PAX6基因突变的无虹膜症患者中糖代谢异常的病理生理学特征  

Pathophysiological characteristics of abnormal glucose metabolism in aniridia patients with PAX6 mutation

作　　者：陈园园[1] 宋书娟[1] 洪天配[1] 刘英芝 任国成 文锦华[1] 李凌松[1] 

机构地区：[1]北京大学第三医院内分泌科、北京大学干细胞研究中心,100191 [2]辽宁省朝阳市中心医院眼科

出　　处：《中国糖尿病杂志》2009年第5期327-330,共4页Chinese Journal of Diabetes

基　　金：国家自然科学基金资助项目(30771032,30700879,30871251);北京市自然科学基金资助项目(7062067);国家973计划资助项目(2006CB503900);国家863计划资助项目(2006AA02A112)

摘　　要：目的探讨PAX6基因突变的无虹膜症患者是否存在糖代谢异常,并阐明其病理生理学特征。方法一个PAX6基因突变所致的无虹膜症家系包括19名健在的患者和4名无突变的正常成员。16名无虹膜症患者参与本研究,4名无突变的家系成员和12名健康成人作为正常对照(NC)组,8名无PAX6基因突变的新诊断2型糖尿病(T2DM)患者作为另一个对照组。通过OGTT,分析血糖、总胰岛素及胰岛素原水平的变化,采用胰岛素耐量试验(ITT)检测胰岛素敏感性。结果在16例PAX6基因突变的无虹膜症患者中,FPG与NC组无显著差别,OGTT 120min血糖显著高于NC组,其中糖耐量受损(IGT)5例和DM4例。PAX6基因突变患者的BMI均<23,胰岛素敏感性未见明显降低,OGTT30min总胰岛素水平显著降低,但胰岛素原/总胰岛素比值显著高于NC组和T2DM组,并且在糖耐量正常时即可见到这种变化。结论 PAX6基因突变患者存在糖代谢异常,大多表现为负荷后高血糖,其病理生理学基础主要是胰岛素原向胰岛素转化过程存在缺陷。Objective To characterize abnormal glucose metabolism and its related pathophysiological changes in aniridia patients with PAX6 mutation. Methods An aniridia pedigree with PAX6 mutation consisted of 19 living patients and four unaffected consanguineous members. Of the 19 patients, 16 were available for this study. Four non-mutation family members and 12 healthy adults were included as normal controls, as well as 8 newly-diagnosed type 2 diabetic patients without PAX6 mutation. All participants were examined for their glucose metabolism state using oral glucose tolerance test （OGTT）. The levels of plasma glucose, insulin and proinsulin were analyzed. Insulin sensitivity was evaluated by insulin tolerance test （ITT）. Results In 16 aniridia patients with PAX6 mutation, fasting blood glucose levels were not different from those in the normal controls. Blood glucose levels at 120 rain after OGTT were significantly higher in the patients with PAX6 mutation than those in the controls. Among the 16 patients, 5 had impaired glucose Tolerance （IGT） and 4 developed diabetes. Body mass index was below 23 and insulin sensitivity was not found to be decreased in the patients with PAX6 mutation. Plasma total insulin levels at 30 rain during OGTT were significantly lower in the patients with PAX6 mutation than those in the controls. However, the mutant patients had higher proinsulin/total insulin ratio than the controls and the patients with type 2 diabetes even when their glucose tolerance was normal.Conclusions Abnormal glucose metabolism is presented in the patients with PAX6 mutation. Defective conversion of proinsulin to insulin is an important pathophysiological basis for their post-load hyperglycemia.

关 键 词：PAX6 葡萄糖代谢 胰岛素原 

分 类 号：R773.1[医药卫生—眼科]