本文選題：2型糖尿病 + 葡萄糖耐量試驗(yàn)��； 參考：《華中科技大學(xué)》2016年碩士論文

【摘要】：目的:探索初診2型糖尿病患者胰島功能與空腹血糖水平的關(guān)系以及可能與其獨(dú)立相關(guān)的因素。方法:收集2013年至2015年我院內(nèi)分泌科門診或住院的初診2型糖尿病患者,按照FPG水平將患者分為1組(FPG7mmol/l)、2組(7mmol/l≤FPG8.2mmol/l)、3組(8.2mmol/l≤FPG11.1mmol/l)、4組(11.1mmol/l≤FPG),所有患者均行口服葡萄糖耐量(OGTT)及胰島素釋放(IRT)試驗(yàn)。計(jì)算HOMA-IR、HOMA-β,糖負(fù)荷后30min胰島素和葡萄糖增加的比值(ΔI30/ΔG30)、胰島素曲線下面積AUCI,各組相關(guān)結(jié)果進(jìn)行統(tǒng)計(jì)學(xué)分析。記錄年齡、性別、血壓、體重指數(shù)(BMI)以及Hb A1c、TC、TG、LDL-C、HDL-C、肌酐(Cr)等指標(biāo),建立多重線性回歸分析模型探索胰島β細(xì)胞功能的獨(dú)立相關(guān)因素及各因素與胰島功能的相關(guān)強(qiáng)度。用EPIDATA軟件進(jìn)行數(shù)據(jù)錄入,spss20.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,正態(tài)分布資料以均數(shù)±方差(?x±s)表示,多組計(jì)量資料比較用單因素方差分析,建立多重線性回歸分析模型探索胰島β細(xì)胞功能獨(dú)立相關(guān)因素,P值小于0.05被認(rèn)為具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、共收集初診T2DM患者176例,各組性別構(gòu)成、收縮壓、舒張壓無顯著差異,各組總膽固醇、肌酐無顯著差異。FPG越高的組,平均年齡越大,甘油三脂、LDL越高,HDL-C越低。1~3組BMI無顯著差異,4組BMI均值較其他三組明顯下降。2、各組FIns、Fc、AUCI比較,相鄰兩組差異無統(tǒng)計(jì)學(xué)意義,其余各組間比較有顯著差異。HOMA-β3組與4組比較無明顯差異,其余各組兩兩比較有顯著差異。隨著FPG升高,FINS、Fc、HOMA-β、AUCI逐漸下降。3、HOMA-IR 1、2、3組間兩兩比較差異無統(tǒng)計(jì)學(xué)意義,4組與1、2、3組分別比較有顯著差異。隨著FPG升高,HOMA-IR有逐漸增強(qiáng)的趨勢(shì)。ΔI 30/ΔG30均值2組1組3組4組,隨著FPG升高,胰島素早相分泌量有逐漸升高然后下降的趨勢(shì),但組間兩兩比較差異無統(tǒng)計(jì)學(xué)意義。4、各組AUC曲線下面積1組2組3組4組。1組胰島素分泌高峰延遲,胰島素早相、晚相分泌明顯高于其他組。2組胰島素分泌高峰延遲,胰島素早相分泌量沒有明顯下降,晚相分泌量略有減少。3組胰島素早相分泌和晚相分泌均明顯下降,分泌高峰延遲,峰值不明顯。4組呈現(xiàn)胰島素分泌的低平曲線,早相分泌及晚相分泌明顯下降,無胰島素分泌高峰。5、線性回歸分析示年齡、Hb A1c、甘油三脂、LDL-C、FPG、2h PG、HOMA-IR與HOMA-β顯著負(fù)相關(guān),HDL-C、FIns與HOMA-β顯著正相關(guān)。年齡、FIns、HOMA-IR為HOMA-β獨(dú)立相關(guān)因素。年齡、甘油三脂、LDL-C、FIns、FPG、2h PG與HOMA-IR顯著正相關(guān),HDL-C與HOMA-IR顯著負(fù)相關(guān)。FIns、FPG、甘油三脂為HOMA-IR獨(dú)立相關(guān)因素。結(jié)論:2型糖尿病發(fā)病有年輕化、高發(fā)化趨勢(shì),應(yīng)加強(qiáng)2型糖尿病高危人群的篩查。FPG是評(píng)估胰島功能的簡易、經(jīng)濟(jì)指標(biāo),對(duì)初步評(píng)價(jià)患者胰島功能、指導(dǎo)臨床治療具有重要意義,初診FPG越高的患者,其基礎(chǔ)和總體胰島素分泌功能越差。FPG 8.2mmol/l為胰島素第一相分泌的轉(zhuǎn)折點(diǎn),FPG8.2mmol/l時(shí)胰島素第一相分泌代償性增加,FPG8.2mmol/l時(shí),胰島素第一相分泌下降。FPG11.1mmol/l為胰島素抵抗的轉(zhuǎn)折點(diǎn),FPG11.1mmol/l時(shí)胰島素抵抗驟然加重。年齡、FIns、HOMA-IR為胰島素分泌功能的獨(dú)立相關(guān)因素;FIns、FPG、甘油三脂為HOMA-IR的獨(dú)立相關(guān)因素。嚴(yán)重高血糖使BMI與胰島功能的相關(guān)性減弱。FIns可能是一個(gè)評(píng)價(jià)胰島功能較FPG更準(zhǔn)確的指標(biāo)。同時(shí),糖脂代謝存在相互影響,因此T2DM的治療應(yīng)提倡綜合管理,控制血糖的同時(shí)積極控制血脂,尤其是LDL-C和HDL-C達(dá)標(biāo)。2型糖尿病患者在其診斷之初,胰島素基礎(chǔ)及總體分泌功能已嚴(yán)重受損,特別是FPG≥11.1mmol/l的患者,對(duì)此類患者行早期胰島素強(qiáng)化治療,迅速降低血糖,阻斷“糖毒性”對(duì)胰島β細(xì)胞的進(jìn)一步損傷,保護(hù)殘余胰島功能,可能會(huì)有較大的獲益。目的:探討不同胰島素干預(yù)方案對(duì)初診2型糖尿病患者胰島β細(xì)胞功能的影響。方法:選取2013年至2015年我院內(nèi)分泌科門診或住院,FPG≥11.1mmol/l或Hb A1c9%,且自愿接受胰島素治療的初診2型糖尿病患者,將患者按照入選先后順序編號(hào),采用隨機(jī)數(shù)字表法,隨機(jī)歸入預(yù)混胰島素類似物每日2次注射組或基礎(chǔ)+餐時(shí)胰島素每日4次注射組或基礎(chǔ)胰島素+口服降糖藥組,隨訪半年,教育患者進(jìn)行日常空腹和餐后2h血糖自我監(jiān)測(cè)并記錄低血糖發(fā)生次數(shù),每三月監(jiān)測(cè)一次Hb A1c,半年復(fù)查OGTT+IRT試驗(yàn),檢測(cè)不同胰島素治療方案血糖及Hb A1C下降程度、血糖控制達(dá)標(biāo)時(shí)間、糖化血紅蛋白達(dá)標(biāo)比率、最大胰島素用量、低血糖發(fā)生次數(shù)等指標(biāo)。采取前后自身對(duì)照及組間比較,依據(jù)兩次OGTT+IRT結(jié)果,探索不同胰島素干預(yù)方案改善胰島β細(xì)胞功能的差異,尤其是對(duì)胰島素第一相分泌的影響。觀察數(shù)據(jù)包括FPG、2h PG、FIns、Fc、Hb A1c、HOMA-IR、HOMA-β、ΔI30/ΔG30、AUCI。用EPIDATA軟件進(jìn)行數(shù)據(jù)錄入,spss20.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,正態(tài)分布資料以均數(shù)±方差(?x±s)表示,用單因素方差分析進(jìn)行多組計(jì)量資料的比較,采用配對(duì)t檢驗(yàn)進(jìn)行治療前后數(shù)據(jù)比較,P0.05被認(rèn)為具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、選取重癥初診2型糖尿病患者共30例,共有27例完成隨訪,不同干預(yù)方式組性別構(gòu)成、年齡、BMI、Hb A1c、甘油三脂、LDL-C、HDL-C無顯著差異。治療后24周FPG、2h PG、Hb A1c、HOMA-IR顯著下降,FIns、Fc、HOMA-β、ΔI30/ΔG30、AUCI顯著增加,具有統(tǒng)計(jì)學(xué)意義。繪制Pre組和Aft組AUC曲線,治療后胰島素總體分泌量明顯增加,胰島素分泌峰值升高,胰島素第一相分泌明顯增加。2、各組治療前后Hb A1c、FPG、2h PG、FIns、Fc、ΔI30/ΔG30、AUCI、HOMA-IR、HOMA-β差值比較,基礎(chǔ)胰島素+口服藥物組與基礎(chǔ)+餐時(shí)胰島素組間Δ(ΔI30/ΔG30)差異有統(tǒng)計(jì)學(xué)意義,其余指標(biāo)組間比較均無統(tǒng)計(jì)學(xué)意義。3、隨訪24周,所有患者Hb A1c平均下降2.58%,不同干預(yù)方式組降低Hb A1c的能力無明顯差異。所有患者體重均明顯增加,其中基礎(chǔ)胰島素+口服降糖藥物組體重平均增加1.8kg,預(yù)混胰島素組體重平均增加2.6kg,基礎(chǔ)+餐時(shí)胰島素組體重平均增加3.1kg。低血糖評(píng)分,基礎(chǔ)胰島素+口服藥物組最低,基礎(chǔ)+餐時(shí)胰島素組明顯高于基礎(chǔ)胰島素+口服藥物組,預(yù)混胰島素組最高并有一例患者曾發(fā)生夜間嚴(yán)重低血糖。4、預(yù)混胰島素組控制血糖達(dá)標(biāo)時(shí)間最長,24周Hb A1c個(gè)體化目標(biāo)達(dá)標(biāo)率、無低血糖Hb A1c個(gè)體化目標(biāo)達(dá)標(biāo)率最低;基礎(chǔ)胰島素+口服藥物組最大胰島素用量最少,24周無低血糖Hb A1c個(gè)體化目標(biāo)達(dá)標(biāo)率最高;基礎(chǔ)+餐時(shí)胰島素組控制血糖達(dá)標(biāo)時(shí)間最短,胰島素用量最大,24周Hb A1c個(gè)體化目標(biāo)達(dá)標(biāo)率最高。結(jié)論:綜上所述,初診T2DM患者行胰島素治療均可明顯改善胰島素抵抗和胰島素分泌功能,尤其是胰島素第一相分泌功能,不同胰島素干預(yù)方式改善胰島素抵抗和胰島素總體分泌功能的能力并無差別,但基礎(chǔ)+餐時(shí)胰島素方案改善胰島素第一相分泌能力的功能較基礎(chǔ)+口服藥方式更好。對(duì)具體的患者,以改善胰島素抵抗為主還是以改善胰島β細(xì)胞分泌功能為主存在個(gè)體差異,可能與遺傳背景或血糖惡化的環(huán)境因素相關(guān)。隨訪24周,所有患者Hb A1c平均下降2.58%,此數(shù)據(jù)較既往研究Hb A1c下降1.5%~2.1%的結(jié)論明顯升高,考慮與入選人群基礎(chǔ)Hb A1c較高、且樣本量小有關(guān)。不同治療方案的Hb A1c改善程度并無差別。預(yù)混胰島素方案因其低血糖發(fā)生率高,且有嚴(yán)重低血糖風(fēng)險(xiǎn),降低患者治療滿意度和依從性,對(duì)于生活不規(guī)律、依從性及其自我管理能力差的患者不推薦此治療方式�；A(chǔ)胰島素+口服降糖藥物組低血糖發(fā)生率低、體重增加少,是一種安全有效的起始胰島素治療方式,但控制血糖和Hb A1c達(dá)標(biāo)時(shí)間長,可能不適用于初診FPG嚴(yán)重升高、胰島素抵抗重的患者�；A(chǔ)+餐時(shí)胰島素治療方案可迅速控制血糖、Hb A1c達(dá)標(biāo),對(duì)于初診FPG較高的患者適用,但注射次數(shù)多降低患者的接受程度,且體重增加明顯、低血糖發(fā)生風(fēng)險(xiǎn)較高,控制血糖平穩(wěn)后逐漸減少胰島素劑量或更改為基礎(chǔ)胰島素+口服藥物方案可能更合適�？偠灾�,胰島素干預(yù)方案的選擇應(yīng)充分考慮機(jī)體異質(zhì)性,制定個(gè)體化治療方案。
[Abstract]:Objective: To explore the relationship between pancreatic islet function and fasting blood glucose level in newly diagnosed type 2 diabetic patients and the factors that may be related to their independence. Methods: the patients with type 2 diabetes in the Department of endocrinology of our hospital from 2013 to 2015 were collected, and the patients were divided into 1 groups (FPG7mmol/l) according to the FPG level, group 2 (7mmol/l < FPG8.2mmol/l), and 3 groups (8.2mmo L/l < < FPG11.1mmol/l), 4 groups (11.1mmol/l < FPG), all patients were treated with oral glucose tolerance (OGTT) and insulin release (IRT) test. The ratio of HOMA-IR, HOMA- beta, the ratio of 30min insulin to glucose after sugar load (delta I30/ Delta G30), the area AUCI under insulin curve, statistical analysis of the related results of each group. Blood pressure, body mass index (BMI) and Hb A1c, TC, TG, LDL-C, HDL-C, creatinine (Cr) and so on, establish the multiple linear regression analysis model to explore the independent factors of islet beta cell function and the correlation between the factors and the islet function. The data are recorded with EPIDATA software, the spss20.0 statistics software is statistically analyzed, normal distribution data are used. The mean variance (? X + s) indicated that the multiple linear regression analysis was used to establish a multiple linear regression analysis model to explore the independent factors of islet beta cell function. The P value was less than 0.05 and was considered to be statistically significant. Results: 1, 176 cases of primary T2DM were collected, and there was no significant difference in sex composition, systolic pressure and diastolic pressure in each group. There was no significant difference in total cholesterol and creatinine in the group with higher.FPG, the greater the average age, the higher the glycerol three, the higher the LDL, the lower the BMI in the.1~3 group, but the BMI mean of the 4 groups was significantly lower than that of the other three groups. There was no significant difference between the groups of FIns, Fc and AUCI in each group, and there was a significant difference between the.HOMA- beta 3 groups and the 4 groups in the other groups. There was no significant difference in the 22 other groups. With the increase of FPG, FINS, Fc, HOMA- beta and AUCI gradually decreased.3, and there was no significant difference between the 22 groups of HOMA-IR 1,2,3 groups. The 4 groups were significantly different from the 1,2,3 groups. As FPG increased, HOMA-IR had a trend to increase gradually. PG increased, the early secretion of insulin increased and then decreased, but there was no significant difference between 22 groups, but there was no statistically significant difference between the groups of 1 groups and 2 groups under the AUC curve. The insulin secretion peak was delayed in the 3 groups, 3 groups and 4 groups, and the early phase and late secretion of insulin were significantly higher than those of the other group.2 group. There was no obvious decrease in the secretion of early phase and late secretion of insulin in.3 group, the secretion peak was delayed, the peak was delayed, the peak was not obvious in the.4 group, the early secretory and late secretory decreased obviously, the insulin secretion peak was.5, the linear regression analysis showed age, Hb A1c, glycerin three fat, LDL-C FPG, 2h PG, HOMA-IR and HOMA- beta are negatively correlated, HDL-C and FIns are positively correlated with HOMA- beta. Age, FIns, HOMA-IR are HOMA- beta independent correlation factors. Age, glycerol three fat, LDL-C, three fat are independent related factors. Conclusion: type 2 diabetes mellitus The disease has the tendency of young and high incidence. The screening of.FPG in the high-risk group of type 2 diabetes should be a simple and easy way to evaluate the function of islet. The economic index is of great significance to the preliminary evaluation of the function of the islet and guiding clinical treatment. The more patients with higher FPG at first visit, the less.FPG 8.2mmol/l is the first phase of insulin in the base and the overall secretion function of islet. At the turning point of the secretion, the first phase of insulin secretion increased compensatory at FPG8.2mmol/l, when FPG8.2mmol/l, the insulin first secretory decreased.FPG11.1mmol/l as the turning point of insulin resistance, and the insulin resistance suddenly aggravated when FPG11.1mmol/l. Age, FIns, HOMA-IR were independent factors of insulin secreting function; FIns, FPG, glycerol three fat were H The independent related factors of OMA-IR. Severe hyperglycemia may weaken the correlation between BMI and islet function..FIns may be a more accurate indicator of islet function than FPG. At the same time, there is a mutual influence on glycemic metabolism. Therefore, the treatment of T2DM should promote comprehensive management, control blood glucose and control blood lipids, especially the LDL-C and HDL-C standard.2 type. At the beginning of the diagnosis of diabetes, the insulin base and the overall secretory function of the patients have been severely damaged, especially in patients with FPG > 11.1mmol/l. The early intensive insulin therapy for such patients, the rapid reduction of blood sugar, the interruption of the further damage of the "sugar toxicity" to the islet beta cells and the protection of the residual islet function may have great benefit. Objective: To investigate the effect of different insulin intervention programs on pancreatic islet beta cell function in patients with newly diagnosed type 2 diabetes. Methods: from 2013 to 2015, the patients with type 2 diabetes, FPG more than 11.1mmol/l or Hb A1c9%, who were voluntarily accepted by insulin, were selected in the Department of endocrinology of our hospital. The patients were numbered according to the sequence of admission and were randomly selected. The digital table method was randomly assigned to a daily 2 injection group of premixed insulin analogues or 4 times daily insulin injection group or basal insulin + oral hypoglycemic group. The patients were followed up for half a year. The patients were monitored for daily fasting and postprandial 2H blood glucose self-monitoring and recorded hypoglycemia, and each March was monitored at a Hb A1c, and OGTT+I was reviewed for half a year. RT test was used to detect the decrease of blood sugar and Hb A1C, the time of blood glucose control, the standard of glycemic hemoglobin, the maximum insulin dosage, the frequency of hypoglycemia, and so on, to explore the different insulin intervention programs to improve the islet beta cells according to the two OGTT+IRT results before and after the comparison. The difference in function, especially the effect on the secretion of insulin first phase. The observation data include FPG, 2h PG, FIns, Fc, Hb A1c, HOMA-IR, HOMA- beta, and delta I30/ Delta G30. Comparison of group measurement data, using paired t test to compare the data before and after treatment, P0.05 was considered to have statistical significance. Results: 1, 30 cases of type 2 diabetic patients with severe initial diagnosis were selected, and 27 cases were followed up. There were no significant differences in sex composition, age, BMI, Hb A1c, glycerin three fat, LDL-C, HDL-C in different intervention groups. 24 weeks after treatment, FPG 2H PG, Hb A1c, HOMA-IR decreased significantly, FIns, Fc, HOMA- beta, Delta I30/ Delta G30, AUCI significantly increased, and had statistical significance. The difference of AUCI, HOMA-IR and HOMA- beta was statistically significant between basal insulin + oral medication group and basal + meal insulin group Delta (delta I30/ Delta G30), and there was no statistically significant difference between the rest of the groups and.3. All patients were followed up for 24 weeks, and the average Hb A1c decreased by 2.58%. There was no significant difference in the ability to reduce Hb A1c in the intervention group. The weight of the group increased significantly, the average weight of the basal insulin + oral hypoglycemic drug group increased by 1.8kg, the average weight of the premixed insulin group increased by 2.6kg, the average weight of the basal + meal insulin group increased by 3.1kg. low blood sugar score, the basal insulin + oral medicine group was the lowest, and the basal + time insulin group was significantly higher than the basic insulin + oral administration. In the group, the premixed insulin group was the highest and there was a patient with severe hypoglycemia.4 at night, the premixed insulin group had the longest blood glucose control time, 24 weeks Hb A1c individualized target target rate, the low blood sugar Hb A1c individualized target target rate was the lowest, the basic insulin + oral medicine group had the least amount of insulin and no hypoglycemic Hb A1c. The rate of individualized target was the highest, the insulin group was the shortest, the insulin dosage was the shortest, the insulin dosage was the highest, the 24 week Hb A1c individualized target reached the highest standard rate. Conclusion: In conclusion, the insulin treatment in the first diagnosis T2DM patients can obviously improve the insulin resistance and islet secretion function, especially the first phase secreting work of insulin. Yes, there is no difference in the ability of insulin intervention to improve insulin resistance and the overall secretory function of insulin, but the function of the basic + meal insulin program to improve the insulin first secretory ability is better than that in the basic + oral administration. To the specific patients, the improvement of insulin resistance is mainly to improve the islet beta cell secretory work. The individual differences could be related to the environmental factors of genetic background or blood glucose deterioration. The average Hb A1c decreased by 2.58% in all patients after 24 weeks of follow-up. This data was significantly higher than the previous study of Hb A1c decreasing 1.5%~2.1%. The higher Hb A1c and smaller sample size of the selected population were related. The Hb A1c improvement of different treatments. There is no difference in degree. The premixed insulin regimen is high in hypoglycemia, and has a severe hypoglycemia risk, lower patient satisfaction and compliance. Patients with poor life, compliance, and poor self management are not recommended for this treatment. The incidence of hypoglycemia in the basic insulin + oral hypoglycemic group is low, and the weight gain is less. It is a safe and effective way of starting insulin treatment, but the control of blood sugar and the long time of Hb A1c may not be suitable for patients with severe early diagnosis of FPG and heavy insulin resistance. Basic + meal insulin therapy can quickly control blood sugar, Hb A1c reaches the standard, it is suitable for patients with higher initial diagnosis of FPG, but the number of injections reduces the patient more. In a word, the choice of insulin intervention should take full account of the heterogeneity of the body and make individualized treatment plans.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R587.1

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