Non-alcoholic Fatty Liver Disease In Type 2 Diabetes Mellitus Research Articles

Interpretation of the 2024 American Diabetes Association guidelines for the comprehensive management of non-alcoholic fatty liver disease combined with diabetes mellitus

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients.

The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM. To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

The Correlation Between Leg Muscle Mass Index and Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.

To analyze the relationship between leg skeletal muscle mass index (LSMI) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) and the ability of LSMI to predict NAFLD. Two hundred patients with T2DM and NAFLD treated at Changzhou Second People's Hospital Affiliated with Nanjing Medical University and the National Metabolic Management Center from June 2022 to June 2023 were divided into four LSMI quartiles. The clinical information from the four patient groups was compared, and the relationship between type 2 diabetes and LSMI and NAFLD was examined. We used receiver operating characteristic curves to determine how well the LSMI predicts NAFLD in T2DM. The lowest quartile (Q1) had a higher prevalence of NAFLD than group Q4 (P < 0.05). LSMI was negatively associated with body mass index, LS, CAP, and other markers (P < 0.05). Receiver operating characteristic curve analysis LSMI predicted NAFLD with an ideal critical value of 0.64 and an area under the curve of 70.9%. The combined predictive value of the LSMI and the appendicular skeletal muscle mass index was more significant. Reduced LSMI is associated with NAFLD.

Dendrobium mixture ameliorates hepatic injury induced by insulin resistance in vitro and in vivo through the downregulation of AGE/RAGE/Akt signaling pathway

Dendrobium mixture (DM) is a patented Chinese herbal medicine which has been shown to ameliorate type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. We aimed to investigate the underlying mechanism of DM as a therapeutic agent in attenuating liver steatosis in relation to type 2 diabetes mellitus (T2DM).DM (16.2 g/kg/d) was administered to db/db mice for 4 weeks. The db/m mice and db/db mice in the control and model groups were given normal saline. Additionally, DM (11.25 g/kg/d) was administered to Sprague-Dawley (SD) rats, and the serum was collected and used in an experiment involving palmitic acid (PA)-induced human liver HepG2 cells with abnormal lipid and glucose metabolism.In db/db mice, the administration of DM significantly alleviated liver steatosis, including histological damage and cell apoptosis. DM was found to prevent the upregulation of the RAGE and AKT1 proteins in liver tissues. The underlying mechanism of DM was further studied in PA-induced HepG2 cells. Post-DM administration serum from SD rats reduced lipid accumulation and regulated glucose metabolism in HepG2 cells. Consequently, it inhibited RAGE/AKT signaling and restored autophagy activity. The upregulated autophagy was associated with the mTOR-AMPK signaling pathway. Furthermore, post-DM administration serum reduced apoptosis of hepatocytes in PA-induced HepG2 cells. Our study supports the potential use of DM as a therapeutic agent for the treatment of NAFLD in T2DM. The mechanism underlying this therapeutic potential is associated with the downregulation of the AGE/RAGE/Akt signaling pathway.

Prevalence of nonalcoholic fatty liver disease in type 2 diabetes mellitus patients from the Eastern region of India

ObjectiveThe risk of nonalcoholic fatty liver disease (NAFLD) is increased significantly in individuals having Type 2 diabetes mellitus (T2DM) and the presence of T2DM enormously drives NAFLD progression. However, in clinical practice, it is overlooked despite the significant clinical effects of NAFLD in T2DM. Our study aimed to estimate the prevalence of NAFLD in T2DM patients from the eastern region of India. MethodsThis cross-sectional study assessed 132 T2DM patients for NAFLD. Anthropometry and lipid estimations were done in all the individuals. Hepatic fibrosis was diagnosed by transient elastography (TE) using a TOUCH 502 Fiber Scanner using M‑probe. A fibrosis score ≥ 11 kgpascals (kPa) was used to define advanced fibrosis (F3). ResultsOverall prevalence of NAFLD in T2DM patients was 57% (75/132 subjects) and the prevalence is higher in males (54.6%). Results showed that approximately 26% of patients with NAFLD will develop into NASH, among them 37.3% developed mild to moderate steatosis and 26.6% developed severe steatosis. ConclusionThe prevalence of NAFLD is high in the eastern region of India, need for early diagnosis and treatment of NAFLD in T2DM. The use of TE with other serum markers can be helpful for the diagnosis of advanced fibrosis.

Serum C1q/TNF-Related Protein 4 Levels are Associated with Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients.

Introduction: There is a strong bidirectional relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), both of which can lead to an increase in harmful metabolism and cardiovascular risk. It was discovered that C1q/TNF-related protein 4 (CTRP4) regulates glucolipid metabolism and feeding behavior. However, the correlation between serum CTRP4 and NAFLD in T2DM patients is not yet fully understood. Methods: This study enrolled 188 T2DM participants who were separated into 2 distinct groups (NAFLD and non-NAFLD) according to abdominal ultrasound imaging results. The enzyme-linked immunosorbent assay was utilized to evaluate the levels of serum CTRP4. Clinical data and CTRP4 concentration were compared between the two groups. Linear and logistic regression analyses were performed to evaluate the correlation of serum CTRP4 levels with NAFLD risk in T2DM patients. Results: Compared with non-NAFLD, the concentration of CTRP4 was lower in NAFLD group (median 2.46 vs. 2.89, P < 0.001). The log(CTRP4) value was found to be negatively correlated with alanine aminotransferase, aspartate aminotransferase, body mass index (BMI), and waist circumference in a Pearson correlation analyses (r = -0.159, -0.156, -0.224, -0.268, all P < 0.05); besides, the trend χ2 test demonstrated that the prevalence of NAFLD rose as CTRP4 concentration decreased (P < 0.001). Regression analysis suggested that NAFLD served as an independent factor influencing log(CTRP4) independently (β-coefficient = -0.12, P = 0.011), even after adjusting for high-sensitivity C-reactive protein and white blood cells. Finally, the results of the logistic regression analysis demonstrated that BMI [odds ratio (OR) = 1.196, P = 0.028], triglyceride (OR = 2.744, P < 0.001), and CTRP4 (OR = 0.615, P = 0.032) were independently associated with NAFLD in T2DM. Conclusions: T2DM patients with NAFLD have lower CTRP4 serum concentrations than those without NAFLD. The risk of NAFLD in patients with T2DM is inversely correlated with serum CTRP4 levels.

Inhibition of VEGF-B signaling prevents non-alcoholic fatty liver disease development by targeting lipolysis in the white adipose tissue

Hepatic steatosis is a hallmark of non-alcoholic fatty liver disease (NAFLD), a common comorbidity in type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD is complex and involves the crosstalk between the liver and the white adipose tissue (WAT). Vascular endothelial growth factor B (VEGF-B) has been shown to control tissue lipid accumulation by regulating the transport properties of the vasculature. The role of VEGF-B signaling and the contribution to hepatic steatosis and NAFLD in T2DM is currently not understood. C57BL/6J mice treated with a neutralizing antibody against VEGF-B, or mice with adipocyte-specific overexpression or under-expression of VEGF-B (AdipoqCre+/VEGF-BTG/+ mice and AdipoqCre+/Vegfbfl/+mice) were subjected to a 6-month high-fat diet (HFD), or chow-diet, whereafter NAFLD development was assessed. VEGF-B expression was analysed in WAT biopsies from patients with obesity and NAFLD in a pre-existing clinical cohort (n= 24 patients with NAFLD and n= 24 without NAFLD) and correlated to clinicopathological features. Pharmacological inhibition of VEGF-B signaling in diabetic mice reduced hepatic steatosis and NAFLD by blocking WAT lipolysis. Mechanistically we show, by using HFD-fed AdipoqCre+/VEGF-BTG/+ mice and HFD-fed AdipoqCre+/Vegfbfl/+mice, that inhibition of VEGF-B signaling targets lipolysis in adipocytes. Reducing VEGF-B signaling ameliorated NAFLD by decreasing WAT inflammation, resolving WAT insulin resistance, and lowering the activity of the hormone sensitive lipase. Analyses of human WAT biopsies from individuals with NAFLD provided evidence supporting the contribution of VEGF-B signaling to NAFLD development. VEGF-B expression levels in adipocytes from two WAT depots correlated with development of dysfunctional WAT and NAFLD in humans. Taken together, our data from mouse models and humans suggest that VEGF-B antagonism may represent an approach to combat NAFLD by targeting hepatic steatosis through suppression of lipolysis. Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in type 2 diabetes mellitus (T2DM) and has a global prevalence of between 25-29%. There are currently no approved drugs for NAFLD, and given the scale of the ongoing diabetes epidemics, there is an urgent need to identify new treatment options. Our work suggests that VEGF-B antagonism may represent an approach to combat NAFLD by targeting hepatic steatosis through suppression of lipolysis. The neutralizing anti-VEGF-B antibody, which was used in this study, has already entered clinical trials for patients with diabetes. Therefore, we believe that our results are of great general interest to a broad audience, including patients and patient organizations, the medical community, academia, the life science industry and the public.

Nonalcoholic fatty liver disease is associated with early left ventricular diastolic dysfunction in patients with type 2 diabeteS

ABSTRACT Background Left ventricular diastolic dysfunction (LVDD) is the first preclinical sign of diabetic cardiomyopathy. Nonalcoholic fatty liver disease (NAFLD) is linked to morbidity and mortality in Type 2 diabetes mellitus (T2DM) and increases the chance of developing cardiovascular disease, the primary cause of death. Aim This work aimed to identify the association of LVDD and NAFLD in T2DM. Methods We recruited 40 patients with T2DM (20 with NAFLD and 20 without NAFLD). Laboratory investigations and abdominal ultrasonography were carried out. The degree of hepatic steatosis was measured by the hepatorenal index (HRI). The LVDD was assessed by echocardiography and tissue doppler imaging. Results The Left atrial volume, left ventricular volume index, and left ventricle filling pressure index (E/é) were higher in the NAFLD group (P < 0.05). The E/é index was correlated with HRI and gamma-glutamyl transpeptidase (P < 0.05). Hepatic steatosis by HRI was the only independent variable associated with LVDD. Conclusion NAFLD is associated and correlated with an increased risk of left ventricular diastolic dysfunction in patients with T2DM regardless of ventricular systolic function.

Novel Sesquiterpene Glycoside from Loquat Leaf Alleviates Type 2 Diabetes Mellitus Combined with Nonalcoholic Fatty Liver Disease by Improving Insulin Resistance, Oxidative Stress, Inflammation, and Gut Microbiota Composition.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Sesquiterpene glycosides from loquat leaf achieved beneficial effects on metabolic syndromes such as NAFLD and diabetes; however, their specific activity and underlying mechanism on T2DM-associated NAFLD have not yet been fully understood. In the present study, we found that sesquiterpene glycoside 3 (SG3), a novel sesquiterpene glycoside isolated from loquat leaf, was able to prevent insulin resistance (IR), oxidative stress, and inflammation. In db/db mice, SG3 administration (25 and 50 mg/kg/day) inhibited obesity, hyperglycemia, and the release of inflammatory cytokines. SG3 (5 and 10 μM) also significantly alleviated hepatic lipid accumulation, oxidative stress, and inflammatory response induced by high glucose combined with oleic acid in HepG2 cells. Western blotting analysis showed that these effects were related to repair the abnormal insulin signaling and inhibit the cytochrome P450 2E1 (CYP2E1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3), both in vivo and in vitro. In addition, SG3 treatment could decrease the ratio of Firmicutes/Bacteroidetes and increase the relative abundance of Lachnospiraceae, Muribaculaceae, and Lactobacillaceae after a high-throughput pyrosequencing of 16S rRNA to observe the changes of related gut microbial composition in db/db mice. These findings proved that SG3 could protect against NAFLD in T2DM by improving IR, oxidative stress, inflammation through regulating insulin signaling and inhibiting CYP2E1/NLRP3 pathways, and remodeling the mouse gut microbiome. It is suggested that SG3 could be considered as a new functional additive for a healthy diet.

Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study.

Background The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM.Methods This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed.Results After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients.Conclusion Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Liver Stiffness Measurement by Using Transient Elastography in Bangladeshi Patients with Type 2 Diabetes Mellitus and Ultrasonography-Diagnosed Nonalcoholic Fatty Liver Disease.

PurposeType 2 diabetes mellitus (T2DM) is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD), and the presence of T2DM tremendously drives NAFLD progression. The use of transient elastography (TE) for assessment of NAFLD has been increasing due to its high sensitivity and specificity. This study aimed to measure liver stiffness in patients with T2DM and ultrasonography (USG)-diagnosed NAFLD and assess the correlations between liver stiffness and other clinical and biochemical parameters.Patients and MethodsThis cross-sectional study assessed 205 adult patients with T2DM and USG-diagnosed NAFLD who were being treated at a specialized endocrine private practice in Bangladesh. All subjects underwent TE for hepatic fibrosis assessment, which was performed using a FibroScan® 402 device. A fibrosis score ≥9.7 kilopascals (kPa) was used to define advanced fibrosis (≥F3).ResultsOut of 205 (65.9% female, mean age 45 ± 27 years, 67.3% obese) patients, the frequencies of Grade 1, Grade 2, and Grade 3 fatty liver on USG were 46.3%, 51.2%, and 2.4%, respectively. According to the TE results, 41 (20%) had advanced fibrosis (≥F3). Subjects with advanced fibrosis had a higher body mass index (BMI), higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and higher frequencies of individuals with elevated ALT and AST and advanced fatty liver grades on USG. The fibrosis score (kPa) was strongly and positively correlated with age, BMI, waist circumference, obesity, serum ALT and AST levels, and the fatty liver grade in USG; the AST:ALT ratio did not correlate with kPa.ConclusionThe data showed that 20% of the subjects with T2DM having NAFLD on USG exhibited advanced fibrosis, demonstrating the need for early diagnosis and treatment of NAFLD in T2DM. The use of TE with other serum markers can be helpful for the diagnosis of advanced fibrosis.

Bicyclol Regulates Hepatic Gluconeogenesis in Rats with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease by Inhibiting Inflammation.

Hepatic gluconeogenesis plays an important role in maintaining the body’s glucose metabolism homeostasis. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases, when combined with type 2 diabetes mellitus (T2DM), it can cause severe glucose metabolism disorders. Studies have confirmed that chronic liver inflammatory lesions are the basis of T2DM combined with NAFLD (T2DM–NAFLD), inhibiting liver inflammation can improve glucose metabolism disorders. It is essential to explore safe and effective drugs to inhibit liver inflammation to improve the body’s glucose metabolism disorders. Bicyclol is a biphenyl derivative that has anti-oxidative and anti-inflammatory properties. In the present study, the hepatoprotective effects and underlying mechanisms of bicyclol in T2DM–NAFLD were investigated, and T2DM–NAFLD with/without bicyclol treatment models were established. The results revealed that bicyclol alleviated fasting blood glucose, serum transaminase levels, insulin resistance, hepatic adipogenesis, lipid accumulation and markedly reduced T2DM–NAFLD rat histological alterations of livers. Not only that, bicyclol markedly attenuated T2DM–NAFLD induced production of inflammation factors (IL-1β and TNF-α). Moreover, bicyclol suppressed the expression of insulin/gluconeogenesis signaling pathway (Akt, PGC-1α and PEPCK). These findings suggested that bicyclol might be a potentially effective drug for the treatment of T2DM–NAFLD and other metabolic disorders.

Prevalence and risk factor analysis for the nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus.

Although non-alcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM), the diagnosis of NAFLD for T2DM patients remains a challenge.This study aimed to investigate the prevalence and risk factors for the NAFLD in T2DM outpatients.This is a retrospective, cross-sectional study that included 2405 T2DM patients treated and admitted for glucose control into the Endocrinology Department of our hospital from April 2017 to March 2019. Using strict exclusion criteria, the target patients were screened and divided into two groups: NAFLD patients (study group) and non-NAFLD patients (control group). Subsequently, 34 factors were compared between the two groups. Furthermore, multivariate analysis of the NAFLD risk factors was performed using logistic regression. Finally, the diagnostic significance of individual biochemical predictors, as well as the combined predictive indicator (CPI), for NAFLD was estimated using receiver operating characteristic (ROC) curve analysis.In this study, the overall prevalence of NAFLD in T2DM patients was 58.67%. Of the target patients, 17 factors were identified by univariate analysis to be associated with NAFLD, and 8 factors were found to be significant predictors for NAFLD using binary logistic regression modeling. Furthermore, the CPI and C-Peptide represent high diagnostic value for NAFLD in T2DM patients.This study provides a more comprehensive risk factor analysis for NAFLD in T2DM patients. These data can be used to provide timely diagnosis and effective management of NAFLD.

Hepatic Steatosis and Fibrosis in Type 2 Diabetes: A Risk-Based Approach to Targeted Screening.

Non-alcoholic fatty liver disease (NAFLD) is common in people with type 2 diabetes mellitus (T2DM). We aimed to explore predictive factors of NAFLD in T2DM and identify high risk subgroups. This was a cross-sectional study including 100 individuals with T2DM and 100 without diabetes matched for age, sex, and body mass index (BMI). Hepatic steatosis grades (calculated by controlled attenuation parameters-CAP score-3), and liver fibrosis stages (F0-F4) were determined using transient elastography. The frequency of NAFLD was comparable between the two study groups. However, CAP scores were significantly higher in individuals with diabetes (294.90 ± 53.12 vs. 269.78 ± 45.05 dB/m; P < 0.001). Fifty percent of individuals with diabetes had severe steatosis (S3), while this figure was 31.6% in those without diabetes (P < 0.05). Significant fibrosis (F2-F4) was more frequent in individuals with T2DM (13% vs. 4.1%, P = 0.02). Individuals with T2DM and advanced fibrosis had significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and CAP score compared to those without fibrosis (P < 0.05). In the regression analysis, a model including BMI, WHR, AST and female gender explained 50% of the variation in CAP score in patients with diabetes (all P < 0.05, adjusted R2 : 0.508). CAP scores were also the major determinant of liver fibrosis in this group (OR: 1.04; CI: 1.017-1.063; P = 0.001). Individuals with diabetes are more likely to have severe fibrosis. Obesity (especially central obesity), the female gender, elevated liver enzymes, and higher degree of insulin resistance are associated with more advanced liver disease in individuals with T2DM.

Clinical spectrum of non-alcoholic fatty liver disease in patients with diabetes mellitus.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully.AimWe explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients.MethodsThis is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software.ResultsAmong 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03–1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28–5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40–13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02–1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00–1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98–1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18–17.62; p = 0.028) were independent factors associated with increased liver stiffness.ConclusionsOur study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.

The relation between serum adipose differentiation-related protein and non-alcoholic fatty liver disease in type 2 diabetes mellitus.

Background:Adipose differentiation-related protein (ADRP) is an adipokine. In vitro and animal studies have verified the role of ADRP in lipid metabolism and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the interaction between levels of ADRP and NAFLD in type 2 diabetes mellitus (T2DM).Methods:Cross-sectional design. A total of 142 patients with T2DM were assigned to NAFLD (Group-I) and non-NAFLD (Group-II). Anthropometric data were collected. Serum ADRP levels and biochemical parameters were also determined. t test or χ2 test was conducted to compare the data between two groups. Receiver operating characteristic (ROC) curve analysis and logistic regression models were used to assess the interaction between ADRP levels and NAFLD in T2DM. Pearson correlation analysis and linear regression model were used to assess the correlations between serum ADRP levels and other parameters.Results:The serum ADRP level was higher in Group-I than in Group-II. Further, binary logistic regression models demonstrated that ADRP was an independent risk factor related to NAFLD in patients with T2DM. Moreover, as the ADRP level elevated across its tertiles, the percentage of NAFLD in T2DM increased. Multivariate logistic regression models demonstrated that the odds ratio of NAFLD was 8.831 in the highest tertile of ADRP, after adjustment for potential confounders. Area under THE ROC curve of ADRP for predicting the presence of NAFLD in T2DM was 0.738. Finally, multiple stepwise regression analysis indicated that age, waist circumference (WC), homeostasis model assessment of insulin resistance index (HOMA-IR) and triglyceride (TG) were independent factors associated with ADRP levels.Conclusion:High serum ADRP level may be used as an independent risk factor for NAFLD in T2DM. The expression of ADRP may be affected by age, WC, HOMA-IR and TG.

Association of leukocyte telomere length with non-alcoholic fatty liver disease in patients with type 2 diabetes.

Background:Leukocyte telomere has been shown to be related to insulin resistance-related diseases, such as type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study investigated the association of leukocyte telomere length (LTL) with NAFLD in T2DM patients.Methods:Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length analysis in 120 T2DM patients without NAFLD and 120 age-matched T2DM patients with NAFLD. NAFLD was clinically defined by manifestations of ultrasonography. The correlation between LTL and clinical and biochemical parameters were analyzed by Pearson correlation or Spearman correlation analysis. Factors for NAFLD in T2DM patients were identified using multiple logistic regressions.Results:LTL in T2DM patients with NAFLD were significantly longer than those without NAFLD (6400.2 ± 71.8 base pairs [bp] vs. 6023.7 ± 49.5 bp, P < 0.001), especially when diabetes duration was less than 2 years. Meanwhile, the trend of shorter LTL was associated with the increased diabetes duration in T2DM patient with NAFLD, but not in T2DM patients without NAFLD. Finally, LTL (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.002, P = 0.001), as well as body mass index (OR: 1.314, 95% CI: 1.169–1.477, P < 0.001) and triglycerides (OR: 1.984, 95% CI: 1.432–2.747, P < 0.001), had a significant association with NAFLD status in T2DM patients.Conclusions:T2DM patients with NAFLD had a significantly longer LTL than those without NAFLD. The longer LTL was especially evident in the early stage of T2DM, indicating that longer LTL may be used as a biomarker for NAFLD in T2DM patients.

Severity of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus: Relationship between Nongenetic Factors and PNPLA3/HSD17B13 Polymorphisms.

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is high, though its severity is often underestimated. Our aim is to provide an estimate of the prevalence of severe NAFLD in T2DM and identify its major predictors.MethodsT2DM patients (n=328) not previously known to have NAFLD underwent clinical assessment, transient elastography with measure of liver stiffness (LS) and controlled attenuation parameter (CAP), and genotyping for patatin like phospholipase domain containing 3 (PNPLA3) and 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13).ResultsMedian LS was 6.1 kPa (4.9 to 8.6). More than one-fourth patients had advanced liver disease, defined as LS ≥7.9 kPa (n=94/238, 29%), and had a higher body mass index (BMI) than those with a LS <7.9 kPa. Carriage of the G allele in the PNPLA3 gene was associated with higher LS, being 5.9 kPa (4.7 to 7.7) in C/C homozygotes, 6.1 kPa (5.2 to 8.7) in C/G heterozygotes, and 6.8 kPa (5.8 to 9.2) in G/G homozygotes (P=0.01). This trend was absent in patients with ≥1 mutated HSD17B13 allele. In a multiple linear regression model, BMI and PNPLA3 genotype predicted LS, while age, gender, disease duration, and glycosylated hemoglobin did not fit into the model. None of these variables was confirmed to be predictive among carriers of at least one HSD17B13 mutated allele. There was no association between CAP and polymorphisms of PNPLA3 or HSD17B13.ConclusionAdvanced NAFLD is common among T2DM patients. LS is predicted by both BMI and PNPLA3 polymorphism, the effect of the latter being modulated by mutated HSD17B13.

The Relationship Between Glycaemic Control and Non-Alcoholic Fatty Liver Disease in Nigerian Type 2 Diabetic Patients

BackgroundMetabolic risk factors associated with non-alcoholic fatty liver disease (NAFLD) include Type 2 diabetes mellitus (T2DM), obesity and dyslipidaemia. Prevention or management of these risk factors with glycaemic control, weight reduction and low serum lipid levels respectively have been reported to reduce the risk of NAFLD or slow its progression. Since ultrasound (USS) is a safe and reliable method of identifying fatty changes in the liver, this study was done to determine the relationship between glycaemic control and ultrasound diagnosed NAFLD in T2DM. Methodology: Demographic data, anthropometric measurements and laboratory tests including glycated haemoglobin (HbA1c), fasting blood glucose (FBG) and serum lipids of 80 T2DM subjects aged 40-80 years were taken. Their livers were evaluated using B-mode ultrasound, and the data obtained were statistically analysed using SPSS version 20. ResultsFifty-five of all participants (68.8%) were diagnosed with NAFLD sonographic grades 1, 2 and 3 made up of 13 (16.3%), 26 (32.5%) and 16 (20.0%), respectively while 25 (37.2%) had grade 0. The prevalence of NAFLD in T2DM varied significantly with BMI (p = 0.001) and glycaemic control (p = 0.048) while the USS grades of NAFLD varied significantly with age (p = 0.043) and BMI (p = 0.006). The independent strong predictors of NAFLD were overweight (r = 0.409, p = 0.012, OR = 6.626) and obesity (r = 0.411 p = 0.009, OR = 11.508), while poor glycaemic control (r = 0.270, p = 0.015, OR = 3.473) was a moderate independent predictor. ConclusionThe prevalence of NAFLD increases with increasing BMI and HBA1c in T2DM, while its ultrasound grade varies with BMI. Overweight, obesity and poor glycaemic control are independent predictors of NAFLD.

Urine uric acid excretion is associated with nonalcoholic fatty liver disease in patients with type 2 diabetes

AimsElevated serum uric acid is closely associated with nonalcoholic fatty liver disease (NAFLD). However, the association of urine uric acid excretion (UUAE) with NAFLD has not been investigated. Our aims were to explore the associations between UUAE and NAFLD and serum alanine aminotransferase (ALT) in type 2 diabetes mellitus (T2DM). MethodsThis cross-sectional study included 2042 Chinese inpatients with T2DM. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartile based on UUAE levels. NAFLD was determined by ultrasonography. Elevated ALT level was defined with an ALT value >65U/L. ResultsThere was an obvious increase in both NAFLD prevalence (26.3%, 34.6%, 43.8%, and 56.2%, respectively, p<0.001 for trend) and ALT value [16 (12–24), 17 (13–27), 20 (14–30), and 24 (15–38) U/L, respectively, p<0.001 for trend] across the UUAE quartiles after controlling for confounders. Multiple logistic regression analyses revealed independent associations between UUAE and NAFLD (p=0.002) and elevated ALT level (p<0.001). Compared with the patients in the first quartile of UUAE, those in the second, third and fourth quartiles had 1.528-, 1.869-, and 1.906-fold risk of NAFLD, and 3.620-, 6.223-, and 10.506-fold risk of elevated ALT level in T2DM, respectively. ConclusionsIncreased UUAE levels were significantly associated with the presence of NAFLD and increase of ALT in T2DM. UUAE may be a clinically significant measure in assessing the risk of NAFLD in T2DM.