本文選題：肥胖 + 胰島素抵抗�。� 參考：《吉林大學(xué)》2015年博士論文

【摘要】：研究背景：肥胖在全球呈蔓延趨勢(shì)，是慢性非傳染性疾病的重要危險(xiǎn)因素，威脅人類的身心健康和生命。本地區(qū)肥胖和超重流行特點(diǎn)及危險(xiǎn)因素等流行病學(xué)資料并不完善，對(duì)肥胖相關(guān)性胰島素抵抗與糖脂代謝紊亂認(rèn)識(shí)不足；另外，如何選擇有效的早期篩查肥胖和胰島素抵抗的簡(jiǎn)便方法尚有爭(zhēng)議。胰島素抵抗是多種肥胖相關(guān)性疾病的共同病理生理基礎(chǔ)，然而其發(fā)生的分子機(jī)制尚不完全明確。 研究目的：明確本地區(qū)肥胖流行現(xiàn)狀及其相關(guān)危險(xiǎn)因素；了解肥胖與糖脂代謝紊亂、心血管疾病等疾病的相關(guān)性和發(fā)生風(fēng)險(xiǎn)；分析肥胖與胰島素抵抗的相關(guān)性；評(píng)價(jià)不同體脂測(cè)量指標(biāo)篩查肥胖及其相關(guān)疾病的價(jià)值；明確本地區(qū)中老年人近年來(lái)糖尿病發(fā)病率及其相關(guān)危險(xiǎn)因素；評(píng)價(jià)不同胰島素抵抗指標(biāo)預(yù)測(cè)糖尿病發(fā)生的價(jià)值；通過(guò)基因組學(xué)的研究方法篩選脂肪組織胰島素抵抗的差異表達(dá)基因，進(jìn)而探討脂肪組織胰島素抵抗發(fā)生的可能機(jī)制及胰島素抵抗發(fā)生過(guò)程中糖脂代謝紊亂特點(diǎn)。 方法：第一部分為橫斷面調(diào)查研究，隨機(jī)抽取長(zhǎng)春市10080名40歲以上成人，進(jìn)行問(wèn)卷調(diào)查、體格檢查和實(shí)驗(yàn)室檢查，且每位調(diào)查對(duì)象均要進(jìn)行口服葡萄糖耐量試驗(yàn)；借助Epidata和Office軟件對(duì)數(shù)據(jù)進(jìn)行整理，通過(guò)PASW統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析；計(jì)算肥胖和超重患病率，進(jìn)行肥胖危險(xiǎn)因素的Logistic多元回歸分析，計(jì)算肥胖體質(zhì)指標(biāo)與糖脂代謝指標(biāo)的偏相關(guān)系數(shù)r，繪制各個(gè)體質(zhì)指標(biāo)篩查ROC曲線，計(jì)算ROC曲線下面積；第二部分為前瞻性隊(duì)列研究，從第一部分非糖尿病患者中隨機(jī)抽取2500人進(jìn)行隨訪，計(jì)算糖尿病發(fā)病率，繪制不同胰島素抵抗指標(biāo)預(yù)測(cè)糖尿病發(fā)生的ROC曲線，計(jì)算ROC曲線下面積；第三部分為基因組學(xué)研究，從Gene Expression Omnibus（GEO）數(shù)據(jù)庫(kù)中下載芯片數(shù)據(jù)，利用frozen robust multiarray analysis（fRMA）算法進(jìn)行數(shù)據(jù)背景校正、標(biāo)準(zhǔn)化和匯總，通過(guò)芯片數(shù)據(jù)顯著性分析（SAM）方法篩選出胰島素抵抗與胰島素敏感組的差異表達(dá)基因，假陽(yáng)性錯(cuò)誤率（FDR）控制在0.05水平，在Genecards數(shù)據(jù)庫(kù)中確定差異表達(dá)基因的生物學(xué)意義，繼而探討胰島素抵抗發(fā)生的可能分子機(jī)制。在各部分研究中，假設(shè)檢驗(yàn)顯著性標(biāo)準(zhǔn)α均取0.05，p0.05表示差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果：第一部分橫斷面研究實(shí)際完成調(diào)查9571人，超重者占43.20%，肥胖者占18.83%；男性超重和肥胖人群發(fā)生胰島素抵抗分別占40.9%和64.9%；女性超重和肥胖人群發(fā)生胰島素抵抗分別占49.4%和73.2%；男性和女性BMI與HOMA-IR的偏相關(guān)系數(shù)r分別為0.378和0.313；男性BMI篩查胰島素抵抗的ROC曲線下面積為0.752，女性BMI篩查胰島素抵抗的ROC曲線下面積為0.725。第二部分實(shí)際完成隨訪2297人，共隨訪6730人年，共發(fā)生糖尿病191例，糖尿病發(fā)病率為2.83人/百人年；胰島素抵抗者發(fā)生糖尿病的風(fēng)險(xiǎn)約為非胰島素抵抗者的2.2倍，超重和肥胖人群約是正常體重人群的1.7和2.3倍，血清甘油三酯邊緣升高和高甘油三酯血癥人群約是正常甘油三酯血癥人群的1.2和2.0倍，血清高密度脂蛋白膽固醇降低人群約是非高密度脂蛋白膽固醇降低人群的1.7倍；HOMA-IR，TG/HDL-C，BMI和空腹胰島素預(yù)測(cè)糖尿病發(fā)生的ROC曲線下面積分別為0.616，0.602，0.599，和0.576。第三部分共納入2項(xiàng)研究，共49例基因芯片數(shù)據(jù)標(biāo)本，篩選出差異表達(dá)基因386個(gè)，上調(diào)表達(dá)330個(gè)，差異較顯著的有IL1RN，PLA2G7和MMP9，，與慢性炎癥反應(yīng)密切相關(guān)；下調(diào)表達(dá)56個(gè)，差異較顯著的有SLC27A2，AGPAT9和ACACB，與脂肪合成密切相關(guān)。 結(jié)論：長(zhǎng)春市中老年人群是肥胖和超重的高發(fā)人群；胰島素抵抗與肥胖關(guān)系密切。BMI是中老年男性人群篩查肥胖的最佳指標(biāo)，而腰圍和腰圍身高比則是中老年女性的最佳篩查指標(biāo)。長(zhǎng)春市40歲以上成人糖尿病發(fā)病率高于其他地區(qū)研究結(jié)果；但糖尿病前期人群糖尿病發(fā)病率較低于其他地區(qū)研究結(jié)果。BMI可作為胰島素抵抗的初篩指標(biāo)，而TG/HDL-C可以作為聯(lián)合HOMA-IR來(lái)評(píng)價(jià)肥胖人群的胰島素抵抗程度并預(yù)測(cè)2型糖尿病的發(fā)生風(fēng)險(xiǎn)的另一指標(biāo)。脂肪組織胰島素抵抗發(fā)生與脂肪細(xì)胞炎癥反應(yīng)有關(guān)，炎癥細(xì)胞浸潤(rùn)及炎癥因子釋放增加抑制脂肪細(xì)胞內(nèi)胰島素信號(hào)通路。脂肪組織胰島素抵抗發(fā)生時(shí)，脂肪代謝紊亂是最主要的代謝異常表現(xiàn)，脂肪細(xì)胞內(nèi)參與脂肪合成的相關(guān)酶系基因表達(dá)下調(diào)，抑制脂肪合成。
[Abstract]:Background : The prevalence of obesity in the world is an important risk factor for chronic non - communicable diseases , threatening the physical and mental health and life of human beings . Epidemiological data such as obesity and overweight in the region and risk factors are not perfect , and there is insufficient understanding of obesity - related insulin resistance and glycolipid metabolism disorder .
In addition , it is controversial how to select a simple and effective method for early screening of obesity and insulin resistance . Insulin resistance is a common pathological basis for multiple obesity - related diseases , but its molecular mechanism is not entirely clear .

Objective : To clarify the present situation of obesity epidemic in the region and its associated risk factors .
To understand the correlation and risk of obesity and glycolipid metabolism disorders , cardiovascular diseases and other diseases ;
To analyze the correlation between obesity and insulin resistance ;
To evaluate the value of different body fat measurement indexes in screening obesity and related diseases ;
The incidence of diabetes mellitus and its associated risk factors in middle - aged and elderly people in the region were identified .
To evaluate the value of different insulin resistance indices in predicting the onset of diabetes ;
The differential expression of insulin resistance in adipose tissue was screened by genomics , and the possible mechanism of insulin resistance in adipose tissue and the characteristics of glycolipid metabolism in insulin resistance were discussed .

Methods : The first part was divided into the cross - sectional survey , and 100 80 adults over 40 years of age were randomly selected to carry out questionnaire , physical examination and laboratory examination , and the oral glucose tolerance test was carried out in each survey subject ;
The data is collated with Epidata and Office software , and the data is analyzed by PASW statistical software ;
To calculate the prevalence of obesity and overweight , Logistic regression analysis of risk factors of obesity was carried out to calculate the correlation coefficient between obesity constitution index and glycolipid metabolism index ( r ) , and the ROC curve of each physical fitness index was drawn , and the area under ROC curve was calculated ;
The second part is prospective cohort study , and 2500 people are randomly selected from the first part of non - diabetic patients for follow - up , the incidence of diabetes is calculated , different insulin resistance indexes are drawn to predict the ROC curve of diabetes , and the area under ROC curve is calculated ;
In the third part , the data was downloaded from the GeneExpression Omnibus ( GEO ) database , and the data background correction , standardization and summarization were carried out by using the frozen robust multiarray analysis ( fRMA ) algorithm . The differential expression gene of insulin resistance and insulin sensitive group was screened by means of a chip data significance analysis ( SAM ) method .

Results : The first part of cross - sectional study actually completed the investigation of 9571 , overweight accounted for 43.20 % , and obesity accounted for 18.83 % ;
Insulin resistance in overweight and obese men accounted for 40.9 % and 64.9 % , respectively .
Insulin resistance in overweight and obese women accounted for 49.4 % and 73.2 % , respectively .
The correlation coefficient r between BMI of male and female was 0.378 and 0.313 , respectively .
The area of ROC curve for BMI screening insulin resistance was 0.752 , and the area under ROC curve of BMI screening insulin resistance was 0.725 . 2297 patients were followed up for 6730 years .
The risk of insulin resistance was 2.2 times that of non - insulin resistance , overweight and obese people were 1.7 and 2.3 times that of normal body weight group , serum triglyceride edge and high triglyceride were 1.2 and 2.0 times that of normal triglyceride group , and that of high density lipoprotein cholesterol in serum was 1.7 times lower than that of non - high density lipoprotein cholesterol .
The ROC curves under ROC curves were 0.616 , 0.602 , 0.599 and 0.576 , respectively .
The expression of SLC27A2 , AGPAT9 and ACACB was significantly correlated with fat synthesis .

Conclusion : The middle - aged and old people in Changchun are obese and overweight .
Insulin resistance is closely related to obesity . BMI is the best index for middle - aged and old men to screen obesity , while waist and waist height ratio is the best screening index for middle - aged and old women . The incidence of diabetes in adults over 40 years of Changchun is higher than that of other regions .
In the early stage of diabetes , the incidence of diabetes is lower than that in other regions . BMI can be used as the primary screening index of insulin resistance , and TG / HDL - C can be used as a combination of the insulin resistance of obese people and predict the risk of insulin resistance in type 2 diabetes mellitus . The fatty tissue insulin resistance is associated with inflammatory response of fat cells , inflammatory cell infiltration and inflammatory factor release increase the insulin signaling pathway in fat cells . In the event of insulin resistance , the lipid metabolism disorder is the most important metabolic abnormality , and the expression of related enzymes involved in fat synthesis is down regulated in fat cells , and fat synthesis is inhibited .
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R589.2

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本文編號(hào)：1977859