延边地区慢性丙型肝炎患者2型糖尿病并发率及其基因型特征分析
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摘要
目的
本研究通过调查延边地区慢性丙型肝炎患者2型糖尿病(DM2)并发率和基因型分析,探讨朝鲜族、汉族慢性丙型肝炎与2型糖尿病之间的关系,并分析朝鲜族与汉族丙型肝炎病毒(HCV)基因型特征。
方法
1.选择367例慢性丙型肝炎(其中朝鲜族218例,汉族149例)、352例慢性乙型肝炎患者和681例除外病毒性肝炎体检者进行对照研究,明确其是否合并糖尿病,并分析合并糖尿病慢性丙型肝炎患者临床特征。
2.用酶联免疫法(ELISA),对851例糖尿病患者及782例非糖尿病人群进行抗-HCV、HBsAg检测。
3.采用实时荧光定量PCR方法(RT-PCR)和PCR-反向点杂交法(PCR-RDB)对62例朝鲜族和57例汉族慢性丙型肝炎患者进行HCV-RNA病毒载量检测和HCV基因型分析,比较HCV基因型在朝鲜族与汉族之间的分布差异,并分析HCV基因型与病毒载量、糖尿病和肝病严重程度之间的关系。
结果
1.慢性丙型肝炎患者糖尿病并发率及其与慢性乙型肝炎、除外病毒性肝炎对照组的比较：朝鲜族与汉族慢性丙型肝炎患者糖尿病并发率分别是24.31%,26.85%,差异无统计学意义(x2=0.18,P>0.05)；朝鲜族、汉族合计慢性丙型肝炎患者糖尿病并发率为25.34%,慢性乙型肝炎患者糖尿病并发率为9.38%,差异有统计学意义(x2=18.36,P<0.01),与除外病毒性肝炎对照组糖尿病并发率9.84%进行比较也有统计学意义(x2=36.60,P<0.01),慢性乙型肝炎患者与除外病毒性肝炎对照组比较,糖尿病并发率差异无统计学意义(x2=1.09,P>0.05)。
2.糖尿病患者肝炎病毒感染情况分析：851例糖尿病患者中抗-HCV阳性72例(8.46%),HBsAg阳性33例(3.88%)；782例非糖尿病人群中抗-HCV阳性23例(2.94%),HBsAg阳性78例(9.97%)。糖尿病组和非糖尿病组比较平均ALT水平、抗-HCV和HBsAg阳性率差异均有统计学意义(tALT=2.91,x2HCV=22.66,x2HBsAg=22.96,P<0.01),糖尿病组平均ALT、抗-HCV阳性率均高于非糖尿病组,而HBsAg阳性率低于非糖尿病组。糖尿病组患者抗-HCV阳性率(8.46%)明显高于HBsAg阳性率(3.88%),差异有统计学意义(x2=14.66,P<0.01),而非糖尿病组抗-HCV阳性率(2.94%)明显低于HBsAg阳性率(9.97%),差异也有统计学意义(x2=30.86,P<0.01)。
3.合并糖尿病慢性丙型肝炎患者临床特征分析：合并糖尿病慢性丙型肝炎患者与未合并糖尿病慢性丙型肝炎患者在年龄、性别、病程及体重指数差异无统计学意义(t年龄=0.89,x2性别=2.33,t病程=1.79,tBMI=1.36,P>0.05),但合并糖尿病的慢性丙型肝炎患者血清ALT水平及总胆红素水平高于未合并糖尿病者(tALT=3.71,tTBIL=15.57,P<0.01),且此组患者中54.84%的人群有糖尿病家族史,与未合并糖尿病的慢性丙型肝炎患者相比差异有统计学意义(x2=95.02,P<0.001),r-谷氨酰转肽酶与白蛋白在两组间差异无统计学意义(tGGT=0.69,tALB=1.50,P>0.05)。
4.朝鲜族与汉族HCV基因型分布特征：在119例HCV-RNA阳性标本中,分别检测出1b型占45.38%(54／119)、2a型占39.49%(47／119)、未分型占15.13%(18／119)。朝鲜族HCV基因型显示,1b型占45.16%(28／62)、2a型占38.71%(24／62)、未分型占16.13%(10／62)；汉族HCV基因型显示,1b型占45.61%(26／57)、2a型占40.35%(23／57)、未分型占14.14%(8／57),朝鲜族、汉族之间各基因型分布差异无统计学意义(p>0.05)。HCV各基因型之间HCV-RNA病毒载量差异和合并糖尿病分布差异之间无统计学意义(p>0.05),而HCV 1b型在中、重度慢性丙型肝炎患者与轻度慢性丙型肝炎患者中所占的比例差异有统计学意义(p<0.05)。
结论
1.慢性丙型肝炎患者易合并2型糖尿病,朝鲜族、汉族之间差异无统计学意义。
2.糖尿病患者中HCV感染率高于非糖尿病人群,提示HCV感染与糖尿病的发生有一定关系。
3.合并糖尿病慢性丙型肝炎患者病情相对较重,有糖尿病家族史的慢性丙型肝炎患者易并发糖尿病。
4.延边地区HCV基因型中以1b型最多,2a型次之,还有少数其它基因型；HCV基因型在朝鲜族与汉族之间分布无差异；HCV基因型与HCV-RNA载量无关；HCV基因型在合并糖尿病者与未合并糖尿病者之间分布无差异；1b型HCV感染者病情相对较重。
Objective To investigate the relationship of type 2 diabetes mellitus and chronic hepatitis C (CHC) between Han and Korean in Yanbian area of Jilin Province, China, and to approach the characteristics of hepatitis C virus (HCV) genotype by investigating the incidence of type 2 diabetes mellitus in chronic hepatitis C patients and the characteristics of HCV genotype.
Methods 367 CHC patients (218 Korean and 149 Han),352 chronic hepatitis B (CHB) patients and 681 healthy examination people were compared and studied in order to confirm whether it is type 2 diabetes mellitus and to analyze the characteristics of diabetes mellitus in patients with CHC. Anti-HCV antibody and HBsAg in the sera of 851 patients with type 2 diabetes mellitus and 782 people without type 2 diabetes mellitus were detected by enzyme linked immunosorbent assay (ELISA). HCV-RNA load and HCV genotype was analyzed in 62 patients of Korean and 57 patients of Han CHC using real-time PCR and PCR-RDB. The difference of the HCV genotypes in Han and Korean was compared. The relationship between the HCV genotypes and HCV-RNA load, diabetes mellitus, severity of the diseases was analyzed.
Results Compared with the incidence of type 2 diabetes mellitus in CHB patients and normal controls, the incidence of type 2 diabetes mellitus in CHC patients in Korean was 24.31% and in Han 26.85%. The difference in incidence between Korean and Han was not significant (χ2= 0.18, P>0.05). The incidence of type 2 diabetes mellitus in patients with CHC was 25.34% in total Han and Korean patients. However, the incidence of type 2 diabetes mellitus in patients with CHB was 9.38%. The difference was significant (χ2= 18.36, P<0.01). It also had a significant difference (χ2= 36.60, P<0.01) compared with the incidence of type 2 diabetes mellitus in the normal control group (9.84%). But compared with the CHB and the normal control group, the incidence of type 2 diabetes mellitus was not significant (χ2=1.09, P>0.05)
The clinical features of CHC in patients with diabetes mellitus were analyzed. The positive cases of Anti-HCV antibody and HBsAg were 72 (8.46%) and 33 (3.88%) respectively in 851 patients with diabetes mellitus, whereas, they were 23 (2.94%) and 78 (9.97%) in 782 control people. The average alanine amino transferase (ALT) level and the positive rate of Anti-HCV antibody and HBsAg were compared between diabetes mellitus group and the control group. The difference was significant (tALT=2.91,χ2HCV=22.66,χ2HBsAg=22.96, P<0.01). The average ALT level and anti-HCV antibody positive rate in diabetes mellitus group were higher than those in the control group, however, HBsAg-positive rate was lower than that in non-diabetic medical group. Anti-HCV antibody positive rate (8.46%) in diabetes mellitus group was higher than HBsAg-positive rate (3.88%), the difference was significant (χ2= 14.66, P<0.01).But, anti-HCV antibody positive rate (2.94%) was lower than HBsAg-positive rate (9.97%) in non-diabetic medical group, the difference was also significant (χ2=30.86, P<0.01)
The analysis of the clinical characteristics of diabetes mellitus in patients with CHC showed that when diabetes mellitus in patients with CHC was compared with non-diabetic CHC patients, there was no significant difference in age, gender, disease duration and body mass index (tage=0.89,χ2sex=2.33, tCourse=1.79, tBMI=1.36, P> 0.05). But, the serum ALT level and total bilirubin levels in diabetes mellitus patients with CHC were higher than those without diabetes mellitus (tALT=3.71, tTBIL=15.57, P<0.01).54.84% patients in this group of people were with diabetes family history. Compared with non-diabetes mellitus in patients with CHC there was statistically significant difference (χ2=95.02, P<0.001). R-glutamyl-GGT and albumin between the two groups was not significantly different (tGGT=0.69, tALB=1.50, P>0.05)
The distribution of HCV genotypes of Korean and Han showed that in the 119 cases of patients with CHC, type 1b was 45.38% (54/119), type 2a was 39.49% (47/119), non-typed was 15.13% (18/119). Korean HCV genotypes showed that type 1b was 45.16%(28/62), type 2a was 38.71% (24/62), non-typed was 16.13% (10/62). Han HCV genotypes revealed that type lb was 45.61% (26/57), type 2a was 40.35% (23/57), non-typed was 14.14%(8/57). There was no significant difference in the distribution of each genotype between Han and Korean (p>0.05). The difference between genotype and the load of HCV-RNA was not significant (p> 0.05). The proportion of HCV lb type in the moderate, severe and mild CHC patients was statistically different (P<0.05)
Conclusion (1) The incidence of type 2 diabetes mellitus in CHC patients is higher and the difference is not significant between Han and Korean. (2) The infection rate of HCV in diabetes mellitus group is higher than that in normal control group. It implies that there is some correlation between diabetes mellitus and HCV infection. (3) Diabetes mellitus in patients with CHC is relatively more serious; diabetes mellitus in patients with CHC with a family history are more complicated by diabetes. (4) The type lb is the most popular HCV genotype in Yanbian area of Jilin Province, China; type 2a is the second and there are still a few other genotypes. There is no significant difference in the distribution of HCV genotypes between Han and Korean. The HCV genotype has nothing to do with the load of HCV-RNA. The distribution of HCV genotypes in CHC patients with and without diabetes mellitus is not significantly different. Type 1b of HCV infection is relatively severe.
本研究通过调查延边地区慢性丙型肝炎患者2型糖尿病(DM2)并发率和基因型分析,探讨朝鲜族、汉族慢性丙型肝炎与2型糖尿病之间的关系,并分析朝鲜族与汉族丙型肝炎病毒(HCV)基因型特征。
方法
1.选择367例慢性丙型肝炎(其中朝鲜族218例,汉族149例)、352例慢性乙型肝炎患者和681例除外病毒性肝炎体检者进行对照研究,明确其是否合并糖尿病,并分析合并糖尿病慢性丙型肝炎患者临床特征。
2.用酶联免疫法(ELISA),对851例糖尿病患者及782例非糖尿病人群进行抗-HCV、HBsAg检测。
3.采用实时荧光定量PCR方法(RT-PCR)和PCR-反向点杂交法(PCR-RDB)对62例朝鲜族和57例汉族慢性丙型肝炎患者进行HCV-RNA病毒载量检测和HCV基因型分析,比较HCV基因型在朝鲜族与汉族之间的分布差异,并分析HCV基因型与病毒载量、糖尿病和肝病严重程度之间的关系。
结果
1.慢性丙型肝炎患者糖尿病并发率及其与慢性乙型肝炎、除外病毒性肝炎对照组的比较：朝鲜族与汉族慢性丙型肝炎患者糖尿病并发率分别是24.31%,26.85%,差异无统计学意义(x2=0.18,P>0.05)；朝鲜族、汉族合计慢性丙型肝炎患者糖尿病并发率为25.34%,慢性乙型肝炎患者糖尿病并发率为9.38%,差异有统计学意义(x2=18.36,P<0.01),与除外病毒性肝炎对照组糖尿病并发率9.84%进行比较也有统计学意义(x2=36.60,P<0.01),慢性乙型肝炎患者与除外病毒性肝炎对照组比较,糖尿病并发率差异无统计学意义(x2=1.09,P>0.05)。
2.糖尿病患者肝炎病毒感染情况分析：851例糖尿病患者中抗-HCV阳性72例(8.46%),HBsAg阳性33例(3.88%)；782例非糖尿病人群中抗-HCV阳性23例(2.94%),HBsAg阳性78例(9.97%)。糖尿病组和非糖尿病组比较平均ALT水平、抗-HCV和HBsAg阳性率差异均有统计学意义(tALT=2.91,x2HCV=22.66,x2HBsAg=22.96,P<0.01),糖尿病组平均ALT、抗-HCV阳性率均高于非糖尿病组,而HBsAg阳性率低于非糖尿病组。糖尿病组患者抗-HCV阳性率(8.46%)明显高于HBsAg阳性率(3.88%),差异有统计学意义(x2=14.66,P<0.01),而非糖尿病组抗-HCV阳性率(2.94%)明显低于HBsAg阳性率(9.97%),差异也有统计学意义(x2=30.86,P<0.01)。
3.合并糖尿病慢性丙型肝炎患者临床特征分析：合并糖尿病慢性丙型肝炎患者与未合并糖尿病慢性丙型肝炎患者在年龄、性别、病程及体重指数差异无统计学意义(t年龄=0.89,x2性别=2.33,t病程=1.79,tBMI=1.36,P>0.05),但合并糖尿病的慢性丙型肝炎患者血清ALT水平及总胆红素水平高于未合并糖尿病者(tALT=3.71,tTBIL=15.57,P<0.01),且此组患者中54.84%的人群有糖尿病家族史,与未合并糖尿病的慢性丙型肝炎患者相比差异有统计学意义(x2=95.02,P<0.001),r-谷氨酰转肽酶与白蛋白在两组间差异无统计学意义(tGGT=0.69,tALB=1.50,P>0.05)。
4.朝鲜族与汉族HCV基因型分布特征：在119例HCV-RNA阳性标本中,分别检测出1b型占45.38%(54／119)、2a型占39.49%(47／119)、未分型占15.13%(18／119)。朝鲜族HCV基因型显示,1b型占45.16%(28／62)、2a型占38.71%(24／62)、未分型占16.13%(10／62)；汉族HCV基因型显示,1b型占45.61%(26／57)、2a型占40.35%(23／57)、未分型占14.14%(8／57),朝鲜族、汉族之间各基因型分布差异无统计学意义(p>0.05)。HCV各基因型之间HCV-RNA病毒载量差异和合并糖尿病分布差异之间无统计学意义(p>0.05),而HCV 1b型在中、重度慢性丙型肝炎患者与轻度慢性丙型肝炎患者中所占的比例差异有统计学意义(p<0.05)。
结论
1.慢性丙型肝炎患者易合并2型糖尿病,朝鲜族、汉族之间差异无统计学意义。
2.糖尿病患者中HCV感染率高于非糖尿病人群,提示HCV感染与糖尿病的发生有一定关系。
3.合并糖尿病慢性丙型肝炎患者病情相对较重,有糖尿病家族史的慢性丙型肝炎患者易并发糖尿病。
4.延边地区HCV基因型中以1b型最多,2a型次之,还有少数其它基因型；HCV基因型在朝鲜族与汉族之间分布无差异；HCV基因型与HCV-RNA载量无关；HCV基因型在合并糖尿病者与未合并糖尿病者之间分布无差异；1b型HCV感染者病情相对较重。
Objective To investigate the relationship of type 2 diabetes mellitus and chronic hepatitis C (CHC) between Han and Korean in Yanbian area of Jilin Province, China, and to approach the characteristics of hepatitis C virus (HCV) genotype by investigating the incidence of type 2 diabetes mellitus in chronic hepatitis C patients and the characteristics of HCV genotype.
Methods 367 CHC patients (218 Korean and 149 Han),352 chronic hepatitis B (CHB) patients and 681 healthy examination people were compared and studied in order to confirm whether it is type 2 diabetes mellitus and to analyze the characteristics of diabetes mellitus in patients with CHC. Anti-HCV antibody and HBsAg in the sera of 851 patients with type 2 diabetes mellitus and 782 people without type 2 diabetes mellitus were detected by enzyme linked immunosorbent assay (ELISA). HCV-RNA load and HCV genotype was analyzed in 62 patients of Korean and 57 patients of Han CHC using real-time PCR and PCR-RDB. The difference of the HCV genotypes in Han and Korean was compared. The relationship between the HCV genotypes and HCV-RNA load, diabetes mellitus, severity of the diseases was analyzed.
Results Compared with the incidence of type 2 diabetes mellitus in CHB patients and normal controls, the incidence of type 2 diabetes mellitus in CHC patients in Korean was 24.31% and in Han 26.85%. The difference in incidence between Korean and Han was not significant (χ2= 0.18, P>0.05). The incidence of type 2 diabetes mellitus in patients with CHC was 25.34% in total Han and Korean patients. However, the incidence of type 2 diabetes mellitus in patients with CHB was 9.38%. The difference was significant (χ2= 18.36, P<0.01). It also had a significant difference (χ2= 36.60, P<0.01) compared with the incidence of type 2 diabetes mellitus in the normal control group (9.84%). But compared with the CHB and the normal control group, the incidence of type 2 diabetes mellitus was not significant (χ2=1.09, P>0.05)
The clinical features of CHC in patients with diabetes mellitus were analyzed. The positive cases of Anti-HCV antibody and HBsAg were 72 (8.46%) and 33 (3.88%) respectively in 851 patients with diabetes mellitus, whereas, they were 23 (2.94%) and 78 (9.97%) in 782 control people. The average alanine amino transferase (ALT) level and the positive rate of Anti-HCV antibody and HBsAg were compared between diabetes mellitus group and the control group. The difference was significant (tALT=2.91,χ2HCV=22.66,χ2HBsAg=22.96, P<0.01). The average ALT level and anti-HCV antibody positive rate in diabetes mellitus group were higher than those in the control group, however, HBsAg-positive rate was lower than that in non-diabetic medical group. Anti-HCV antibody positive rate (8.46%) in diabetes mellitus group was higher than HBsAg-positive rate (3.88%), the difference was significant (χ2= 14.66, P<0.01).But, anti-HCV antibody positive rate (2.94%) was lower than HBsAg-positive rate (9.97%) in non-diabetic medical group, the difference was also significant (χ2=30.86, P<0.01)
The analysis of the clinical characteristics of diabetes mellitus in patients with CHC showed that when diabetes mellitus in patients with CHC was compared with non-diabetic CHC patients, there was no significant difference in age, gender, disease duration and body mass index (tage=0.89,χ2sex=2.33, tCourse=1.79, tBMI=1.36, P> 0.05). But, the serum ALT level and total bilirubin levels in diabetes mellitus patients with CHC were higher than those without diabetes mellitus (tALT=3.71, tTBIL=15.57, P<0.01).54.84% patients in this group of people were with diabetes family history. Compared with non-diabetes mellitus in patients with CHC there was statistically significant difference (χ2=95.02, P<0.001). R-glutamyl-GGT and albumin between the two groups was not significantly different (tGGT=0.69, tALB=1.50, P>0.05)
The distribution of HCV genotypes of Korean and Han showed that in the 119 cases of patients with CHC, type 1b was 45.38% (54/119), type 2a was 39.49% (47/119), non-typed was 15.13% (18/119). Korean HCV genotypes showed that type 1b was 45.16%(28/62), type 2a was 38.71% (24/62), non-typed was 16.13% (10/62). Han HCV genotypes revealed that type lb was 45.61% (26/57), type 2a was 40.35% (23/57), non-typed was 14.14%(8/57). There was no significant difference in the distribution of each genotype between Han and Korean (p>0.05). The difference between genotype and the load of HCV-RNA was not significant (p> 0.05). The proportion of HCV lb type in the moderate, severe and mild CHC patients was statistically different (P<0.05)
Conclusion (1) The incidence of type 2 diabetes mellitus in CHC patients is higher and the difference is not significant between Han and Korean. (2) The infection rate of HCV in diabetes mellitus group is higher than that in normal control group. It implies that there is some correlation between diabetes mellitus and HCV infection. (3) Diabetes mellitus in patients with CHC is relatively more serious; diabetes mellitus in patients with CHC with a family history are more complicated by diabetes. (4) The type lb is the most popular HCV genotype in Yanbian area of Jilin Province, China; type 2a is the second and there are still a few other genotypes. There is no significant difference in the distribution of HCV genotypes between Han and Korean. The HCV genotype has nothing to do with the load of HCV-RNA. The distribution of HCV genotypes in CHC patients with and without diabetes mellitus is not significantly different. Type 1b of HCV infection is relatively severe.
引文
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[33]Chen LK, Hwang SJ, Tsai ST, et al. Glucose intolerance in Chinese patients with chronic hepatitis C. World J Gastroenterol,2003,9:505-508.
[34]Knobler H, Zhomicky T, Sandler A, et al. TNF-induced insulin resistance may mediate the HCV-diabetes association[J]. Am J Gastroenterol,2003,98(12): 2751-2756.
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