Acute Phase Inflammatory Proteins, Gut Microbiota Dysbiosis and Severity of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus (original) (raw)
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International journal of molecular medicine, 2018
Several mechanisms contribute to the pathogenesis of non‑alcoholic fatty liver disease (NAFLD). The intestinal microbiota (IM) and liver immune cells (LIC) may serve a role, but there has been no previous study assessing potential associations between IM and LIC. The aim of the present study was to investigate whether there are differences in LIC markers between patients with NAFLD and healthy controls (HC), and to determine whether these markers are associated with specific IM. The present prospective, cross‑sectional study examined a cohort of adults with liver biopsy‑confirmed NAFLD and HC. Clinical and laboratory data were collected. Fecal IM was assessed by quantitative polymerase chain reaction and LIC, by immunohistochemistry. NAFLD activity score (NAS) was used for disease severity. Liver immune cell counts were increased in patients with NAFLD (n=34) vs. HC (n=8) and this was associated with disease severity. Hematopoietic cell marker cluster of differentiation (CD)45+ and ...
Journal of Translational Medicine
Background Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants. Methods Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography exami...
Gut Microbiota as a Driver of Inflammation in Nonalcoholic Fatty Liver Disease
Mediators of Inflammation
The prevalence of nonalcoholic fatty liver disease and the consequent burden of metabolic syndrome have increased in recent years. Although the pathogenesis of nonalcoholic fatty liver disease is not completely understood, it is thought to be the hepatic manifestation of the dysregulation of insulin-dependent pathways leading to insulin resistance and adipose tissue accumulation in the liver. Recently, the gut-liver axis has been proposed as a key player in the pathogenesis of NAFLD, as the passage of bacteria-derived products into the portal circulation could lead to a trigger of innate immunity, which in turn leads to liver inflammation. Additionally, higher prevalence of intestinal dysbiosis, larger production of endogenous ethanol, and higher prevalence of increased intestinal permeability and bacterial translocation were found in patients with liver injury. In this review, we describe the role of intestinal dysbiosis in the activation of the inflammatory cascade in NAFLD.
Gut Microbiota: The Missing Link in Obesity Induced Nonalcoholic Liver Disease
Background and objective: Recent research has elucidated a close association between intestinal microbiota, obesity, insulin resistance and nonalcoholic hepatic injury. Various studies have also indicated an increase in hepatic marker enzymes in obesity. Hence, this study aims to evaluate the association of gut microbiota with obesity, insulin resistance and hepatic marker enzymes. Material and Method: This case-control study was conducted during March 2015 to October 2016 At S.C.B Medical College, Cuttack, Odisha. The study included 186 subjects (86 irritable bowel syndrome patients as per the Rome III criteria and hundred matched controls). Plasma fasting glucose, serum lipid profile, hepatic marker enzymes were analysed by commercial kits adapted to automated clinical chemistry analyser and serum fasting insulin was estimated by kits adapted to Lisa Scan. Observation: Compared to controls the Irritable bowel syndrome patients had significantly higher Body mass index (20.9± 5.6 vs 30.1±0.22), Waist-hip ratio (0.9 ± 0.11 vs 1.02 ± 0.06), lipid profile, hepatic marker enzymes and insulin resistance. Conclusion: IBS patients were obese, and exhibited dyslipidemia, insulin resistance, elevated hepatic enzymes suggesting development of NAFLD.
Scientific reports, 2018
This study aimed to determine if there is an association between dysbiosis and nonalcoholic fatty liver disease (NAFLD) independent of obesity and insulin resistance (IR). This is a prospective cross-sectional study assessing the intestinal microbiome (IM) of 39 adults with biopsy-proven NAFLD (15 simple steatosis [SS]; 24 nonalcoholic steatohepatitis [NASH]) and 28 healthy controls (HC). IM composition (llumina MiSeq Platform) in NAFLD patients compared to HC were identified by two statistical methods (Metastats, Wilcoxon). Selected taxa was validated using quantitative PCR (qPCR). Metabolites in feces and serum were also analyzed. In NAFLD, 8 operational taxonomic units, 6 genera, 6 families and 2 phyla (Bacteroidetes, Firmicutes) were less abundant and; 1 genus (Lactobacillus) and 1 family (Lactobacillaceae) were more abundant compared to HC. Lower abundance in both NASH and SS patients compared to HC were confirmed by qPCR for Ruminococcus, Faecalibacterium prausnitzii and Copro...
OBJECTIVE: This study assessed the association of inflammatory markers, high-sensitivity C-reactive protein (hsCRP), and total leukocyte count with nonalcoholic fatty liver disease (NAFLD) in urban South Indians.SUBJECTS AND METHODS: We randomly selected subjects with and without NAFLD (n=100 each) from the Chennai Urban Rural Epidemiology Study conducted in Chennai in south India. NAFLD was diagnosed by ultrasonography. hsCRP was measured by nephelometry, and leukocyte count was measured by flow cytometry. Insulin resistance was analyzed by homeostasis assessment model using the following expression: fasting insulin (μIU/mL)×fasting glucose (mmol/L)/22.5.RESULTS: Mean hsCRP values were significantly higher in subjects with NAFLD compared with those without (4.2±1.2 mg/L vs. 2.2±0.4 mg/L; P<0.001). Leukocyte count was also higher in subjects with NAFLD compared with those without (7.8±1.4×10(3)/μL vs 6.9±0.9×10(3)/μL, P<0.001). Both hsCRP (P<0.001) and leukocyte count (P<0.001) increased with increasing severity of NAFLD. Multiple logistic regression analysis was done using NAFLD as the dependent variable and hsCRP and leukocyte count as independent variables. Both hsCRP (odds ratio 1.293, 95% confidence interval 1.13-1.470, P<0.001) and leukocyte count (odds ratio 1.293, 95% confidence interval 1.069-1.564, P=0.008) had a significant association with NAFLD even after adjusting for waist circumference, insulin resistance, serum triglycerides, and presence of type 2 diabetes.CONCLUSIONS: hsCRP and leukocyte count are associated with NAFLD after adjusting for conventional cardiometabolic risk factors.
The role of the gut microbiota in nonalcoholic fatty liver disease
Nature Reviews Gastroenterology & Hepatology, 2010
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Its prevalence increases with increasing rates of obesity, insulin resistance, and diabetes mellitus. The pathogenesis of NAFLD involves many factors, including the gastrointestinal microbiota. However, there is still debate about the impact of gut dysbiosis in the NAFLD disease progression. Therefore, this paper aims to review the relationship between gut microbiota and other risk factors for NAFLD and how gut dysbiosis plays a role in the pathogenesis of NAFLD. Hopefully, this paper can make an appropriate contribution to the development of NAFLD research in the future.
International Journal of Scientific Research and Management
Background and aim: The aim of this study was to evaluate the role of gut microbiota with wide variety of clinical manifestations of patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Methods: The study enrolled 133 cases of patients with NAFLD/NASH who were diagnosed at Enmedic Clinic, Tbilisi/Georgia and carried out between May 2017 and May 2021. Patients were 21-65 years of age attending our clinic. Patients were diagnosed with NASH/NAFLD based on fibroscan of liver and ultrasound investigation, and additionaly for NASH with raised serum alanine aminotransferase (ALT) and aspartat aminotrasnferase (AST) levels greater than upper limit of normal (40 IU/ ml). Trial profile of patients is shown on figure 1. 10 patients loss follow up The 123 patients were divided into three groups. Group A (61 patients) was diagnosed with NAFLD, the 42 patients of group B were diagnosed with NASH and group C (control) were 20 healthy volunteers. Res...
BMC Research Notes, 2016
Background: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease commonly associated with obesity, type 2 diabetes, and inflammation-all features of insulin resistant syndrome. However, very limited data are available regarding the association of subclinical inflammation and insulin resistance with NAFLD in a prediabetic state. We, therefore, conducted the study to assess this relationship among this population. Methods: We studied a cross-sectional analytical design of 140 [male/female, 77/63; age in years (ranges), 45 (25-68)] prediabetic subjects after confirming with 75 g oral glucose tolerance test. The diagnosis of NAFLD was made by ultrasonic examination of the liver and divided into groups of without NAFLD (n = 63) and NAFLD (n = 77). All individuals underwent anthropometric and clinical examinations. Among laboratory investigations, serum glucose was estimated by glucose oxidase method, serum lipid profile and liver enzymes were measured by the enzymatic colorimetric method and glycated hemoglobin was measured by high performance liquid chromatography technique. Serum insulin and high sensitivity C reactive protein (hsCRP) were measured by enzyme immunoassay technique. Insulin resistance (HOMA-IR) was calculated by homeostasis model assessment (HOMA). Results: There was significantly higher levels of hsCRP (2.82 ± 1.60 vs. 1.39 ± 0.66 mg/l, P < 0.001) and HOMA-IR (4.03 ± 1.39 vs. 1.98 ± 1.04, P < 0.001) in NAFLD subjects compared to their without NAFLD counterparts. hsCRP [odds ratio (OR) = 5.888, 95 % confidence interval (CI) 2.673-12.970, P < 0.001] and HOMA-IR (OR = 4.618, 95 % CI 2.657-8.024, P < 0.001) showed significant determinants of NAFLD after potential confounders of body mass index and triglyceride were adjusted. Conclusions: Subclinical chronic inflammation and insulin resistance seem to be independent mediators of the association between NAFLD and prediabetes. The data also indicate that the inflammatory condition and insulin resistance are associated with each other and these, in turn, are affected by adiposity and dyslipidemia in prediabetic subjects.