Association of TCF7L2 and GCG Gene Variants with Insulin Secretion, Insulin Resistance, and Obesity in New-onset Diabetes / 生物医学与环境科学（英文）

This cohort study was designed to evaluate the association of transcription factor 7-like 2 (TCF7L2) and proglucagon gene (GCG) variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. A total of 7,751 non-T2DM participants ⋝18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between TT genotype and the recessive model of TCF7L2 rs7903146 and increased risk of T2DM [hazard ratio (HR)=4.068, 95% confidence interval (CI): 1.270-13.026; HR=4.051, 95% CI: 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.

Association of the ADIPOQ Rs2241766 and Rs266729 Polymorphisms with Metabolic Syndrome in the Chinese Population: A Meta-analysis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This meta-analysis was performed to summarize the association of the ADIPOQ rs2241766 and rs266729 polymorphisms with metabolic syndrome (MS) in the Chinese population.</p><p><b>METHODS</b>We searched for articles in MEDLINE via PubMed, EMBASE, HuGE Navigator, CNKI, and Wanfang databases and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to determine the strength of associations in fixed- or random-effects models.</p><p><b>RESULTS</b>We included 21 articles in the meta-analysis: 17 reports of ADIPOQ rs2241766 with 3628 cases and 3000 controls and 8 of rs266729 with 2021 cases and 2226 controls. We found an increased risk of MS with the ADIPOQ rs2241766 polymorphism in some genetic models (allele model: OR=1.12, 95% CI: 1.03-1.21; dominant model: OR=1.15, 95% CI: 1.04-1.28; homozygote model: OR=1.22, 95% CI: 1.00-1.49) but no association with the ADIPOQ rs266729 polymorphism (allele model: OR=0.98, 95% CI: 0.82-1.17; dominant model: OR=0.90, 95% CI: 0.79-1.02; recessive model: OR=1.09, 95% CI: 0.85-1.39; homozygote model: OR=1.03, 95% CI: 0.80-1.33).</p><p><b>CONCLUSION</b>The results of this meta-analysis suggest an association between the ADIPOQ rs2241766 polymorphism and MS in the Chinese population. G allele of ADIPOQ rs2241766 increases the risk of MS. Better designed studies with different ethnic populations and larger sample sizes are needed for assessing the relationship between ADIPOQ rs2241766 and rs266729 polymorphisms and MS in the future.</p>

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese: a Case-control Study / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the association between low-density lipoprotein receptor-related protein 5 (LRP5) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese.</p><p><b>METHODS</b>A total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression.</p><p><b>RESULTS</b>In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P<0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls.</p><p><b>CONCLUSION</b>No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.</p>

General characteristics and clinical practices of Chinese patients with non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China.</p><p><b>METHODS</b>NAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines.</p><p><b>RESULTS</b>A total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline.</p><p><b>CONCLUSION</b>Data indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.</p>

The relationship of leptin and adiponectin with insulin resistance in nonalcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the serum leptin and adiponectin levels in nonalcoholic fatty liver disease (NAFLD) patients, and their relationship with insulin resistance.</p><p><b>METHODS</b>A total of 120 cases were enrolled and divided into two groups: NAFLD group (n = 60) and normal control group (n = 60). The serum levels of leptin and adiponectin were measured by ELISA. The body mass index (BMI), waist-to-hip ratio (WHR), triglyceride (TG), total cholesterol (Tchol), high-density lipoprotein cholesterol (HDL-C) , aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), fasting blood glucose (FBG) and HOMA-IR (homeostasis model assessment insulin resistance) were detected and analyzed.</p><p><b>RESULTS</b>Compared with control group, the serum leptin level in NAFLD group was Significantly higher [(12.37+/-1.99) microg/L vs (5.20+/-1.03) microg/L, P less than 0.01], while the serum adiponectin level was significantly lower [(12.69+/-2.83) mg/L vs (22.83+/-4.61) mg/L, P less than 0.01]. HOMA-IR was also much higher in NAFLD group than that in control group[(4.86+/-0.63) vs (1.91+/-0.41), P less than 0.01]. Logistic regression analysis showed that leptin was positively correlated with WHR (beta value = 8.175, P less than 0.01), HOMA-IR (beta value = 0.974, P less than 0.01 ), FBG (beta value = 0.564, P less than 0.01 ). In contrast, adiponectin inversely associated with HOMA-IR (beta value = -0.495, P less than 0.01 ) and BMI (beta value = -0.314, P less than 0.01) respectively.</p><p><b>CONCLUSION</b>The increased serum leptin level and decreased serum adiponectin level in NAFLD patients independently associated with HOMA-IR.</p>

Correlations between MELD score and left ventricular function in patients with end-stage liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the correlations between MELD score and left ventricular function in patients with end-stage liver disease.</p><p><b>METHODS</b>A total of 92 patients who prepared for orthotopic liver transplantation from January 2002 to May 2008 were enrolled in this study. Of these Patients, 75 were males and 17 were females, and the mean age was 50.3+/-9.5 years; 85 were cirrhosis, 7 were cirrhosis with primary liver cancer. Preoperative information, including biochemical parameters, coagulation parameters, indicators of hepatitis virology, two-dimensional echocardiography and electrocardiogram were collected. According to MELD (the Model for End-stage Liver Disease) scoring system, these subjects were categorized into three groups: MELD score is less than or equal to 9 points (31 cases, 33.7%); 10 is less than or equal to MELD score is less than or equal to 19 points (45 cases, 48.9%); MELD score is more than or equal to 20 points (16 cases, 17.4%). The relationships between MELD score and classification and cardiac function were determined by chi-square test, analysis of variance, rank sum test and correlation analysis, et al.</p><p><b>RESULTS</b>MELD score was significantly correlated with left atrial diameter (LAD), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDD), aortic flow (AF), cardiac output (CO), QRS interval (QRSI) and corrected QT interval (QTc) (r = 0.317, 0.341, 0.228, 0.387, 0.325, 0.209 and 0.347, respectively; P value less than 0.01, respectively); except QRSI, these variables and left ventricular posterior wall thickness (LVPWT) were also correlated with INR (a MELD component) (r = 0.282, 0.319, 0.322, 0.435, 0.275, 0.320 and 0.237, respectively; P value less than 0.01, respectively); LAD, LVEDD, AF, CO and QTc were correlated with serum total bilirubin (r = 0.241, 0.219, 0.357, 0.246 and 0.253, respectively; P value less than 0.05, respectively); IVST and E/A ratio (A blood flow [from left atrium to left ventricular] velocity ratio between early diastole [E wave] and late diastole[A wave] ) were correlated with serum creatinine (r = 0.216 and -0.343; P value less than 0.05 and 0.01); the proportion of E/A is less than or equal to 1 in all subjects was 46.7% (43/92), and 48.4% (15/31), 35.6% (16/45) and 75.0% (12/16) in each group, besides, there was statistically significant difference between 10 is less than or equal to MELD score is less than or equal to 19 points group and MELD score is more than or equal to 20 points group (X2 = 7.359, P = 0.009).</p><p><b>CONCLUSIONS</b>There are different degrees of left ventricular structure, function and electrophysiological changes in patients with end-stage liver disease, these anomalies also will be increased with the MELD score increasing.</p>

Capsule metadoxine in the treatment of alcoholic liver disease: a randomized, double-blind, placebo-controlled, multicenter study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease.</p><p><b>METHODS</b>A randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy.</p><p><b>RESULTS</b>254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L (before treatment) to 41.1 U/L, 36.0 U/L, 57.0 U/L (after 6 weeks therapy). The improvement in liver function was more significant in metadoxine group than in placebo group (P less than 0.05). For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group (55.7% , P=0.0000). For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group (44.8%, P=0.1767). The CT value ratio of liver to spleen was significantly improved in metadoxine group (P=0.0023), and there was no significant difference between the two groups (P=0.6293). The rate of adverse was 1.6% in both of groups.</p><p><b>CONCLUSION</b>Capsule metadoxine is an effective and safe treatment for alcoholic liver disease.</p>

The influence of alcohol on the liver sinusoids endothelial cell fenestrae of rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the influence of alcohol on the liver sinusoids endothelial cell (LSEC) fenestrae of rats.</p><p><b>METHODS</b>Setting up the rat model of alcoholic liver disease by orogastric administration of alcohol, then kill the experimental and control groups of rats at the end of 4 weeks, 8 weeks and 12 weeks after alcohol feeding, and also at the end of another 12 weeks after balance foods feeding succeeding with alcohol feeding for 12 weeks. Staining the liver tissue by means of HE method and observing the successive change of LSEC fenestrae by transmission electron microscope.</p><p><b>RESULTS</b>The normal LSEC was flat with nucleus and organelle arranged regularly. The distal cytoplasm displayed as lamina with many fenestrae, not accompanied by basement membrane (BM) formation under the endothelial cell. At the end of 4 weeks of alcohol feeding, fenestrae decreased at the partial distal LSEC cytoplasm, but no BM developed. At the end of 8 weeks, fenestrae decreased significantly, even disappeared, with the BM developed incompletely under the endothelial cell. Concomitantly, fibroblast with active function developed. At the end of 12 weeks, the changes became more obvious; the complete BM could even be seen. However, this kind of changes was mostly limited in the single or adjoining sinusoids, as well as with little widespread formation of fibrosis. At the end of 12 weeks of stopping alcohol feeding, defenestrae and development of BM attenuated obviously.</p><p><b>CONCLUSION</b>The defenestrae and BM of LSEC develop gradually with the chronic alcohol stimulation. Sinusoid capillarization and liver fibrosis even form when significant changes happen. The early change of the limited defenestrae and capillarization may be the basis of alcohol periportal fibrosis formation. This kind of liver fibrosis can be reversible after stopping alcohol feeding.</p>