Experimental studies on the liver injury in diabetes mellitus

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

Download Full-text

Mesenchymal Stem Cell Therapy for Acetaminophen-Related Liver Injury: A Systematic Review and Meta-Analysis of Experimental Studies in Vivo

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666211007092055 ◽

2021 ◽

Vol 16 ◽

Author(s):

Li Wang ◽

Yiwen Zhang ◽

Jiajun Zhong ◽

Yuan Zhang ◽

Shuisheng Zhou ◽

...

Keyword(s):

Systematic Review ◽

Stem Cell ◽

Liver Injury ◽

Mesenchymal Stem Cell ◽

Small Sample Size ◽

Meta Analysis ◽

Experimental Studies ◽

Small Sample ◽

Control Group

Objective: The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen-induced liver injury. Methods: Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE’s risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/SE 16.0 software. Results: Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) − 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD − 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD − 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05). Conclusion: Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen-related liver injury.

Download Full-text

Monitorização glicêmica de adolescentes brasileiros com diabetes tipo 1

Revista de Enfermagem UFPE on line ◽

10.5205/1981-8963-v12i7a231277p2012-2020-2018 ◽

2018 ◽

Vol 12 (7) ◽

pp. 2012

Author(s):

Isabele Gouveia Muniz Alencar ◽

Gisele Gouveia Muniz ◽

Carla Muniz Medeiros ◽

Camila Muniz Medeiros

Keyword(s):

Diabetes Mellitus ◽

Glycosylated Hemoglobin ◽

Measurement Techniques ◽

Experimental Studies ◽

Type I ◽

Level Of Evidence ◽

Self Monitoring ◽

Hemoglobin A ◽

Diabetes Mellitus Type I ◽

Blood Glucose Self Monitoring

RESUMOObjetivo: verificar os métodos utilizados por adolescentes brasileiros com DM1 na monitorização glicêmica e conceitos associados a essa prática. Método: revisão integrativa, realizada entre fevereiro a agosto de 2017, por meio da MEDLINE, LILACS e SCIELO. A análise dos estudos considerou o nível de evidência. Os resultados foram apresentados considerando a sequência cronológica decrescente e as temáticas advindas da análise dos artigos. Resultados: observaram-se as temáticas “1. Perspectivas de estudos sobre Diabetes Mellitus Tipo 1 (DM1) em adolescentes no Brasil”; “2. Monitorização da glicemia em adolescentes brasileiros com DM1: conceitos e métodos” e “3. O papel das técnicas de mensuração primária para o controle do DM1 em adolescentes”. Conclusão: aponta-se que a análise da Hemoglobina A Glicosilada (HbA1c) foi o método mais empregado para a monitorização de adolescentes com DM1. Verifica-se, também, que há dificuldades da comunidade científica em incluir crianças e adolescentes com DM1 em estudos experimentais. Descritores: Adolescentes; Insulina; Automonitorização da Glicemia; Hemoglobina A Glicosilada; Diabetes Mellitus Tipo I; Educação em Saúde.ABSTRACT Objective: to verify the methods used by Brazilian adolescents with DM1 in glycemic monitoring and concepts associated with this practice. Method: integrative review, carried out between February and August of 2017, through MEDLINE, LILACS and SCIELO. The analysis of the studies considered the level of evidence. The results were presented considering the decreasing chronological sequence and the themes coming from the analysis of the articles. Results: the themes "1. Perspectives of studies on Type 1 Diabetes Mellitus (DM1) in adolescents in Brazil "; "2. Monitoring of glycemia in Brazilian adolescents with DM1: concepts and methods "e" 3. The role of primary measurement techniques for the control of DM1 in adolescents " were observed. Conclusion: it is pointed out that the analysis of Glycosylated Hemoglobin A (HbA1c) was the most used method for the monitoring of adolescents with DM1. It is also verified that there are difficulties of the scientific community to include children and adolescents with DM1 in experimental studies. Descriptors: Adolescent; Insulin; Blood Glucose Self-Monitoring; Hemoglobin A, Glycosylated; Diabetes Mellitus, Type I, Health Education.RESUMEN Objetivo: verificar los métodos utilizados por adolescentes brasileños con DM1 en la monitorización glucémica y conceptos asociados a esta práctica. Método: revisión integrativa, realizada entre febrero a agosto de 2017, por medio de MEDLINE, LILACS y SCIELO. El análisis de los estudios consideró el nivel de evidencia. Los resultados fueron presentados considerando la secuencia cronológica decreciente y las temáticas provenientes del análisis de los artículos. Resultados: se observaron las temáticas: “1. Perspectivas de estudios sobre Diabetes Mellitus Tipo 1 (DM1) en adolescentes en Brasil”; “2. Monitoreo de la glucemia en adolescentes brasileños con DM1: conceptos y métodos”; y “3. El papel de las técnicas de medición primaria para el control del DM1 en adolescentes”. Conclusión: se señala que el análisis de la Hemoglobina A Glicosilada (HbA1c), fue el método más empleado para monitorización de adolescentes con DM1. Se verifica, también, que hay dificultades de la comunidad científica en incluir niños y adolescentes con DM1 en estudios experimentales. Descriptores: Adolescente; Insulina; Automonitorización de la Glucosa Sanguínea; Hemoglobina A Glicosilada; Diabetes Mellitus Tipo I, Educacion en Salud.

Download Full-text

P0751METFORMIN, A CLASSIC TREATMENT FOR TYPE 2 DIABETES WITH POSSIBLE RENOPROTECTIVE EFFECTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0751 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Adriana Acosta Barrios ◽

Marian Goicoechea ◽

Eduardo Verde ◽

Ángela González-Rojas ◽

Andres Delgado ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Kidney Disease ◽

Experimental Studies ◽

Diabetic Patients ◽

Metformin Treatment ◽

End Point ◽

Progression Of Kidney Disease

Abstract Background and Aims Metformin is the antidiabetic of choice in patients with type 2 diabetes mellitus. Experimental studies and clinical observations have shown that metformin could have a beneficial effect on the progression of kidney disease through the activation of cAMP due to its anti-inflammatory, antifibrotic, and anti-oxidative action. The objective was to compare the progression of CKD in diabetic patients with or without metformin as antidiabetic in their treatment and the prevalence of cardiovascular events in both groups. Method Unicentric retrospective observational analysis. Inclusion criteria: outpatients seen in nephrology consultation during the year of 2012 with diabetes mellitus and stage 3 CKD. Renal, cardiovascular outcomes and mortality were analyzed between patients treated with / without metformin. Median follow-up of 76.5 months (41-84). Renal end-point: estimated glomerular filtration rate drop (MDRD-4) by 50% and / or start of dialysis program. Cardiovascular end-point: ischemic heart disease, stroke, arterial revascularization and / or amputation. Cardiovascular or any cause mortality. Results 148 patients (96M, 52W) with a mean age of 75±9 years and an eGFR of 40±9 ml / min / 1.73 m2 were included. In relation to hypoglycemic therapy: 45 received metformin, 61 insulin and 31 DPP4i. 80% received treatment with RAAS blockers. After the follow-up, the progression of the renal disease was greater in patients who did not receive metformin: eGFR fall of -7.0±16 vs -0.15±16 ml / min in those treated with metformin (p = 0.019). 25 patients in the group without metformin suffered a renal event vs. 5 in the metformin group (logRank: 4.186, p = 0.045). In the Cox analysis, metformin treatment decreases the progression of kidney disease in a model adjusted for baseline renal function and treatment with RAASB (HR 0.368, p = 0.043), losing its predictive power in a proteinuria-adjusted model. During the follow-up, 45 patients died (20 metformin, 25 non-metformin) and 45 patients suffered a cardiovascular event (15 metformin, 30 non-metformin), with no differences between the two groups. Conclusion Metformin treatment in patients with stage 3 CKD could slow the progression of CKD, this effect should be demonstrated in randomized studies with larger sample size.

Download Full-text

Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats

Frontiers in Endocrinology ◽

10.3389/fendo.2020.565858 ◽

2020 ◽

Vol 11 ◽

Author(s):

Chengdong Xia ◽

Xiuli Zhang ◽

Tianshu Cao ◽

Jiannong Wang ◽

Cuidan Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Liver Injury ◽

Er Stress ◽

Molecular Pathogenesis ◽

Clinical Indices ◽

Zdf Rats ◽

Hepatic Transcriptome

Around 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat provides a successful animal model to study the pathogenesis of T2DM. Although previous hepatic transcriptome studies revealed some novel genes associated with the occurrence and development of T2DM, there still lacks the comprehensive transcriptomic analysis for the liver tissues of ZDF rats. We performed comparative transcriptome analyses between the liver tissues of ZDF rats and healthy ZCL rats and also evaluated several clinical indices. We could identify 214 and 104 differentially expressed genes (DEGs) and lncRNAs in ZDF rats, respectively. Pathway and biofunction analyses showed a synergistic effect between mRNAs and lncRNAs. By comprehensively analyzing transcriptomic data and clinical indices, we detected some typical features of T2DM in ZDF rats, such as upregulated metabolism (significant increased lipid absorption/transport/utilization, gluconeogenesis, and protein hydrolysis), increased inflammation, liver injury and increased endoplasmic reticulum (ER) stress. In addition, of the 214 DEGs, 114 were known and 100 were putative T2DM-related genes, most of which have been associated with substance metabolism (particularly degradation), inflammation, liver injury and ER stress biofunctions. Our study provides an important reference and improves understanding of molecular pathogenesis of obesity-associated T2DM. Our data can also be used to identify potential diagnostic markers and therapeutic targets, which should strengthen the prevention and treatment of T2DM.

Download Full-text