Metabolism and target organ damage最新文献_第6页

Arresting type 1 diabetes: are we there yet? Obstacles and opportunities 控制1型糖尿病:我们做到了吗?障碍与机遇

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.16

Chantal Mathieu, P. Martens

{"title":"Arresting type 1 diabetes: are we there yet? Obstacles and opportunities","authors":"Chantal Mathieu, P. Martens","doi":"10.20517/mtod.2022.16","DOIUrl":"https://doi.org/10.20517/mtod.2022.16","url":null,"abstract":"More than 100 years after the discovery of insulin, the exact etiology and pathophysiology of type 1 diabetes (T1D) remains elusive, but our knowledge is growing. This leads to louder calls to initiate a risk screening for T1D in the general population. This risk screening could be based on the genetic risk (in the general population or targeted HLA genotyping in family members of persons with T1D) or on the screening for autoantibodies in blood (e.g., antibodies against insulin, GAD, IA2, or ZnT8). The presence of autoantibodies is known to convey a clearly increased risk of progressing to T1D, particularly when two or more antibody types are present. It remains a point of discussion whether screening efforts are cost-effective. At present, in the absence of interventions capable of delaying the onset of disease, the only benefit of screening is the earlier diagnosis of T1D, thus avoiding life-threatening diabetic ketoacidosis (DKA). Nevertheless, large consortia (e.g., INNODIA and TrialNet) are currently focusing on not only disease biomarkers but also biomarkers of therapeutic effect of interventions. All hope is thus focused on the arrival of intervention strategies that could arrest the ongoing immune destruction of the beta cell and thus delay clinical disease onset. Thus far, attempts have focused on either protecting the beta cell or arresting the immune response, but the future seems to be one of combination therapy. Here, we perform a scoping review on the pathogenesis of T1D, discuss screening strategies, and present promising intervention strategies.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer in individuals with obesity and metabolic disorders. A preventable epidemic? 肥胖和代谢紊乱患者的癌症。一种可预防的流行病?

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.28

F. Lonardo

引用次数: 1

Insights on the disruption of glucose metabolism and hepatic insulin resistance induced by hepatitis C virus 丙型肝炎病毒诱导的糖代谢紊乱和肝脏胰岛素抵抗的研究进展

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2021.18

P. Solís-Muñoz, Ángela Berlana, Elvira del Pozo-Maroto, Lucía Domínguez-Alcón, Liliam Elbouayadi, C. García-Monzón, Á. González-Rodríguez

{"title":"Insights on the disruption of glucose metabolism and hepatic insulin resistance induced by hepatitis C virus","authors":"P. Solís-Muñoz, Ángela Berlana, Elvira del Pozo-Maroto, Lucía Domínguez-Alcón, Liliam Elbouayadi, C. García-Monzón, Á. González-Rodríguez","doi":"10.20517/mtod.2021.18","DOIUrl":"https://doi.org/10.20517/mtod.2021.18","url":null,"abstract":"Hepatitis C virus (HCV) is still considered as a major public health problem because in 2015 around 71 million people were chronically infected worldwide. It is important to note that chronic HCV infection is a systemic disease that is associated with diverse extrahepatic disorders including insulin resistance and type 2 diabetes mellitus. The discovery of new direct-acting antiviral agents (DAAs) has become a huge advance in the treatment of HCV infection. The complex interplay between HCV and glucose metabolic pathways remains to be fully elucidated, but it is becoming clearer that elimination of chronic HCV infection halts the progression of liver disease, but more evidence is still needed to better understand how successful antiviral treatment influences insulin resistance and other abnormalities of glucose metabolism linked to HCV infection. This review provides a comprehensive overview of the glucose metabolism disturbances related to chronic HCV infection, highlighting the new insights into the molecular basis of insulin resistance induced by HCV and the mechanisms underlying the reversion of this metabolic disorder by DAAs.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liver-derived lipoproteins and inflammation: from pathophysiology to pharmacological targets in metabolic liver disease 肝源性脂蛋白和炎症:从病理生理到代谢性肝病的药理靶点

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.09

A. Baragetti

{"title":"Liver-derived lipoproteins and inflammation: from pathophysiology to pharmacological targets in metabolic liver disease","authors":"A. Baragetti","doi":"10.20517/mtod.2022.09","DOIUrl":"https://doi.org/10.20517/mtod.2022.09","url":null,"abstract":"Low density lipoproteins (LDL) reduction remains the key goal for reducing the risk of atherosclerotic cardiovascular diseases (CVD) in people with high residual risk and metabolic complications including liver disease. Notwithstanding, epidemiological projections support a key role of liver-derived apolipoprotein B (ApoB) containing lipoproteins, namely very low density lipoproteins (VLDL) and their “remnants” (TG), undergoing the activity of lipases, in eliciting atherosclerotic inflammatory sequelae of a comparable order of magnitude to that of LDL. Disparate experimental evidence supports that triglycerides (TG), residual cholesterol content, or the large apolipoprotein set on the surface of these lipoproteins can elicit a number of plausible immune-inflammatory mechanisms that foster the vascular atherosclerotic process. Therapeutic options that convincingly lowered the plasma levels of liver-derived ApoB containing lipoproteins, either by reducing the hepatic synthesis or by improving the peripheral lipolysis of the lipid content, did not exert robust CVD risk reduction, and the effect on inflammation was questionable. Understanding the mechanisms linking liver-derived lipoproteins with chronic inflammation will provide pathophysiological insights for the identification of new therapeutic targets for people at high CVD risk and with metabolic complications. In this perspective, this topic is of immediate interest for the prevention of CVD in patients affected by non-alcoholic fatty liver disease (NAFLD) and, even more, for NAFLD patients with diabetes, insulin resistance, or other comorbidities (metabolic-associated fatty liver disease). This review resumes the principal physio-pathological insights regarding the metabolism of liver-derived lipoproteins and provides an update on the current pharmacological options that can be considered for improving CVD prevention in metabolic liver diseases.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sarcopenia in the setting of nonalcoholic fatty liver 非酒精性脂肪肝的肌少症

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2021.16

M. Arrese, C. Cabello-Verrugio, J. Arab, F. Barrera, R. Baudrand, F. Guarda, I. Gul, D. Cabrera

{"title":"Sarcopenia in the setting of nonalcoholic fatty liver","authors":"M. Arrese, C. Cabello-Verrugio, J. Arab, F. Barrera, R. Baudrand, F. Guarda, I. Gul, D. Cabrera","doi":"10.20517/mtod.2021.16","DOIUrl":"https://doi.org/10.20517/mtod.2021.16","url":null,"abstract":"Nonalcoholic fatty liver is a worldwide common problem with more prevalence in non-Asian populations that is closely correlated with the muscle-related disorder sarcopenia. The incidence of both health issues has been observed to be strongly interlinked where presence of one exacerbates the other. Nonalcoholic fatty liver disease (NAFLD) pathophysiology increases the muscle loss, while the onset of NAFLD in sarcopenic patients aggravates the liver problems as compared to non-sarcopenic patients. Scarcity of research on the subject provides very little evidence about the cause and effect of disorders. No FDA approved drugs are available to date for NAFLD and sarcopenia. Research is underway to understand the complex biochemical pathways involved in the development of both disorders. This review is a small contribution toward understanding sarcopenia in the setting of NAFLD that provides insight on the common pathophysiological profile of sarcopenia and NAFLD and portrays a novel way of delving into the subject by introducing the concept of cortisol crosstalk with the muscle-liver axis. Sarcopenia and NAFLD are considered metabolism-related problems, and cortisol, being a glucocorticoid, plays an important role in metabolism of fats, carbohydrates, and proteins. Cushing’s syndrome, characterized by abnormally elevated concentrations of blood cortisol/enhanced intracellular activity, shares many pathologic conditions (such as insulin resistance, metabolic syndrome, abnormal levels of specific cytokines, and obesity) with NAFLD and sarcopenia. Hence, cortisol can be a potential biomarker in sarcopenia and NAFLD. As cortisol activity at cellular level is controlled by 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1/2) enzymes that convert inactive steroid precursor into active cortisol, these enzymes can be targeted for the study of sarcopenia and NAFLD. Combined studies on NAFLD and sarcopenia with respect to cortisol open a new avenue of research in the understanding of both disorders.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Colon cancer in a 12-year-old girl with hypertriglyceridemia 12岁高甘油三酯血症女孩结肠癌

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2021.12

M. Pedroni, M. P. Leòn, L. R. Bonetti, A. Viel, D. Noto, F. Nascimbeni, P. Sena, L. Roncucci

{"title":"Colon cancer in a 12-year-old girl with hypertriglyceridemia","authors":"M. Pedroni, M. P. Leòn, L. R. Bonetti, A. Viel, D. Noto, F. Nascimbeni, P. Sena, L. Roncucci","doi":"10.20517/mtod.2021.12","DOIUrl":"https://doi.org/10.20517/mtod.2021.12","url":null,"abstract":"Colorectal cancer is usually considered a disease of the elderly; however, in a small fraction of patients (2%-3% of all affected individuals), colorectal malignancies may develop earlier. The reasons whereby some individuals develop colorectal cancer at a young age are poorly understood. In a 12-year-old girl, a malignancy was diagnosed in the ascending colon. There was no familial history of Lynch syndrome or familial adenomatous polyposis. The metabolic profile of the patient revealed hypertriglyceridemia and low high-density lipoprotein cholesterol levels at nine years, then diagnosed as familial hypertriglyceridemia due to a constitutional mutation in the APOA5 gene (c.427delC). Moreover, variants possibly increasing the risk of cancer were detected in MSH6 (c.3438+11_3438+14delCTTA, intron 5) and APC (I1307K). The patient showed a rather unusual dietary pattern, since her basic alimentation from weaning consisted almost exclusively of meat homogenates and, subsequently, roasted meat or cutlets. Other foods, including fish, vegetables, sweets, and pasta, were refused. In this case, genetic and environmental factors could have acted in a particularly accelerated manner. Indeed, the genetic background of the patient (familial hypertriglyceridemia and polymorphisms predisposing to colorectal cancer) may have favored a dietary-driven colorectal carcinogenesis, resulting in an extremely early onset development of malignancy.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liver transplantation and nonalcoholic steatohepatitis: the state of the art 肝移植和非酒精性脂肪性肝炎:最新进展

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.04

S. Gitto, Nicolò Mannelli, A. Tassi, F. Gabrielli, F. Nascimbeni, P. Andreone

引用次数: 0

The growing prevalence of nonalcoholic fatty liver disease (NAFLD), determined by fatty liver index, amongst young adults in the United States. A 20-year experience 由脂肪肝指数确定的非酒精性脂肪性肝病(NAFLD)在美国年轻人中日益流行。20年的经验

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.24

Wenhao Li, C. Ng, Jingxuan Quek, K. Chan, C. Tan, R. Zeng, J. Yong, H. Tay, D. Tan, W. Lim, Douglas Chee, Jinyang Ho, N. Chew, L. Mak, M. Siddiqui, A. Sanyal, W. Alazawi, Naim Alkouri, M. Muthiah, M. Noureddin

{"title":"The growing prevalence of nonalcoholic fatty liver disease (NAFLD), determined by fatty liver index, amongst young adults in the United States. A 20-year experience","authors":"Wenhao Li, C. Ng, Jingxuan Quek, K. Chan, C. Tan, R. Zeng, J. Yong, H. Tay, D. Tan, W. Lim, Douglas Chee, Jinyang Ho, N. Chew, L. Mak, M. Siddiqui, A. Sanyal, W. Alazawi, Naim Alkouri, M. Muthiah, M. Noureddin","doi":"10.20517/mtod.2022.24","DOIUrl":"https://doi.org/10.20517/mtod.2022.24","url":null,"abstract":"Aim: The Global burden of nonalcoholic fatty liver disease (NAFLD) has significantly increased recently, with its prevalence mirroring increasing obesity and diabetes. However, population-specific evidence for young adults remains limited. Herein, we provide a 20-year trend analysis of NAFLD in young adults and examine factors associated with NAFLD and major adverse cardiovascular events (MACE) prevalence. Methods: This study uses data from the United States National Health and Nutrition Examination Survey (NHANES) 1999-2018. Fatty liver was examined with the fatty liver index (FLI) and United States-FLI (US-FLI), and advanced fibrosis was examined with the fibrosis-4 index. Clustered multivariate logistic regression analysis on the year of study was applied to obtain odds ratios (OR) for the estimation of events. Results: 13.31% (95%CI: 12.71% to 13.94%) of young adults had NAFLD. The prevalence increased from 9.98% in 1999 to 19.49% in 2018, with a statistically significant trend (P < 0.001). 9.52% and 5.29% of patients have clinically significant and advanced fibrosis, respectively. In multivariate analysis, diabetes (3.48, 95%CI: 2.37 to 5.11), hypertension (2.03, 95%CI: 1.62 to 2.55), elevated body mass index (1.22, 95%CI: 1.20 to 1.23, P < 0.001) significantly increases odds of NAFLD. The largest increase in odds was related to obesity (OR: 21.61, 95%CI: 16.95 to 27.55, P < 0.001). Young adults with NAFLD had a borderline non-significant increase in the prevalence of MACE compared to individuals without NAFLD (OR: 1.603, 95%CI: 0.949 to 2.708, P = 0.078). Conclusion: The rising prevalence of NAFLD in young adults depicts the changing landscape of NAFLD and its association with a significant increase in MACE. The challenge of effective risk stratification and education of these individuals remains.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Screening for advanced liver fibrosis in overweight and obese patients with NAFLD 超重和肥胖NAFLD患者的晚期肝纤维化筛查

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.29

N. Stefan

引用次数: 0

From liver fat to full-blown metabolic disorder: the kidney as target organ 从肝脏脂肪到全面代谢紊乱:肾脏为靶器官

Metabolism and target organ damage Pub Date : 2022-01-01 DOI: 10.20517/mtod.2022.17

M. Petroni, G. Marchesini

引用次数: 1