scholarly journals Predictors of Insulin Resistance and Liver Steatosis in the Miami Adult Studies on HIV (MASH) Cohort

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1540-1540
Author(s):  
Colby Teeman ◽  
Jacqueline Hernandez ◽  
Yongjun Huang ◽  
Jose Bastida Rodriguez ◽  
Nicholas Gonzalez ◽  
...  

Abstract Objectives Immune activation is central to developing insulin resistance and is implicated in the pathophysiology of liver steatosis. People living with HIV (PLWH) have elevated biomarkers of immune activation, which may play a role in faster development of insulin resistance and liver steatosis. The objective of this study was to examine if HIV status and immune activation are related to insulin resistance and liver steatosis. Methods Demographic and anthropometric data on MASH cohort participants were obtained. Insulin resistance was estimated using the triglyceride-glucose (TyG) index from fasting blood. HIV status was abstracted from participants’ medical records. Immune activation biomarkers soluble CD163 (sCD163), sCD27, sCD14, and monocyte chemoattractant protein (MCP-1) measured with multiplex flow cytometry in Dr. Sherman's laboratory. High sensitivity C-Reactive Protein (hsCRP), measure of inflammation, was determined by LabCorp. Liver steatosis was defined as liver fat >3.5% obtained with magnetic resonance elastography scans. Statistics included descriptive analysis, Mann-Whitney tests, multivariate linear, and logistic regressions, controlled for age, sex, and BMI. Results Of the 712 participants (age 54.24 ± 7.48 years), 336 were PLWH with suppressed viral load, and 376 were uninfected healthy participants. PLWH had higher levels of sCD27 (P = 0.003) and MCP-1 (P = 0.034) than uninfected participants. Multiple linear regressions showed HIV status and sCD163 were independently associated with higher insulin resistance (HIV status b = 0.130, P = 0.014, sCD163 Multiple logistic regressions showed higher levels of sCD163 (OR = 1.097, 95% CI: 1.01–1.19, P = 0.032) and insulin resistance (OR = 7.126, 95% CI: 2.59–19.58, P < 0.001) were significant predictors of liver steatosis. HIV status, sCD14, sCD27, hsCRP, or MCP-1 were not related to liver steatosis. Conclusions These results indicate that HIV infection and sCD163, a marker of immune activation, are independent predictors of insulin resistance, and sCD163 was associated with greater odds of liver steatosis. Lifestyle interventions and anti-inflammatory agents aimed at reducing insulin resistance and immune activation in PLWH may help to reduce the risk of liver steatosis and other co-morbidities. Funding Sources Grant Number: U01DA040381.

2006 ◽  
Vol 291 (2) ◽  
pp. E282-E290 ◽  
Author(s):  
Riikka Lautamäki ◽  
Ronald Borra ◽  
Patricia Iozzo ◽  
Markku Komu ◽  
Terho Lehtimäki ◽  
...  

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.


2011 ◽  
Vol 26 (suppl 2) ◽  
pp. 45-50 ◽  
Author(s):  
Gabriela S. F. Castro ◽  
João F. R. Cardoso ◽  
Helio Vannucchi ◽  
Sérgio Zucoloto ◽  
Alceu Afonso Jordão

PURPOSE: The increase in fructose consumption is paralleled by a higher incidence of obesity worldwide. This monosaccharide is linked to metabolic syndrome, being associated with hypertriglyceridemia, hypertension, insulin resistance and diabetes mellitus. It is metabolized principally in the liver, where it can be converted into fatty acids, which are stored in the form of triglycerides leading to NAFLD. Several models of NAFLD use diets high in simple carbohydrates. Thus, this study aimed to describe the major metabolic changes caused by excessive consumption of fructose in humans and animals and to present liver abnormalities resulting from high intakes of fructose in different periods of consumption and experimental designs in Wistar rats. METHODS: Two groups of rats were fasted for 48 hours and reefed for 24 or 48 hours with a diet containing 63% fructose. Another group of rats was fed an diet with 63% fructose for 90 days. RESULTS: Refeeding for 24 hours caused accumulation of large amounts of fat, compromising 100% of the hepatocytes. The amount of liver fat in animals refed for 48 hours decreased, remaining mostly in zone 2 (medium-zonal). In liver plates of Wistar rats fed 63% fructose for 45, 60 and 90 days it's possible to see that there is an increase in hepatocytes with fat accumulation according to the increased time; hepatic steatosis, however, is mild, compromising about 20% of the hepatocytes. CONCLUSIONS: Fructose is highly lipogenic, however the induction of chronic models in NAFLD requires long periods of treatment. The acute supply for 24 or 48 hours, fasted rats can cause big changes, liver steatosis with macrovesicular in all lobular zones.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Colby Teeman ◽  
Yongjun Huang ◽  
Qingyun Liu ◽  
Jacqueline Hernandez ◽  
Javier Tamargo ◽  
...  

Abstract Objectives One of the major comorbidities among people living with HIV (PLWH) is liver disease. MetS is common in this population and may also play a role in the development of liver disease. In order to better understand the mechanisms of liver disease in PLWH, it is important to investigate the relationship between components of MetS and the risk of fatty liver, an early precursor to liver disease. The objective of this study was to determine if the 5 criteria used to diagnose MetS contribute to liver steatosis. Methods Crossectional analyses of data from the MASH cohort were analyzed. Waist circumference (WC) and blood pressure (BP) were measured by a research nurse. Serum triglycerides (TRG), glucose (GLU), and HDL were determined in fasting by LabCorp. Liver fat % was estimated with proton density fat fraction using Magnetic Resonance Elastography conducted on a 3T Siemens MAGNETOM Prisma MRI. Liver fat >5% was defined as stage 1 steatosis. Components of MetS were taken from the NCEP ATP III definition of MetS. Spearman correlations and logistic regression were used for analyses. Results A total of 324 PLWH aged 53.5 ± 7.5 years were included. Liver fat% was correlated with WC (r = 0.394, P < 0.001), TRG (r = 0.332, P < 0.001), GLU (r = 0.358, P < 0.001), and systolic BP (r = 0.183, P = 0.011), inversely correlated with HDL (r = −0.236, P = 0.001), and trended toward significance with diastolic BP (r = 0.133, P = 0.065). Participants with stage 1 steatosis had a larger WC (41.02in ± 5.3 vs 36.95 ± 5.5, P = 0.001), higher TRG (210.3 mg/dL ± 173.9 vs 121.3 ± 67.9, P = 0.002), and higher GLU (126.1 mg/dL ± 77.7 vs 93.92 ± 50.8, P = 0.001) than those without steatosis. No significant difference was found for HDL cholesterol, SBP, or DBP. A logistic regression model that included all 5 MetS criteria and was controlled for age, gender, and alcohol AUDIT score >8 found that WC (OR 1.11, 95% CI 1.01–1.23, P = 0.030), TRG (OR 1.01, 95% CI 1.00–1.01, P = 0.040), and GLU (OR 1.01, 95% CI 1.00–1.03, P = 0.033) are significant predictors of stage 1 steatosis. Conclusions WC, TRG, and GLU, three of the 5 criteria for diagnosing MetS were significant predictors of stage 1 steatosis in PLWH. Future studies investigating the risk of liver disease progression in PLWH need to account for these confounding factors as they explore HIV specific mechanisms for liver disease. Funding Sources National Institutes on Drug Abuse #5UO1DA040381.


Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 842
Author(s):  
Duanghathai Pasanta ◽  
Khin Thandar Htun ◽  
Jie Pan ◽  
Montree Tungjai ◽  
Siriprapa Kaewjaeng ◽  
...  

The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renaud Cezar ◽  
Delphine Desigaud ◽  
Manuela Pastore ◽  
Lucy Kundura ◽  
Anne-Marie Dupuy ◽  
...  

AbstractWe tested the hypothesis that a particular immune activation profile might be correlated with insulin resistance in a general population. By measuring 43 markers of immune, endothelial, and coagulation activation, we have previously shown that five different immune activation profiles may be distinguished in 150 volunteers. One of these profiles, Profile 2, characterized by CD4+ T cell senescence, inflammation, monocyte, B cell, and endothelial activation, presented elevated insulinemia, glycemia, triglyceridemia, and γ-glutamyl transferase, a marker of liver injury, in comparison with other profiles. Our data are compatible with a model in which a particular immune activation profile might favor the development of insulin resistance and metabolic syndrome. In this hypothesis, identification of this profile, that is feasible with only 3 markers with an error rate of 5%, might allow to personalize the screening and prevention of metabolic syndrome-driven morbidities as liver steatosis.


2020 ◽  
Author(s):  
Jacques L Tamuzi ◽  
Ayele T Birhanu ◽  
Constance S Shumba ◽  
Olatunji Adetokunboh ◽  
Jeannine Uwimana-Nico ◽  
...  

Abstract Background: The triple burden of COVID-19, tuberculosis and human immunodeficiency virus is one of the major global health challenges of the 21st century. In high burden HIV/TB countries, the spread of COVID-19 among people living with HIV is a well-founded concern. A thorough understanding of HIV/TB and COVID-19 pandemics is important as the three diseases interact. This may clarify HIV/TB/COVID-19 as a newly related field. However, several gaps remain in the knowledge of the burden of COVID-19 on patients with TB and HIV. This study was conducted to review different studies on SARS-CoV, MERS-CoV or COVID-19 associated with HIV/TB co-infection or only TB, to understand the interactions between HIV, TB and COVID-19 and its implications on the burden of the COVID-19 among HIV/TB co-infected or TB patients, screening algorithm and clinical management.Methods: We conducted an electronic search of potentially eligible studies published in English in the Cochrane Controlled Register of Trials, PubMed, Medrxiv, Google scholar and Clinical Trials Registry databases. We included case studies, case series and observational studies published between January, 2002 and July, 2020 in which SARS-CoV, MERS-CoV and COVID-19 co-infected to HIV/TB or TB in adults. We screened titles, abstracts and full articles for eligibility. Descriptive and meta-analysis were done and results have been presented in graphs and tables.Results: After removing 95 duplicates, 58 out of 437 articles were assessed for eligibility, of which 14 studies were included for descriptive analysis and seven studies were included in the meta-analysis. Compared to the descriptive analysis, the meta-analysis showed strong evidence that current TB exposure was high-risk COVID-19 group (OR 1.67, 95% CI 1.06-2.65, P= 0.03). The pooled of COVID-19/TB severity rate increased from OR 4.50 (95% CI 1.12-18.10, P=0.03), the recovery rate was high among COVID-19 compared to COVID-19/TB irrespective of HIV status (OR 2.23, 95% CI 1.83-2.74, P < 0.001) and the mortality was reduced among non-TB group (P<0.001).Conclusion: In summary, TB was a risk factor for COVID-19 both in terms of severity and mortality irrespective of HIV status. Structured diagnostic algorithms and clinical management are suggested to improve COVID-19/HIV/TB or COVID-19/TB co-infections outcomes.


2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Zhe Zheng ◽  
Yue Li ◽  
Siyuan Fan ◽  
Jie An ◽  
Xi Luo ◽  
...  

AbstractNonalcoholic fatty liver disease (NAFLD) is prevalent clinically and can lead to more serious chronic liver disease. However, the pathological mechanism is still unclear, and thus, there are no approved drugs on the market. Transcriptional coactivator WW domain-binding protein 2 (WBP2) is a newly discovered oncogene that has an important relationship with the occurrence and development of breast cancer and mediates the interaction between Wnt and various other signaling pathways. The expression level of WBP2 was decreased in NAFLD. Overexpression of WBP2 with AAV in vivo alleviated liver fat deposition and insulin resistance induced by a high-fat diet (HFD). Knockdown of WBP2 with AAV aggravated HFD-induced fatty liver and insulin resistance. In vitro experiments showed that in the human normal hepatocyte cell line LO2 and primary hepatocytes isolated from mice, overexpression of WBP2 reduced fat deposition, and knocking out or knocking down WBP2 aggravated PA-induced fat deposition. Through mass spectrometry, we found that WBP2 can bind to AMPKβ1, and by mutating AMPKβ1, we found that WBP2 can induce phosphorylation of AMPKβ1 at S108 and then activate the AMPK pathway to affect lipid metabolism. The effect of WBP2 on NAFLD provides a possible new direction for future research on NAFLD.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jacques L. Tamuzi ◽  
Birhanu T. Ayele ◽  
Constance S. Shumba ◽  
Olatunji O. Adetokunboh ◽  
Jeannine Uwimana-Nicol ◽  
...  

Abstract Background The triple burden of COVID-19, tuberculosis and human immunodeficiency virus is one of the major global health challenges of the twenty-first century. In high burden HIV/TB countries, the spread of COVID-19 among people living with HIV is a well-founded concern. A thorough understanding of HIV/TB and COVID-19 pandemics is important as the three diseases interact. This may clarify HIV/TB/COVID-19 as a newly related field. However, several gaps remain in the knowledge of the burden of COVID-19 on patients with TB and HIV. This study was conducted to review different studies on SARS-CoV, MERS-CoV or COVID-19 associated with HIV/TB co-infection or only TB, to understand the interactions between HIV, TB and COVID-19 and its implications on the burden of the COVID-19 among HIV/TB co-infected or TB patients, screening algorithm and clinical management. Methods We conducted an electronic search of potentially eligible studies published in English in the Cochrane Controlled Register of Trials, PubMed, Medrxiv, Google scholar and Clinical Trials Registry databases. We included case studies, case series and observational studies published between January, 2002 and July, 2020 in which SARS-CoV, MERS-CoV and COVID-19 co-infected to HIV/TB or TB in adults. We screened titles, abstracts and full articles for eligibility. Descriptive and meta-analysis were done and results have been presented in graphs and tables. Results After removing 95 duplicates, 58 out of 437 articles were assessed for eligibility, of which 14 studies were included for descriptive analysis and seven studies were included in the meta-analysis. Compared to the descriptive analysis, the meta-analysis showed strong evidence that current TB exposure was high-risk COVID-19 group (OR 1.67, 95% CI 1.06–2.65, P = 0.03). The pooled of COVID-19/TB severity rate increased from OR 4.50 (95% CI 1.12–18.10, P = 0.03), the recovery rate was high among COVID-19 compared to COVID-19/TB irrespective of HIV status (OR 2.23, 95% CI 1.83–2.74, P < 0.001) and the mortality was reduced among non-TB group (P < 0.001). Conclusion In summary, TB was a risk factor for COVID-19 both in terms of severity and mortality irrespective of HIV status. Structured diagnostic algorithms and clinical management are suggested to improve COVID-19/HIV/TB or COVID-19/TB co-infections outcomes.


2011 ◽  
Vol 81 (6) ◽  
pp. 398-406 ◽  
Author(s):  
Akcam ◽  
Boyaci ◽  
Pirgon ◽  
Kaya ◽  
Uysal ◽  
...  

Objective: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD). Methods: Sixty-seven obese adolescents with liver steatosis (age range, 9 - 17 years) were included in the study. The metformin group received an 850-mg dose of metformin daily and the vitamin E group received 400 U vitamin E /daily, in capsule form for 6 months, plus an individually tailored diet, exercise, and behavioral therapy. Results: After 6 months later, there was a significant decline in body mass index, and fasting insulin and homeostatic model assessment (HOMA) values in all three groups. Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study. There were no significant differences for changes of adiponectin, TNF-alpha, in all three groups after 6 months study. Conclusion: These data suggest that metformin treatment is more effective than dietary advice and vitamin E treatment in reducing insulin resistance, and also in ameliorating metabolic parameters such as fasting insulin and lipid levels, in obese adolescents having NAFLD.


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