【摘要】：背景 妊娠期糖尿病(Gestational diabetes mellitus, GDM)是妊娠期首次診斷或發(fā)生的糖尿病,為妊娠期常見的并發(fā)癥之一。發(fā)病率約為8%～14%,并有逐年增高的趨勢。GDM嚴重威脅孕婦和胎兒健康,可導致巨大兒、羊水過多、自然流產(chǎn)、胎兒畸形、胎兒窘迫、死胎、死產(chǎn)、新生兒低血糖、產(chǎn)傷等。GDM其病因及發(fā)病機制目前尚未闡明,近年來的研究發(fā)現(xiàn)某些多肽分子可能參與妊娠期血糖和能量代謝,并與GDM發(fā)病有關(guān)。肥胖抑制素(Obestatin)是新近發(fā)現(xiàn)的一種多肽分子,由已知的Ghrelin基因經(jīng)過翻譯,經(jīng)不同修飾后產(chǎn)生的不同于Ghrelin的生物活性肽,廣泛存在于多種物種機體內(nèi),并在不同物種間的氨基酸組成上具有高度保守性。Obestatin廣泛分布于大腸、小腸、胃、脾、大腦皮層、胰腺及血漿內(nèi),并可能通過內(nèi)分泌、旁分泌、自分泌、遠距分泌、神經(jīng)內(nèi)分泌等多種不同途徑發(fā)揮多種調(diào)節(jié)作用。最早的研究認為Obestatin具有拮抗Ghrelin的生物效應(yīng),即可減緩胃排空,抑制食欲,進而減少進食,降低體重,對抗肥胖的作用,因此Obestatin與肥胖癥、糖尿病等多種代謝疾病之間的關(guān)系受到學者的重視�，F(xiàn)有的一些研究結(jié)果表明Obestatin可促進胰島p細胞增殖、對抗細胞因子介導的胰島p細胞凋亡,并抑制外周炎癥,從而達到保護胰島β細胞,改善胰島素抵抗(insulin resistance, IR)的作用,甚至可能直接影響胰島素的分泌。鑒于Obestatin維持能量代謝、抑制凋亡等方面存在重要作用,有學者推測妊娠期間Obestatin的改變可能涉及妊娠期間能量代謝的紊亂,可能是GDM的重要發(fā)病機制之一。已有國內(nèi)外學者對Obestatin與GDM之間的關(guān)系進行了一些探索,但報道尚少,且尚無統(tǒng)一結(jié)果。 目的 通過比較GDM孕婦與正常孕婦的外周血Obestatin水平及糖、脂代謝指標,探討Obestatin與GDM的發(fā)生發(fā)展之間是否存在相關(guān)性。 方法 選取2011年4月到2012年4月在浙江大學醫(yī)學院附屬婦產(chǎn)科醫(yī)院產(chǎn)科門診定期產(chǎn)檢并住院分娩的孕婦,根據(jù)IADPSG標準診斷為GDM的孕婦37例,同期隨機選擇OGTT正常,且年齡、孕周、孕前體重指數(shù)等指標與實驗組相匹配的孕婦37例作為正常對照組,兩組孕婦均在37周～42周之間住院并抽取空腹靜脈血。測定Obestatin、空腹血糖(Fast Plasm Glucose, FPG)、空腹胰島素(Fast Insulins, Fins)、甘油三酯(Triglyceride, TG)、高密度脂蛋白(High-density lipoprotein, HDL-C)、低密度脂蛋白(Low-density lipoprotein, LDL-C)、膽固醇水平(Total Cholesterole, TC),用HOMA穩(wěn)態(tài)模型=(FPG×Fins/22.5)評估胰島素抵抗指數(shù)(HOMA-IR),比較兩組之間Obestatin水平的差異以及Obestatin與糖脂代謝指標、胰島素抵抗水平之間的關(guān)系。結(jié)果 (1)GDM組孕婦與正常對照組孕婦的年齡、孕周、產(chǎn)次、孕次、BMI、孕期體重增加方面差異無統(tǒng)計學意義(P0.05)。(2)GDM組患者空腹外周血Obstatin水平顯著高于正常對照組(分別為1151619.33μg/L和102.51±19.41μg/LP0.001); GDM組FPG. Fins. HbA1c. HOMA-IR、TG、LDL、TC均高于正常對照組(分別為5.40±0.54mmol/L,14.03±2.98mu/L,6.09±1.86%,1.94±0.38,2.06±0.48mmol/L,3.34±0.93mmol/L,5.92±2.10mmol/L和4.38±0.53mmol/L,7.76±2.80mu/L,5.13±0.87%,1.19±0.35,1.56±0.45mmol/L,2.89±0.51mmol/L,4.74±1.79mmol/L, P均0.05),而HDL水平顯著低于正常對照組(分別為1.60±0.39mmol/L和2.10±0.46mmol/L, p0.01).(3)正常對照組Obestatin與FPG (r=-0.455, P0.01)、LDL (r=-0.369, P0.05)呈負相關(guān),與Fins (r=0.394, P0.05)、TG(r=0.427, P0.05)呈正相關(guān),而GDM組Obestatin水平與Fins(r=0.337, P0.05)、HDL(r=0.365, P0.05)成正相關(guān),與HOMA-IR (r=-0.376, P0.05)、TC(r=-0.513, P0.01)呈負相關(guān)。結(jié)論 (1)Obestatin參與正常妊娠期血糖、血脂代謝調(diào)節(jié)；(2)Obestatin水平在GDM組升高,而且與血糖、血脂代謝紊亂有關(guān)；可能是針對GDM組糖脂代謝異常、胰島素抵抗情況啟動的可逆性自我保護機制之一。
[Abstract]:background
Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy. The incidence of GDM is about 8%-14% and is increasing year by year. Stillbirths, stillbirths, neonatal hypoglycemia, birth injuries, etc. The etiology and pathogenesis of GDM have not been elucidated. Recent studies have found that some polypeptide molecules may be involved in glucose and energy metabolism during pregnancy and may be related to the pathogenesis of GDM. Obestatin is widely distributed in the large intestine, small intestine, stomach, spleen, cerebral cortex, pancreas and plasma, and may be secreted by endocrine, paracrine, autocrine, and remote secretion. The earliest studies suggest that Obestatin has antagonistic biological effects on Ghrelin, which can slow gastric emptying, inhibit appetite, thereby reducing food intake, weight loss and anti-obesity. Obestatin's relationship with obesity, diabetes and other metabolic diseases has been studied. Existing studies have shown that Obestatin can promote the proliferation of pancreatic P cells, resist the apoptosis of pancreatic P cells mediated by cytokines, and inhibit peripheral inflammation, thereby protecting pancreatic beta cells, improving insulin resistance (IR), and even directly affecting insulin secretion. Some scholars speculate that the change of Obestatin during pregnancy may involve the disorder of energy metabolism during pregnancy and may be one of the important pathogenesis of GDM. Result.
objective
By comparing the levels of Obestatin in peripheral blood and glucose and lipid metabolism between GDM pregnant women and normal pregnant women, the relationship between Obestatin and the occurrence and development of GDM was explored.
Method
From April 2011 to April 2012, 37 pregnant women with GDM diagnosed according to IADPSG criteria were randomly selected as normal control group. 37 pregnant women with normal OGTT, matching age, gestational age, pre-pregnancy body mass index were selected as normal control group. Obestatin, fasting plasma glucose (FPG), fasting insulin (Fast Insulins, Fins), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), cholesterol were measured. Total Cholesterole (TC), HOMA homeostasis model = (FPG *Fins/22.5) was used to evaluate insulin resistance index (HOMA-IR). Obestatin levels were compared between the two groups and the relationship between Obestatin and glucose and lipid metabolism, insulin resistance.
(1) There was no significant difference in age, gestational age, parity, gestational age, BMI and weight gain between GDM group and normal control group (P 0.05). (2) Obstatin level in fasting peripheral blood of GDM group was significantly higher than that of normal control group (1151619.33 ug/L and 102.51 (+19.41 ug/LP0.001), FPG.Fins.HbA1c.HOMA-IR, TG, LDL, TC, etc. They were all higher than those in the normal control group (5.40 (+ 0.54 mmol/L, 14.03 (+ 2.98 mu/L, 14.03 (+ 2.98 mu/L, 6.09 (+ 1.86%, 1.94 (+ 0.38, 2.06 (+ 0.48 mmol/L, 2.06 (+) 0.48 mmol/L, 3.34 (+ 0.93 mmol/L, 5.34 (+ 0.93 mmol/L), 5.92 (+ 2.10 mmol/L) and 4.38 (+ 0.53 mmol/L), 7.76 (+ 2.80 mu/L, 2.80 mu/L, 5.13 (+ 0.87%, 5.87%, 1.19 (+ 0 The level of HDL was significantly lower than that of normal control group. Obestatin was negatively correlated with FPG (r = - 0.455, P 0.01), LDL (r = - 0.369, P 0.05), LDL (r = - 0.369, P 0.05), Fins (r = 0.394, P 0.05), TG (r = 0.427, P 0.05), FinTG (r = 0.427, P 0.05), FinFinFinTG (r = 0 0.427, P 0.05), Obestatin GDM group was positipositipositively correlwith s (r = 0.337, P 0.337, P 0.05), HDL (r = 0.365, HDL (r = 0.365, P 0.365, P 0.365, P 0.365, P 0.05), HOHOand HOMA-IR (r=-0.376, P 0.05), TC (r=-0.513, P0.01) was negatively correlated.
(1) Obestatin participates in the regulation of blood glucose and lipid metabolism in normal pregnancy; (2) Obestatin level is elevated in GDM group, and is related to the disorder of blood glucose and lipid metabolism; it may be one of the reversible self-protection mechanisms against abnormal glucose and lipid metabolism and insulin resistance in GDM group.
【學位授予單位】：浙江大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R714.256

【參考文獻】

相關(guān)期刊論文 前1條

1 姜殿林;董桂虎;徐霞;;正常妊娠婦女血脂及載脂蛋白水平的變化[J];實用臨床醫(yī)學;2006年04期

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