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Journal of Clinical Lipidology May 2024In recent years, scientific interest in triglyceride-rich lipoproteins (TRL) and remnant cholesterol has increased, focusing on the evidence that these lipoproteins are...
BACKGROUND AND AIMS
In recent years, scientific interest in triglyceride-rich lipoproteins (TRL) and remnant cholesterol has increased, focusing on the evidence that these lipoproteins are a causal factor for developing atherosclerotic cardiovascular disease (ASCVD). Furthermore, a high remnant concentration (>38 mg/dL) has been associated with several non-cardiovascular risks. We aimed in this study to describe the percentile distribution of remnant cholesterol. Additionally, we evaluated the association between remnant cholesterol plasma concentration and epidemiologically relevant cardio-metabolic outcomes such as hypertension, type 2 diabetes (T2D), and ASCVD.
METHODS
We analyzed data from 9,591 adults from the National Survey of Health and Nutrition (ENSANUT) 2018 with fasting blood samples and complete medical history questionnaires. We built multivariate models to evaluate the association between chronic diseases and blood remnant concentration. To compare our 2018-sub-sample against a population reference, we used the NHANES (2005-2014) publicly available datasets by ethnicity.
RESULTS
Remnants were independently associated with cardiovascular risk, diabetes, hypertension, obesity, and metabolic syndrome. For all outcomes, the blood remnant concentration was a stronger predictor than LDL. At all deciles, the blood remnant concentration was higher in ENSANUT-2018.
CONCLUSIONS
A remnant blood concentration above 38 mg/dL was highly prevalent among Mexicans. Remnants were significantly associated with a higher risk of diabetes, hypertension, obesity, and cardiovascular risk. This association occurred independently of other lipid markers.
PubMed: 38942690
DOI: 10.1016/j.jacl.2024.05.002 -
Aging Jun 2024Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress...
Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.
PubMed: 38942607
DOI: 10.18632/aging.205970 -
Metabolism: Clinical and Experimental Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are...
Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: systematic analysis from the global burden of disease study 2019.
OBJECTIVE
Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.
METHODS
From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.
RESULTS
Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.
CONCLUSION
The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.
PubMed: 38942169
DOI: 10.1016/j.metabol.2024.155958 -
The American Journal of Clinical... Jun 2024The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some...
BACKGROUND
The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child.
OBJECTIVE
To determine the association between pregnancy weight gain below the lower limit of the current Institute of Medicine (IOM) recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity.
METHODS
We used data from a prospective cohort study of US nulliparae with prepregnancy overweight (n=955) or obesity (n=897) followed from the first trimester to 2-7 years postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity).
RESULTS
Pregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of -2 standard deviations in pregnancies with overweight (equivalent to 3.6kg at 40 weeks) and obesity (-2.8kg at 40 weeks) were 0.99 (0.91, 1.06) and 0.97 (0.87, 1.07).
CONCLUSIONS
These findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy BMI groups.
PubMed: 38942117
DOI: 10.1016/j.ajcnut.2024.06.011 -
Journal of Reproductive Immunology Jun 2024The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain...
Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals.
BACKGROUND
The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial.
AIMS
This study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls.
METHODS
A case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored.
RESULTS
In comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels.
CONCLUSION
In women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.
PubMed: 38941927
DOI: 10.1016/j.jri.2024.104281 -
International Immunopharmacology Jun 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with insulin resistance (IR) and hyperandrogenaemia (HA). Metabolic inflammation (MI),... (Review)
Review
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with insulin resistance (IR) and hyperandrogenaemia (HA). Metabolic inflammation (MI), characterized by a chronic low-grade inflammatory state, is intimately linked with chronic metabolic diseases such as IR and diabetes and is also considered an essential factor in the development of PCOS. Insulin-like growth factor 1 (IGF-1) plays an essential role in PCOS pathogenesis through its multiple functions in regulating cell proliferation metabolic processes and reducing inflammatory responses. This review summarizes the molecular mechanisms by which IGF-1, via MI, participates in the onset and progression of PCOS, aiming to provide insights for studies and clinical treatment of PCOS.
PubMed: 38941670
DOI: 10.1016/j.intimp.2024.112529 -
JMIR Public Health and Surveillance Jun 2024Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given...
BACKGROUND
Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given this relationship, the concepts of metabolically healthy and unhealthy obesity, considering metabolic status, have been evolving. Attention is being directed to metabolically healthy people with obesity who have relatively low transition rates to noncommunicable diseases. As obesity rates continue to rise and unhealthy behaviors prevail among young adults, there is a growing need for obesity management that considers these metabolic statuses. A nomogram can be used as an effective tool to predict the risk of transitioning to metabolically unhealthy obesity from a metabolically healthy status.
OBJECTIVE
The study aimed to identify demographic factors, health behaviors, and 5 metabolic statuses related to the transition from metabolically healthy obesity to unhealthy obesity among people aged between 20 and 44 years and to develop a screening tool to predict this transition.
METHODS
This secondary analysis study used national health data from the National Health Insurance System in South Korea. We analyzed the customized data using SAS (SAS Institute Inc) and conducted logistic regression to identify factors related to the transition from metabolically healthy to unhealthy obesity. A nomogram was developed to predict the transition using the identified factors.
RESULTS
Among 3,351,989 people, there was a significant association between the transition from metabolically healthy to unhealthy obesity and general characteristics, health behaviors, and metabolic components. Male participants showed a 1.30 higher odds ratio for transitioning to metabolically unhealthy obesity than female participants, and people in the lowest economic status were also at risk for the transition (odds ratio 1.08, 95% CI 1.05-1.1). Smoking status, consuming >30 g of alcohol, and insufficient regular exercise were negatively associated with the transition. Each relevant variable was assigned a point value. When the nomogram total points reached 295, the shift from metabolically healthy to unhealthy obesity had a prediction rate of >50%.
CONCLUSIONS
This study identified key factors for young adults transitioning from healthy to unhealthy obesity, creating a predictive nomogram. This nomogram, including triglycerides, waist circumference, high-density lipoprotein-cholesterol, blood pressure, and fasting glucose, allows easy assessment of obesity risk even for the general population. This tool simplifies predictions amid rising obesity rates and interventions.
Topics: Humans; Republic of Korea; Male; Female; Adult; Young Adult; Obesity, Metabolically Benign; Metabolic Syndrome; Nomograms; Obesity; Health Behavior; Risk Factors
PubMed: 38941611
DOI: 10.2196/52103 -
PloS One 2024The study of non-communicable diseases (NCDs) in a developing country like Thailand has rarely been conducted in long-term cohorts, especially among the working-age...
Metabolic and genetic risk factors associated with pre-diabetes and type 2 diabetes in Thai healthcare employees: A long-term study from the Siriraj Health (SIH) cohort study.
BACKGROUND
The study of non-communicable diseases (NCDs) in a developing country like Thailand has rarely been conducted in long-term cohorts, especially among the working-age population. We aim to assess the prevalence and incidence of risk factors and their associations underlying NCDs, especially type-2 diabetes mellitus (T2DM) among healthcare workers enrolled in the Siriraj Health (SIH) study cohort.
METHODS
The SIH study was designed as a longitudinal cohort and conducted at Siriraj hospital, Thailand. A total of 5,011 participants (77% women) were recruited and follow-up. Physical examinations, blood biochemical analyses, family history assessments, behavior evaluations, and genetics factors were assessed.
RESULTS
The average age was 35.44±8.24 years and 51% of participants were overweight and obese. We observed that men were more likely to have a prevalence of T2DM and dyslipidemia (DLP) compared to women. Aging was significantly associated with pre-diabetes and T2DM (P<0.001). Additionally, aging, metabolic syndrome, and elevated triglycerides were associated with the development of pre-diabetes and T2DM. The minor T allele of the rs7903146(C/T) and rs4506565 (A/T) were associated with a high risk of developing pre-diabetes with odds ratios of 2.74 (95% confidence interval [CI]: 0.32-23.3) and 2.71 (95% CI: 0.32-23.07), respectively; however, these associations were statistically insignificant (P>0.05).
CONCLUSION
The findings of the SIH study provide a comprehensive understanding of the health status, risk factors, and genetic factors related to T2DM in a specific working population and highlight areas for further research and intervention to address the growing burden of T2DM and NCDs.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Thailand; Adult; Risk Factors; Health Personnel; Middle Aged; Prediabetic State; Longitudinal Studies; Prevalence; Genetic Predisposition to Disease; Cohort Studies; Metabolic Syndrome; Polymorphism, Single Nucleotide; Southeast Asian People
PubMed: 38941315
DOI: 10.1371/journal.pone.0303085 -
Revista de La Facultad de Ciencias... Jun 2024Introducción: El síndrome metabólico (SM) está asociado a un incremento del riesgo cardiovascular. Los donantes de sangre son una población aparentemente sana en...
UNLABELLED
Introducción: El síndrome metabólico (SM) está asociado a un incremento del riesgo cardiovascular. Los donantes de sangre son una población aparentemente sana en donde ciertas características cardiometabolicas no son evaluadas en su selección, existiendo limitada información sobre su presencia.
OBJETIVO
Determinar la frecuencia de síndrome metabólico y sus características metabólicas en donantes de sangre. Materiales y métodos: Estudio transversal realizado en 244 donantes de sangre entre 18 y 55 años que acudieron al Servicio de Hemoterapia y Banco de sangre del Hospital Cayetano Heredia en Lima- Perú, durante el mes de mayo del 2023. Se realizó el diagnóstico de SM según los criterios del Adult Treatment Panel III (ATP III). Se realizó un análisis bivariado entre el SM y características metabólicas con el sexo y se consideró un nivel de significancia del 5%.
RESULTADOS
El 63.9% de los donantes de sangre fueron del sexo masculino. El 43.6 % de la población presentó SM. Las características más frecuentes fueron la hipertrigliceridemia (54.5%), obesidad abdominal (51.2%) y lipoproteina de alta densidad (HDL) bajo (48.8%). El rango de edad de 40 a 49 años presentó la mayor frecuencia de SM (14.3%). La hipertrigliceridemia y presión arterial elevada estuvieron asociadas al sexo masculino (p=0.003 y p=0.019 respectivamente), mientras que el HDL bajo al sexo femenino (p <0.001).
CONCLUSIONES
Los donantes de sangre presentan una frecuencia elevada de SM. La detección de SM en poblaciones aparentemente sanas como parte de la atención primaria podría permitir formular estrategias de detección temprana de factores de riesgo cardiovascular.
Topics: Humans; Metabolic Syndrome; Male; Female; Blood Donors; Adult; Cross-Sectional Studies; Middle Aged; Young Adult; Adolescent; Peru; Risk Factors; Obesity, Abdominal; Sex Factors; Sex Distribution
PubMed: 38941225
DOI: 10.31053/1853.0605.v81.n2.42446 -
The Journal of Clinical Endocrinology... Jun 2024Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive,...
Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive, catecholaminergic, and immunomodulation mechanisms, followed by a reset via cortisol. Stress system components, the sympathoadrenomedullary system, hypothalamic-pituitary-adrenal axis, and limbic structures are implicated in many chronic diseases by establishing an altered homeostatic state, allostasis. Consequent "primary stress system disorders" were popularly accepted, with phenotypes based on conditions such as Cushing syndrome, pheochromocytoma, and adrenal insufficiency. Cardiometabolic and major depressive disorders are candidates for hypercortisolemic etiology, contrasting the "hypocortisolemic symptom triad" of stress sensitivity, chronic fatigue, and pain. However, acceptance of chronic stress etiology requires cause-and-effect associations, and practical utility such as therapeutics altering stress system function. Inherent predispositions to stress system perturbations may be relevant. Glucocorticoid receptor (GR) variants have been associated with metabolic/neuropsychological states. The SERPINA6 gene encoding corticosteroid-binding globulin (CBG), was the sole genetic factor in a single-nucleotide variation-genome-wide association study linkage study of morning plasma cortisol, a risk factor for cardiovascular disease, with alterations in tissue-specific GR-related gene expression. Studies showed genetically predicted high cortisol concentrations are associated with hypertension and anxiety, and low CBG concentrations/binding affinity, with the hypocortisolemic triad. Acquired CBG deficiency in septic shock results in 3-fold higher mortality when hydrocortisone administration produces equivocal results, consistent with CBG's role in spatiotemporal cortisol delivery. We propose some stress system disorders result from constitutional stress system variants rather than stressors themselves. Altered CBG:cortisol buffering may influence interstitial cortisol ultradian surges leading to pathological tissue effects, an example of stress system variants contributing to stress-related disorders.
PubMed: 38941154
DOI: 10.1210/clinem/dgae412