Dataset Information

Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis C Undergoing Antiviral Therapy.

ABSTRACT:

Background

Recent studies have indicated that abnormal glucose levels and diabetes are negatively associated with the prognosis of patients with chronic hepatitis C virus (HCV) infection. The genetic polymorphism of the promoter region -1260 of a gene encoding the enzyme 1-alpha-hydroxylase (CYP27B1-1260) has been shown to have an impact on the signaling pathways involved in insulin secretion.

Objectives

The aim is to investigate the effect of CYP27B1-1260 polymorphism on the fasting plasma glucose (FPG) levels in patients with chronic HCV undergoing antiviral therapy.

Patients and methods

A total of 461 patients with chronic HCV infection and 300 volunteers without HCV infection were enrolled in an observational cohort study in the China-Japan Union hospital of Jilin University and the Second Hospital of Daqing, Changchun, Jilin Province. Both groups were further divided into normal and abnormal FPG subgroups. The frequencies of the three CYP27B1-1260 genotypes (AA, AC, and CC) were determined in each subgroup. FPG levels were monitored at baseline in HCV and control participants, and both during and after antiviral therapy in HCV infected patients. The frequency of each genotype was determined. Logistic regression analysis was performed to evaluate the risk factors associated with abnormal FPG levels in HCV infected patients undergoing antiviral therapy.

Results

In HCV infected patients with abnormal FPG levels, the frequency of the genotype CC was significantly higher than that in patients with normal FPG levels (19% vs. 7%, P < 0.001). In contrast, in the control participants, the CC genotype was not significantly different between FPG groups. At baseline, the CC genotype was associate with four times more risk of IFG after adjusting for multiple variables (OR: 4.11; 95%CI: 1.98 - 8.52, P = 0.0001). During 24 weeks of anti-HCV treatment, 38 HCV participants developed newly-diagnosed impaired fasting glucose. The CC genotype markedly increased the risk for newly developed IFG (OR: 26.54; 95%CI: 7.80 - 90.32, P < 0.0001). Other risk factors included age and body mass index.

Conclusions

CYP27B1-1260 polymorphism is associated with abnormal glucose metabolism in HCV infected patients. HCV infected individuals with CYP27B1-1260 genotype CC appeared to have an increased risk of developing abnormal FPG levels.

SUBMITTER: Sun D

PROVIDER: S-EPMC5088439 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis C Undergoing Antiviral Therapy.

Sun Derong D Qi Wenqian W Wang Song S Wang Xu X Zhang Yonggui Y Wang Jiangbin J

Hepatitis monthly 20160528 9

<h4>Background</h4>Recent studies have indicated that abnormal glucose levels and diabetes are negatively associated with the prognosis of patients with chronic hepatitis C virus (HCV) infection. The genetic polymorphism of the promoter region -1260 of a gene encoding the enzyme 1-alpha-hydroxylase (CYP27B1-1260) has been shown to have an impact on the signaling pathways involved in insulin secretion.<h4>Objectives</h4>The aim is to investigate the effect of CYP27B1-1260 polymorphism on the fast ...[more]

PMID: 27822255

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Project description:BACKGROUND:Around 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease. OBJECTIVES:The objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG). SEARCH STRATEGY:We searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials. SELECTION CRITERIA:Randomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias. MAIN RESULTS:This review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58). However, all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study. Moreover, results could have been confounded by rates of natural reversion to normal glucose levels. AUTHORS' CONCLUSIONS:The positive evidence in favour of Chinese herbal medicines for the treatment of IGT or IFG is constrained by the following factors: lack of trials that tested the same herbal medicine, lack of details on co-interventions, unclear methods of randomisation, poor reporting and other risks of bias.

Project description:AimTo evaluate the effect of single nucleotide polymorphisms of interleukin (IL)-28B, rs12979860 on progression and treatment response in chronic hepatitis C.MethodsPatients (n = 64; 37 men, 27 women; mean age, 44 ± 12 years) with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was performed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, aminotransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured.ResultsA sustained virological response (SVR) was significantly associated with IL28B polymorphism (CC vs TT allele: odds ratio (OR), 25; CC vs CT allele: OR, 5.4), inflammation activity (G < 1 vs G > 1: OR, 3.9), fibrosis (F < 1 vs F > 1: OR, 5.9), platelet count (> 200 × 10(9)/L vs < 200 × 10(9)/L: OR, 4.7; OR in patients with genotype CT: 12.8), fatty liver (absence vs presence of steatosis: OR, 4.8), insulin resistance index (< 2.5 vs > 2.5: OR, 3.9), and baseline HCV viral load (< 10(6) IU/mL vs > 10(6) IU/mL: OR, 3.0). There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance (P = 0.064) of increased fibrosis in patients with the TT allele, and no differences in the insulin resistance index between groups of patients with CC, CT and TT alleles (P = 0.12). Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively (P < 0.001). Significant differences were found in the insulin resistance index (P = 0.01) between patients with and without steatosis. Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon (P = 0.07).ConclusionIL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.

Project description:To determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI).In this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured.Compared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 +/- 0.2 vs. 6.1 +/- 0.9 and 6.4 +/- 0.5, P < 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 +/- 69 vs. 1,470 +/- 197 and 1,461 +/- 172 pmol/l, P < 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 +/- 40 vs. 583 +/- 45 pmol/l, P < 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 +/- 236 vs. 987 +/- 296, P < 0.0234) and adiponectin level (11.1 +/- 1.1 vs. 6.2 +/- 0.8 ng/ml, P < 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 +/- 130 vs. 268 +/- 68, P < 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone-binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG.Patients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.

Dataset Information

Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis C Undergoing Antiviral Therapy.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis C Undergoing Antiviral Therapy.

Similar Datasets

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