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Frontiers in Endocrinology 2023
Topics: Humans; Environmental Exposure; Air Pollution; Metabolic Diseases
PubMed: 37867520
DOI: 10.3389/fendo.2023.1298687 -
Clinical Gastroenterology and... Mar 2024The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted.
METHODS
To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated.
RESULTS
One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD.
CONCLUSIONS
The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.
Topics: Humans; Fatty Liver; Metabolic Syndrome; Cardio-Oncology; Diabetes Mellitus
PubMed: 37775028
DOI: 10.1016/j.cgh.2023.09.018 -
Journal of Hepatology Feb 2024
Topics: Humans; Non-alcoholic Fatty Liver Disease; Metabolic Diseases
PubMed: 37558135
DOI: 10.1016/j.jhep.2023.07.031 -
Nature Human Behaviour Aug 2023Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health...
Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health policies, we need fine-grained causal evidence on which dimensions of socio-economic status affect longevity and the mediating roles of modifiable factors such as lifestyle and disease. Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n = 248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n = 28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30-59% higher odds of self-longevity, suggesting that education was the primary determinant. By contrast, each one-standard-deviation-higher income and one-point-higher occupation was causally associated with 3.06-year-longer and 1.29-year-longer parental lifespans, respectively, but not independently of the other socio-economic indicators. We found no evidence for causal effects of income or occupation on self-longevity. Mediation analyses conducted in predominantly European-descent individuals through two-step Mendelian randomization suggested that among 59 candidates, cigarettes per day, body mass index, waist-to-hip ratio, hypertension, coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, type 2 diabetes, heart failure and lung cancer individually played substantial mediating roles (proportion mediated, >10%) in the effect of education on specific longevity outcomes. These findings inform interventions for remediating longevity disparities attributable to socio-economic inequality.
Topics: Humans; Longevity; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Genome-Wide Association Study; European People; Social Class
PubMed: 37386110
DOI: 10.1038/s41562-023-01646-1 -
Annual Review of Nutrition Aug 2023Gluconeogenesis is a critical biosynthetic process that helps maintain whole-body glucose homeostasis and becomes altered in certain medical diseases. We review... (Review)
Review
Gluconeogenesis is a critical biosynthetic process that helps maintain whole-body glucose homeostasis and becomes altered in certain medical diseases. We review gluconeogenic flux in various medical diseases, including common metabolic disorders, hormonal imbalances, specific inborn genetic errors, and cancer. We discuss how the altered gluconeogenic activity contributes to disease pathogenesis using data from experiments using isotopic tracer and spectroscopy methodologies. These in vitro, animal, and human studies provide insights into the changes in circulating levels of available gluconeogenesis substrates and the efficiency of converting those substrates to glucose by gluconeogenic organs. We highlight ongoing knowledge gaps, discuss emerging research areas, and suggest future investigations. A better understanding of altered gluconeogenesis flux may ultimately identify novel and targeted treatment strategies for such diseases.
Topics: Animals; Humans; Gluconeogenesis; Metabolic Diseases; Glucose; Knowledge
PubMed: 37603427
DOI: 10.1146/annurev-nutr-061121-091507 -
Journal of Diabetes and Its... Aug 2023Diabetes mellitus is a metabolic disease, characterized by chronic hyperglycemia caused by an abnormality in insulin secretion or action. Millions of people across the... (Review)
Review
Diabetes mellitus is a metabolic disease, characterized by chronic hyperglycemia caused by an abnormality in insulin secretion or action. Millions of people across the world are affected by diabetes mellitus which has serious implications for their health. Over the past few decades, diabetes has become a major cause of mortality and morbidity across the world due to its rapid prevalence. Treatment for diabetes that focuses on insulin secretion and sensitization can lead to unwanted side effects and/or poor compliance, as well as treatment failure. A promising way to treat diabetes is through gene-editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR/Cas9). However, issues such as efficiency and off-target effects have hindered the use of these technologies. In this review, we summarize what we know today about CRISPR/Cas9 technology's therapeutic potential for treating diabetes. We discuss how different strategies are employed, including cell-based therapies (such as stem cells and brown adipocytes), targeting critical genes involved in diabetes pathogenesis, and discussing the challenges and limitations associated with this technology. A novel and powerful treatment approach to diabetes and other diseases can be found with CRISPR/Cas9 technology, and further research should be carried out in this field.
Topics: Humans; Gene Editing; CRISPR-Cas Systems; Genetic Therapy; Stem Cells; Diabetes Mellitus
PubMed: 37295292
DOI: 10.1016/j.jdiacomp.2023.108524 -
Cell Metabolism May 2024On average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However,... (Review)
Review
On average, aging is associated with unfavorable changes in cellular metabolism, which are the processes involved in the storage and expenditure of energy. However, metabolic dysregulation may not occur to the same extent in all older individuals as people age at different rates. Those who are aging rapidly are at increased risk of adverse health outcomes and are said to be "frail." Here, we explore the links between frailty and metabolism, including metabolic contributors and consequences of frailty. We examine how metabolic diseases may modify the degree of frailty in old age and suggest that frailty may predispose toward metabolic disease. Metabolic interventions that can mitigate the degree of frailty in people are reviewed. New treatment strategies developed in animal models that are poised for translation to humans are also considered. We suggest that maintaining a youthful metabolism into older age may be protective against frailty.
Topics: Aged; Animals; Humans; Aging; Energy Metabolism; Frail Elderly; Frailty; Metabolic Diseases
PubMed: 38614092
DOI: 10.1016/j.cmet.2024.03.012 -
Frontiers in Endocrinology 2023
Topics: Humans; Reproduction; Metabolic Diseases
PubMed: 37859986
DOI: 10.3389/fendo.2023.1245239 -
Advanced Biology Dec 2023
Topics: Humans; Metabolic Diseases
PubMed: 38115206
DOI: 10.1002/adbi.202300464 -
Cell Metabolism Feb 2024While the successes of modern medicine have significantly extended the human lifespan, the burden of chronic metabolic disease increasingly impacts the quality of life...
While the successes of modern medicine have significantly extended the human lifespan, the burden of chronic metabolic disease increasingly impacts the quality of life of almost two billion people worldwide. It is now imperative that we recognize metabolic disease as a pandemic and urgently prioritize preventive measures to halt its expansion.
Topics: Humans; Quality of Life; Chronic Disease; Metabolic Diseases
PubMed: 38325334
DOI: 10.1016/j.cmet.2024.01.010