2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647976摘要：計畫背景與目的：妊娠糖尿病會同時影響媽媽與新生兒的健康，造成許多週產期的異常並增加媽媽未來罹患糖尿病的機會。妊娠糖尿病的診斷標準經過多次修正，如果依照最新的標準來診斷，盛行率高達 17.8%，影響許多孕婦。過去的標準大多依據西方人的研究，然而在我們回顧性研究的的初步結果顯示，台灣孕婦血糖與周產期異常的關係與西方人不同。因此，本研究的第一個目的，為建立前瞻性的妊娠糖尿病世代，以找出適合東方人妊娠糖尿病診斷的標準。此外，目前利用葡萄糖耐糖試驗來診斷妊娠糖尿病，既不方便，成本也高。雖然在非懷孕的成人，研究指出可以利用 hemoglobin A1c來減少葡萄糖耐糖試驗，然而這個方法並不適用於孕婦。本研究的第二個目的，將利用本實驗室建立的方法，測定可代表 2-4週平均血糖的糖化白蛋白，並研究糖化白蛋白是否可用於診斷妊娠糖尿病，並減少葡萄糖耐糖試驗的需求，以改善診斷流程。除此之外，本研究的第三個目的，將利用代謝體方法，以 global profiling的方式同時測定血中 380種代謝產物，尋找可預測與診斷妊娠糖尿病的小分子生物標記，，並可在進一步的細胞或動物實驗探討其機轉。同時也將以 targeted metabolomics的方式，測定文獻中發表過的代謝物，並評估這些代謝物應用於臨床的表現。 研究設計與方法：本計畫將進行三年，第一年與第二年採用縱斷式世代研究法收集妊娠糖尿病的世代，預計收錄 1000 人。妊娠糖尿病將採用 IADPSG的篩檢方式，於第一次產檢測定血糖，以排除未診斷的糖尿病並診斷部分妊娠糖尿病，並於 24-28週時進行葡萄糖耐糖試驗以確診妊娠糖尿病。此外，將記錄懷孕與生產過程，媽媽與新生兒的健康狀況，以及所有會影響妊娠糖尿病與周產期併發症的危險因子。第二年與第三年，進行血中糖化白蛋白與代謝體的測定，之後進行統計分析。糖化白蛋白將利用酵素法測定，並以標準曲線回推濃度與比值。代謝體將以 LC-QTOF MS及 GC-TOF MS測定。血糖與周產期併發症的關係，將以曲線圖及邏輯式迴歸分析，同時調整相關危險因子。之後將透過地毯式搜索，分析不同切點周產期併發症的關係，以決定適合東方人的切點，再以ROC curve分析切點的好壞。針對糖化白蛋白與代謝體，跟周產期併發症的關係，將以邏輯式迴歸分析造成疾病的機會，同時調整相關危險因子。接著將地毯式的探索不同的切點用於預測周產期併發症，以及診斷妊娠糖尿病的表現，以了解糖化白蛋白與代謝體是否可用於診斷妊娠糖尿病。<br> Abstract: Objectives: Gestational diabetes is a disease of two generations, affecting both the pregnant women and her babies. Gestational diabetes increases the risk of perinatal adverse outcomes and the incidence of diabetes after delivery. The diagnosis of gestational diabetes has revised several times. According to the updated criteria, the prevalence of gestational diabetes is high (17.8%). The diagnostic cutoffs are based on the studies with most of the study subjects to be Caucasians. However, our preliminary results from a retrospective study showed different relationships between plasma glucose and perinatal outcomes in women in Taiwan, compared with the findings from Caucasians. Therefore, the specific aim 1 in this study is to establish a cohort for gestational diabetes, in order to find cutoffs suitable for Asians. Besides, oral glucose tolerance tests are used in the diagnosis of gestational diabetes. However, it is inconvenient and costly. In non-pregnant adults, we have shown that hemoglobin A1c can reduce the need of oral glucose tolerance tests. Nonetheless, it is not useful in pregnant women. We have established an assay to measure serum glycated albumin, which stands for the average plasma glucose in the past 2-4 weeks. The specific aim 2 in this study, is to evaluate if glycated albumin can be used to diagnose gestational diabetes, and if glycated albumin can reduce the need of oral glucose tolerance tests. Moreover, we will measure blood metabolome in these pregnant women by global profiling metabolomic methods, which includes 380 metabolites. We will search for metabolites which can predict or diagnose gestational diabetes. The findings will lead to further studies on the pathogenesis of these metabolites. Besides, we will measure metabolites ever reported in the literature using targeted metabolomics approach. Their performance to diagnose and predict gestational diabetes will be evaluate. Research design and methods: This project will be completed in 3 years. In the first two years, we will recruit 1000 pregnant women to establish a cohort of gestational diabetes. Gestational diabetes will be diagnosed according to the recommendations by the IADPSG. Fasting plasma glucose will be measured at first visit. At 24-28 weeks, oral glucose tolerance tests will be done. Besides, we will record all the perinatal outcomes and potential confounders for gestational diabetes and perinatal adverse outcomes. In the second and third year, we will measure serum glycated albumin and metabolome, followed by statistic analyses. Glycated albumin will be measured by an enzymatic assay. A standard curve will be created to estimate the concentrations and percentages of glycated albumin in the samples. Metabolome will be measured by LC-QTOP MS and GC-TOP MS. The relationship between plasma glucose and perinatal adverse outcomes will be analyzed by scatter plots and logistic regression analyses adjusting for confounders. A detailed search will be performed to analyze the effect of different cutoffs on the prediction ability of perinatal outcomes, in order to develop cutoffs suitable for Asians. The relationships among glycated albumin, metabolome, and perinatal adverse outcomes will be analyzed by logistic regression, adjusting for confounders. A search for different cutoffs will be done to evaluate if glycated albumin and metabolome can be used to diagnose or improve the diagnosis of gestational diabetes.計畫背景與目的：妊娠糖尿病會同時影響媽媽與新生兒的健康，造成許多週產期的異常 並增加媽媽未來罹患糖尿病的機會。妊娠糖尿病的診斷標準經過多次修正，如果依照最 新的標準來診斷，盛行率高達 17.8%，影響許多孕婦。過去的標準大多依據西方人的研 究，然而在我們回顧性研究的的初步結果顯示，台灣孕婦血糖與周產期異常的關係與西 方人不同。因此，本研究的第一個目的，為建立前瞻性的妊娠糖尿病世代，以找出適合 東方人妊娠糖尿病診斷的標準。此外，目前利用葡萄糖耐糖試驗來診斷妊娠糖尿病，既 不方便，成本也高。雖然在非懷孕的成人，研究指出可以利用 hemoglobin A1c來減少葡 萄糖耐糖試驗，然而這個方法並不適用於孕婦。本研究的第二個目的，將利用本實驗室 建立的方法，測定可代表 2-4週平均血糖的糖化白蛋白，並研究糖化白蛋白是否可用於 診斷妊娠糖尿病，並減少葡萄糖耐糖試驗的需求，以改善診斷流程。除此之外，本研究 的第三個目的，將利用代謝體方法，以 global profiling的方式同時測定血中 380種代謝 產物，尋找可預測與診斷妊娠糖尿病的小分子生物標記，，並可在進一步的細胞或動物 實驗探討其機轉。同時也將以 targeted metabolomics的方式，測定文獻中發表過的代謝 物，並評估這些代謝物應用於臨床的表現。 研究設計與方法：本計畫將進行三年，第一年與第二年採用縱斷式世代研究法收集妊娠 糖尿病的世代，預計收錄 1000 人。妊娠糖尿病將採用 IADPSG的篩檢方式，於第一次 產檢測定血糖，以排除未診斷的糖尿病並診斷部分妊娠糖尿病，並於 24-28週時進行葡 萄糖耐糖試驗以確診妊娠糖尿病。此外，將記錄懷孕與生產過程，媽媽與新生兒的健康 狀況，以及所有會影響妊娠糖尿病與周產期併發症的危險因子。第二年與第三年，進行 血中糖化白蛋白與代謝體的測定，之後進行統計分析。糖化白蛋白將利用酵素法測定， 並以標準曲線回推濃度與比值。代謝體將以 LC-QTOF MS及 GC-TOF MS測定。血糖與 周產期併發症的關係，將以曲線圖及邏輯式迴歸分析，同時調整相關危險因子。之後將 透過地毯式搜索，分析不同切點周產期併發症的關係，以決定適合東方人的切點，再以 ROC curve分析切點的好壞。針對糖化白蛋白與代謝體，跟周產期併發症的關係，將以 邏輯式迴歸分析造成疾病的機會，同時調整相關危險因子。接著將地毯式的探索不同的 切點用於預測周產期併發症，以及診斷妊娠糖尿病的表現，以了解糖化白蛋白與代謝體 是否可用於診斷妊娠糖尿病。Objectives: Gestational diabetes is a disease of two generations, affecting both the pregnant women and her babies. Gestational diabetes increases the risk of perinatal adverse outcomes and the incidence of diabetes after delivery. The diagnosis of gestational diabetes has revised several times. According to the updated criteria, the prevalence of gestational diabetes is high (17.8%). The diagnostic cutoffs are based on the studies with most of the study subjects to be Caucasians. However, our preliminary results from a retrospective study showed different relationships between plasma glucose and perinatal outcomes in women in Taiwan, compared with the findings from Caucasians. Therefore, the specific aim 1 in this study is to establish a cohort for gestational diabetes, in order to find cutoffs suitable for Asians. Besides, oral glucose tolerance tests are used in the diagnosis of gestational diabetes. However, it is inconvenient and costly. In non-pregnant adults, we have shown that hemoglobin A1c can reduce the need of oral glucose tolerance tests. Nonetheless, it is not useful in pregnant women. We have established an assay to measure serum glycated albumin, which stands for the average plasma glucose in the past 2-4 weeks. The specific aim 2 in this study, is to evaluate if glycated albumin can be used to diagnose gestational diabetes, and if glycated albumin can reduce the need of oral glucose tolerance tests. Moreover, we will measure blood metabolome in these pregnant women by global profiling metabolomic methods, which includes 380 metabolites. We will search for metabolites which can predict or diagnose gestational diabetes. The findings will lead to further studies on the pathogenesis of these metabolites. Besides, we will measure metabolites ever reported in the literature using targeted metabolomics approach. Their performance to diagnose and predict gestational diabetes will be evaluate. Research design and methods: This project will be completed in 3 years. In the first two years, we will recruit 1000 pregnant women to establish a cohort of gestational diabetes. Gestational diabetes will be diagnosed according to the recommendations by the IADPSG. Fasting plasma glucose will be measured at first visit. At 24-28 weeks, oral glucose tolerance tests will be done. Besides, we will record all the perinatal outcomes and potential confounders for gestational diabetes and perinatal adverse outcomes. In the second and third year, we will measure serum glycated albumin and metabolome, followed by statistic analyses. Glycated albumin will be measured by an enzymatic assay. A standard curve will be created to estimate the concentrations and percentages of glycated albumin in the samples. Metabolome will be measured by LC-QTOP MS and GC-TOP MS. The relationship between plasma glucose and perinatal adverse outcomes will be analyzed by scatter plots and logistic regression analyses adjusting for confounders. A detailed search will be performed to analyze the effect of different cutoffs on the prediction ability of perinatal outcomes, in order to develop cutoffs suitable for Asians. The relationships among glycated albumin, metabolome, and perinatal adverse outcomes will be analyzed by logistic regression, adjusting for confounders. A search for different cutoffs will be done to evaluate if glycated albumin and metabolome can be used to diagnose or improve the diagnosis of gestational diabetes.