Mechanism of retinopathy associated with Gestational diabetes mellitus and its appilidation for clinical diagnosis

2011年度～2012年度科学研究費補助金(研究活動スタート支援)研究成果報告書妊娠糖尿病(Gestational diabetes mellitus, GDM) で併発した網膜症は、劇症化することがあり、通常と異なる機序が関与している。類似した病態である、血糖コントロールに伴う網膜症劇症化にBetacellulin (BTC)という蛋白質が関与し、これが、血管内皮増殖因子 (VEGF) とともに本疾患の原因となると考え、正常・妊婦・糖尿病・GDM妊婦の血中濃度とマウスモデルの網膜における発現をしらべた。 血中のVEGFはGDM群で低下していたがBTCは増加していた。マウス網膜でも同様の傾向であり、血管透過性亢進がGDM群で認められた。以上から、GDMではVEGFでなくBTCが劇症化に関与する可能性が示唆された。It is possible for patients with Gestational Diabetes Mellitus (GDM) to have a complication of Diabetic Retinopathy (GDM-DR). It can become a fulminant GDM-DR rapidly unlike the common retinopathy, and there is a different mechanism working. Betacellulin (BTC) is a pathology that is similar to GDM-DR. It is a protein that is involved in the blood glucose control associated with the fulminant GDM-DR. It is also possible for Vascular Endothelial Growth Factor (VEGF) to become the cause of GDM-DR along with BTC. Under the approval of the ethics committee, blood samples from healthy, pregnant, diabetic females and pregnant females with GDM were collected and analyzed. At the same time, mouse models were made and the protein expressions in the retina was studied. In human blood, VEFG in the GDM group had decreased. And there was a tendency of BTC to increase. In the mouse models, similar trends were seen in the VEGF and BTC expressions increase of vasopermeability was seen in the GDM group. From these results, the possibility that VEGF is inhibited but BTC is increased in the GDM group and that it is involved with the increase of vasopermeability and onset of retinopathy were indicated