Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease

AimsHemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD.MethodsA retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010.ResultsGraded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men (P for trend = 0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06–3.10) for women and 1.43 (1.00–2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men (P for trend = 0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73–1.91) in women and 1.76 (1.16–2.66) in men.ConclusionsThe risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD.     

Low adiponectin levels at baseline and decreasing adiponectin levels over 10 years of follow-up predict risk of the metabolic syndrome

AimAdiponectin is the most abundant adipokine and may play a key role in the interplay between obesity, inflammation, insulin resistance and the metabolic syndrome (MetS). Thus, this large population-based cohort investigated whether adiponectin at baseline and/or a decrease in adiponectin during follow-up is associated prospectively with the risk of incident MetS.MethodsUsing a prospective study design, the development of MetS was examined in 1134 healthy participants from the community. Plasma adiponectin was measured at study entry and again after a median follow-up of 9.4 years (IQR: 9.2–9.7). During follow-up, 187 participants developed MetS, and 439 presented with at least two components of MetS.ResultsDuring follow-up, adiponectin decreased in participants who developed MetS, whereas adiponectin was increased in those who did not develop MetS (P < 0.001). Those with low adiponectin levels (quartile 1) at baseline had an increased risk of developing MetS (OR: 2.92, 2.08–6.97; P < 0.001) compared with those with high levels (quartile 4). After adjusting for confounding variables, low adiponectin levels at baseline remained independently associated with MetS (OR: 2.24, 1.11–4.52; P = 0.017). Similarly, participants with a decrease in adiponectin during follow-up also had an increased risk of MetS (OR: 2.96, 2.09–4.18; P < 0.001). This association persisted after multivariable adjustments, including for baseline adiponectin (OR: 4.37, 2.77–6.97; P < 0.001). Finally, adiponectin levels at follow-up were inversely associated with an increase in the number of components of MetS (P < 0.001); geometric mean adiponectin levels were 9.5 mg/L (95% CI: 9.0–10.0) for participants with no components vs 7.0 mg/L (95% CI: 6.3–7.9) for those with four to five components.Conclusions/interpretationLow plasma adiponectin levels at baseline and decreasing adiponectin levels during follow-up are both associated with an increased risk of MetS.     

Postprandial glucose is correlated with an increasing risk of liver fibrosis in Chinese patients with nonalcoholic fatty liver disease

AimType 2 diabetes (T2DM) is closely related to nonalcoholic fatty liver disease (NAFLD) and is an important risk factor for the progression of liver fibrosis, but the role of 2-h postprandial blood glucose (PPG) as a biomarker in this process remains unclear. This study was designed to investigate the relationship between PPG and liver fibrosis in Chinese NAFLD populations with or without T2DM.MethodsThis study included three independent NAFLD populations: 1) 618 inpatients with T2DM or pre-diabetes, 2) 255 patients with T2DM or pre-diabetes who underwent liver biopsy, and 3) a prospective community-based cohort without diabetes who completed a median of 4.22 years follow-up. The degree of liver fibrosis was assessed by liver fibrosis stage in subjects with a liver biopsy, and by NAFLD fibrosis score (NFS) in subjects without liver biopsy.ResultsIn the first population, PPG {OR 0.02, [95% CI (0.01–0.03)], P< 0.001} was positively correlated with NFS. In the second population, an increasing PPG was associated with increase in the proportion of advanced liver fibrosis (P = 0.012). Multivariate line regression revealed that PPG {OR 0.03 [95% CI (0.00–0.06)], P = 0.049}was positively associated with liver fibrosis stages. In the third population, PPG {OR 0.103, [95% CI (0.011–0.194) P = 0.028} at baseline was positively associated with NFS at follow-up. Furthermore, changes in PPG were significantly associated with NFS change after follow-up. We did not find a similar association between fasting glucose or HbA1c and liver fibrosis.ConclusionsPPG was independently associated with the severity of liver fibrosis in the Chinese NAFLD population.     

Blood lead level is associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A nationwide survey (NHANES 2011–2016)

Introduction and objectivesNon-Alcoholic Fatty Liver Disease (NAFLD) is linked to obesity and metabolic syndrome, but increasing evidence also implicates environmental toxins. In this study, we aim to show that in elevated blood Lead levels in NAFLD patients result in worsening liver fibrosis.Materials and methods30,172 patients from NHANES 2011–2016 met inclusion criteria. 2499 patients ages 20–74 were identified with NAFLD as determined by the Fatty Liver Index score, and 425 with advanced liver fibrosis were identified using the NAFLD Fibrosis Score. Simple linear regression, Student's T-test, and Rao-Scott Chi-Square test was used for continuous and categorical variables. Multivariate regression analysis was used to adjust for confounders to determine odds of Advanced Fibrosis.ResultsIncreased serum Lead level was independently associated with increased risk of Advanced Fibrosis (OR 5.93, 95% CI 2.88–12.24) in the highest Lead quartile (Q4). In subgroup analysis stratified by BMI, a significant association between advanced liver fibrosis and blood Lead levels was consistently present, Q4 (OR 5.78, 95% CI 0.97–33.63) and Q4 (OR 6.04, 95% CI 2.92–12.48) in BMI <30 and >30, respectively. Increased Lead exposure was also evident in patients who were older, less educated, male, and drank alcohol and smoked tobacco.ConclusionsOur findings show that advanced liver fibrosis is up to six times more likely in NAFLD patients with increased Lead exposure.     

Metabolic dysfunction-associated fatty liver disease and risk of incident chronic kidney disease: A nationwide cohort study

AimsThe recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) has been suggested to better reflect the metabolic components of fatty liver disease (FLD), compared to nonalcoholic fatty liver disease (NAFLD). This study investigated whether MAFLD identifies a higher proportion of individuals at risk of developing chronic kidney disease (CKD).Methods268,946 participants aged 40–64 years, who underwent National Health Insurance Service health examinations between 2009 and 2015 were included. Participants were categorized by presence of FLD, according to MAFLD or NAFLD. In participants with FLD, participants were categorized into three groups: non-metabolic risk (non-MR) NAFLD, MAFLD but not NAFLD, and overlapping FLD. Incident CKD was defined as the occurrence of eGFR < 60 mL/min/1.73m² or proteinuria (≥ trace) on two consecutive health examinations.Results73,726 (27.4%) and 88,762 (33.0%) participants had NAFLD and MAFLD, respectively. During a median follow-up of 5.1 years, CKD occurred in 8,335 (6.2/1,000 person-years) participants. Compared to non-NAFLD participants, the adjusted hazard ratio (aHR) for incident CKD was 1.33 (95% CI, 1.27–1.39; P < 0.001) for participants with NAFLD. Compared to non-MAFLD participants, the aHR for participants with MAFLD was 1.39 (95% CI, 1.33–1.46; P < 0.001). When the analysis was confined to participants with FLD, compared to non-MR NAFLD participants, the aHRs for participants with MAFLD but not NAFLD, and those with overlapping FLD were 1.18 (95% CI, 1.01–1.39; P = 0.040) and 1.36 (95% CI, 1.19–1.54; P < 0.001), respectively.ConclusionMAFLD identified a higher proportion of individuals at risk of developing CKD than NAFLD.     

Association of serum C-peptide with all-cause and cardiovascular disease mortality in ultrasound-defined nonalcoholic fatty liver disease

ObjectiveTo determine the prognostic value of C-peptide in long-term nonalcoholic fatty liver disease (NAFLD) mortality.MethodsA total of 4670 participants with NAFLD were enrolled in this study. Multivariable Cox regression models evaluated the links between C-peptide levels and all-cause and cardiovascular disease (CVD) mortality risk using adjusted hazard ratios (aHR). In addition, a two?piecewise Cox model with penalized splines was adapted to investigate the nonlinear relationships between C-peptide and mortality.ResultsAfter a mean follow?up period of 20 years, 1714 deaths from all causes were recorded. In an adjusted Cox regression analysis, using the low C-peptide group as the reference (quartile 1), higher C-peptide (quartile 4) was notably associated with increased all-cause mortality (aHR =1.39; 95% CI: 1.18–1.65) and CVD death (aHR = 1.97; 95% CI: 1.41–2.76). Spline analyses demonstrated that the association between C-peptide levels and all-cause mortality was U-shaped, with a threshold value of 0.41 nmol/L. Below the threshold, every one-unit increment in C-peptide had a 70% reduced risk of all-cause death (aHR = 0.30, 95% CI: 0.1–0.7). Above the threshold, the C-peptide levels were associated with a higher probability of all-cause death (aHR = 1. 3, 95% CI:1.2–1.4).ConclusionsIn the US NAFLD population defined by ultrasound, a U-shaped association was detected between baseline serum C-peptide level and all-cause mortality.     

Comparison of cardiovascular mortality between MAFLD and NAFLD: A cohort study

Background and aimsA new diagnostic criterion of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. However, only few studies have shown that MAFLD predicts cardiovascular disease (CVD) mortality better than non-alcoholic fatty liver disease (NAFLD). Therefore, a cohort study was conducted to assess this relationship.Methods and resultsHealth examination data from health care centers in South Korea were assessed after excluding participants with missing covariates and cancer history (n = 701,664). Liver ultrasonography reports, laboratory and anthropometric data were extracted. Diagnoses of NAFLD and MAFLD were performed according to standard definitions. Participants were categorized based on the presence of NAFLD and MAFLD. In addition, participants were classified into five categories: no fatty liver disease (no FLD), NAFLD-only, MAFLD-only, both FLDs, and alcoholic FLD (AFLD) and non-MAFLD. Multivariable regression modeling was performed.The median follow-up duration was 8.77 years, and 52.56% of participants were men. After stratifying the cohort into no-MAFLD and MAFLD groups, MAFLD was associated with increased CVD mortality (adjusted HR 1.14, 95% CI 1.02–1.28). When participants were divided into no-NAFLD and NAFLD groups, there was a non-significant trend towards an increase in CVD mortality in NAFLD group (adjusted HR 1.07, 95% CI 0.95–1.21). When participants were divided into five categories, MAFLD-only group showed increased CVD mortality (adjusted HR 1.35, 95% CI 1.07–1.70) while NAFLD-only group showed no significant association with CVD mortality (adjusted HR 0.67, 95% CI 0.38–1.19).ConclusionsIn conclusion, MAFLD is associated with increased CVD mortality in a relatively young Korean population.     

Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease

Objective Retinol‐binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin‐resistant states. We investigated the relationship between non‐alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults. Methods One hundred and fifty‐nine nondiabetic, non‐alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography. Results Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l vs. 51·7 ± 14·6 mg/l, P < 0·0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ‐glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0·3097, P = 0·0002). Conclusion Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.     

Nonalcoholic fatty liver disease and risk of intracerebral hemorrhage

Background and aimsThis study aimed to investigate the association between the steatosis severity of nonalcoholic fatty liver disease (NAFLD) and future intracerebral hemorrhage (ICH) risk.Methods and resultsWe used data from the Kailuan study. Participants without a history of stroke, myocardial infarction, cancer, other liver diseases or alcohol abuse were enrolled. NAFLD and the severity of liver steatosis were assessed by abdominal ultrasonography. We stratified the participants into different groups according to the severity changes in liver steatosis status across the first 4-year follow-up period. The outcome was the first occurrence of ICH during the next 6-year follow-up period. Hazard ratios (HRs) and 95% CI of ICH were estimated using Cox models adjusted for potential risk factors. A total of 49,906 participants were enrolled in this study. During a median of 6.79 years of follow-up, 193 incident ICH cases were identified. Compared with persistent nonfatty liver participants, the hazard ratios (HRs) for participants with persistent mild steatosis, persistent moderate steatosis, persistent severe steatosis, alleviating steatosis, and aggravating steatosis were 1.28 (95% CI, 0.75–2.18), 2.33 (95% CI, 1.24–4.38), 1.63 (95% CI, 0.22–12.11), 1.41 (95% CI, 0.91–2.18), and 1.37 (95% CI, 0.94–2.00), respectively, in the fully adjusted model.ConclusionsNAFLD with persistent moderate steatosis was significantly related to an increased risk of future ICH, independent of other conventional risk factors.     

Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The relationship of NAFLD with thyroid function parameters and hypothyroidism remains controversial.AimTo clarify the effect of thyroid function parameters and hypothyroidism on the development of NAFLD and progression to nonalcoholic steatohepatitis (NASH).MethodsPubMed, EMBASE, and Cochrane library databases were searched. Study quality was assessed. Weighted mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated.ResultsTwenty six studies involving 61,548 participants were eligible, most of which were of high quality. NAFLD/NASH patients had significantly higher TSH levels than controls in adults (NAFLD versus health: WMD = 0.105, 95%CI = 0.012–0.197; NAFLD versus euthyroidism: WMD = 0.100, 95%CI = 0.005–0.194; NASH versus NAFLD: WMD = 0.540, 95%CI = 0.136–0.944) and children/adolescents (NAFLD versus lean controls: WMD = 1.039, 95%CI = 0.104–1.973; NAFLD versus overweight/obese controls: WMD = 0.485, 95%CI = 0.267–.703). Unclassified hypothyroidism was positively associated with the risk of NAFLD/NASH in adults (NAFLD versus health: OR = 1.605, 95%CI = 1.180–2.183; NASH versus NAFLD: OR = 2.317, 95%CI = 1.425–3.768) and children/adolescents (NAFLD versus overweight/obese controls: OR = 2.015, 95%CI = 1.246–3.258). However, the statistical results were inconsistent among the subgroup meta-analyses of subclinical and overt hypothyroidism. Association of NAFLD with FT3 and FT4 levels was heterogeneous among population.ConclusionTSH level may be an important risk factor for the development and progression of NAFLD, independent of thyroid hormones.     

Alpha-1-Antitrypsin Pi*MZ variant increases risk of developing hepatic events in nonalcoholic fatty liver disease patients,

AimsHeterozygous alpha-1-antitrypsin (A1AT) Pi*MZ variant has been shown to increase the risk of developing liver cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine the association between heterozygous Pi*MZ and Pi*MS variants and development of hepatic decompensation events in NAFLD patients.MethodsWe included patients with NAFLD who also had A1AT genotyping performed from 2005 to 2020. We recorded demographic and clinical variables, and data on hepatic events (ascites, hepatic encephalopathy, esophageal variceal bleed, or hepatocellular carcinoma), if any. We performed binary logistic regression analysis to assess the association between A1AT variants and hepatic events, and calculated Odds ratio (OR) with their 95% confidence intervals (Cl).ResultsWe included 1532 patients with NAFLD, of which 1249 patients had Pi*MM, 121 had Pi*MS, and 162 had Pi*MZ. Of the 1532 patients, hepatic events developed in 521 (34%) patients. The percentage of patients with Pi*MZ variant was significantly higher in patients with hepatic events as compared to patients without hepatic events (18.7 % vs 8.1%, p<0.0001). Pi*MZ variant was noted to significantly increase the odds of developing hepatic events in NAFLD patients, unadjusted OR: 1.82 (1.3–2.5, p<0.001), adjusted OR (for age, sex, body mass index, and diabetes mellitus) 1.76 (1.2–2.5, p = 0.002). Pi*MS variant did not increase the odds of hepatic events in NAFLD patients, OR: 0.92 (0.6–1.4, p = 0.70).ConclusionPatients with NAFLD and A1AT Pi*MZ variant are at increased risk for developing hepatic decompensation. NAFLD patients should be offered A1AT genotyping for risk stratification, counseling, and multidisciplinary intervention for NAFLD.     

Alcohol Consumption and 5-Year Change in Left Atrial Volume Among Patients With Coronary Heart Disease: Results From the Heart and Soul Study

BackgroundHeavy alcohol consumption is a risk factor for developing atrial fibrillation, but whether chronic alcohol use affects left atrial volume is unknown. We evaluated the association of self-reported alcohol consumption with 5-year change in left atrial volume among patients with coronary heart disease (CHD).MethodsWe studied 601 participants with stable CHD who underwent 2-dimensional echocardiography at baseline (2000–2002) and after 5 years of follow-up (2005–2007). Alcohol consumption was determined at baseline with the use of the Alcohol Use Disorders Identification Test consumption questions (AUDIT-C), with a standard cutoff point of ≥3 used to define at-risk drinking. We used logistic regression to evaluate the association of baseline alcohol use with 5-year increase in left atrial end-systolic volume index (defined as being in the highest tertile of percent change).ResultsAfter adjustment for covariates, each standard deviation (2.4-point) increase in AUDIT-C score was associated with a 24% greater odds of experiencing a 5-year increase in left atrial volume index (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 1.04–1.48; P = .02). Compared with the 369 participants who had AUDIT-C scores of <3, the 171 participants with scores of 3–5 had a 51% greater odds (OR 1.51, 95% CI, 1.11–2.25) and the 61 participants with scores of >5 a 98% greater odds (OR 1.98, 95% CI, 1.10–3.56) of experiencing a 5-year increase in left atrial volume index.ConclusionsIn patients with CHD, heavier alcohol consumption is associated with a 5-year increase in left atrial volume. Whether greater left atrial volume contributes to the increased risk of atrial fibrillation associated with alcohol use deserves further study.     

Incidence and predictors of vision loss complicating type 2 diabetes: The Fremantle Diabetes Study Phase II

Background and purposeAlthough diabetes is associated with multiple ocular complications, there are limited data on the incidence and predictors of visual acuity (VA) loss in type 2 diabetes. The aim of this study was to determine the 4-year cumulative incidence of visual impairment and blindness, and the predictors of vision loss, in a representative community-based cohort.MethodsThe longitudinal Fremantle Diabetes Study Phase II recruited 1551 participants with type 2 diabetes between 2008 and 2011. Participants attended biennial face-to-face assessments including VA measurement. Multivariable logistic regression was used to determine the predictors of vision loss (defined as a decrease in VA by >10 letters at the Year 4 assessment), excluding those with visual impairment (VA >6/19 and ≤6/48) and blindness (VA >6/48) at baseline.Results882 participants with normal/near normal vision at baseline had VA data at Year 4 available. During a median [interquartile range] 4.1 [4.0–4.4] years of follow-up, the cumulative incidences of visual impairment and vision loss were 0.9% (n = 8) and 2.9% (n = 26), respectively. No participants developed blindness and 1.9% (n = 17) improved their VA. Multivariable logistic regression showed baseline smoking (OR: 3.17 (95% CI: 1.15–8.76)), prior severe hypoglycemia (5.59 (1.32–23.61)) and urinary albumin:creatinine ratio (uACR) (1.42 (1.09–1.84) for an increase of 1 in ln(uACR)) had higher odds of vision loss during follow-up.ConclusionsSmoking cessation and management strategies that avoid severe hypoglycemia and preserve kidney function may potentially prevent vision loss in people with type 2 diabetes.     

Exercise reduces the risk of chronic kidney disease in individuals with nonalcoholic fatty liver disease: A nationwide cohort study

AimsRecent studies of individuals with nonalcoholic fatty liver disease (NAFLD) have indicated benefits of exercise in improving outcomes. We investigated whether exercise reduces the risk of chronic kidney disease (CKD) in individuals with NAFLD.MethodsA total of 7275 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) cohort, and 40,418 participants with NAFLD from the National Health Insurance Service (NHIS) cohort were included for the cross-sectional and longitudinal analyses, respectively. For the cross-sectional analysis, the primary outcome was prevalent CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m². For the longitudinal analysis, the primary outcome was incident CKD, defined as the occurrence of eGFR <60 mL/min/1.73m² or proteinuria (≥ trace) on two consecutive measurements during follow-up.ResultsIn the KNHANES cohort, prevalent CKD was observed in 229 (6.1%), 48 (2.6%), and 36 (2.1%) participants in the 0, 1-2, and ≥ 3 exercise sessions/week groups, respectively. The likelihood of prevalent CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted OR 0.49; 95% CI, 0.33-0.71; P < 0.001). During a median follow-up of 5.0 years in the NHIS cohort, incident CKD occurred in 1,047 (9.7/1,000 person-years), 188 (7.3/1,000 person-years), and 478 (7.4/1,000 person-years) participants in the 0, 1-2, and ≥ 3 sessions/week groups, respectively. The risk of incident CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted HR 0.85; 95% CI, 0.76-0.95; P = 0.004).ConclusionsExercise was significantly associated with a reduced risk of both prevalent and incident CKD in individuals with NAFLD.     

Determinants of successful glycemic control among participants in the BARI 2D Trial: A Post-hoc Analysis

ObjectiveThe BARI 2D trial compared insulin provision (IP) versus insulin sensitization (IS) for the primary outcome of total mortality in participants with T2DM and cardiovascular disease (CVD). In this analysis we examine baseline characteristics that are associated with successful long-term glycemic control.Research design and methodsIn a 2 × 2 factorial design, 2368 participants were randomized to either IP or IS therapy, and to either prompt revascularization with medical therapy or medical therapy alone. Successful long-term glycemic control (success) was defined by simultaneously meeting 1) a mean HbA1c level of < 7.0% after each participant's third year of follow-up period, and 2) adherence with medications only from the assigned glycemic treatment arm during > 80% of the BARI 2D follow-up. The association between baseline variables and success was determined using unadjusted and adjusted logistic regression models.Results1917 participants (962 IP and 955 IS participants) had sufficiently long follow-up and data for this analysis. Among these IP and IS participants, 235 and 335 participants met both criteria of success, respectively (p < 0.001). Those not on insulin at entry had higher odds of success (OR 2.25; CI 1.79–2.82) when treated with IS versus IP medications, irrespective of baseline HbA1c levels. Younger age, shorter duration of T2DM, and lower HbA1c at baseline were also each independently associated with higher success when treated with IS versus IP medications.ConclusionPatients similar to those in the BARI 2D trial may have a higher chance of achieving success with IS versus IP medications if they are younger, have shorter duration of T2DM, have lower HbA1c levels, have moderate or strenuous physically activity, and are not on insulin. In contrast, increasing age, longer duration of T2DM, higher HbA1c, and insulin therapy are associated with increased chance of success if treated with IP medications.     

Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease

Aim:  Retinol-binding protein-4 (RBP4) has been proposed as a new adipokine that regulates insulin action in muscles and the liver, and contributes to the pathogenesis of insulin resistance. As non-alcoholic fatty liver disease (NAFLD) is related to insulin resistance, we aimed to evaluate RBP4 levels in the serum and liver of patients with NAFLD.
Methods:  Serum RBP4 was measured in 30 NAFLD patients and 30 matched healthy controls. RBP4 expression in the liver of NAFLD patients was shown by immunohistochemistry.
Results:  Serum RPB4 was significantly lower in NAFLD patients compared with controls (25.15 vs 34.66 µg/mL, P  < 0.001) and there was no correlation with metabolic parameters or insulin resistance. RBP4 liver tissue immunostaining was more extensive and intense in NAFLD liver compared with normal liver and the RBP4 immunohistochemical score was positively correlated with the grade of steatosis, grade of non-alcoholic steatohepatitis activity and stage of fibrosis.
Conclusions:  In NAFLD patients, serum RBP4 was significantly lower as compared with controls and did not correlate with insulin resistance. In contrast, RBP4 liver tissue expression was enhanced and correlated with NAFLD histology.     

Effect of longitudinal changes of body fat on the incidence and regression of nonalcoholic fatty liver disease

AimsTo investigate the longitudinal association between changes in body fat amount and the incidence and regression of nonalcoholic fatty liver disease (NAFLD).MethodsWe performed a cohort study of 2017 subjects without liver disease or significant alcohol consumption from 2007 to 2008 and participated in a voluntary follow-up between 2011 and 2013. Of the 2017 subjects, we enrolled 956 (47.4%) subjects who had available abdominal fat data in both 2007–2008 and 2011–2013. NAFLD was diagnosed on the basis of ultrasonographic findings. Adipose tissue area was evaluated by computed tomography.ResultsWe observed 145 incident cases of NAFLD (22.6% of 642), and 79 subjects experienced a regression of NAFLD (25.2% of 314) during a median of 4.64 years. An increasing change in visceral adipose tissue (VAT) area was associated with a higher incidence of NAFLD (highest tertile vs. lowest tertile of VAT hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.56–3.85, P for trend <0.001) in the multivariable analysis. An increasing change in VAT area was inversely associated with the regression of NAFLD (highest tertile vs. lowest tertile of VAT HR 0.40, 95% CI 0.20–0.80, P for trend = 0.008).ConclusionsAn increasing change in VAT area was longitudinally associated with a higher risk of incident NAFLD and inversely associated with the regression of NAFLD.     

Visceral adipose tissue quality was associated with nonalcoholic fatty liver disease,independent of its quantity

Background and aimsNonalcoholic fatty liver disease (NAFLD) is a serious liver disease. Recent studies have shown that both visceral adipose tissue (VAT) quantity and density (as an indirect measure of quality) are associated with metabolic profiles. Therefore, we investigated the association between VAT quantity and quality, and the prevalence and incidence of NAFLD.Methods and resultsIn this cross-sectional, retrospective cohort study, the prevalence and incidence of NAFLD were analyzed in 627 and 360 middle-aged subjects, respectively. VAT was evaluated using an unenhanced computed tomography scan, while NAFLD was evaluated using ultrasonography. The VAT area was normalized to the square value of the subjects’ height in meters, the visceral fat area (VFA) index. The VAT density was described as the visceral fat density (VFD). The VFA index and VFD had an interaction effect on the prevalence of NAFLD (P = 0.0059). The VFA index (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.07; P = 0.0145, per 1.0 cm²/m²) and the VFD (OR, 0.90; 95% CI, 0.84–0.96; P = 0.0026, per 1.0 Hounsfield unit [HU]) were independently associated with the prevalence of NAFLD. In our cohort, 36 subjects developed NAFLD. The VFD (adjusted hazards ratio [HR], 0.84; 95% CI, 0.77–0.91; P < 0.0001, per 1.0 HU) was independently associated with the incidence of NAFLD, whereas the VFA index was not.ConclusionBoth the VFA index and VFD were independently associated with NAFLD prevalence. The VFD might be more related to the incidence of NAFLD than the VFA index.     

Association between the soluble receptor for advanced glycation end products (sRAGE) and NAFLD in participants in the Atherosclerosis Risk in Communities Study

BackgroundInflammation is key in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD) – a common progressive liver disease. The soluble receptor for advanced glycation end products (sRAGE) attenuates inflammatory signaling; low levels of sRAGE are correlated with increased inflammation.AimWe sought to describe associations between sRAGE and NAFLD.MethodsWe conducted a cross-sectional analysis of 1088 Atherosclerosis Risk in Communities (ARIC) Study participants and used logistic regression to investigate the associations between sRAGE and NAFLD defined by elevated liver enzymes and fibrosis score.ResultsIn this community-based sample (n = 1,088, mean age 56 years, 61% female, 78% Caucasian), persons in the lowest vs. highest quartile of sRAGE had significantly higher odds of elevated ALT (OR 2.82, 95% CI 1.18-6.76) but not elevated AST (OR 1.16, 95% CI 0.45-2.99); persons in the lowest vs. highest quartile had significantly lower odds of elevated FIB-4 index (OR 0.56, 95% CI 0.37-0.84).ConclusionsWe found an inverse cross-sectional association between sRAGE and liver inflammation; this is consistent with prior studies linking low sRAGE to inflammatory states. However, we observed a direct association between sRAGE and fibrosis. Our findings suggest that sRAGE is dynamic in NAFLD and patterns may vary with different stages of disease.     

Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease.