scholarly journals TLT-1, a Potential Regulator of Inflammatory Pathogenesis in Obesity and Non-Alcoholic Fatty Liver Disease (NAFLD)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1005-1005
Author(s):  
Siobhan Laken Branfield ◽  
Benjamin Nieves Lopez ◽  
Matthew E Poynter ◽  
Anthony Valance Washington
Keyword(s):  
Adipose Tissue ◽  
Histological Analysis ◽  
Conflicts Of Interest ◽  
Western Diet ◽  
Binding Motif ◽  
Pathophysiological Mechanism ◽  
Specific Receptor ◽  
Ligand Interaction ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

Abstract Background: Obesity, a nationwide health issue, has related medical costs ranging between $147-210 billion per year in United States and has been associated with a 3.5-fold increased risk of developing NAFLD. In obesity, platelets work in a pleotropic manner with vascular and immune cells to amplify the chronic inflammatory process. Interestingly, studies have demonstrated that platelet numbers and reactivity are increased in obese individuals. The emerging role of activated platelets during obesity induced inflammation introduces the novel concept of platelet targeted therapeutic interventions. Kopec et al, further supports the idea that the mechanism underlying the progression of obesity lies in a platelet mediated pro-inflammatory state, illustrating that there is extravascular fibrin(ogen) deposition, macrophages and inflammatory cytokines within white adipose tissue and liver of mice on western diet. Kopec et al uses a fibrinogen mutant mouse (Fiby390-396 ) which lacks the binding motif for Mac-1 and inhibits the ligand interaction with leukocytes, diminishing inflammation, reducing macrophage counts, reducing weight, protects mice from NAFLD and glucose dysmetabolism. Taken together, all evidence points towards a platelet/fibrinogen/leukocyte pathophysiological mechanism underlying the development of obesity. TREM-Like Transcript-1 (TLT-1) is a platelet specific receptor found in the a-granules of platelets and released to the surface upon platelet activation. TLT-1 is a type 1 receptor that, like the integrin a2bb3, binds fibrinogen and facilitates platelet aggregation . However, although TLT-1 may assist in clot formation and hemostasis to arrest bleeding in a non-inflammatory/nonimmune mediated setting, TLT-1's main association is with regulating inflammatory-derived bleeding. This is demonstrated by increased hemorrhage after inflammatory treatments such as lipopolysaccharide LPS in the treml1 -/- mice as compared to controls. Considering the emerging evidence in support of a platelet-fibrinogen receptor ligand interaction as a key mechanism underlying the development of obesity and that TLT-1, a platelet specific receptor binds fibrinogen and mediates leukocyte trafficking, our laboratory set out to determine whether TLT-1 could be implicated as the main culprit underlying this mechanism. When placed on a western diet, treml1 -/-mice are more prone to weight gain, based on these finding we hypothesize that: The TLT-1/Fibrinogen molecular interaction regulates metabolic inflammation in obesity Aims: Evaluate the effects of western diet on obesity and NAFLD in the treml1 -/- mouse model Methods: TLT-1 (treml1 -/-) - apolipoprotein E (apoe -/-) double null (AT-DKO;n=11) mice and control apoe +/-/treml1 +/- littermate controls (AT-Hets;n=20) were fed western diet for 20 weeks. Plasma samples were collected for adipokine, glucose, insulin, liver enzyme and lipid profiling. Mouse were perfused, liver and adipose tissue were collected for histological analysis. Results: Overall AT-DKO mice gained more weight compared to AT-Hets (12.94±1.90 vs 8.51±1.70 grams p=0.02). Plasma analysis demonstrates that the AT-DKO have higher levels of TNF-a (0.54±0.60 vs 0.118±0.17 pg/ml p=0.03), and IL-10 (2.50±1.40 vs 1.50±2.10 pg/ml p=0.004) compared to littermate controls. Histological analysis of livers illustrates increased lipid vacuoles and inflammatory foci in the AT-DKO mice as compared to controls, while preliminary data is not significant for these differences, liver damage in the AT-DKO was significantly greater as demonstrated by increased AST levels (166.21±91.00 vs 102±68.10 U/L p=0.02). Moreover, the AT-DKO mice had higher levels of ALT, direct bilirubin, cholesterol, pai-1 , triglycerides and lower IL-6 and Adiponectin (Table 1 data not significant). These findings suggest that in the absence of TLT-1 these mice are more prone to liver disfunction , hyperlipidemia and inflammatory alterations. Conclusions: Mutant AT-DKO mice are more prone to obesity and NAFLD compared to littermate controls, suggesting that TLT-1, a platelet gene, plays a surprising role in metabolism. Further investigation could adjudicate TLT-1 administration as a potential therapeutic intervention for prevention and amelioration of Obesity and related pathologies. The current state of this project will be reported here. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Elevated circulating follistatin associates with an increased risk of type 2 diabetes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chuanyan Wu ◽  
Yan Borné ◽  
Rui Gao ◽  
Maykel López Rodriguez ◽  
William C. Roell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Genome Wide Association Study ◽  
Regulatory Protein ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

scholarly journals A Case of Mistaken Identity: TTP-like State Due to Heroin Overdose

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4905-4905
Author(s):  
Phani Borra ◽  
Cory Edward Mellon
Keyword(s):  
Plasma Exchange ◽  
Clinical Picture ◽  
Total Bilirubin ◽  
Conflicts Of Interest ◽  
Adverse Outcomes ◽  
Learning Objective ◽  
Severe Thrombocytopenia ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Ct Head

Learning Objective 1: Recognize that multiple etiologies can play a role in the overall presentation of patient's thrombocytopenia. Learning Objective 2: Rethink the original working diagnosis when there is discordance with clinical picture. Case: 52-year old male with a PMHx of heroin and alcohol abuse presented to ED after being found unresponsive due to heroin OD. Patient (Pt) was initially seen in the ED 4days prior for left leg cellulitis and was sent home on oral Bactrim. Lab values during that visit showed a platelet (plt) count of 80 K/UL, Hgb 10.1 g/dl and creatinine (Cr) of 1.46 mg/dl. On his 2nd ED visit, his WBC count was 12.7 K/UL, Hgb 7.7g/dl, plt 23K/UL, haptoglobin <8.0mg/dl and reticulocyte count of 4.1%. His BUN and Cr were elevated at 32 mg/dl and 2.97mg/dl respectively and UA showed large blood with 3-5 RBC, CPK was 24806 IU/L, LFTs demonstrated an AST of 414 IU/L, ALT of 90 IU/L, total bilirubin 2.0mg/dl, direct bilirubin 0.8mg/dl, LDH of 2339 IU/L and ESR >140 mm/hr. Coagulation parameters were normal. Pt's urine toxicology was positive for opiates and methadone. Manual differential was initially negative for schistocytes, helmet cells or bite cells. HIV was non-reactive, RPR and acute hepatitis panel were negative. On exam, pt was drowsy, had icteric sclera and faint left pedal pulses without purpuric rash. Pt was started on IV fluids for oliguric AKI and rhabdomyolysis. Arterial doppler revealed no detectable blood flow in his left distal superficial femoral, tibial and popliteal arteries. Initial CT head was negative for acute findings. Hematology consulted for possible diagnosis of TTP. Consultant didn't think clinical picture was consistent with TTP as total bilirubin at the time of consultation was normal therefore plasma exchange wasn't recommended. However, primary service still considered TTP highest on the differential therefore, ADAMTS13 was ordered but no plasma exchange was initiated. Given the fact pt received oral Bactrim for diagnosis of lower extremity cellulitis, G6PD deficiency was included in the differential however, testing was done early after hemolytic event and while reticulocytes were elevated, therefore results were not diagnostic. Of note, plts were transfused per vascular surgery prior to a planned thrombectomy of left leg, and plts increased to 81 K/UL. Pt underwent unsuccessful left leg thrombectomy due to chronic changes in the vessels and collaterals. CPK levels continued to increase and renal function continued to worsen as did his mental status. Pt was started on hemodialysis (HD) by end of 2nd day. There was persistent effort to incorporate all lab derangements into one all-inclusive diagnosis. Hematology was asked to review the case again as pt's plts continued to drop, ADAMTS13 activity was low at <2.0% and schistocytes were now noted on the peripheral smear. TTP was again not seen as the primary cause of the pt's clinical picture as total bilirubin continued to be normal, schistocytes only appeared after HD was initiated and low ADAMTS13 was thought to be secondary to liver dysfunction, inflammation and heroin OD. A repeat CT-head done showed left cerebellar hypodensities suspicious for acute CVA. Pt continued to deteriorate requiring mechanical ventilation. Troponins were checked which showed a level of 31.90ng/dl and ECG done simultaneously showed sinus tachycardia and no ischemic changes. Cardiology was consulted who determined trop elevation was likely due to skeletal muscle injury and possibly due to NSTEMI. However, due to pt's severe thrombocytopenia, Cardiology determined he was not a candidate for antiplatelet therapy or anticoagulation. Despite aggressive resuscitative measures, patient died Discussion: We reviewed the literature to evaluate other causes of this pt's clinical picture. While pt has overlapping features of TTP except fever, other causes for his mild hemolytic anemia and low plts include polysubstance abuse, rhabdomyolysis, poor nutritional status, presence of alcoholic fatty liver and uremia. Thrombocytopenia is associated with an increased risk of adverse outcomes, regardless of the causes. It has been documented in literature that heroin OD can cause rhabdomyolysis, renal failure, cardiac dysfunction, and permanent neurologic complications. The original diagnosis of TTP was anchored on and we persisted in trying to make the clinical picture fit that diagnosis and delayed in looking at overall clinical picture of the pt. Disclosures No relevant conflicts of interest to declare.

Abstract 19405: Association of Deep and Superficial Abdominal Subcutaneous Tissue With Hepatic Fat Content

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Inge v Munckhof ◽  
Tessa Brand ◽  
Marinette v Graaf ◽  
Jacqueline d Graaf ◽  
Joost Rutten
Keyword(s):  
Adipose Tissue ◽  
Alcohol Use ◽  
Hepatic Steatosis ◽  
Subcutaneous Adipose Tissue ◽  
Large Population ◽  
Univariate Analysis ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Subcutaneous Adipose

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Visceral adipose tissue (VAT) is regarded to be an important factor in the pathogenesis of NAFLD. Subcutaneous adipose tissue (SAT) is separated by the fascia superficialis into the deep SAT (dSAT) and superficial SAT (sSAT). It has been suggested that dSAT is related to an increased risk for obesity related complications, whereas sSAT has a more favorable profile. The aim of this study was to investigate the association of superficial and deep subcutaneous adipose tissue with hepatic steatosis. Methods: We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 133 subjects, BMI > 27 kg/m 2 , aged 55-81 years. Abdominal magnetic resonance imaging was performed at level L4-L5 to measure VAT, dSAT and sSAT volumes. The amount of liver fat was quantified by MR spectroscopy. Results: Men had significantly higher volumes of VAT and lower volumes of sSAT compared with women. No differences in volumes of dSAT were observed. In univariate analysis, the VAT volume was found to be correlated with hepatic steasosis (r = 0.339; p <0.001), while no significant correlation was found between total SAT, sSAT or dSAT with hepatic steatosis. After adjustment for age, alcohol use and sex, VAT was still positively correlated with hepatic steatosis with a standardized β of 0,276 (p=0.007), and sSAT, but not total SAT or dSAT, was negatively correlated with hepatic steatosis with a standardized β of -0,363 (p=0.033). Conclusions: VAT as measured by MRI is positively correlated with hepatic steatosis, in contrast to sSAT which is negatively correlated after adjustment for age, alcohol use and sex. We found no significant correlation between total SAT or dSAT and hepatic steatosis.

scholarly journals A CD209 ligand and a sialidase inhibitor differentially modulate adipose tissue and liver macrophage populations and steatosis in mice on the Methionine and Choline-Deficient (MCD) diet

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244762
Author(s):  
Darrell Pilling ◽  
Tejas R. Karhadkar ◽  
Richard H. Gomer
Keyword(s):  
Adipose Tissue ◽  
Liver Steatosis ◽  
Adipocyte Size ◽  
Alcoholic Fatty Liver ◽  
Sialidase Inhibitor ◽  
Liver Macrophage ◽  
Increased Risk ◽  
Macrophage Populations ◽  
White Fat

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes and is characterized by the accumulation of fat in the liver (steatosis). NAFLD can transition into non-alcoholic steatohepatitis (NASH), with liver cell injury, inflammation, and an increased risk of fibrosis. We previously found that injections of either 1866, a synthetic ligand for the lectin receptor CD209, or DANA, a sialidase inhibitor, can inhibit inflammation and fibrosis in multiple animal models. The methionine and choline-deficient (MCD) diet is a model of NASH which results in the rapid induction of liver steatosis and inflammation. In this report, we show that for C57BL/6 mice on a MCD diet, injections of both 1866 and DANA reversed MCD diet-induced decreases in white fat, decreases in adipocyte size, and white fat inflammation. However, these effects were not observed in type 2 diabetic db/db mice on a MCD diet. In db/db mice on a MCD diet, 1866 decreased liver steatosis, but these effects were not observed in C57BL/6 mice. There was no correlation between the ability of 1866 or DANA to affect steatosis and the effects of these compounds on the density of liver macrophage cells expressing CLEC4F, CD64, F4/80, or Mac2. Together these results indicate that 1866 and DANA modulate adipocyte size and adipose tissue macrophage populations, that 1866 could be useful for modulating steatosis, and that changes in the local density of 4 different liver macrophages cell types do not correlate with effects on liver steatosis.

Inter-Tissue and Intra-Tissue Co-Expression Networks in Human Metabolism: Morphological Evaluation of the Link Between Transcription Factors ERβ and NFAT in Morbid Obesity

2020 ◽  
Vol 17 (1) ◽  
pp. 63-80
Author(s):  
Athina Chasapi ◽  
Kostas Balampanis ◽  
Eleni Kourea ◽  
Fotios Kalfaretzos ◽  
Vaia Lambadiari ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Adipose Tissue ◽  
Clinicopathological Parameters ◽  
Morbidly Obese ◽  
Human Metabolism ◽  
Activated T Cells ◽  
Alcoholic Fatty Liver ◽  
Morphological Evaluation ◽  
Underlying Mechanisms

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive “cross-talk” with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2). Introduction: Our study is an “in situ” morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored. The aim of the present study was to determine the role of ERβ and NFAT in the underlying pathophysiology of obesity and related comorbidities. We have investigated the expression of specific proteins using immunochemistry methodologies. Methods: Our population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver and the differential protein expression was evaluated by immunohistochemistry. Results: We demonstrated an extensive intra- and inter-tissue co-expression network, which confirms the tissue-specific and integral role of each one of the investigated proteins in morbid obesity. Moreover, a beneficial role of ERβ and NFATc1 against NAFLD is implicated, whereas the distinct roles of TIF2 still remain an enigma. Conclusions: We believe that our findings will shed light on the complex underlying mechanisms and that the investigated biomarkers could represent future targets for the prevention and therapy of obesity and its comorbidities.

scholarly journals Interleukin-6 mediated exercise-induced alleviation of adiposity and hepatic steatosis in mice

2021 ◽  
Vol 9 (1) ◽  
pp. e001431
Author(s):  
Long Li ◽  
Caoxin Huang ◽  
Hongyan Yin ◽  
Xiaofang Zhang ◽  
Dongmei Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Exercise Training ◽  
Hepatic Steatosis ◽  
Interleukin 6 ◽  
Body Weight Gain ◽  
Treadmill Running ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Ppar Γ

IntroductionExercise training has been shown to be the most effective strategy to combat obesity and non-alcoholic fatty liver disease. However, exercise promotes loss of adipose tissue mass and improves obesity-related hepatic steatosis through mechanisms that remain obscure.Research design and methodsTo study the role of interleukin-6 (IL-6) in high-fat diet (HFD)-induced adiposity and hepatic steatosis during treadmill running, IL-6 knockout (IL-6 KO) mice and wild-type (WT) mice were randomly divided into lean, obese (fed a HFD) and trained obese groups (fed a HFD and exercise trained).ResultsAfter 20 weeks of HFD feeding and 8 weeks of treadmill running, we found that exercise obviously reduced HFD-induced body weight gain, inhibited visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) expansion and almost completely reversed obesity-related intrahepatic fat accumulation in WT mice. However, IL-6 knockout (IL-6 KO) mice are refractory to the benefits of treadmill training on body weight, VAT and SAT mass elevation, and hepatic steatosis. Moreover, a panel of lipolytic-related and thermogenic-related genes, including ATGL, HSL and PGC-1α, was upregulated in the VAT and SAT of WT mice that received exercise training compared with untrained mice, which was not observed in IL-6 KO mice. In addition, exercise training resulted in a significant inhibition of hepatic peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in WT mice, and these effects were not noted in IL-6 KO mice.ConclusionThese results revealed that IL-6 is involved in the prevention of obesity and hepatic fat accumulation during exercise training. The mechanisms underlying these antiobesity effects may be associated with enhanced lipolysis and thermogenesis in white adipose tissue. The improvement in hepatic steatosis by exercise training may benefit from the marked inhibition of PPAR-γ expression by IL-6.

scholarly journals A214 BARIATRIC SURGERY PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE HAVE DIFFERENT VISCERAL ADIPOSE TISSUE GENE EXPRESSION COMPARED TO THOSE WITH NORMAL LIVER

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 245-247
Author(s):  
S Keshavjee ◽  
J Yadav ◽  
K Schwenger ◽  
S Fischer ◽  
T D Jackson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bariatric Surgery ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Inflammatory Markers ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Visceral Adipose ◽  
Healthy Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation. Aims This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX. Methods Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05. Results We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL. Conclusions Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity. Funding Agencies CIHRCanadian Liver foundation

scholarly journals Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fat Mass ◽  
Metabolic Disorders ◽  
Later Life ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

Early kidney dysfunction in non-alcoholic fatty liver disease - is transient elastography useful as a screening method?

2021 ◽  
Author(s):  
Marta Freitas ◽  
Vítor Macedo Silva ◽  
Sofia Xavier ◽  
Joana Magalhes ◽  
Carla Marinho ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Screening Method ◽  
Kidney Dysfunction ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Significant Liver Fibrosis

Introduction: Increasing evidence suggests an association between metabolic associated fatty liver disease (MAFLD) and chronic kidney disease (CKD). Timely prediction of early kidney dysfunction (EKD) is thus essential in this population, although a screening method is not stablished. We aimed to evaluate the role of transient elastography (TE) in predicting EKD in patients with MAFLD. Methods: Prospective cohort study that included patients with MAFLD scheduled for evaluation, between May/2019 and January/2020. Demographic, clinical and laboratory data, and TE parameters were obtained. EKD was defined as microalbuminuria (urinary albumin-to-creatinine ratio 30-300mg/g) and estimated glomerular filtration rate≥60mL/min/1.73m2. Significant liver fibrosis was defined as liver stiffness measurement (LSM)≥8.2kPa. Results: Included 45 patients with MALFD, 53.3% female gender, mean age of 53.5±10.9years. EKD was found in 17.8% of patients. MAFLD patients with EKD were significantly more obese (body mass index≥30) (75.0% vs 32.4%,p=0.045) and had significantly higher LSM (8.5±4.1 vs 5.8±2.2kPa,p=0.01). After adjustment of potential confounders for EKD the presence of liver fibrosis, remained a significant predictor of EKD, being associated with a 14.3-fold increased risk of EKD (p=0.04). The optimal cutoff value of LSM to predict EKD was 6.1kPa (sensitivity:85.7%; specificity:67.6%). Conclusion: Significant liver fibrosis is associated with a significant increased risk of EKD in patients with MAFLD, regardless of other comorbidities. Higher levels of LSM, particularly >6.1kPa, alert for timely identification of EKD and associated comorbidities, as well as their control, in order to prevent the development of CKD in the long term.

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