Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome.

Introduction: The pathogenesis of Post-Transplant Diabetes Mellitus (PTDM) is complex and multifactorial and it resembles that of Type-2 Diabetes Mellitus (T2DM). One risk factor specific to PTDM differentiates both entities: the use of immunosuppressive therapy. Specifically, Tacrolimus interacts with obesity and insulin resistance (IR) in accelerating the onset of PTDM. In a genotypic model of IR, the obese Zucker rats, Tacrolimus is highly diabetogenic by promoting the same changes in beta-cell already modified by IR. Nevertheless, genotypic animal models have their limitations and may not resemble the real pathophysiology of diabetes. In this study, we have evaluated the interaction between beta-cell damage and Tacrolimus in a non-genotypic animal model of obesity and metabolic syndrome. Methods: Sprague Dawley rats were fed a high-fat enriched diet during 45 days to induce obesity and metabolic dysregulation. On top of this established obesity, the administration of Tacrolimus (1mg/kg/day) during 15 days induced severe hyperglycaemia and changes in morphological and structural characteristics of the pancreas. Results: Obese animals administered with Tacrolimus showed increased size of islets of Langerhans and reduced beta-cell proliferation without changes in apoptosis. There were also changes in beta-cell nuclear factors such as a decrease in nuclear expression of MafA and a nuclear overexpression of FoxO1A, PDX-1 and NeuroD1. These animals also showed increased levels of pancreatic insulin and glucagon. Discussion: This model could be evidence of the relationship between the T2DM and PTDM physiopathology and, eventually, the model may be instrumental to study the pathogenesis of T2DM.

Telmisartan ameliorates nephropathy and restores the hippo pathway in rats with metabolic syndrome.

The main objective of this study was to determine if the telmisartan-ameliorative effects of metabolic syndrome (MetS)-evoked nephropathy are attributed to the Hippo pathway. A secondary objective was to investigate the potential of vitamin D3 to enhance telmisartan-favourable effects. A diet composed of 24% fat and 3% salt, along with drinking water containing 10% fructose, was administered for 12 weeks to induce MetS. MetS-rats were given telmisartan (5 mg/kg/day), vitamin D3 (10 µg/kg/day) or both by gavage, starting in the sixth week of experimental diet administration. Assessments performed at closure included renal function, histological examination, catalase, malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphatase and tensin homolog (PTEN), and transforming growth factor-ß (TGF-ß). Matrix metalloproteinase-9 (MMP-9) immunostaining was conducted. The expression of the Hippo pathway components, as well as that of angiotensin II type 1 and type 2 (AT1 and AT2), receptors was evaluated. Telmisartan attenuated MetS-evoked nephropathy, as demonstrated by improvement of renal function and histological features, enhancement of catalase, reduction of MDA, inflammation (NF-κB, IL-6), and renal fibrosis (increased PPAR-γ and PTEN and reduced MMP-9 and TGF-ß). Telmisartan downregulated AT1-receptor, upregulated AT2-receptor and restored the Hippo pathway. Vitamin D3 replicated most of the telmisartan-elicited effects and enhanced the antifibrotic actions of telmisartan. The alleviative effects of telmisartan on MetS-evoked nephropathy may be related to the restoration of the Hippo pathway. The combination of vitamin D3 and telmisartan exerted more favourable effects on metabolic and nephropathic biomarkers compared with either one administered alone.

Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Cardiac remodeling associated with chronic kidney disease is enhanced in a rat model of metabolic syndrome: Preparation of mesenchymal transition.

Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD). The main objective of this study was to assess if pre-existing metabolic disease exacerbates CKD-induced cardiac alterations. In addition, we hypothesised that endothelial to mesenchymal transition participates in this enhancement of cardiac fibrosis. Rats fed cafeteria type diet for 6 months underwent a subtotal nephrectomy at 4 months. Cardiac fibrosis was evaluated by histology and qRT-PCR. Collagens and macrophages were quantified by immunohistochemistry. Endothelial to mesenchymal transitions were assessed by qRT-PCR (CD31, VE-cadherin, α-SMA, nestin) and also by CD31 immunofluorescence staining. Rats fed with cafeteria type regimen were obese, hypertensive and insulin resistant. Cardiac fibrosis was predominant in CKD rats and was highly majored by cafeteria regimen. Collagen-1 and nestin expressions were higher in CKD rats, independently of regimen. Interestingly, in rats with CKD and cafeteria diet we found an increase of CD31 and α-SMA co-staining with suggest an implication of endothelial to mesenchymal transition during heart fibrosis. We showed that rats already obese and insulin resistant had an enhanced cardiac alteration to a subsequent renal injury. Cardiac fibrosis process could be supported by a involvement of the endothelial to mesenchymal transition phenomenon.

Mesenchymal stem cell-derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy.

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%-25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy, promising a holistic shift. MSC-EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC-EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC-EVs therapy for treating MetS.

Metabolic Syndrome is Associated with Prostate Cancer Diagnosed on Biopsy but not the Gleason Score and the Number of Cancer-Positive Cores: A Prospective Controlled Study.

OBJECTIVE: We aimed to investigate the association between metabolic syndrome (MetS) and prostate cancer (PCa) in patients undergoing prostate biopsy. MATERIALS AND METHODS: Between January 2018 and December 2022, MetS was investigated according to Adult Treatment Panel III (ATP III) criteria in men who underwent prostate biopsy with transrectal ultrasound (TRUS). Clinicopathological factors such as, digital rectal examination (DRE), prostate-specific antigen (PSA), prostate volume, waist circumference, body mass index (BMI), age, blood pressure, testosterone, lipid profiles, fasting blood glucose level, C-reactive protein (CRP) and MetS were analyzed. RESULTS: A total of 908 men underwent biopsies, of which 492 (51.5%) had MetS according to ATP III criteria. The number of patients diagnosed with PCa in biopsy was 270 (29.7%). PCa cases were significantly older, with a lower prostate volume and a higher PSA value and higher blood pressure compared to patients without PCa (p < 0.001). 146 of 416 (35.0%) patients with MetS had PCa while 124 of 492 (25.2%) patients without MetS had PCa (p < 0.001). Out of 270 patients with PCa, 174 (64.4%) had Gleason score <7 and 96 (35.6%) had Gleason score ≥7. In patients with a Gleason score ≥7, PSA, DRE(+) and core positive number were significantly higher compared to patients with Gleason score <7, while glycemia and high-density lipoprotein (HDL) cholesterol levels were significantly lower (p < 0.001). Multivariate analysis showed that age, PSA, positive DRE, prostate volume (p < 0.001), diastolic blood pressure, CRP and MetS were the only independent parameters associated with a higher risk of cancer on biopsy (p < 0.05). CONCLUSIONS: Our findings show that MetS is associated with PCa diagnosed on biopsy but not with the Gleason score and the number of cancer-positive cores. However, these results should be confirmed by larger, multicenter and prospective studies.

Mesenchymal Stem/Stromal Cells Therapy for Metabolic Syndrome: Potential Clinical Application?

Mesenchymal stem/stromal cells (MSCs), a class of cells with proliferative, immunomodulatory, and reparative functions, have shown therapeutic potential in a variety of systemic diseases, including metabolic syndrome (MetS). The cluster of morbidities that constitute MetS might be particularly amenable for the application of MSCs, which employ an arsenal of reparative actions to target multiple pathogenic pathways simultaneously. Preclinical studies have shown that MSCs can reverse pathological changes in MetS mainly by inhibiting inflammation, improving insulin resistance, regulating glycolipid metabolism, and protecting organ function. However, several challenges remain to overcome before MSCs can be applied for treating MetS. For example, the merits of autologous versus allogeneic MSCs sources remain unclear, particularly with autologous MSCs obtained from the noxious MetS milieu. The distinct characteristics and relative efficacy of MSCs harvested from different tissue sources also require clarification. Moreover, to improve the therapeutic efficacy of MSCs, investigators have explored several approaches that improved therapeutic efficacy but may involve potential safety concerns. This review summarized the potentially useful MSCs strategy for treating MetS, as well as some hurdles that remain to be overcome. In particular, larger-scale studies are needed to determine the therapeutic efficacy and safety of MSCs for clinical application.

Steatotic hepatocellular carcinoma: Association of MRI findings to underlying liver disease and clinicopathological characteristics.

BACKGROUND & AIMS: Fatty change is commonly observed in hepatocellular carcinoma (HCC); however, the characteristics of steatotic and steatohepatitic HCCs are not well understood. METHODS: This retrospective study included patients with HCCs who underwent resection between January 2014 and December 2019 to evaluate clinicopathological and magnetic resonance imaging features. Tumours were categorized as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs and were defined as HCCs with ≥50% steatosis on in-and-oppose phase images, ≥34% tumour cells with lipid droplets and ≥50% tumour areas with steatohepatitic features on light microscopy respectively. RESULTS: Of 465 HCCs, 38 (8%), 23 (5%) and 15 (3%) were diagnosed as magnetic resonance imaging-steatotic, pathology-steatotic and steatohepatitic HCCs respectively. These HCC variants were less likely to be associated with hepatitis B virus infections than with type 2 diabetes mellitus, metabolic syndrome, non-tumour liver steatosis and steatohepatitis. Moreover, microvascular invasion was less likely to be associated with them than either tumour size or differentiation. Type 2 diabetes and non-tumour steatosis were independent risk factors for magnetic resonance imaging-steatotic HCCs. Pathology-steatotic HCCs and steatohepatitic HCCs were significantly associated with magnetic resonance imaging-steatotic HCCs. A targetoid appearance in the transitional or hepatobiliary phase was also more prevalent in steatohepatitic-HCCs than in non-steatohepatitic-HCCs. When magnetic resonance imaging-steatotic HCCs were combined with one or more ancillary features, the sensitivity and specificity were 60% and 97% respectively. CONCLUSION: Underlying fatty liver disease and metabolic syndrome are strongly associated with both steatotic and steatohepatitic HCCs. Clinicoradiological characteristics help identify steatohepatitic HCC with high specificity.

Deciphering Intertwined Molecular Pathways Underlying Metabolic Syndrome Leading to Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that gradually develops over time in a progressive manner. The main culprit behind the disease pathology is dopaminergic deficiency in Substantia nigra Pars Compacta (SNpc) due to neuronal degeneration. However, there are other factors that are not only associated with it but also somehow responsible for inception of pathology. Metabolic syndrome is one such risk factor for PD. Metabolic syndrome is a cluster of diseases mainly including diabetes, hypertension, obesity, and hyperlipidemia which pose a risk for developing cardiovascular disorders. All of these disorders have their own pathological pathways that intertwine with PD pathology. This leads to alpha-synuclein aggregation, neuroinflammation, mitochondrial dysfunction, and oxidative stress which are facets in initiating PD pathology. Although few reports are available, this area is underexplored and has contradictory views. Hence, further studies are needed in order to establish a definite relationship between PD and metabolic syndrome. In this review, we aim to elucidate the molecular mechanisms to confirm the association between them and pave the way for potential repurposing of therapies.

Prediction of Bilaterality in Patients With 1 Posterosuperior Rotator Cuff Tear.

BACKGROUND: In patients with a known unilateral posterosuperior rotator cuff tear (PSRCT), the ability to predict a contralateral PSRCT may assist in earlier diagnosis and improved patient outcomes. PURPOSE: To determine factors associated with bilateral PSRCT and their most predictive combinations using a nonhospitalized general population. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study involved 736 individuals (n = 1472 shoulders) drawn from a rural cohort. PSRCT was diagnosed using magnetic resonance imaging. Symptoms of the contralateral shoulder were not considered. The demographic, physical, social, metabolic, and imaging factors, as well as comorbidities, were evaluated using logistic regression analysis. Cutoff values for the significantly associated variables obtained from multivariable logistic regression analysis were calculated using the receiver operating characteristic (ROC) curve. The areas under the ROC curve (AUCs) of the combinations of significantly associated variables were compared using the DeLong method to determine the combination most predictive of bilateral PSRCT. The likelihood ratio and the posttest probability for each of the combinations were assessed. RESULTS: Age ≥61 years, manual labor, critical shoulder angle (CSA) ≥35°, retraction degree of Patte ≥ grade 2, biceps tendon injury, and metabolic syndrome were significantly associated with bilateral PSRCT in multivariable analysis (P < .001). The 1-by-1 combination of any 4 of the 6 associated factors significantly increased the AUC of any smaller combinations of those 6 factors (P < .001). The AUCs of the 4-somes were all similar (P ≥ .383) and were not significantly increased by further addition of identified associated factors (P ≥ .422). Any combination of 4 of the 6 associated factors was highly predictive of bilateral PSRCT, each having a minimum AUC of 0.70, a likelihood ratio of >10, and a minimum posttest probability of 80%. CONCLUSION: Unilateral PSRCT, accompanied by any 4 of the variables of age ≥61 years, manual labor, CSA ≥35°, retraction degree of Patte ≥ grade 2, biceps tendon injury, and metabolic syndrome, is highly predictive of PSRCT in the other shoulder.

Liver Steatosis: A Marker of Metabolic Risk in Children.

Obesity is one of the greatest health challenges affecting children of all ages and ethnicities. Almost 19% of children and adolescents worldwide are overweight or obese, with an upward trend in the last decades. These reports imply an increased risk of fat accumulation in hepatic cells leading to a series of histological hepatic damages gathered under the acronym NAFLD (Non-Alcoholic Fatty Liver Disease). Due to the complex dynamics underlying this condition, it has been recently renamed as 'Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)', supporting the hypothesis that hepatic steatosis is a key component of the large group of clinical and laboratory abnormalities of Metabolic Syndrome (MetS). This review aims to share the latest scientific knowledge on MAFLD in children in an attempt to offer novel insights into the complex dynamics underlying this condition, focusing on the novel molecular aspects. Although there is still no treatment with a proven efficacy for this condition, starting from the molecular basis of the disease, MAFLD's therapeutic landscape is rapidly expanding, and different medications seem to act as modifiers of liver steatosis, inflammation, and fibrosis.

Correlation of insulin resistance with neutrophil to lymphocyte ratio and serum ferritin in male patients of metabolic syndrome.

OBJECTIVE: To determine the correlation of insulin resistance with neutrophil-to-lymphocyte ratio and serum ferritin, and to evaluate whether NLR and serum ferritin can predict insulin resistance in metabolic syndrome. METHODS: The cross-sectional analytical study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to 2019, and comprised male patients of metabolic syndrome and healthy controls. The correlation involving insulin resistance, serum ferritin and neutrophil-to-lymphocyte ratio was determined. Data was analysed using SPSS 22. RESULTS: Of the 210 subjects, 160(76.2%) were cases with a median age of 45 years (interquartile range: 39-50 years), and 50(23.8%) were controls with a median age of 41 years (interquartile range: 35-50 years). Serum ferritin, alanine aminotransferase, total neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio were significantly higher among the cases than the controls (p<0.05). Significant positive correlation of insulin resistance was observed with serum ferritin and neutrophil-to-lymphocyte ratio (p<0.05)) among the cases. Neutrophil-to-lymphocyte ratio significantly predicted insulin resistance among the cases (p<0.05). Conclusion: Neutrophil-to-lymphocyte ratio was fund to be a significant predictor of insulin resistance in metabolic syndrome.

Metabolic impact of the VDR rs1544410 in diabetic retinopathy.

AIMS: To investigate the association between BsmI and DM2 in patients with and without DR and to correlate with clinical parameters in a population in northeastern Brazil. METHODS: Cross-sectional case-control study in which data were collected from 285 individuals, including 128 patients with DM2 and 157 with DR. Clinical, biochemical and anthropometric parameters were analyzed, in addition to the single nucleotide polymorphism (SNP) BsmI of the VDR gene (rs1544410), genotyped by PCR-RFLP. RESULTS: In the DR group we found a greater number of patients using insulin therapy (p = 0.000) and with longer duration of DM2 (p = 0.000), in addition to higher serum creatinine values (p = 0.001). Higher fasting glucose levels and higher frequency of insulinoterapy were independently observed in patients with DR and b allele carriers, when compared to BB. CONCLUSION: The association of the bb/Bb genotypes (rs1544410) of the VDR gene with increased blood glucose levels and insulinoterapy may represent worse glicemic control in rs1544410 b allele carriers in DR Latin American individuals.

Low calf circumference can predict nutritional risk and mortality in adults with metabolic syndrome aged over 80 years.

BACKGROUND: Metabolic disorders and malnutrition are a double burden worldwide. The aim was to determine whether low calf circumference (CC) could predict nutritional risk and the cut-off values of CC for predicting nutritional risk in metabolic syndrome (MetS) patients aged over 80 years. We aimed to evaluate the risk factors for predicting mortality in MetS. METHODS: A total of 514 patients aged over 80 years with MetS were enrolled and followed for 2.5 years. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with a Nutritional Risk Screening 2002 (NRS 2002) total score ≥ 3 were considered to have nutritional risk. RESULTS: The CC level was significantly lower in the nutritional risk group than in the non-nutritional risk with MetS group (27.1 ± 4.0 cm vs. 30.8 ± 3.9 cm). Logistic regression analysis of nutritional risk revealed that increasing CC (adjusted OR, 0.81; 95% CI, 0.74-0.88) was an independent protective factor against nutrition risk. The best CC cut-off value for predicting nutritional risk according to the NRS 2002 was 28.8 cm. Cox regression multivariate models showed nutritional risk (HR, 2.48; 95% CI, 1.22-5.04) and decreased CC (HR, 2.78; 95% CI, 1.27-5.98) remained independent risk factors for mortality. CONCLUSION: Decreased CC could predict not only nutritional risk but also mortality in MetS patients aged over 80 years. The elderly who had MetS with nutritional risk should be discovered early, early intervention and early treatment. CC may be a valuable index to screen out this population.

Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women.

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.

The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome.

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

Association between being metabolically healthy/unhealthy and metabolic syndrome in Iranian adults.

INTRODUCTION: The prevalence of metabolically healthy obesity (MHO) varies based on different criteria. We assessed the prevalence of MHO and metabolic unhealthiness based on body mass index (BMI) and their association with metabolic syndrome (MetS) in a nation-wide study. METHODS: Data were taken from the STEPs 2016 study, from 18,459 Iranians aged ≥25 years. Demographic, metabolic, and anthropometric data were collected. Subjects were stratified by BMI, metabolic unhealthiness, and having MetS. The latter was defined based on National Cholesterol Education Program Adult Treatment Panel III 2004 (NCEP ATP III), was then assessed. RESULTS: The prevalence of MHO and metabolic unhealthiness in obese subjects was 7.5% (about 3.6 million) and 18.3% (about 8.9 million), respectively. Most of the metabolic unhealthy individuals were female (53.5%) or urban residents (72.9%). Low physical activity was significantly and positively associated (Odds Ratio: 1.18, 95% CI: 1.04-1.35) with metabolic unhealthiness, while being a rural residence (0.83, 0.74-0.93), and having higher education (0.47, 0.39-0.58) significantly but negatively affected it. Dyslipidemia was the most frequent MetS component with a prevalence rate of 46.6% (42.1-51.1), 62.2% (60.8-63.6), 76.3% (75.1-77.5), and 83.4% (82.1-84.6) among underweight, normal weight, overweight and obese phenotypes, respectively. CONCLUSION: BMI aside, an additional set of criteria such as metabolic markers should be taken into account to identify normal weight but metabolically unhealthy individuals. Given the highest prevalence of dyslipidemia among obese subjects, further interventions are required to raise public awareness, promote healthy lifestyles and establish lipid clinics.

Non-obese non-alcoholic fatty liver disease (NAFLD) in Asia: an international registry study.

BACKGROUND: A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients. METHODS: 1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients. FINDINGS: One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p < 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease. CONCLUSION: A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

Association Between Metabolic Syndrome and Immunohistochemical Profile at Breast Cancer Diagnosis in Postmenopausal Women.

BACKGROUND: The aim of this study was to evaluate the association between metabolic syndrome (MetS) and the immunohistochemical profile of breast cancer (BC) in postmenopausal women. METHODS: This cross-sectional cohort study included 189 women, aged 45 to 75years and amenorrhea >12 months, with newly diagnosed BC and no previous cancer treatment. Clinical, anthropometric and biochemical data were collected, as well as data on BC hormone status (estrogen receptor, ER; progesterone receptor, PR; human epidermal growth factor receptor-2, HER-2), and epithelial proliferative activity (Ki-67). Tumors were divided into 5 subtypes:luminal A, luminal B HER-2 negative, luminal B HER-2 positive, non-luminal HER-2, and triple negative. Women with three or more of the following criteria were diagnosed with MetS: waist circumference ≥88cm; triglycerides ≥150mg/dL; HDL-cholesterol <50mg/dL; blood pressure ≥130/85mmHg; glucose ≥100mg/dL. RESULTS: Sixty-three (33.3%) of the 189 patients had MetS at the time of diagnosis. Women with MetS had a higher frequency of tumors ≤ 2cm than women without MetS (49.2% vs. 31.8%) (P = .038). There were no differences in histological grade, staging, or axillary lymph node metastasis (P > .05). The proportion of PR-positive (P = .006), HER-2-negative (P = .034), and luminal B HER-2-negative (P = .038) tumors was higher among patients with MetS compared to women without MetS (79.4% vs. 61.8%, 89.9% vs. 78.6% and 44.5% vs. 27.8%, respectively). Multivariate analysis adjusted for age, time since menopause and BMI showed a higher risk for luminal B HER-2-negative tumors among women with MetS (OR 2.00, 95% CI 1.03-3.89), obese patients (OR 2.03, 95% CI 1.06-3.90), and women with abdominal obesity (OR 1.96, 95% CI 1.01-4.03). CONCLUSION: In postmenopausal women with newly diagnosed BC, the presence of MetS was associated with smaller tumor size, PR-positive and HER-2-negative status, and the luminal B tumor subtype.

Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV-HIV Co-infected Adults.

BACKGROUND: There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. AIMS: To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation. METHODS: Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV-HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated. RESULTS: HBV-HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV-HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV-HIV. Negative predictive values were higher than positive predictive values for all scores in both groups. CONCLUSION: The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.