FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

Gene variants and the response to childhood obesity interventions: A systematic review and meta-analysis.

BACKGROUND: Multiple lifestyle-based childhood obesity interventions have been conducted to address childhood obesity, but individual's response to the universal intervention approach varied greatly. Whether gene variants related to children and adolescents' varied responses to obesity interventions remained unclear. AIMS: To determine the associations of gene variants with the changes in obesity- and metabolism-related indicators after obesity interventions in children and adolescents. METHODS: Ten databases and registers (including grey literature) were searched. The lifestyle-based obesity interventions in children and adolescents (≤18 years) that reported the changes in obesity- (body mass index (BMI), BMI Z-score, waist circumference (WC), waist-to-hip ratio (WHR), etc) and metabolism-related (glucose, cholesterol, etc) indicators by genotype after interventions were included. Our primary outcome was the mean difference of the changes in BMI Z-score by genotype after interventions, and secondary outcomes were changes in the remaining obesity- and metabolism-related indicators after interventions. We used the random-effects model to synthesize the results. RESULTS: This review included 50 studies (15,354 children and adolescents with overweight/obesity) covering 102 genes and 174 single nucleotide polymorphisms (SNPs). Approximately three-quarters of SNPs showed no evidence of association with the changes in obesity- or metabolic-related indicators after interventions. One quarter of SNPs were minorly associated with the changes in the BMI Z-score (median effect size: 0.001) with little clinical significance. Only 6 (12 %) studies focused on the accumulated effect of multiple gene variants. CONCLUSIONS: Gene variants that have been explored appear to play a minor role in lifestyle-based obesity interventions in children and adolescents. More high-quality studies based on the design of randomized controlled trials are needed to examine the accumulated effect of multiple gene variants in childhood obesity interventions. PROSPERO REGISTRY NUMBER: This systematic review and meta-analysis was registered at PROSPERO as CRD42022312177.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Role of omega-3 fatty acids in the prevention and treatment of cardiovascular Diseases: A consensus statement from the Experts' Committee Of National Society Of Cardiometabolic Medicine.

Low-density lipoprotein cholesterol (LDL-C) has been considered as the primary target for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, there are still residual cardiovascular risks in some patients even if LDL-C achieves the target level. Emerging evidence suggestes that elevated triglyceride (TG) level or triglyceride-rich lipoprotein (TRL) cholesterol (TRL-C) is one of the important components of the residual cardiovascular risks. Omega-3 fatty acids have been shown to be one of the effective drugs for reducing TG. However, its efficacy in reducing the risk of ASCVD is inconsistent in large randomized clinical trials. There is lack of consensus among Experts regarding the application of omega-3 fatty acids in cardiovascular diseases including heart failure, arrhythmia, cardiomyopathy, hypertension, and sudden death. Hence, the current consensus will comprehensively and scientifically present the detailed knowledge about the omega-3 fatty acids from a variety of aspects to provide a reference for its management of omega-3 fatty acids application in the Chinese population.

Expert Consensus on Cognitive Dysfunction in Diabetes.

The incidence of diabetes is gradually increasing in China, and diabetes and associated complications, such as cognitive dysfunction have gained much attention in recent time. However, the concepts, clinical treatment, and prevention of cognitive dysfunction in patients with diabetes remain unclear. The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes. Based on research both in China and other countries worldwide, the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients. This consensus presents an overview, definition and classification, epidemiology and pathogenesis, risk factors, screening, diagnosis, differential diagnosis, treatment, and prevention of cognitive dysfunction in patients with diabetes.

The Sichuan Mental Health Survey: Methodology.

The Sichuan Mental Health Survey (SMHS) is a provincially representative survey with a coherent methodology to obtain the prevalence of multiple mental disorders and data of services used and to analyze the psychological and social risk factors or correlates in Sichuan, China. Mental disorders include anxiety disorders, mood disorders, schizophrenia, and other psychotic disorders, drug use and alcohol use disorders, impulse control disorder, and eating disorders. A cross-sectional design is employed to sample adults from 200 communities/villages in all 21 prefectural-level municipalities of Sichuan Province in a five-stage provincially representative disproportionate stratified sampling design. The participants need to be interviewed face to face by trained interviewers from local primary healthcare institutions and by psychiatrists. The quality control staff implement data quality control by checking records and statistics in the interview system, and then re-interviewing checks are done by the psychiatrists. Data is weighted to adjust the sample distribution to match the whole population. The outcomes of the SMHS would not only demonstrate the serious challenges posed by the high burdens of mental disorders but also offer baseline data for policymakers and healthcare professionals to study and resolve the factors that influence mental health in Sichuan, China.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

FSHR ablation induces depression-like behaviors.

Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr-/-). We found that Fshr-/- mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg-1 · d-1, i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr-/- mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons.

FSH signaling is involved in affective disorders.

Affective disorders are a set of mental disorders and particularly disrupt the mental health of susceptible women during puberty, pregnancy, parturition and menopause transition, which are characterized by dramatic changes in reproductive hormone profiles. The serum FSH level changes significantly during these periods; yet, the role of FSH in mood regulation is poorly understood. In the current study, FSHR knockout (Fshr-/-) mice displayed enhanced affective disorder behaviors in an open field test and a forced swim test, accompanied by altered gene expression profiles. The differentially expressed genes between Fshr-/- mice and Fshr+/+ mice were enriched in multiple neuroendocrine metabolic pathways. FSHR deletion significantly increased/decreased the mRNA and/or protein expression levels of AOX1, RDH12, HTR3a and HTR4 in mood-mediating brain regions, including the hippocampus and prefrontal cortex. These results reveal that FSH signaling is involved in the development of affective disorders.

Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders.

Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome, obesity, and diabetes mellitus. Fat toxicity, chronic inflammation, and oxidative stress, which may change cellular functions, are considered to play an essential role in the pathogenetic progress of metabolic disorders. Recent studies have found that cells secrete nanoscale vesicles containing proteins, lipids, nucleic acids, and membrane receptors, which mediate signal transduction and material transport to neighboring and distant cells. Exosomes, one type of such vesicles, are reported to participate in multiple pathological processes including tumor metastasis, atherosclerosis, chronic inflammation, and insulin resistance. Research on exosomes has focused mainly on the proteins they contain, but recently the function of exosome-associated microRNA has drawn a lot of attention. Exosome-associated microRNAs regulate the physiological function and pathological processes of metabolic disorders. They may also be useful as novel diagnostics and therapeutics given their special features of non-immunogenicity and quick extraction. In this paper, we summarize the structure, content, and functions of exosomes and the potential diagnostic and therapeutic applications of exosome-associated microRNAs in the treatment of metabolic disorders.

Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro.

AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a 51Cr releasing test. T cell responses induced by RNA-loaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12. RESULTS: The anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DC-tumor-anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated (P < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA (P < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group (P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls (P < 0.01). CONCLUSION: DCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network.

KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR GENES AND THEIR HLA-C LIGANDS IN HASHIMOTO THYROIDITIS IN A CHINESE POPULATION.

OBJECTIVE: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis. METHODS: The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels. RESULTS: Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001). CONCLUSION: Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases. ABBREVIATIONS: HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients.

AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus. METHODS: This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level. RESULTS: In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM. CONCLUSIONS: We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.

CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis.

AIM: To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran's Q-statistic and I(2) tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger's linear regression test were inspected for indication of publication bias. RESULTS: A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222-1.886, P < 0.001). CONCLUSION: CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk.

Review on the effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus (T2DM), dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors were widely used to treat T2DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor (GLP-1R) is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride (TG) content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and mRNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial.

BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone. METHODS: This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment. RESULTS: At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 µU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 µU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups. CONCLUSIONS: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated. REGISTRATION NUMBER: ChiCTR-TRC-13003776.