Higher Risk Of Metabolic Disease Research Articles

Exploring Stroke Risk through Mendelian Randomization: A Comprehensive Study Integrating Genetics and Metabolic Traits in the Korean Population.

Numerous risk factors play a role in the causation of stroke, and the cardiometabolic condition is a one of the most important. In Korea, various treatment methods are employed based on the constitutional type, which is known to differ significantly in cardiometabolic disease. In this study, we compared the estimates obtained for different groups by applying the Mendelian randomization method to investigate the causal effects of genetic characteristics on stroke, according to constitutional type. In clinical analysis, the subtypes differ significantly in diabetes or dyslipidemia. The genetic association estimates for the stroke subtype risk were obtained from MEGASTROKE, the International Stroke Genetics Consortium (ISGC), UKbiobank, and BioBank Japan (BBJ), using group-related SNPs as instrumental variables. The TE subtypes with higher risk of metabolic disease were associated with increased risk (beta = 4.190; s.e. = 1.807; p = 0.035) of cardioembolic stroke (CES), and the SE subtypes were associated with decreased risk (beta = -9.336, s.e. = 1.753; p = 3.87 × 10-5) of CES. The findings highlight the importance of personalized medicine in assessing disease risk based on an individual's constitutional type.

Abstract 1035: C/EBPα Has Depot-specific Roles In White Adipose Tissue Development And Function.

Obesity, defined as excess white adipose tissue (WAT), associates with a higher risk of metabolic disease and comorbidities, and continues to be on the rise in the developed world. However, different WAT depots associate with differing levels of cardiometabolic risk. Expansion of visceral WAT (vWAT) correlates with increased risk for cardiovascular disease and type 2 diabetes, while expansion of subcutaneous WAT (sWAT) does not. These observations suggest mechanistic differences between the two depots, and elucidating these mechanisms may provide insights into promoting cardiometabolic health in humans. Human GWAS have shown that SNPs near the gene CEBPA associate with waist-to-hip ratio, a metric of vWAT mass in humans, suggesting CEBPA plays a specific role in vWAT. CEBPA encodes the transcription factor C/EBPα, a known regulator of adipogenesis. We established adipocyte-specific Cebpa knockout (Cebpa_ASKO) mice and found they lack gonadal WAT (gWAT), the largest vWAT depot in mice. Conversely, sWAT is still present in Cebpa_ASKO mice, although with reduced mass (-23%, p<0.05) and larger adipocytes. Additionally, Cebpa_ASKO mice have reduced lipolysis (-26% NEFAs, p<0.05), plasma adiponectin (-89%, p<0.0001) and leptin (-82%, p<0.05), suggesting the remaining sWAT is dysfunctional. Together, these data suggest that C/EBPα has WAT depot-specific roles, being required for vWAT development, but only for function in mature sWAT. Given the myriad roles for vWAT in metabolism and the absence of vWAT in Cebpa_ASKO mice, we investigated downstream metabolic consequences of this phenotype. Cebpa_ASKO mice have increased brown adipose tissue (BAT) mass (+118%, p<0.001) due to increased ectopic lipid deposition. Cebpa_ASKO mice also have increases in plasma cholesterol (+20%, p<0.05), liver mass (+24%, p<0.01), and hepatic fat content (+329%, p<0.01). Overall, these results demonstrate that adipocyte C/EBPα significantly influences whole body metabolism. Ongoing studies center on delineating the different mechanisms through which C/EBPα functions in vWAT and sWAT. Understanding the depot-specific mechanisms of C/EBPα could have practical implications for new clinical targets of obesity and metabolic disease.

Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals.

Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort. We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.

Lipid profiles of people with human immunodeficiency virus with dyslipidemia after switching from efavirenz to dolutegravir.

Introduction: Human immunodeficiency virus (HIV) infection and the long-term use of antiretroviral therapy, especially efavirenz (EFV)-based regimens, impact lipid profiles due to insulin resistance and lead to a higher risk of metabolic diseases. Dolutegravir (DTG) is an integrase inhibitor with better lipid profiles than EFV. However, data on treatment experience in Thailand are limited. The primary outcome was lipid profile changes at 24 weeks after switching therapy. Methods: We conducted a prospective, open-label, cohort study in people with HIV aged ≥18 years who had undergone at least 6 months of EFV-based therapy, had HIV-1 ribonucleic acid levels &lt;50 copies/mL for ≥6 months before switching, and were diagnosed with dyslipidemia or had risk factors for atherosclerosis cardiovascular disease based on modified National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: Sixty-four patients were enrolled. The mean age (standard deviation [SD]) was 48.20 ± 10.46 years, and 67.19% were male. At week 24, there were decreases from baseline in mean total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. However, mean body weight and waist circumference had increased. Conclusions: DTG resulted in better lipid profiles after switching from EFV-based therapy, suggesting that this switch could benefit patients with a high risk of cardiovascular disease. However, it is essential to note that weight gain and increased waist circumference were also observed.

PS-C23-4: I CHOOSE ULTRA PROCESSED FOOD SINCE MORE PRACTICAL AND TASTIER: A QUALITATIVE STUDY OF ULTRA-PROCESSED FOOD CONSUMPTION AMONG ADULTS

Objective: Industrialization, as an impact of globalization, produced more ultra processed food (UPF) which triggered a nutrition transition. The UPF, which is dominated by instant and junk foods, caused a higher risk of metabolic diseases. Although the UPF consumption was not high (±15%) among Indonesian adults yet the factors of choosing UPF should be explored to design the best nutrition intervention for improving diet quality. Design and method: We performed four focused group discussions (FGD) and observations in four administrative cities in a province during December 2021. Each group of the FGD consisted of 8 to 10 adults aged above 20 years. The FGD session was conducted by a trained moderator and assisted by two trained enumerators. The data were transcribed verbatim and analyzed using an inductive thematic approach. An FGD lasted between 50 to 60 minutes, covering three topics regarding dietary patterns, the type of food commonly consumed, including the reason for consuming UPF during the last month. Simultaneously, a market survey was performed at street vendors, food outlets, and supermarkets around the sampling areas to check the food availability, especially the UPF mentioned by the subjects in the FGD. Results: There were 24 adults, which was dominated by females (87.5%). Four initial themes determined UPF consumption, namely (1) family preferences, (2) practical reason, (3) taste, and (4) nutrient content. The UPF commonly consumed was instant noodles, canned sardines, biscuits, white bread, sugar-sweetened beverages (SSB), sausages, instant coffee drinks, and packaged milk. Those food and drink were easily found around their dwelling area. The frequency of consuming UPF was not often. I choose instant foods when I or my family was in a hurry and have no time to cook fresh food (Mrs. R, 45 years, a housewife). Some adults were already aware of the negative side of UPF, yet the good taste kept them consuming the food. I know that instant food is bad for health. However, I thought that if we did not consume the food frequently, it would still be safe (Mrs. Y, 40 years, a local cadre). Conclusions: The main factors that triggered UPF consumption were preferences, practicality, taste, and nutrient content. Instead of avoiding the bad effects of UPF on health, some adults still attach importance to other aspects related to preferences and sensory appeal. Beyond nutrition education and campaign, creating a healthier food environment is also important to support the habitual changes for better diet quality.

Monocyte-to-high-density lipoprotein ratio and systemic inflammation response index are associated with the risk of metabolic disorders and cardiovascular diseases in general rural population.

BackgroundThe present study aimed to clarify the effects of four inflammatory indicators (monocyte-to-high-density lipoprotein ratio [MHR], neutrophil-to-lymphocyte ratio [NLR], systematic immune-inflammation index [SII], and systemic inflammation response index [SIRI]) in evaluating the risk of metabolic diseases and cardiovascular disease (CVD), filling the gap of inflammation-metabolism system research in epidemiology.MethodsWe conducted a cross-sectional study and multivariable logistic regression analysis to elucidate the association between inflammatory indicators and metabolic diseases and CVD risk. Metabolic diseases were defined as metabolic disorders (MetDs) or their components, such as metabolic syndrome (MetS), dyslipidemia, and central obesity. We calculated the Framingham risk score (FRS) to evaluate 10-year CVD risk.ResultsOdds ratios for the third vs. the first tertile of MHR were 2.653 (95% confidence interval [CI], 2.142–3.286) for MetD, 2.091 (95% CI, 1.620–2.698) for MetS, 1.547 (95% CI, 1.287–1.859) for dyslipidemia, and 1.515 (95% CI, 1.389–1.652) for central obesity. Odds ratios for the third vs. the first tertile of SIRI were 2.092 (95% CI, 1.622–2.699) for MetD, 3.441 (95% CI, 2.917–4.058) for MetS, 1.417 (95% CI, 1.218–1.649) for dyslipidemia, and 2.080 (95% CI, 1.613–2.683) for central obesity. The odds ratio of a 10-year CVD risk of >30% for the third vs. the first tertile of MHR was 4.607 (95% CI, 2.648–8.017) and 3.397 (95% CI, 1.958–5.849) for SIRI.ConclusionsMHR and SIRI had a significant association with MetD and its components, in which a higher level of MHR or SIRI tended to accompany a higher risk of metabolic diseases. Furthermore, they also correlated with CVD, and the increment of these indicators caused a gradually evaluated risk of 10-year CVD risk.

Polyunsaturated fatty acids and metabolic health: novel insights.

This review aims to discuss the potential roles of omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) in the prevention and treatment of metabolic diseases, to provide the latest evidence from epidemiological and clinical studies, and to highlight novel insights into this field. Higher dietary or circulating ω-3 PUFA levels are related to a lower risk of metabolic syndrome. Novel findings in obesity indicate higher proportions of ω-6 and ω-3 PUFAs, a modulated oxylipin profile and an altered transcriptome in subcutaneous white adipose tissue, that seem resistant to the effects of ω-3 PUFAs compared with what occurs in normal weight individuals. ω-3 PUFAs may improve the blood lipid profile and glycemic outcomes in patients with type 2 diabetes mellitus and reduce liver fat in nonalcoholic fatty liver disease (NAFLD); the findings of several recent meta-analyses support these effects. Genetic background affects inter-individual variability in the insulin sensitivity response to ω-3 PUFA supplementation. ω-3 PUFAs have prebiotic effects, altering the gut microbiota. Although evidence for health benefits of ω-3 PUFAs is strong, recent findings suggest a more personalized approach to ω-3 PUFA intake for individuals at high risk for metabolic diseases.

Obese Individuals With and Without Phlegm-Dampness Constitution Show Different Gut Microbial Composition Associated With Risk of Metabolic Disorders.

BackgroundObesity is conventionally considered a risk factor for multiple metabolic diseases, such as dyslipidemia, type 2 diabetes, hypertension, and cardiovascular disease (CVD). However, not every obese patient will progress to metabolic disease. Phlegm-dampness constitution (PDC), one of the nine TCM constitutions, is considered a high-risk factor for obesity and its complications. Alterations in the gut microbiota have been shown to drive the development and progression of obesity and metabolic disease, however, key microbial changes in obese patients with PDC have a higher risk for metabolic disorders remain elusive.MethodsWe carried out fecal 16S rRNA gene sequencing in the present study, including 30 obese subjects with PDC (PDC), 30 individuals without PDC (non-PDC), and 30 healthy controls with balanced constitution (BC). Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt.ResultsObese individuals with PDC had higher BMI, waist circumference, hip circumference, and altered composition of their gut microbiota compared to non-PDC obese individuals. At the phylum level, the gut microbiota was characterized by increased abundance of Bacteroidetes and decreased levels of Firmicutes and Firmicutes/Bacteroidetes ratio. At the genus level, Faecalibacterium, producing short-chain fatty acid, achieving anti-inflammatory effects and strengthening intestinal barrier functions, was depleted in the PDC group, instead, Prevotella was enriched. Most PDC-associated bacteria had a stronger correlation with clinical indicators of metabolic disorders rather than more severe obesity. The PICRUSt analysis demonstrated 70 significantly different microbiome community functions between the two groups, which were mainly involved in carbohydrate and amino acid metabolism, such as promoting Arachidonic acid metabolism, mineral absorption, and Lipopolysaccharide biosynthesis, reducing Arginine and proline metabolism, flavone and flavonol biosynthesis, Glycolysis/Gluconeogenesis, and primary bile acid biosynthesis. Furthermore, a disease classifier based on microbiota was constructed to accurately discriminate PDC individuals from all obese people.ConclusionOur study shows that obese individuals with PDC can be distinguished from non-PDC obese individuals based on gut microbial characteristics. The composition of the gut microbiome altered in obese with PDC may be responsible for their high risk of metabolic diseases.

Update of Indoles: Promising molecules for ameliorating metabolic diseases.

Obesity and metabolic disorders have gradually become public health-threatening problems. The metabolic disorder is a cluster of complex metabolic abnormalities which are featured by dysfunction in glucose and lipid metabolism, and results from the increasing prevalence of visceral obesity. With the core driving factor of insulin resistance, metabolic disorder mainly includes type 2 diabetes mellitus (T2DM), micro and macro-vascular diseases, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and the dysfunction of gut microbiota. Strategies and therapeutic attention are demanded to decrease the high risk of metabolic diseases, from lifestyle changes to drug treatment, especially herbal medicines. Indole is a parent substance of numerous bioactive compounds, and itself can be produced by tryptophan catabolism to stimulate glucagon-like peptide-1 (GLP-1) secretion and inhibit the development of obesity. In addition, in heterocycles drug discovery, the indole scaffold is primarily found in natural compounds with versatile biological activity and plays a prominent role in drug molecules synthesis. In recent decades, plenty of natural or synthesized indole deriviatives have been investigated and elucidated to exert effects on regulating glucose hemeostasis and lipd metabolism. The aim of this review is to trace and emphasize the compounds containing indole scaffold that possess immense potency on preventing metabolic disorders, particularly T2DM, obesity and NAFLD, along with the underlying molecular mechanisms, therefore facilitate a better comprehension of their druggability and application in metabolic diseases.

Current Research on the Effects of Non-Digestible Carbohydrates on Metabolic Disease

Metabolic diseases (MDs), including cardiovascular diseases (CVDs) and diabetes, occur when the body’s normal metabolic processes are disrupted. Behavioral risk factors such as obesity, physical inactivity, and dietary habits are strongly associated with a higher risk of MD. However, scientific evidence strongly suggests that balanced, healthy diets containing non-digestible carbohydrates (NDCs), such as dietary fiber and resistant starch, can reduce the risk of developing MD. In particular, major properties of NDCs, such as water retention, fecal bulking, viscosity, and fermentation in the gut, have been found to be important for reducing the risk of MD by decreasing blood glucose and lipid levels, increasing satiety and insulin sensitivity, and modifying the gut microbiome. Short chain fatty acids produced during the fermentation of NDCs in the gut are mainly responsible for improvement in MD. However, the effects of NDCs are dependent on the type, source, dose, and duration of NDC intake, and some of the mechanisms underlying the efficacy of NDCs on MD remain unclear. In this review, we briefly summarize current studies on the effects of NDCs on MD and discuss potential mechanisms that might contribute to further understanding these effects.

CD8+ T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs.

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPRdn, hIAPP and PNPLA3I148M. Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8+ T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs’ liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.

Oil emulsion from Plukenetia huayllabambana (Sacha inchi) modifies nitric oxide and leptin in the liver and antioxidant and inflammation markers in the adipose tissue in obese rats

Background: Obesity is characterized by excessive accumulation of adipose tissue and is associated with higher risk of metabolic diseases and other comorbidities. Efficacious strategies including a diet high in “functional foods” are promising. Plukenetia huayllabambana known as Sacha Inchi (SI), is a legume which seeds are rich in proteins, tocopherols, and fatty acids such as omega-3 (ω-3). The latter has emerged as a potential protective nutrient against the cardiometabolic risks associated with obesity. Omega-3 changes the membrane lipid profile of hepatic and adipose cells triggering the expression of antioxidant and anti-inflammatory genes. However, there are few reports in relation to the effect of these oils in inflammatory and stress response related to obesity. In this sense, the present study evaluated the effect of SI oil emulsion on nitric oxide and leptin levels in the liver and some markers of oxidative stress and inflammation in adipose tissue from the rodent obesity model.Methods: Six groups were formed: Not obese control group (Noc), obese control (Oc), two groups treated with the emulsion of SI oil (Os1:0.25g ω-3/day; Os2:0.5g ω-3/day), one obese group treated with atorvastatin (Oa) and one group treated with atorvastatin plus the emulsion of SI oil (Oas2).Results: Os1 and Os2 lowered nitric oxide and increased liver leptin levels. In the adipose tissue, the superoxide dismutase and reducing antioxidant power increased significantly in Os1 and Os2 groups. The anti-inflammatory marker IL-4 wasalso increased in Os2, Oa and Oas2 compared to the Oc and IL-10 increased in Oas2 group.Conclusion: Our study suggests that the emulsion of SI oil can modify the inflammatory and stress responses associated with obesity and it can be incorporated as a promising functional food.Keywords: Inflammation, leptin, obesity, nitric oxide, oxidative stress, SI oil emulsion.

The relationships between obstructive sleep apnea and psychiatric disorders: a narrative review

Abstract Introduction: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Its prevalence tends to increase worldwide. Untreated sleep apnea is associated with a higher risk of metabolic diseases, cardiovascular diseases, stroke, road accidents, and death, but also it is suggested that it increases the risk of mental disorders. Method: The literature review was based on a search of articles on Medline, Pubmed, and Google Scholar from 2003 to 2021 using the keywords: obstructive sleep apnea; mental disorders; cognitive functions; affective disorders; depression; bipolar disorder; schizophrenia; psychotic disorders. The analysis included original studies, meta-analysis, and review articles. Discussion: The result obtained from researches published so far does not allow for drawing unequivocal conclusions. There is a lot of bias present in study protocols and inclusion/exclusion criteria. Nonetheless, it seems that some disorders have a better proven correlation with OSA. Cognitive impairment, depression, and anxiety disorders are linked to OSA not only in terms of the overlapping of symptoms but also of a causal relationship. Psychotic disorders and bipolar disorders connections with OSA are confirmed, but they are not yet well understood. All correlations are found to be possibly bidirectional. Conclusion: 1. Multiple lines of evidence increasingly point towards a bidirectional connection between OSA and mental disorders, and the cause and effect relationship between these two groups of disorders requires further research. 2. Due to reports of an increased risk of OSA with antipsychotic drugs, caution should be exercised when initiating therapy with this type of drug in patients with known risk factors for it. 3. Screening for OSA in psychiatric patients should be introduced as OSA can increase cognitive impairment, affective, and psychotic symptoms.

Global food quality in the migrant population residing in Chile

Introduction: the migration process involves change, modification, or acquisition of new eating patterns and ways of eating, which do not always positively impact the health of migrants, being frequently associated with a higher risk of metabolic diseases and excess malnutrition when the quality of food is not adequate. Objective: to analyze the global food quality index (GQI) in the Colombian migrant population in Chile, comparing it with the Chilean population and non-migrant Colombians. Methods: the total sample consisted of 834 individuals over 18 years of age - 206 Colombian migrants residing in Chile, 266 Colombians residing in Colombia, and 362 Chileans. A global food quality index survey was applied to categorize the healthiness of the participants' dietary patterns. Results: there were significant differences in all the ICGA scores analyzed regarding healthy foods, unhealthy foods, and mealtimes. It was observed that Colombians residing in Colombia have the highest score in the healthy classification, while Colombian migrants have the highest figures in the unhealthy condition. Regarding meal times, Chileans are the least compliant with meal times. However, other influences related to food groups stand out. Conclusion: it is necessary to delve deeper into variables linked to the sociodemographic context, analyze potential changes over time, and replicate in migrants of other nationalities to have more information on the relationship between food quality and the migration process.

Characterization of dietary patterns and assessment of their relationships with metabolomic profiles: A community-based study

Determining dietary patterns in China is challenging due to lack of external validation and objective measurements. We aimed to characterize dietary patterns in a community-based population and to validate these patterns using external validation cohort and metabolomic profiles. We studied 5145 participants, aged 18-80 years, from two districts of Hangzhou, China. We used one district as the discovery cohort (N=2521) and the other as the external validation cohort (N=2624). We identified dietary patterns using a k-means clustering. Associations between dietary patterns and metabolic conditions were analyzed using adjusted logistic models. We assessed relationships between metabolomic profile and dietary patterns in 214 participants with metabolomics data. We identified three dietary patterns: the traditional (rice-based), the mixed (rich in dairy products, eggs, nuts, etc.), and the high-alcohol diets. Relative to the traditional diet, the mixed (ORadj=1.7, CI 1.3-2.4) and the high-alcohol diets (ORadj=1.9, CI 1.3-2.7) were associated with type 2 diabetes and hypertension, respectively. Similar results were confirmed in the external validation cohort. In addition, we also identified 18 and 22 metabolites that could distinguish the mixed (error rate=12%; AUC=96%) and traditional diets (error rate=19%; AUC=88%) from the high-alcohol diet. Despite the complexity of Chinese diet, identifying dietary patterns helps distinguish groups of individuals with high risk of metabolic diseases, which can also be validated by external population and metabolomic profiles.

Abstract B093: Upregulated and downregulated microRNA-signatures in thyroid cancer health disparities

Abstract Filipino Americans (FA) are known to have a higher incidence, recurrence, and mortality of thyroid cancer (TC) than other Asians Americans or European Americans (EA). Understanding the molecular mechanisms that underpin the genetic defect in metabolism and their impact on thyroid cancer oncogenesis in FA are critical for addressing the health disparity. Mechanisms that link genetic defects and lifestyle factors to thyroid cancer progression have not been defined. Lifestyle and genetic variations among FA lead them to a higher risk of metabolic diseases but no study showed to elucidate the mechanism of thyroid health disparities cancer so far. Recent studies clearly demonstrate that miRNA plays an important role in carcinogenesis via targeting both oncogene and tumor suppressor gene and lifestyle changes may potentially alter miRNA signatures. Therefore, we hypothesize that miRNA expression contributes to tumor grade, prognosis, and thyroid cancer health disparities. We examined miRNA expression profiles in FA vs. EA. We analyzed miRNA-sequence (miRNA-seq) by next-generation sequencing (NGS). The pathways linked to miRNAs were analyzed by ingenuity pathway analysis (IPA) software. Correlations between disease staging to miRNA upregulation and downregulation were elucidated. Both upregulated and downregulated miRNAs were validated by quantitative real-time PCR (qPCR) using miRNA extracted from paraffin-embedded thyroid tissues. We found hundreds of upregulated and downregulated miRNA and piRNA from this study. We chose 10 miRNA down-regulated, and 10 up-regulated miRNA FA compared to EA TC patients (p&amp;lt;0.05). Quantitative PCR (qPCR) was done to confirm our NGS data. Differential miRNA expressions between FA vs. EA patient tumor tissues were observed with advanced staging. Evolutionarily conserved miRNA clusters, which are known to initiate malignancy, were shown to be upregulated in FATC vs. EATC. While those miRNAs are known to regulate pathways involved in cancer invasion and metastasis, they were shown to be down-regulated in FATC patients vs. EATC. The significantly top ten down-regulated/upregulated miRNA-signature suggests that it can be a diagnostic, prognostic, and predictive biomarker in TC health disparities. Citation Format: Ryan Davis, Yan C Wongworawat, Mia C Perez, Krystal Santiago, Saurav Roy, Charles Wang, Alfred A Simental, Salma Khan. Upregulated and downregulated microRNA-signatures in thyroid cancer health disparities [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B093.

Longitudinal Study of Metabolic Biomarkers among Conventional and Organic Farmers in Thailand.

The aim of this longitudinal study is to assess how pesticide use may impact metabolic biomarkers by collecting and comparing data from conventional (n = 13) and organic farmers (n = 225) every eight months for four rounds. Farmers were interviewed about family health history, food consumption behaviors, self-reported health problems, agricultural activities, and history of pesticide use. Systolic and diastolic blood pressure and body mass index (BMI) were measured. Blood samples were collected for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), blood glucose, and triglycerides. A linear mixed model with random intercepts for subjects was used to compare the metabolic biomarkers between conventional and organic farmers and to examine the impact of the number of pesticide spray days for all four rounds after controlling for covariates. The conventional farmers reported using insecticides, herbicides, and fungicides. The marginal means for chemical farmers were significantly higher than organic farmers for total cholesterol, LDL, HDL, glucose, systolic and diastolic blood pressure, BMI, and waist circumference. Increasing the number of days of spraying either insecticides or fungicides was associated with an increase in HDL, LDL, and cholesterol levels. Increasing the number of herbicide spray days was associated with an increase in systolic and diastolic blood pressure and a decrease in BMI. These findings suggest that pesticide-using conventional farmers may be at higher risk of metabolic disease in the future.

Factors Influencing Residents’ Decision to Participate in Health Screening in Taiwan: A Qualitative Study

Introduction: Chronic diseases have affected the health and quality of life of people in a vast number of countries. Critically, chronic diseases have been rapidly increasing worldwide and inflicting a heavy burden on society. As such, health screening has been applied to reduce individuals’ risks of developing chronic diseases and to initiate health promotion or disease prevention. However, the participant rate is low, especially for people living in rural areas. The purpose of this study was to identify the factors that influence people’s decisions to undergo health screening. Method: Semi-structured interviews were undertaken for 16 people aged between 30 - 60 years, and all interviewees had never attended health screening at our hospital despite being invited. Interviewees were from four districts in Taiwan: Anle District of Keelung City; and Ruifang, Gongliao, and Wanli Districts of New Taipei City. These districts were sampled to represent urban and rural areas, respectively, and people in these rural areas were suspected to have high risk of metabolic diseases, kidney and lung diseases or cancers. Interviews were audio-recorded and transcribed verbatim, and NVivo 11 was used for data management. Result: Six motivating factors or barriers were identified: 1) Health attitudes and beliefs about the benefits of participating in health screening; 2) expectation of health screening from the perspective of participants; 3) cost consideration; 4) impact of social influence on willingness to participate in health screening; 5) the experiences of health screening; and 6) practical motivations or barriers of undergoing health screening. Conclusion: Health attitudes and beliefs about the benefits of having a health screening, personal health expectations, and free health services were identified as the top three important factors that influence a resident’s decision to undergo health screening for chronic diseases in Taiwan.

Vitamin D regulation of adipogenesis and adipose tissue functions.

Vitamin D insufficiency is associated with obesity and its related metabolic diseases. Adipose tissues store and metabolize vitamin D and expression levels of vitamin D metabolizing enzymes are known to be altered in obesity. Sequestration of vitamin D in large amount of adipose tissues and low vitamin D metabolism may contribute to the vitamin D inadequacy in obesity. Vitamin D receptor is expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including adipogenesis as well as metabolic and endocrine function of adipose tissues that can contribute to the high risk of metabolic diseases in vitamin D insufficiency. We will review current understanding of vitamin D regulation of adipose biology focusing on vitamin D modulation of adiposity and adipose tissue functions as well as the molecular mechanisms through which vitamin D regulates adipose biology. The effects of supplementation or maintenance of vitamin D on obesity and metabolic diseases are also discussed.

IMPACT OF HIGH BODY MASS INDEX ON FRAILTY AND MORTALITY IN MIDDLE-AGED AND OLDER ADULTS

Obesity is associated with higher risk of metabolic diseases. How body mass index (BMI) relates to mortality across frailty levels is controversial. We investigated the association of high BMI with frailty, and their effects on mortality. We included 36,583 participants aged ≥50 years from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) cohorts (7,372) and 29,211 participants aged ≥50 years from wave 1 (2004) of Survey of Health Ageing and Retirement in Europe (SHARE). BMI was categorized as: normal: 18.5-24.9 kg/m2, overweight: 25-29.9, obese I: 30-34.9 and obese II+III: >35. A frailty index (FI) was constructed excluding nutrition-related items using 36 items for NHANES and 68 items for SHARE. Mortality data were obtained until 2015. All analyses were adjusted for educational, marital, working and smoking status. In participant aged 50-65 years, higher BMI was associated with greater frailty. Being obese level II+III increased mortality risk in male participants aged 50-65 years with FI≤0.1 [NHANES (hazard ratio (HR) 2.10, 95%CI 1.17-3.79); SHARE (2.35,1.14-4.87)]. In males aged >65 years with FI>0.3, being overweight and obese (any level) decreased mortality risk. In females aged 50-65 years, higher BMI was not associated with mortality across all frailty levels. BMI and frailty were cross-sectionally associated. The subsequent mortality impact differed by age, sex, and frailty. Obesity was not associated with mortality in middle-aged females, regardless of the degree of frailty. In males, obesity was harmful in those who were fit in middle age and protective in moderately/severely frail older ones.