Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans (HAIR-AN) Syndrome Reflects Adipose Tissue Dysfunction (“Adiposopathy” or “Sick Fat”) in Asian Indian Girls

Dermatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Kritika Agrawal ◽  
Rachita Mathur ◽  
Naincy Purwar ◽  
Sandeep Kumar Mathur ◽  
Deepak Kumar Mathur
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Markers ◽  
Tertiary Care ◽  
Serum Adiponectin ◽  
Primary Role ◽  
Care Hospital ◽  
Adipose Tissue Dysfunction ◽  
Tnf Α

<b><i>Background:</i></b> Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of “adiposopathy.” <b><i>Materials and Methods:</i></b> A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. <b><i>Results:</i></b> Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (<i>p</i> &#x3c; 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (<i>p</i> &#x3e; 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. <b><i>Conclusion:</i></b> The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction (“adiposopathy”) in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

scholarly journals Adipose Tissue Insulin Resistance Is Longitudinally Associated With Adipose Tissue Dysfunction, Circulating Lipids, and Dysglycemia: The PROMISE Cohort

2021 ◽  
Author(s):  
Zhila Semnani-Azad ◽  
Philip W. Connelly ◽  
Richard P. Bazinet ◽  
Ravi Retnakaran ◽  
David J. A. Jenkins ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Total Cholesterol ◽  
Estimating Equation ◽  
Adipose Tissue Dysfunction ◽  
Increased Risk ◽  
Tnf Α ◽  
Design And Methods

<b>Aim: </b>Our objective was to determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. <div><p><b>Research design and methods</b>: Adults at-risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n=468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and non-esterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and sCD163), circulating lipids (total cholesterol, HDL, LDL, TG), and systemic inflammation (Il-6 and TNF-α). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes.</p> <p><b>Results</b>: GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin: -4.20% (95%CI, -6.40 to –1.95); sCD163: 4.36% (95%CI, 1.73 – 7.06), HDL (-3.87% (95%CI, -5.15 to -2.57)) and TG (9.26% (95%CI, 5.01 to 13.69)). Adipo-IR was associated with increased risk of incident dysglycemia (OR=1.59; 95%CI, 1.09 to 2.31, per SD increase). Associations remained significant after adjustment for waist circumference, and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with Il-6, TNF-α, total cholesterol, or LDL.</p> <p><b>Conclusion</b>: Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.</p> </div> <b><br> </b>

scholarly journals The role of obesity and adipose tissue dysfunction in gestational diabetes mellitus

2018 ◽  
Vol 238 (2) ◽  
pp. R63-R77 ◽  
Author(s):  
Patrik Šimják ◽  
Anna Cinkajzlová ◽  
Kateřina Anderlová ◽  
Antonín Pařízek ◽  
Miloš Mráz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Current Knowledge ◽  
Peripheral Insulin Resistance ◽  
Adipose Tissue Dysfunction ◽  
History Of

Gestational diabetes mellitus is defined as diabetes diagnosed in the second or third trimester of pregnancy in patients with no history of diabetes prior to gestation. It is the most common complication of pregnancy. The underlying pathophysiology shares some common features with type 2 diabetes mellitus (T2DM) combining relatively insufficient insulin secretion with increased peripheral insulin resistance. While a certain degree of insulin resistance is the physiological characteristics of the second half of pregnancy, it is significantly more pronounced in patients with gestational diabetes. Adipose tissue dysfunction and subclinical inflammation in obesity are well-described causes of increased insulin resistance in non-pregnant subjects and are often observed in individuals with T2DM. Emerging evidence of altered adipokine expression and local inflammation in adipose tissue in patients with gestational diabetes suggests an important involvement of adipose tissue in its etiopathogenesis. This review aims to summarize current knowledge of adipose tissue dysfunction and its role in the development of gestational diabetes. We specifically focus on the significance of alterations of adipokines and immunocompetent cells number and phenotype in fat. Detailed understanding of the role of adipose tissue in gestational diabetes may provide new insights into its pathophysiology and open new possibilities of its prevention and treatment.

scholarly journals sMAdCAM:IL-6 (sMIL Index): A novel signature associated with COVID-19 disease progression and development of anti-SARS-CoV-2 antibodies

2020 ◽  
Author(s):  
Dhanashree Jagtap ◽  
Vikrant M Bhor ◽  
Shilpa Bhowmick ◽  
Nandini Kasarpalkar ◽  
Pooja Sagvekar ◽  
...  
Keyword(s):  
Disease Progression ◽  
Inflammatory Mediators ◽  
Inflammatory Markers ◽  
Tertiary Care ◽  
Fold Change ◽  
Care Hospital ◽  
Antiviral Responses ◽  
Disease States ◽  
Plasma Antibody

IMPORTANCERecent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored.OBJECTIVETo evaluate the role of systemic and gut inflammatory markers in disease progression and development of anti-viral humoral immunity following SARS-CoV-2 infection.DESIGN, SETTING AND PARTICIPANTSThis cohort study (n=58) of SARS-CoV-2 infected individuals included a group of in-patients (n=36) at various stages of disease progression together with convalescent individuals (n=22) recruited between April and June 2020 (peak of the epidemic) from a tertiary care hospital in Mumbai, India. Follow-up of 11 in-patients at day 7 post diagnosis was carried out, resulting in a total of 47 in-patient samples.EXPOSURESDiagnosis of SARS-CoV-2 infections was confirmed by reverse transcriptase–polymerase chain reaction-based testing of nasopharyngeal/oropharyngeal samples.MAIN OUTCOMES AND MEASURESPrimary outcomes were the measurement of inflammatory markers including Th1/Th2/Th17 cytokines and levels of soluble mucosal addressin cell adhesion molecule (sMAdCAM) in plasma. Anti-viral humoral response was measured by rapid antibody test (IgG, IgM) and chemiluminescent immunoassay (CLIA) (IgG). Also antibodies binding to SARS-CoV-2 proteins were measured by surface plasmon resonance (SPR). Secondary outcomes were correlation of the inflammatory signature with clinical information, including age, sex, disease duration and co-morbidities.RESULTSTwenty eight of 36 (78%) in-patients and 19 of 22 (86%) convalescents were males. Out of 47 in-patient samples, 22 (46%), 11 (23%) and 14 (30%) were IgG-/IgM-, IgG+/IgM+ and IgG+/IgM-respectively. Of 22 convalescent samples, 3 (14%), 1 (4%) and 17 (77%) were respectively IgG-/IgM-, IgG+/IgM+ and IgG+/IgM-. Two out of 22 (9%) convalescents showed high IL-6 levels (>100pg/ml) and 4 (18%) had high TNF levels (>30pg/ml). However, the convalescents (n =22) had significantly lower levels of IL-6 [Median=27.48 (IQR=23.54-39.92)] compared to followed up in-patients (n = 11) at day 0 [Median=111(IQR=68-129.7), p =0.0002] and higher levels of sMAdCAM [Median=1940 (1711-2174) pg/ml] compared to these individuals at day 0 [Median=1701 (IQR=1532-1836) pg/ml; p=0.032] and day 7 [Median=1534 (IQR=1236-1654) pg/ml; p=0.0007]. Further, IL-6 and sMAdCAM levels among in-patients inversely correlated with one another (r = −0.374, p = 0.009, CI = 95%). When expressed as a novel integrated marker –sMIL (sMAdCAM/IL-6 ratio) index, these levels were incrementally and significantly higher across various disease states with convalescents exhibiting the highest values [Median= 64.74 (IQR=47.33-85.58)]. Also, the sMIL index was significantly higher in convalescents (with class-switched responses) compared to IgG+/IgM+ individuals at early stages of infection [Median=28.65 (IQR=13.63-96.26), p = 0.034]. Real-time measurement by SPR of plasma antibody binding to viral nucleocapsid (NC), receptor binding domain (RBD) and spike (S) revealed waxing and waning of plasma antibody responses to all 3 targets. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of RBD-binding (r = 0.462, p = 0.03, CI = 95%) and fold change in binding to S (r = 0.68, p = 0.050, CI = 95%) respectively.CONCLUSION AND RELEVANCEOur results highlight key systemic and gut-associated immune parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.KEY POINTSQuestionDo systemic and gut inflammatory mediators play a role in disease progression as well as development of antiviral responses in SARS-CoV-2 infection?FindingsIL-6 and sMAdCAM expressed as a novel integrative marker (sMIL index) are associated both with disease-states (early infection and convalescence) as well as development of antiviral humoral responses.MeaningFurther investigation into the utility of using sMIL index as a biomarker for disease progression and recovery, including the development of potentially neutralizing antiviral responses is warranted.

scholarly journals Adipose Tissue Insulin Resistance Is Longitudinally Associated With Adipose Tissue Dysfunction, Circulating Lipids, and Dysglycemia: The PROMISE Cohort

2021 ◽  
Author(s):  
Zhila Semnani-Azad ◽  
Philip W. Connelly ◽  
Richard P. Bazinet ◽  
Ravi Retnakaran ◽  
David J. A. Jenkins ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Total Cholesterol ◽  
Estimating Equation ◽  
Adipose Tissue Dysfunction ◽  
Increased Risk ◽  
Tnf Α ◽  
Design And Methods

<b>Aim: </b>Our objective was to determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. <div><p><b>Research design and methods</b>: Adults at-risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n=468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and non-esterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and sCD163), circulating lipids (total cholesterol, HDL, LDL, TG), and systemic inflammation (Il-6 and TNF-α). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes.</p> <p><b>Results</b>: GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin: -4.20% (95%CI, -6.40 to –1.95); sCD163: 4.36% (95%CI, 1.73 – 7.06), HDL (-3.87% (95%CI, -5.15 to -2.57)) and TG (9.26% (95%CI, 5.01 to 13.69)). Adipo-IR was associated with increased risk of incident dysglycemia (OR=1.59; 95%CI, 1.09 to 2.31, per SD increase). Associations remained significant after adjustment for waist circumference, and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with Il-6, TNF-α, total cholesterol, or LDL.</p> <p><b>Conclusion</b>: Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.</p> </div> <b><br> </b>

TO DETERMINE THE ROLE OF CA125 IN THE DIAGNOSIS OF ACUTE APPENDICITIS

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Vinod Kumar ◽  
Bhupen Songra ◽  
Richa Jain ◽  
Deeksha Mehta
Keyword(s):  
Acute Appendicitis ◽  
Clinical Diagnosis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Ca 125 ◽  
Care Hospital ◽  
Serum Samples ◽  
Roc Curve Analysis ◽  
Surgery Department

Background: the present study was under taken to determine the role of CA-125 in the diagnosis of acute appendicitis (AA), to prevent its complications and also in preventing negative appendicectomies in tertiary care hospital. Methods: The study was conducted at a tertiary care and research center between 01/03/2018 to 30/06/2019. Patients admitted to the surgery department with diagnosis of AA were considered for the study. After informed consent, a, standardized history was obtained as a case Performa. Serum samples from all the cases with clinical diagnosis of AA were obtained and stored. Only the cases with histopathologically approved AA were included in the study. Cases operated for clinical diagnosis of AA, but not histopathologically proven AA was not included in the study. CA125 levels in cases with definitive diagnosis of AA were measured. Results: In present study, ROC curve analysis revealed the sensitivity of 87.27 % and specificity of 90.91 % when the CA 125 cut-off value of > 16.8 was taken to diagnose acute appendicitis. AUC was 0.911 with a standard error of 0.0292. Conclusion: In this study we have observed that CA125 showed a positive correlation with acute appendicitis, that was statistically not significant (P>0.05). We didn’t evaluate the correlation with the disease severity. We consider that CA125 can be used as a marker in acute appendicitis cases although further research is still needed. Keywords: CA125, Acute Appendicitis, Surgery.

The role of the clinical pharmacist in guiding adjuvant hormonal therapy in patients with breast cancer

2021 ◽  
pp. 107815522110293
Author(s):  
Amanda V Pirolli ◽  
Tatiana Brusamarello ◽  
Stella S Everton ◽  
Vânia M S Andrzejevski
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Hormonal Therapy ◽  
Clinical Pharmacist ◽  
Tertiary Care ◽  
Structured Interview ◽  
Care Hospital ◽  
Adjuvant Hormonal Therapy ◽  
Breast Cancers

Breast cancer is the most prevalent type of cancer among women, affecting about 2.1 million worldwide and is responsible for the highest number of cancer-related deaths among women. Approximately 80% of breast cancers express on the surface of hormone receptor cells, such as progesterone and estrogen. In these cases, Adjuvant Hormonal Therapy (AHT) is indicated for a period of five to ten years and consists of taking a daily oral pill. The two most used drugs in AHT are tamoxifen and Aromatase Inhibitors. One of the issues most faced by individuals who are subjected to long periods of treatment is the lack of medication adherence and, consequently, therapeutic inefficiency. It is believed that the monitoring by the pharmacist can contribute to the reduction of errors inherent to the medication, making the treatment more effective and improving the patient's quality of life. The present study aimed to know the perception of patients who live with breast cancer and who do AHT in relation to the educational performance of the clinical pharmacist. This is a qualitative, descriptive and exploratory study, carried out from March to October 2020, with 15 women undergoing treatment at the oncology unit of a tertiary-care hospital in south of Brazil. The data were obtained through a semi-structured interview using an instrument composed of two parts, one referring to the characterization of the participants and the other with the guiding question of the research: "How do you perceive the role of the pharmacist in relation to the guidelines for the use of adjuvant hormonal therapy?". The method of theoretical saturation was used to perform the sample closure and the thematic analysis was used to analyze the data. The participants were between 32 and 74 years old, seven were on tamoxifen therapy and eight on anastrozole, ten were on the first year of treatment, two on the second and three on the third year. The themes that emerged were: pharmacist-patient interaction as a safety factor in hormone therapy; role of the pharmacist in the development of strategies for self-management of the patients during hormone therapy; and, challenges for the pharmacist in relation to hormone therapy through continued guidance. It was evident that the pharmacist's educational action encouraged the participants to carry out the treatment in a more confident and assertive manner according to their particularities and beliefs.

scholarly journals N-Acetylcysteine (NAC): Impacts on Human Health

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 967
Author(s):  
Micaely Cristina dos Santos Tenório ◽  
Nayara Gomes Graciliano ◽  
Fabiana Andréa Moura ◽  
Alane Cabral Menezes de Oliveira ◽  
Marília Oliveira Fonseca Goulart
Keyword(s):  
Human Health ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Primary Role ◽  
Necrosis Factor Alpha ◽  
Biochemical Basis ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

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