Obesity Epidemic Research Articles

Liver Cancer in the Middle East and North Africa: Epidemiology, Trends, and Risk Factors

Objectives: Considering the growing concerns about the rising incidence of this cancer in the Middle East and North Africa (MENA), this literature review presents the local epidemiology and trends of liver cancer, along with a practical estimation of its epidemiology and contributing risk factors. Design: Review Article. Setting(s): Middle East and North Africa. Outcome Measures: MEDLINE (via PubMed), Scopus, and Web of Science databases, as well as Google Scholar, were searched up to September 2024 using representative keywords and MeSH terms. Studies reporting the epidemiology of liver and intrahepatic cholangiocarcinoma in the region or an analysis of the contributing infectious diseases, non-communicable disorders, genetic predispositions, behavioral aspects, and environmental factors were included. A qualitative synthesis was performed, and the results were presented using thematic narrative synthesis. Results: Liver cancer, particularly hepatocellular carcinoma (HCC), is rapidly growing in the MENA region, driven by a combination of viral hepatitis, underlying metabolic disorders, and environmental exposures. Liver cancer epidemiology varies across the region, with countries like Egypt historically burdened by hepatitis C, while Gulf states experience rising cases linked to metabolic disorders. Projections indicate a continued increase in the incidence of liver cancer due to the ongoing obesity and diabetes epidemics. Conclusions: Despite the success of viral hepatitis management campaigns in some countries, the region faces significant challenges in controlling the rising burden of liver cancer related to metabolic disorders. Prevention strategies should focus on lifestyle and dietary interventions, alongside the need for improved cancer registries, better data collection, and policy reforms. A multidisciplinary approach, combining public health initiatives and targeted healthcare improvements, is essential to reduce regional liver cancer incidence and improve outcomes.

Gestational diabetes: an update sixty years after O'Sullivan and Mahan.

Sixty years after the landmark publication by O'Sullivan and Mahan, the current paper seeks to review and place into context the importance of gestational diabetes (GDM) both as a marker of increased risk of adverse maternal and fetal pregnancy outcomes and as an indicator of future maternal and infant health risks. We review the evolution of GDM as a diagnosis, the ongoing debate regarding diagnostic approaches, the underlying pathophysiology, the epidemiology and the importance of GDM in the context of the global epidemics of diabetes and obesity. Focusing on clinical management, we review lifestyle based therapy and pharmacotherapy for GDM, consider obstetric management and outline the short term and lifelong health risks posed by a GDM diagnosis.

Great debate: pre-diabetes is not an evidence-based treatment target for cardiovascular risk reduction.

With the increasing burden of diabetes as a cause of macro- and microvascular disease linked to the epidemics of obesity, attention is being paid to dysglycaemic states that predict and precede the development of type 2 diabetes. Such conditions, termed pre-diabetes, are characterized by fasting plasma glucose, or plasma glucose levels on an oral glucose tolerance test, or values of glycated haemoglobin intermediate between 'normal' values and those characterizing diabetes. These last are by definition associated, in epidemiological terms, with a higher incidence of microvascular disease-mostly retinopathy. Pre-diabetes overlaps with the components of the 'metabolic syndrome'-among which are excess visceral adiposity; hypertension; hypertriglyceridaemia; high levels of small, dense low-density lipoproteins; and metabolic-associated fatty liver disease. There is little doubt that pre-diabetes has important prognostic implications, especially for the occurrence of myocardial infarction, ischaemic stroke, and peripheral arterial disease. It is disputed, however, whether pre-diabetes is itself an actionable disease entity, in addition to the risk factors characterizing it. Because of this uncertainty, the latest European Society of Cardiology guidelines chose not to include pre-diabetes as a treatment target for atherosclerotic cardiovascular disease, at variance from the three previous editions of such guidelines. This is spurring a debate, the Pro and Contra arguments featured in the present debate article.

Differential Efficacy of Weight Loss Interventions in Patients with Versus Without Diabetes.

Obesity is both a major risk factor for diabetes and a serious comorbidity of the condition. The twin epidemics of obesity and diabetes have spread globally over the past few decades. Treatment of obesity in patients with diabetes provides a host of clinical benefits that encompass virtually all body systems. Despite this, multiple lines of evidence suggest that the efficacy of most therapies for weight loss is significantly reduced among patients with diabetes. With this background, we summarize the evidence of a differential effect of lifestyle, pharmacological, and surgical treatments for obesity in patients with existing diabetes, and explore the potential mechanisms involved in this phenomenon. This information is then used to formulate strategies to improve weight loss outcomes for patients with diabetes.

Maternal Malnutrition and Elevated Disease Risk in Offspring.

US populations have seen dramatic increases in the prevalence of chronic disease over the past three generations. Rapid increases in type 2 diabetes and obesity have occurred in all the states but have been particularly striking in the Deep South. These increases have contributed to decreases in life expectancy and to painful elevations in health care costs. The causes of worsening population health are complex and incompletely understood. However, there is strong evidence that vulnerability to chronic conditions is determined in early life. Most chronic diseases are developmentally driven. There are specific stressors experienced in early life that influence epigenetic and structural changes during development. These include malnutrition, severe levels of social stress, toxic chemicals, and low oxygen levels. Most US populations have experienced a decrease in the quality of the food they consume as industrial foods have replaced garden-grown foods. Thus, the consumption of too few nutrients before and during pregnancy and during lactation influences the growth of the placenta and fetal organs and their level of resilience when faced with stresses in postnatal life and particularly as adults. Animal studies have shown that the effects of poor nutrition can be passed on to future generations. The most powerful way that the current epidemics of obesity and insulin resistance can be reversed is by providing key nutrients to prospective mothers and those already pregnant.

Unraveling cysteine deficiency-associated rapid weight loss.

Forty percent of the US population and 1 in 6 individuals worldwide are obese, and the incidence of this disease is surging globally1,2. Various dietary interventions, including carbohydrate and fat restriction, and more recently amino acid restriction, have been explored to combat this epidemic3-6. We sought to investigate the impact of removing individual amino acids on the weight profiles of mice. Compared to essential amino acid restriction, induction of conditional cysteine restriction resulted in the most dramatic weight loss, amounting to 20% within 3 days and 30% within one week, which was readily reversed. This weight loss occurred despite the presence of substantial cysteine reserves stored in glutathione (GSH) across various tissues7. Further analysis demonstrated that the weight reduction primarily stemmed from an increase in the utilization of fat mass, while locomotion, circadian rhythm and histological appearance of multiple other tissues remained largely unaffected. Cysteine deficiency activated the integrated stress response (ISR) and NRF2-mediated oxidative stress response (OSR), which amplify each other, leading to the induction of GDF15 and FGF21, hormones associated with increased lipolysis, energy homeostasis and food aversion8-10. We additionally observed rapid tissue coenzyme A (CoA) depletion, resulting in energetically inefficient anaerobic glycolysis and TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds and amino acids. In summary, our investigation highlights that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings may pave the way for innovative strategies for addressing a range of metabolic diseases and the growing obesity crisis.

Predictive Modeling of Future Trends in US Healthcare Data and Outcomes

Predictive modeling has great potential to help guide healthcare policymaking and planning through forecasting future trends in domains such as disease prevalence, resource utilization, and costs. However, past research in this area has been limited by mostly examining small, narrow datasets that only captured specific illnesses or geographic regions. This study aimed to leverage more sophisticated predictive analytics to generate informed estimations of the most consequential healthcare trends anticipated in the United States throughout the next decade. The analysis drew upon an extensive collection of over 50 million longitudinal electronic health records spanning a 5-year timeframe, comprehensive national public health statistics from the same period, and Medicare claims encompassing 72 million beneficiaries. Advanced machine learning techniques, including neural networks and Bayesian additive regression trees, were applied to identify nonlinear relationships and temporal patterns across 500 variables related to patient demographics, medical diagnoses, therapeutic procedures, reimbursement amounts, and clinical outcomes. Models were trained using data from 2010 to 2015 then utilized to project trends and forecasts for the years 2020 to 2025. Five-fold cross-validation testing was conducted to evaluate the accuracy and generalizability of the predictive models. The model projections indicate that chronic disease prevalence nationwide will rise by approximately 40% by the conclusion of 2025, primarily fueled by growing epidemics of obesity and an increasingly aging American population. Additionally, heart disease and stroke are estimated to maintain their positioning as leading causes of death, but cases of dementia and Alzheimer's disease specifically are projected to climb even more sharply at over a 50% increase. Healthcare costs on the whole are anticipated to rise on average between 4-6% annually, and costs may potentially double for elderly patients presenting with multiple morbidities. As outpatient and home-based care options expand further, inpatient hospital facility utilization may drop marginally between 10-15%. Improved management of chronic medical conditions within local community settings could reduce preventable hospital readmissions from 25-30%. Primary care, nursing, and mental healthcare roles are likely to face looming staffing shortages as well. Telehealth adoption is forecasted to surge by approximately 45% as virtual visit formats help address access obstacles. By 2025, biologics and gene therapies could account for over 25% of total drug spending pertaining to oncology and rare disease treatment. Larger Medicaid, Medicare, and ACA commercial coverage markets may motivate higher rates of health insurance enrollment over the next few years.

Environmental burden of excessive food intake: Exploring new opportunities to enhance food and environmental sustainability in China

China faces increasing challenges in producing sufficient food sustainably while confronting a worsening overweight and obesity crisis caused partly by overeating. Building on the China Health and Nutrition Survey data, this study estimated the agricultural and environmental implications of overeating based on human metabolic theory and life cycle assessment. The results show that the average excess food intake per person is twice the amount of household edible food waste (53.85 vs. 26.88 g/capita/day). The total excessive food intake is equivalent to 18.7 Mt of annual cereal production, approximately 4.3 times China's recent annual cereal production growth (4.4 Mt). Excessive food intake also embodies substantial carbon, water, energy, and ecological footprints, amounting to 39.15 Mt CO2e, 31.40 Gm3, 11.18 Mtce, 544.69 × 108 gm2, respectively, significantly exceeding the corresponding domestic food waste footprints. Cereals and meats have a dominant role in excessive food intake and related environmental impacts, with significant differences linked to demographic characteristics and urbanization levels. China has implemented various national policies, including an anti-food-waste law, to address agri-food sustainability challenges. This study suggests that addressing overeating can significantly enhance China's ability to tackle these challenges and improve public health outcomes.

Metabolic dysfunction-associated liver disease and diabetes: Matrix remodeling, fibrosis, and therapeutic implications.

Metabolic dysfunction-associated liver disease (MASLD) and steatohepatitis (MASH) are becoming the most common causes of chronic liver disease in the United States and worldwide due to the obesity and diabetes epidemics. It is estimated that by 2030 close to 100 million people might be affected and patients with type 2 diabetes are especially at high risk. Twenty to 30% of patients with MASLD can progress to MASH, which is characterized by steatosis, necroinflammation, hepatocyte ballooning, and in advanced cases, fibrosis progressing to cirrhosis. Clinically, it is recognized that disease progression in diabetic patients is accelerated and the role of various genetic and epigenetic factors, as well as cell-matrix interactions in fibrosis and stromal remodeling, have recently been recognized. While there has been great progress in drug development and clinical trials for MASLD/MASH, the complexity of these pathways highlights the need to improve diagnosis/early detection and develop more successful antifibrotic therapies that not only prevent but reverse fibrosis.

Butyrate and tributyrin reduce LPS-induced inflammatory cytokine production from human visceral fat.

The current obesity crisis has resulted in many people with excess adipose tissue suffering from chronic inflammation. This inflammation is largely due to the release of cytokines and chemokines from visceral fat. The aim of this study was to identify potential anti-inflammatory agents that might alleviate obesity-induced chronic inflammation. To identify agents that might alleviate this obesity-induced chronic inflammation we have developed a simple protocol for incubating intact pieces of human visceral adipose tissue in 35 mm tissue culture plates, in the presence of low-dose lipopolysaccharide (LPS) and co-incubating these samples with potential anti-inflammatory agents. RNA-Seq analysis was performed to identify enriched gene expression signatures among the most significantly differentially expressed genes. From this screen, we have identified the short-chain fatty acid (SCFA) sodium butyrate and its triacylglyceride form, tributyrin, as effective agents, significantly reducing the production of LPS-induced inflammatory cytokines and chemokines from all adipose tissue samples tested. As well, these agents appear to be non-toxic at the concentrations tested. RNA-Seq analysis has revealed that IL36γ is one of the most upregulated genes in response to LPS and one of the most downregulated when sodium butyrate is added to human fat samples stimulated with LPS. IL-36γ ELISAs confirmed this holds true at the protein level as well. These studies suggest that the short-chain fatty acid, sodium butyrate, and its triacylglyceride form, tributyrin, might alleviate the chronic inflammation that is associated with many individuals with obesity.

Management of intrahepatic and perihilar cholangiocarcinomas: Guidelines of the French Association for the Study of the Liver (AFEF).

Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.

Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, has increased worldwide along with the epidemics of obesity and related dysmetabolic conditions characterized by impaired glucose metabolism and insulin signaling, such as type 2 diabetes mellitus (T2D). MASLD can be defined as an excessive accumulation of lipid droplets in hepatocytes that occurs when the hepatic lipid metabolism is totally surpassed. This metabolic lipid inflexibility constitutes a central node in the pathogenesis of MASLD and is frequently linked to the overproduction of lipotoxic species, increased cellular stress, and mitochondrial dysfunction. A compelling body of evidence suggests that the accumulation of lipid species derived from sphingolipid metabolism, such as ceramides, contributes significantly to the structural and functional tissue damage observed in more severe grades of MASLD by triggering inflammatory and fibrogenic mechanisms. In this context, MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), which represents the advanced form of MASLD, and hepatic fibrosis. In this review, we discuss the role of sphingolipid species as drivers of MASH and the mechanisms involved in the disease. In addition, given the absence of approved therapies and the limited options for treating MASH, we discuss the feasibility of therapeutic strategies to protect against MASH and other severe manifestations by modulating sphingolipid metabolism.

Combating the Obesity Crisis: The Role of Community Pharmacists in Addressing the Rising Obesity Numbers

The last decade has seen a significant increase in obesity and overweight cases globally. The World Health Organization estimates that 1 in every 8 people globally were living with overweight and obesity in 2022. This is approximately 2.5 billion who are overweight and 890 million who are obese. The rate at which the obesity prevalence is an indication that it is ending towards being an epidemic. Considering that obesity is multifactorial, isolating the exact causes is a significant problem. As a result, there is a need to dedicate more resources towards addressing the problem. One of the ways that can be used to deal with the rising obesity prevalence is expanding the role of healthcare providers more so community pharmacists to address the problem. Community pharmacists can do more than drug management in managing the growing obesity crisis. They can be involved in weight management, guidance on lifestyle modifications, and counselling on behavior modifications. They can also be involved in community-based interventions that aim to address obesity. Keywords: obesity, obesity crisis, community pharmacists, energy intake, energy expenditure, weight management

Significance of the Gut-Brain Axis in the Development of Overweight and Obesity

Introduction: The global obesity crisis results from inactive lifestyles and poor diets, increasing the risk of metabolic disorders. Emerging research links obesity with gut microbiome changes influenced by factors like age, genetics, and diet. Gut-brain communication via neural, endocrine, and inflammatory pathways, influenced by microbial compounds, affects nervous system function. Materials and Methods of Research: A thorough literature review was performed using PubMed and Google Scholar, employing keywords related to the gut-brain axis and obesity. Results: Obesity shifts gut microbiota composition due to factors like childbirth method, diet, antibiotics, and environment. This imbalance impacts metabolism, appetite, and insulin sensitivity. Gut microbes influence the brain, regulating energy balance and inflammation. Dysregulated tryptophan metabolism leads to insulin resistance. Gut-brain communication via the vagal nerve affects nutrient metabolism. Hormones like insulin and leptin, along with microbial metabolites, affect lipid metabolism and appetite. Gut microbiota abundance correlates with leptin signaling, and changes in ghrelin levels relate to microbiota composition. Microbial presence affects food cravings. Inflammation in obesity is linked to gut microbiota changes, mediated by bile acids and microbial metabolites. Interventions like probiotics and fecal microbiota transplantation offer potential for managing obesity. Emerging therapies like peptide D3 hold promise but require further study. Conclusion: The microbiome-gut-brain axis is vital in obesity, affecting metabolism, inflammation, and appetite. Utilizing interventions such as dietary adjustments and probiotics targeting gut-brain signaling shows promise in managing obesity. Personalized approaches are crucial due to microbiome complexity. Further research is needed to develop effective therapies for the obesity epidemic.

Beyond Obesity and Overweight: The Clinical Assessment and Treatment of Excess Body Fat in Children : Part 1 - Insulin Resistance as the Root Cause of Pediatric Obesity.

Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

Beyond Obesity and Overweight: the Clinical Assessment and Treatment of Excess Body Fat In Children : Part 2 - the Prescription of Low-Carbohydrate Eating as the First Approach.

Pediatric obesity and comorbidities related to insulin resistance continue to be a growing public health crisis. If lifestyle measures are unsuccessful, pharmacological and surgical interventions are offered. In this paper, we describe the driving force of the obesity crisis: hyperinsulinemia and the development of insulin resistance. We give historical background of key policy issues which have contributed to this pandemic as well as the physiologic mechanisms of insulin resistance. The prevalence of obesity will continue to rise unless the root cause of hyperinsulinemia is addressed. Current research on insulin resistance demonstrates that a decreased consumption of carbohydrates is an effective first-line dietary intervention for the treatment of obesity and related metabolic diseases. Evidence shows it is safe and beneficial. A low-carbohydrate eating pattern can be helpful to address pediatric obesity. However, there must be policy guardrails in place to ensure that this is a sustainable and viable option for children and their families. There must be a change in the nutritional environment to help individuals battle the chronic disease of obesity.

How to 'drug' our way out of the obesity crisis (or not): the roll-out of semaglutide.

How to 'drug' our way out of the obesity crisis (or not): the roll-out of semaglutide.

Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury.

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.

Childhood obesity in the ED: A prospective Australian study.

To determine (i) the prevalence of overweight and obesity among children presenting to all EDs in a large regional Australian city and (ii) whether age, sex, socioeconomic status (SES) or hospital setting (public vs private) were associated with overweight and obesity. This prospective observational study included children aged ≥2 and <18 years who presented to any of three EDs over an 18 month period who had their height and weight measured. Age, sex and residential postcode were collected. Weight category was determined by sex and age standardised body mass index (BMI) z-score. Weight category was assessed by sex, age, SES and hospital setting with chi-squared tests, and ordinal logistic regression with cluster sandwich error estimators. Results were reported using odds ratios (OR) with 95% confidence intervals (CI). Data were collected for 3827 children, of which 11.6% were obese and 19.8% overweight. The prevalence of obesity was highest in those aged 8-14 years and in those from lower SES postcodes. The likelihood of obesity was higher in the public than the private hospitals (OR 0.66, 95% CI 0.51-0.86), whereas the likelihood of overweight was similar (OR 1.00, 95% CI 0.83-1.22). Almost one-third of children who presented to EDs were overweight or obese. Obesity was particularly high in those aged 8-14 years and those from lower SES postcodes. In the evolving obesity crisis, the high proportion of children presenting to EDs above a healthy weight might represent an opportunity for EDs to identify and refer children for body weight and lifestyle management.

The Notch-PDGFRβ axis suppresses brown adipocyte progenitor differentiation in early post-natal mice

De novo brown adipogenesis holds potential in combating the epidemics of obesity and diabetes. However, the identity of brown adipocyte progenitor cells (APCs) and their regulation have not been extensively explored. Here, through invivo lineage tracing and mouse modeling, we observed that platelet-derived growth factor receptor beta (PDGFRβ)+ pericytes give rise to developmental brown adipocytes but not to those in adult homeostasis. By contrast, T-box 18 (TBX18)+ pericytes contribute to brown adipogenesis throughout both developmental and adult stages, though in a depot-specific manner. Mechanistically, Notch inhibition in PDGFRβ+ pericytes promotes brown adipogenesis by downregulating PDGFRβ. Furthermore, inhibition of Notch signaling in PDGFRβ+ pericytes mitigates high-fat, high-sucrose (HFHS)-induced glucose and metabolic impairment in mice during their development and juvenile phases. Collectively, these findings show that the Notch/PDGFRβ axis negatively regulates developmental brown adipogenesis, and its repression promotes brown adipose tissue expansion and improves metabolic health.