2018-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/708602摘要：代謝症候群是指生理代謝層面的心血管危險因子的聚集現象，這些危險因子主要包括高血壓、血脂異常、糖尿病、肥胖、以及高尿酸與凝血因子的不正常等等，代謝症候群時常會導致心血管疾病以及第二型糖尿病。同樣地，妊娠高血壓、妊娠糖尿病以及子癲前症等妊娠併發症也會增加日後發生心血管疾病以及第二型糖尿病的機會。目前的證據亦顯示，妊娠早期即出現代謝症候群的話，也會增加日後發展出妊娠併發症的風險。懷孕本身就會產生獨特的生理、代謝變化以及心血管壓力，特別是在懷孕過程會產生心血管的不穩定性以及遽烈的血行變化，這些因素都可能讓孕婦的相關代謝指標與非孕婦有許多的相異之處。因此，我們提出一個全新的概念--「妊娠期代謝症候群」，我們假設在懷孕初期的孕婦若是具有某些異常的代謝症候群相關指標，日後在孕程中就較可能會出現妊娠併發症，同時，正因為孕婦的生理及代謝有巨幅的變動，妊娠代謝症候群的診斷標準可能也會與一般成人不同。 此外，脂肪組織目前被認為是另一個內分泌的器官，它的主要功能室儲存三酸甘油脂，研究顯示脂肪介質(adipokine)以及細胞介質會調控脂肪的分布、胰島素抗性以及發炎反應，過多的脂肪介質可能會導致過多的脂肪組織堆積，過高的三酸甘油酯進而引發系統性的發炎反應，然後增加妊娠併發症的風險，當然也增加了日後發生心血管疾病及第二型糖尿病的機率。 此研究計劃的目的即在於(1)找出「妊娠期代謝症候群」的診斷標準，並檢視其與妊娠併發症發生率的相關性 (2) 期望在第一孕期就能找到脂肪介質、細胞介質以及異常DNA甲基化的生物指標 (3) 在第一孕期就能找出危險因子用以篩檢高危險群患者，提早治療或預防，改善各種妊娠併發症的預後。 我們在第一年的計劃中將會以迴歸分析，找出「妊娠期代謝症候群」的診斷標準，第二年及第三年將會利用第一孕期的檢體找出在妊娠代謝症候群孕婦血中脂肪介質、細胞介質以及異常DNA甲基化的生物指標，第四年的計劃將更進一步直接檢視孕婦皮下脂肪的這些生物指標，希望能找出妊娠糖尿病/妊娠高血壓/子癲前症等疾病的相關致病機轉。 此計畫不僅僅提出了全新的妊娠期代謝症候群概念，也透過檢視脂肪介質、細胞介質以及DNA甲基化等生物指標來驗證疾病的病態生理變化，這樣的嶄新的概念或可提供妊娠併發症篩檢、診斷或者病因研究的新里程碑。<br> Abstract: The metabolic syndrome (MetS), which represents a cluster or grouping of specific clinical abnormalities that appear to be linked together, has become a household phrase, and a subject of enormous interest. CVD and T2DM regarded as a major outcome of MetS. Pregnancy disorders, including hypertensive disorder of pregnancy (HDP), preeclampsia(PE) and gestational diabetes mellitus (GDM) are risk factors for CVD and T2DM. Evidence illustrated that the presence of MetS during the early gestation is an independent risk factor for the development pregnancy disorders. Metabolic risk factors, including increasing BP, increasing pre-BMI, increasing FPG, increasing TG, impart much greater risk for the development of pregnancy disorders, and subsequent CVD and T2DM. Pregnancy is a unique metabolic and cardiovascular stress and is also a dynamic process associated with significant physiological changes in the cardiovascular system. Therefore, the value of metabolic risk factors will be at a totally different situation, which might be much lower than the diagnose criteria of MetS. Therefore, we propose a new concept of “gestational metabolic syndrome (GMetS)”, which is a constellation of interrelated risk factors of metabolic origin—metabolic risk factors during pregnancy—that appear to directly promote the development of pregnancy disorders. In the other hand, adipose tissue has been recognized as an active endocrine organ in addition to its role as the main storage depots for triglyceride(TG). Adipokines and cytokines contribute to the regulation of fat distribution, insulin sensitivity, and inflammation. Systemic inflammation caused by excessive adipose tissues mediated by adipocytokines associated with impaired TG storage in pregnant women superimposes an additional risk of developing HDP, PE, GDM, and progression to T2DM and CVD. The aims of the project will examine the maternal circulating concentrations of key adipokines and cytokines between the GMetS group and non- GMetS. Furthermore, we hypothesized that these cadipocytokine changes are mediated by dysregulated DNA methylatio, which then lead to HDP/PE/GDM. The role of DNA methylation as a potential modulator and future predictor of human disease has been the focus of recent studies investigating the development of gestational complications, including GDM and HDP/PE. The difference of the profile between the tissues will guide us the possible pathway from maternal to fetus. It is very likely that a comprehensive endocrine network and metabolic homeostasis could be established in the foreseeable future. Such a blueprint of maternal and fetal crosstalk would have far-reaching impact on the development of effective therapies against pregnancy disorders.代謝症候群/妊娠期代謝症候群/糖尿病/高血壓/子癲前症/脂肪介質/細胞介質/甲基化Metabolic syndrome/Gestational metabolic syndrome/diabetes mellitus/hypertension/preeclampsia/adipokine/cytokine/DNA methylation