慢性丙型肝炎病人血糖血脂的變化及抗病毒治療對(duì)其影響
發(fā)布時(shí)間：2018-07-27 18:55
【摘要】：背景及目的：慢性丙型肝炎（CHC）與糖脂代謝紊亂相關(guān)，但其引起血清血糖及血脂譜的變化趨勢(shì)存在爭(zhēng)議；干擾素聯(lián)合利巴韋林抗HCV治療后如何影響機(jī)體糖代謝及脂代謝，目前尚無定論。本文旨在探討慢性丙型肝炎患者血糖、血脂的變化，以及普通干擾素聯(lián)合利巴韋林抗病毒治療對(duì)血脂、血糖及胰島β細(xì)胞功能指標(biāo)的影響。 方法：本實(shí)驗(yàn)分為兩部分，第一部分：從吉林大學(xué)第一醫(yī)院肝膽胰內(nèi)科2009年在吉林省某地流行病學(xué)調(diào)查中獲得的樣本中，篩選771例未經(jīng)治療的慢性丙型肝炎患者及679例健康對(duì)照人群。測(cè)定兩組人群肝功、空腹血糖(FBG)、血清總膽固醇（TC）、甘油三酯（TG）。第二部分：從上述慢性丙型肝炎患者中篩選出183例接受規(guī)范普通干擾素（IFNα-2b）聯(lián)合利巴韋林（RBV）治療者。測(cè)定治療前（0周）、治療結(jié)束（48周）及治療結(jié)束后24周（72周）時(shí)血清TC、TG、空腹胰島素（FINS）、空腹C肽（FCP），并利用HOMA穩(wěn)態(tài)模型計(jì)算各時(shí)間點(diǎn)胰島素抵抗指數(shù)（HOMA-IR）、胰島β細(xì)胞功能指數(shù)（HOMA-β）、胰島素敏感性指數(shù)（ISI）。 結(jié)果：第一部分：CHC組，血清TC水平顯著低于健康組（4.82±1.10mmol/l vs5.29±1.16，P0.0001），，TG值亦較低（1.27±0.81mmol/l vs1.80±1.19mmol/l，P0.0001）。CHC組空腹血糖（FBG）明顯高于健康組（5.77±2.23mmol/l vs5.37±1.43，P0.019）。Logistic回歸分析可知，低總膽固醇（P0.0001，OR=0.714，95%CI：0.632，0.806），低甘油三酯（P0.0001，OR=0.629，95%CI：0.542，0.730），高齡（P0.0001，OR=1.123，95%CI：1.104，1.141）為CHC獨(dú)立相關(guān)因素。 第二部分：基線血清TC及TG在SVR組與非SVR組之間無差別（TC:P=0.111；TG：P=0.261）。SVR組患者血清TC在治療結(jié)束時(shí)與基線相比較，顯著下降（4.06±1.04vs4.51±0.95mmol/l，P0.0001），隨訪24周結(jié)束時(shí)，TC上升至4.45±0.89mmol/l，與基線水平持平。非SVR組，治療過程，TC亦呈下降趨勢(shì)，48周時(shí)明顯低于基線水平（4.42±0.93mmol/l vs4.72±0.97mmol/l，P=0.010），但治療結(jié)束后24周，TC值與48周時(shí)比較無差異，仍明顯低于基線（4.39±0.78mmol/l vs4.72±0.97mmol/l，P=0.004）。 SVR組患者血清TG抗病毒治療后由基線1.18±0.47mmol/l，升至1.61±1.07mmol/l（P0.0001)，隨訪24周結(jié)束時(shí)，持續(xù)處于較高水平，與基線相比顯著差異（1.54±0.77mmol/l vs1.18±0.48mmol/l，P0.0001）。非SVR組，48周時(shí)TG較基線水平，亦明顯升高（1.70±0.95mmol/l vs1.32±0.67mmol/l，P=0.03），而隨訪過程，TG下降，72周時(shí)較48周明顯降低（1.42±0.87mmol/l vs1.70±0.95mmol/l，P=0.037），回復(fù)至基線水平（P=0.319）。 SVR組患者空腹胰島素水平在治療48周結(jié)束后，明顯下降（7.88±4.15uU/ml vs8.30±3.80uU/ml，P=0.007），空腹C肽也呈現(xiàn)相同變化趨勢(shì)（0.72±0.26nmol/l vs0.92±0.25nmol/l, P0.0001）。而非SVR組患者空腹胰島素及空腹C肽在治療前后均未出現(xiàn)明顯變化。 SVR組患者，胰島素抵抗（HOMA-IR）經(jīng)抗病毒治療后明顯改善（1.62±0.94vs2.00±1.02，P0.0001），隨訪24周，SVR組胰島素抵抗指數(shù)持續(xù)低于基線水平（1.86±1.20vs2.00±1.02，P=0.05）。同樣的，胰島素敏感性指數(shù)（ISI），治療結(jié)束時(shí)較基線明顯上升（-3.45±0.54vs-3.70±0.45，P0.0001），72周時(shí)，仍優(yōu)于基線水平（P=0.05）。而非SVR組患者，HOMA-IR在治療后亦出現(xiàn)下降，但與基線相比差異無顯著性（2.16±1.42vs2.27±1.37，P=0.281），治療結(jié)束后24周時(shí)，胰島素抵抗即回復(fù)至基線水平，而ISI在治療前后無變化。HOMA-β（β細(xì)胞功能），經(jīng)治療后，不論SVR與非SVR組，均出現(xiàn)明顯升高（P0.0001），隨訪24周，較48時(shí)下降，但仍高于基線水平（SVR:P=0.01，NSVR:P=0.08）。 Logistic回歸分析顯示，高齡（P=0.004，OR=1.072，95%CI：1.023，1.123）、高病毒載量（P0.0001，OR=2.316，95%CI：1.596，3.362），基因型為1b型（P0.0001，OR=2.016，95%CI：1.116，3.122）為病毒學(xué)應(yīng)答不佳的獨(dú)立危險(xiǎn)因素。 結(jié)論： 1、慢性丙型肝炎患者血清總膽固醇、甘油三酯低于健康人群，血糖高于健康人群，在經(jīng)抗病毒后有望恢復(fù)正常。 2、治療前血清總膽固醇、甘油三酯與病毒學(xué)應(yīng)答率無關(guān)。 3、血清總膽固醇經(jīng)干擾素治療呈現(xiàn)下降趨勢(shì)，而甘油三酯水平上升。 4、有效抗病毒治療可改善機(jī)體胰島素抵抗、高胰島素血癥及胰島β細(xì)胞功能。
[Abstract]:Background and purpose: chronic hepatitis C (CHC) is associated with glucose and lipid metabolism disorder, but the trend of blood glucose and blood lipid profiles in serum is controversial. The influence of interferon combined with ribavirin on glycometabolism and lipid metabolism after HCV treatment is not conclusive. The purpose of this study is to explore the blood glucose and blood lipid changes in chronic hepatitis C patients. And the effects of antiviral therapy combined with interferon and ribavirin on blood lipids, blood glucose and pancreatic beta cell function.
Methods: the experiment was divided into two parts. The first part: from the epidemiological survey of Jilin province in 2009, 771 cases of chronic hepatitis C and 679 healthy controls were selected from the hepatobiliary and pancreatic Department of No.1 Hospital of Jilin University. Two groups of human group liver function, fasting blood glucose (FBG), serum total cholesterol (TC) were measured. ), triglyceride (TG). Second: 183 patients were screened from the above chronic hepatitis C patients with normal interferon (IFN alpha -2b) combined with Leigh Bhave Lin (RBV). The serum TC, TG, FINS, FCP, and HOMA homeostasis were measured before treatment (0 weeks), treatment end (48 weeks) and 24 weeks (72 weeks) after the end of treatment. The insulin resistance index (HOMA-IR), islet beta cell function index (HOMA- beta) and insulin sensitivity index (ISI) at different time points were calculated by the model.
Results: the first part: in group CHC, the level of serum TC was significantly lower than that in the healthy group (4.82 + 1.10mmol/l vs5.29 + 1.16, P0.0001), and the TG value was also lower (1.27 + 0.81mmol/l vs1.80 + 1.19mmol/l, P0.0001).CHC group (FBG) was significantly higher than that of the healthy group (5.77 + 1.43. OR=0.714,95%CI:0.632,0.806), low triglyceride (P0.0001, OR=0.629,95%CI:0.542,0.730) and advanced age (P0.0001, OR=1.123,95%CI:1.104,1.141) were independent factors of CHC.
The second part: the baseline serum TC and TG were not different between the SVR group and the non SVR group (TC:P=0.111; TG:P=0.261).SVR group. The serum TC was significantly decreased (4.06 + 1.04vs4.51 + 0.95mmol/l, P0.0001) at the end of the treatment. At the end of the 24 weeks of follow-up, the TC increased to 4.45 + and was equal to the baseline level. TC also showed a downward trend, which was significantly lower than baseline (4.42 + 0.93mmol/l vs4.72 + 0.97mmol/l, P=0.010) at 48 weeks, but there was no difference between TC and 48 weeks at the end of the treatment, and still significantly lower than the baseline (4.39 + 0.78mmol/l vs4.72 + 0.97mmol/l, P=0.004).
The antiviral treatment of serum TG in group SVR was increased to 1.61 + 1.07mmol/l (P0.0001) after the baseline of 1.18 + 0.47mmol/l. At the end of the 24 week of follow-up, it continued to be at a higher level, compared with the baseline (1.54 + 0.77mmol/l vs1.18 + 0.48mmol/l, P0.0001). The non SVR group was also significantly higher than the baseline at 48 weeks (1.70 + 0.95mmol/l). L/l, P=0.03), and during the follow-up, TG decreased, and decreased significantly at 72 weeks compared with 48 weeks (1.42 + 0.87mmol/l vs1.70 + 0.95mmol/l, P=0.037), and returned to baseline (P=0.319).
The level of fasting insulin in group SVR was significantly decreased after 48 weeks of treatment (7.88 + 4.15uU/ml vs8.30 + 3.80uU/ml, P=0.007), and the same change trend was found in the fasting C peptide (0.72 + 0.26nmol/l vs0.92 + 0.25nmol/l, P0.0001), but there was no significant change in the fasting insulin and fasting C peptide in the non SVR group before and after treatment.
In group SVR, insulin resistance (HOMA-IR) improved significantly after antiviral therapy (1.62 + 0.94vs2.00 + 1.02, P0.0001), and followed up for 24 weeks. The insulin resistance index in SVR Group continued to be lower than the baseline (1.86 + 1.20vs2.00 + 1.02, P=0.05). Similarly, the insulin sensitivity index (ISI) and the baseline of treatment were significantly higher (-3.45 + 0.54vs-3.70 + 0.45). P0.0001) was still better than baseline (P=0.05) at 72 weeks. But in non SVR group, HOMA-IR was also decreased after treatment, but there was no significant difference compared with baseline (2.16 + 1.42vs2.27 + 1.37, P=0.281). At the end of the treatment, insulin resistance returned to the baseline level, and ISI had no change of.HOMA- beta (beta cell function) before and after treatment, and the treatment was treated before and after treatment. After treatment, both SVR and non SVR group increased significantly (P0.0001). After 24 weeks of follow-up, they decreased at 48, but still higher than baseline (SVR:P=0.01, NSVR:P=0.08).
Logistic regression analysis showed that the elderly (P=0.004, OR=1.072,95%CI:1.023,1.123), high viral load (P0.0001, OR=2.316,95%CI:1.596,3.362) and genotype 1b (P0.0001, OR=2.016,95%CI:1.116,3.122) were independent risk factors for virological response.
Conclusion:
1, serum total cholesterol and triglycerides in patients with chronic hepatitis C are lower than those in healthy people. Blood glucose is higher than healthy people, and is expected to return to normal after antiviral treatment.
2, serum total cholesterol and triglyceride were not correlated with virological response rate before treatment.
3, serum total cholesterol showed a downward trend after interferon treatment, while triglyceride level increased.
4, effective antiviral therapy can improve insulin resistance, hyperinsulinemia and islet beta cell function.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.63
本文編號(hào)：2148829
[Abstract]:Background and purpose: chronic hepatitis C (CHC) is associated with glucose and lipid metabolism disorder, but the trend of blood glucose and blood lipid profiles in serum is controversial. The influence of interferon combined with ribavirin on glycometabolism and lipid metabolism after HCV treatment is not conclusive. The purpose of this study is to explore the blood glucose and blood lipid changes in chronic hepatitis C patients. And the effects of antiviral therapy combined with interferon and ribavirin on blood lipids, blood glucose and pancreatic beta cell function.
Methods: the experiment was divided into two parts. The first part: from the epidemiological survey of Jilin province in 2009, 771 cases of chronic hepatitis C and 679 healthy controls were selected from the hepatobiliary and pancreatic Department of No.1 Hospital of Jilin University. Two groups of human group liver function, fasting blood glucose (FBG), serum total cholesterol (TC) were measured. ), triglyceride (TG). Second: 183 patients were screened from the above chronic hepatitis C patients with normal interferon (IFN alpha -2b) combined with Leigh Bhave Lin (RBV). The serum TC, TG, FINS, FCP, and HOMA homeostasis were measured before treatment (0 weeks), treatment end (48 weeks) and 24 weeks (72 weeks) after the end of treatment. The insulin resistance index (HOMA-IR), islet beta cell function index (HOMA- beta) and insulin sensitivity index (ISI) at different time points were calculated by the model.
Results: the first part: in group CHC, the level of serum TC was significantly lower than that in the healthy group (4.82 + 1.10mmol/l vs5.29 + 1.16, P0.0001), and the TG value was also lower (1.27 + 0.81mmol/l vs1.80 + 1.19mmol/l, P0.0001).CHC group (FBG) was significantly higher than that of the healthy group (5.77 + 1.43. OR=0.714,95%CI:0.632,0.806), low triglyceride (P0.0001, OR=0.629,95%CI:0.542,0.730) and advanced age (P0.0001, OR=1.123,95%CI:1.104,1.141) were independent factors of CHC.
The second part: the baseline serum TC and TG were not different between the SVR group and the non SVR group (TC:P=0.111; TG:P=0.261).SVR group. The serum TC was significantly decreased (4.06 + 1.04vs4.51 + 0.95mmol/l, P0.0001) at the end of the treatment. At the end of the 24 weeks of follow-up, the TC increased to 4.45 + and was equal to the baseline level. TC also showed a downward trend, which was significantly lower than baseline (4.42 + 0.93mmol/l vs4.72 + 0.97mmol/l, P=0.010) at 48 weeks, but there was no difference between TC and 48 weeks at the end of the treatment, and still significantly lower than the baseline (4.39 + 0.78mmol/l vs4.72 + 0.97mmol/l, P=0.004).
The antiviral treatment of serum TG in group SVR was increased to 1.61 + 1.07mmol/l (P0.0001) after the baseline of 1.18 + 0.47mmol/l. At the end of the 24 week of follow-up, it continued to be at a higher level, compared with the baseline (1.54 + 0.77mmol/l vs1.18 + 0.48mmol/l, P0.0001). The non SVR group was also significantly higher than the baseline at 48 weeks (1.70 + 0.95mmol/l). L/l, P=0.03), and during the follow-up, TG decreased, and decreased significantly at 72 weeks compared with 48 weeks (1.42 + 0.87mmol/l vs1.70 + 0.95mmol/l, P=0.037), and returned to baseline (P=0.319).
The level of fasting insulin in group SVR was significantly decreased after 48 weeks of treatment (7.88 + 4.15uU/ml vs8.30 + 3.80uU/ml, P=0.007), and the same change trend was found in the fasting C peptide (0.72 + 0.26nmol/l vs0.92 + 0.25nmol/l, P0.0001), but there was no significant change in the fasting insulin and fasting C peptide in the non SVR group before and after treatment.
In group SVR, insulin resistance (HOMA-IR) improved significantly after antiviral therapy (1.62 + 0.94vs2.00 + 1.02, P0.0001), and followed up for 24 weeks. The insulin resistance index in SVR Group continued to be lower than the baseline (1.86 + 1.20vs2.00 + 1.02, P=0.05). Similarly, the insulin sensitivity index (ISI) and the baseline of treatment were significantly higher (-3.45 + 0.54vs-3.70 + 0.45). P0.0001) was still better than baseline (P=0.05) at 72 weeks. But in non SVR group, HOMA-IR was also decreased after treatment, but there was no significant difference compared with baseline (2.16 + 1.42vs2.27 + 1.37, P=0.281). At the end of the treatment, insulin resistance returned to the baseline level, and ISI had no change of.HOMA- beta (beta cell function) before and after treatment, and the treatment was treated before and after treatment. After treatment, both SVR and non SVR group increased significantly (P0.0001). After 24 weeks of follow-up, they decreased at 48, but still higher than baseline (SVR:P=0.01, NSVR:P=0.08).
Logistic regression analysis showed that the elderly (P=0.004, OR=1.072,95%CI:1.023,1.123), high viral load (P0.0001, OR=2.316,95%CI:1.596,3.362) and genotype 1b (P0.0001, OR=2.016,95%CI:1.116,3.122) were independent risk factors for virological response.
Conclusion:
1, serum total cholesterol and triglycerides in patients with chronic hepatitis C are lower than those in healthy people. Blood glucose is higher than healthy people, and is expected to return to normal after antiviral treatment.
2, serum total cholesterol and triglyceride were not correlated with virological response rate before treatment.
3, serum total cholesterol showed a downward trend after interferon treatment, while triglyceride level increased.
4, effective antiviral therapy can improve insulin resistance, hyperinsulinemia and islet beta cell function.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.63
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1 李雁;劉正穩(wěn);韓群英;李晗;;載脂蛋白B基因多態(tài)性及血脂水平與慢性丙型肝炎的相關(guān)性[J];世界華人消化雜志;2005年23期
2 劉淑娥,肖丹;肝源性糖尿病臨床分析[J];中日友好醫(yī)院學(xué)報(bào);2003年03期
3 牛培廣;史道華;;雷帕霉素抑制mTOR活性調(diào)控糖脂代謝的研究進(jìn)展[J];中國藥師;2010年11期
本文編號(hào)：2148829
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