scholarly journals Growth differentiation factor-15 and the association between type 2 diabetes and liver fibrosis in NAFLD

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Josh Bilson ◽  
Eleonora Scorletti ◽  
Laure B. Bindels ◽  
Paul R. Afolabi ◽  
Giovanni Targher ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Fibrosis ◽  
Transient Elastography ◽  
Characteristic Curve ◽  
Test Statistic ◽  
Alcoholic Fatty Liver ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
The Relationship

Abstract Background Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations. Methods Ninety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively. Results Patients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed ≥F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting ≥F2 or ≥F3 fibrosis (≥F2 fibrosis AUROC 0.75, (95% CI 0.63–0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and ≥F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001). Conclusions GDF-15 concentrations are a predictor of liver fibrosis and potentially involved in the association between T2DM and liver fibrosis in NAFLD. HbA1c concentrations explain a large proportion of the variance in GDF-15 concentrations.

scholarly journals Gut Microbiota and Non-Alcoholic Fatty Liver Disease Severity in Type 2 Diabetes Patients

2021 ◽  
Vol 11 (3) ◽  
pp. 238
Author(s):  
Hui-Ju Tsai ◽  
Yi-Chun Tsai ◽  
Wei-Wen Hung ◽  
Wei-Chun Hung ◽  
Chen-Chia Chang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Alcoholic Fatty Liver ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) remains an important health issue worldwide. The increasing prevalence of NAFLD is linked to type 2 diabetes (T2D). The gut microbiota is associated with the development of NAFLD and T2D. However, the relationship between gut microbiota and NAFLD severity has remained unclear in T2D patients. The aim of this study was to evaluate the relationship of gut microbiota with the severity of NAFLD in T2D patients. Methods: This cross-sectional study used transient elastography (FibroScan) to evaluate the severity of hepatic steatosis. We utilized qPCR to measure the abundance of Bacteroidetes, Firmicutes, Faecalibacterium prausnitzii, Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. Results: Of 163 T2D patients, 83 with moderate to severe NAFLD had higher abundance of bacteria of the phylum Firmicutes with respect to 80 patients without NAFLD or with mild NAFLD. High abundance of the phylum Firmicutes increased the severity of NAFLD in T2D patients. A positive correlation between NAFLD severity and the phylum Firmicutes was found in T2D male patients with body mass index ≥24 kg/m2 and glycated hemoglobin <7.5%. Conclusion: Enrichment of the fecal microbiota with the phylum Firmicutes is significantly and positively associated with NAFLD severity in T2D patients. The gut microbiota is a potential predictor of NAFLD severity in T2D patients.

scholarly journals Relationship between plasma growth differentiation factor-15 levels and diabetic retinopathy in individuals with type 2 diabetes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jin Ook Chung ◽  
Seon-Young Park ◽  
Dong Hyeok Cho ◽  
Dong Jin Chung ◽  
Min Young Chung
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Growth Differentiation Factor 15 ◽  
Type 2 Dm ◽  
Differentiation Factor ◽  
Significant Difference ◽  
The Relationship

AbstractThe purpose of our study was to investigate the relationship between plasma growth differentiation factor-15 (GDF-15) concentrations and diabetic retinopathy in patients with type 2 diabetes mellitus (DM). We evaluated 235 patients with type 2 DM in a cross-sectional study. Significantly increased levels of the plasma GDF-15 were found in individuals with diabetic retinopathy versus those without. According to the degree of diabetic retinopathy, there was a significant difference in the average plasma GDF-15 levels (no diabetic retinopathy, 1114 ng/L; nonproliferative diabetic retinopathy, 1327 ng/L; proliferative diabetic retinopathy, 1445 ng/L; p for trend = 0.035) after adjustments for confounders. Logistic regression analyses indicated that plasma GDF-15 concentrations were significantly associated with diabetic retinopathy (odds ratio per 1 standard deviation increment in the log-transformed value, 1.78; 95% confidence interval, 1.05–3.03, p = 0.032). Our study showed a significant positive relationship between plasma GDF-15 concentrations and diabetic retinopathy in type 2 DM patients.

scholarly journals The Relationship Between Circulating Growth Differentiation Factor 15 Levels and Diabetic Retinopathy in Patients With Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Yixin Niu ◽  
Weiwei Zhang ◽  
Jie Shi ◽  
Yueming Liu ◽  
Hongmei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Imaging System ◽  
Digital Camera ◽  
Albumin Creatinine Ratio ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Increased Risk ◽  
The Relationship

ObjectiveGrowth differentiation factor 15 (GDF-15) is a member of the TGF-β superfamily that has anti-inflammatory properties. The objective of this study was to evaluate the relationship between circulating GDF-15 levels and diabetic retinopathy (DR) in patients with type 2 diabetes.Materials/MethodsA case–control study was performed in which 402 patients with type 2 diabetes were enrolled. Of these, 171 patients had DR and the remaining 231 patients without DR acted as controls. The plasma GDF-15 levels were measured using ELISA, while DR was diagnosed using the canon ophthalmic digital imaging system and the Canon EOS 10D digital camera (Canon, Tokyo, Japan) through a non-pharmacologically dilated pupil.ResultsThe levels of GDF-15 were significantly higher in patients with DR [168.9 (112.9–228.3) pg/ml vs. 127.8 (96.1–202.8) pg/ml, P &lt; 0.001] compared to controls. Results of the Spearman correlation analysis showed that the GDF-15 levels were positively associated with the duration of diabetes morbidity, fasting plasma glucose, systolic blood pressure, albumin/creatinine ratio, creatinine, and liver enzymes, but negatively associated with eGFR (both P &lt; 0.001). The participants in the highest GDF-15 quartile had a significantly increased risk for DR (OR = 2.15, 95% CI 1.53–3.02) after adjusting for potential cofounders.ConclusionsThe circulating GDF-15 levels are positively associated with DR independent of potential cofounders.

scholarly journals Clinical Applicability of Transient Elastography for Estimating Liver Stiffness in Patients with Type 2 Diabetes Mellitus

2016 ◽  
Vol 3 (1) ◽  
pp. 249-254
Author(s):  
P.R. van Dijk ◽  
G.W.D. Landman ◽  
S. Hoving ◽  
N. Kleefstra ◽  
H.J.G. Bilo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Success Rate ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Alcoholic Fatty Liver

Background: Type 2 diabetes mellitus (T2DM) is a risk factor for the development of non-alcoholic fatty liver disease, which can lead to liver fibrosis and ultimately to cirrhosis. Transient elastography (TE), by using the FibroScan, and is a non-invasive ultrasonography method to measure liver elasticity. TE has been related with the degree of liver fibrosis. Objective: To investigate the applicability of TE in daily clinical practice among T2DM patients. Method: In a non-academic teaching hospital, T2DM patients without a history of liver disease the degree of liver stiffness was measured using TE. Successful measurements were defined as 10 validated measurements per patient and an interquartile range (IQR) to median ratio of ≤30%. Results: In 90 of 126 patients (71%) valid measurements were be obtained. Among the patients with invalid measurements, 33 had < 10 valid measurements and 3 had a IQR to median ratio of <30%. The percentage of invalid measurements was 12% in patients with a BMI <30 kg/m2 and 39% in patients with a BMI ≥30 kg/m2. Among the 90 patients with valid liver stiffness measurements, the median liver stiffness was 6.7 [4.6-8.5] kPa with a IQR of measurements of 1.1 [0.6-1.8] kPa and IQR to median ratio of 17 (13-23)%. Conclusion: The success rate of TE measurements using the FibroScan in patients with T2DM was 71%, with a lower success rate in patients with a BMI ≥ 30 kg/m2. This diagnostic modality needs further investigation being introduced as a marker of fibrosis in daily diabetes practice.

scholarly journals Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001189
Author(s):  
Yoshitaka Hashimoto ◽  
Masahide Hamaguchi ◽  
Ayumi Kaji ◽  
Ryosuke Sakai ◽  
Noriyuki Kitagawa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Liver Fibrosis ◽  
Proliferative Diabetic Retinopathy ◽  
Binding Protein ◽  
Protein Glycosylation ◽  
Diabetic Microangiopathy ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

IntroductionNon-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people with type 2 diabetes. The purpose of this cross-sectional study was to investigate the association between serum mac-2 binding protein glycosylation isomer (M2BPGi) levels and diabetic complications in people with type 2 diabetes.Research design and methodsSerum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normoalbuminuria, microalbuminuria, or macroalbuminuria. Retinopathy was divided into three groups: no-diabetic retinopathy (NoDR), non-proliferative-diabetic retinopathy (NPDR), or proliferative-diabetic retinopathy (PDR) .ResultsThe mean age for the 363 studied subjects (212 males) was 66.4±10.6 years, the median serum M2BPGi level was 0.77 (0.57–1.04) C.O.I., and the median UAE was 22 (9–82.1) mg/g creatinine. M2BPGi levels in microalbuminuria (0.83 (0.61 to 1.18) C.O.I.) and macroalbuminuria (0.88 (0.67 to 1.22) C.O.I.) cases were higher than those in normoalbuminuria cases (0.71 (0.54 to 0.92) C.O.I.). M2BPGi levels in NPDR (0.93 (0.68 to 1.28) C.O.I.) and PDR (0.95 (0.71 to 1.31) C.O.I.) cases were higher than in cases with NoDR (0.73 (0.56 to 0.99) C.O.I.). Furthermore, M2BPGi levels in subjects with a history of cardiovascular diseases were higher than in those with no such history (0.82 (0.65 to 1.22) vs 0.76 (0.55 to 1.03) C.O.I., p=0.019). The logarithm of (M2BPGi+1) was associated with the logarithm of UAE values after adjusting for covariates (standardized β=0.107, p=0.031).ConclusionsThis study reveals a close association between serum M2BPGi levels and diabetic microangiopathy and macroangiopathy in people with type 2 diabetes. The results also show that liver fibrosis, evaluated by M2BPGi, is independently associated with an increased risk of albuminuria.

Decreased Serum Growth Differentiation Factor 15 Levels After Lifestyle Intervention in Patients With Newly Diagnosed Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Xingxing He ◽  
Jiaorong Su ◽  
Xiaojing Ma ◽  
Jingyi Lu ◽  
Yufei Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lifestyle Intervention ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Glucose ◽  
Model Assessment ◽  
Newly Diagnosed ◽  
Serum Samples ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Abstract Background: Recent studies noted that circulating growth differentiation factor 15 (GDF15) were closely related to metabolic states. The study aimed to explore the changes of GDF15 levels and their influencing factors after 4 weeks of lifestyle intervention (LI) or LI combined with breakfast meal replacement (LI+MR) in newly diagnosed type 2 diabetes patients. Methods: A total of 84 patients with available serum samples at both baseline and Week 4 were enrolled in this biomarker substudy. All subjects underwent a 2-hour 75g oral glucose tolerance test at baseline and Week 4. Serum GDF15 levels were determined by a sandwich enzyme-linked immunosorbent assay. Results: After 4-weeks of LI, GDF15 levels overall significantly decreased compared with baseline (P<0.05). ∆GDF15 levels were significantly and negatively associated with baseline GDF15 levels (r=–0.450, P<0.001). The optimal cut-off point of baseline GDF15 levels for predicting a GDF15 decrease after 4-weeks of LI was 904.57 pg/ml, with an area under curve of 0.699. Based on the cut-off point of 900 pg/ml, patients with baseline GDF15 ≥900 pg/ml had significantly decreased GDF15 levels after LI, while those <900 pg/ml had no significant changes. Regression models showed that baseline GDF15 level was an independent positive factor for the improvement of fasting plasma glucose and homeostasis model assessment for insulin resistance only in patients with baseline GDF15 levels ≥900 pg/ml. Conclusions: LI led to significantly decreased GDF15 levels among patients with newly diagnosed type 2 diabetes and its effect was more significant among patients with baseline GDF15 levels ≥900 pg/ml.Trial registration: ClinicalTrials.gov, NCT02248714. Registered 25 September 2014 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02248714?term=NCT02248714&draw=2&rank=1

scholarly journals Tissue inhibitor matrix metalloproteinase 1 and risk of type 2 diabetes in a Chinese population

2020 ◽  
Vol 8 (1) ◽  
pp. e001051
Author(s):  
Yeli Wang ◽  
Jian-Min Yuan ◽  
An Pan ◽  
Woon-Puay Koh
Keyword(s):  
Type 2 Diabetes ◽  
Liver Fibrosis ◽  
Conditional Logistic Regression ◽  
Diabetes Risk ◽  
Tissue Inhibitor ◽  
Alcoholic Fatty Liver ◽  
Amino Terminal ◽  
Hba1c Levels

IntroductionThe non-invasive enhanced liver fibrosis (ELF) score—comprising tissue inhibitor of matrix metalloproteinases-1 (TIMP1), hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PIIINP)—has been shown to accurately predict fibrosis stages among patients with non-alcoholic fatty liver disease (NAFLD). However, no study has examined whether the ELF score or its components would also be predictive of type 2 diabetes, which commonly coexists and shares the same pathogenic abnormalities with NAFLD. Therefore, we prospectively investigated their associations with type 2 diabetes risks for the first time.Research design and methodsThe ELF score was measured among 254 type 2 diabetes cases and 254 age-matched and sex-matched controls nested within the prospective Singapore Chinese Health Study. Cases had hemoglobin A1c (HbA1c) levels <6.5% at blood collection (1999–2004) and reported to have diabetes during follow-up II (2006–2010). Controls had HbA1c levels <6.0% at blood-taking and remained free of diabetes at follow-up II. Multivariable conditional logistic regression models were used to assess the ELF-diabetes association.ResultsHigher TIMP1 levels were associated with increased type 2 diabetes risk, and the OR comparing the highest versus lowest quartiles was 2.56 (95% CI 1.23 to 5.34; p trend=0.035). However, ELF score, PIIINP and HA were not significantly associated with type 2 diabetes risks.ConclusionsHigher TIMP1 levels, but not ELF score, PIIIMP and HA, were associated with increased type 2 diabetes risk in Chinese adults. Our results suggested that elevated TIMP1 levels may contribute to the type 2 diabetes development through pathways other than liver fibrosis.

scholarly journals Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Benedetta M. Motta ◽  
Christoph Grander ◽  
Martin Gögele ◽  
Luisa Foco ◽  
Vladimir Vukovic ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Stiffness ◽  
Alcoholic Fatty Liver ◽  
Study Participants ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

Abstract 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 examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out. Results We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean − 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean − 1.30, SD, 1.17). Discussion Given the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.

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