gInstituto de Investigación IdiPAZ, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain hSteno Diabetes Center, Gentofte, Denmark iInstitute of Biomedical Engineering, National Research Council, Padova, Italy jDiabetology Department, Southern Hospital, University Hospital, Rennes, France.
J Hypertens. 2016 Apr;34(4):685-91. doi: 10.1097/HJH.0000000000000842.
It is a common belief that early atherosclerosis in prediabetes is causally linked to endothelial insulin resistance. Another condition, a low insulin secretion, may be associated with insufficient insulin action on the vascular wall and consequently favor atherosclerosis. Our aim was to test this hypothesis in people without diabetes, taking into account the gold-standard measurement of insulin sensitivity, a major confounder in the relationship between insulin secretion and atherosclerosis.
We studied the European Relationship between Insulin Sensitivity and Cardiovascular Risk cohort of 451 men and 593 women (44 ± 8 years, mean ± SD) who were free of diabetes, hypertension, dyslipidemia, and other known chronic or acute conditions. All underwent an oral glucose tolerance test, a euglycemic-hyperinsulinemic clamp (M/I measured insulin sensitivity), and B-mode carotid ultrasound.
Intima-media thickness (IMT) in the common carotid artery was negatively associated with insulin secretion indexes, with Spearman partial correlation coefficients: -0.09, -0.08, -0.06 for respectively, the disposition index, the early insulin response and the beta cell glucose sensitivity, after adjusting for established factors, including clamp-measured insulin sensitivity (all P < 0.05). For quartiles 1 (lowest) to 4 of the disposition index, the covariate-adjusted geometric means of IMT (mm) were 0.605 (95% confidence interval: 0.596-0.614), 0.596 (0.587-0.605), 0.597 (0.587-0.606), and 0.586 (0.577-0.596) (Ptrend = 0.004). Similar results were found for the two other surrogate measures of insulin secretion. No interaction with sex was observed.
Insulin secretion was associated with early carotid atherosclerosis in nondiabetic individuals, independently of other risk factors, including insulin sensitivity measured by the gold-standard method.
人们普遍认为，糖尿病前期的早期动脉粥样硬化与内皮胰岛素抵抗存在因果关系。另一种情况，即胰岛素分泌不足，可能与胰岛素对血管壁的作用不足有关，从而促进动脉粥样硬化。我们的目的是在无糖尿病患者中验证这一假设，同时考虑胰岛素敏感性的金标准测量方法，这是胰岛素分泌与动脉粥样硬化关系中的一个主要混杂因素。
我们研究了欧洲胰岛素敏感性与心血管风险队列中的451名男性和593名女性（44±8岁，均值±标准差），这些人无糖尿病、高血压、血脂异常及其他已知的慢性或急性疾病。所有人都接受了口服葡萄糖耐量试验、正常血糖高胰岛素钳夹试验（M/I测量胰岛素敏感性）以及B型颈动脉超声检查。
在调整包括钳夹测量的胰岛素敏感性等既定因素后，颈总动脉内膜中层厚度（IMT）与胰岛素分泌指标呈负相关，Spearman偏相关系数分别为：处置指数为-0.09、早期胰岛素反应为-0.08、β细胞葡萄糖敏感性为-0.06（所有P<0.05）。对于处置指数的第1四分位数（最低）至第4四分位数，协变量调整后的IMT几何均值（mm）分别为0.605（95%置信区间：0.596 - 0.614）、0.596（0.587 - 0.605）、0.597（0.587 - 0.606）和0.586（0.577 - 0.596）（P趋势 = 0.004）。另外两种胰岛素分泌替代指标也得到了类似结果。未观察到与性别之间的相互作用。
在非糖尿病个体中，胰岛素分泌与早期颈动脉粥样硬化相关，独立于其他风险因素，包括采用金标准方法测量的胰岛素敏感性。
