Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.
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ABSTRACT:
SUBMITTER: Pietzner M
PROVIDER: S-EPMC8127079 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMultimorbidity is the co-occurrence of two or more chronic diseases.ObjectiveThis study, based on self-reported medical diagnosis, aims to investigate the dynamic distribution of multimorbidity across sociodemographic levels and its impacts on health-related issues over 15 years in Brazil using national data.MethodsData were analyzed using descriptive statistics, hypothesis tests, and logistic regression. The study sample comprised 679,572 adults (18-59 years of age) and 115,699 elderly people (≥60 years of age) from the two latest cross-sectional, multiple-cohort, national-based studies: the National Sample Household Survey (PNAD) of 1998, 2003, and 2008, and the Brazilian National Health Survey (PNS) of 2013.ResultsOverall, the risk of multimorbidity in adults was 1.7 times higher in women (odds ratio [OR] 1.73, 95% CI 1.67-1.79) and 1.3 times higher among people without education (OR 1.34, 95% CI 1.28-1.41). Multiple chronic diseases considerably increased with age in Brazil, and people between 50 and 59 years old were about 12 times more likely to have multimorbidity than adults between 18 and 29 years of age (OR 11.89, 95% CI 11.27-12.55). Seniors with multimorbidity had more than twice the likelihood of receiving health assistance in community services or clinics (OR 2.16, 95% CI 2.02-2.31) and of being hospitalized (OR 2.37, 95% CI 2.21-2.56). The subjective well-being of adults with multimorbidity was often worse than people without multiple chronic diseases (OR=12.85, 95% CI: 12.07-13.68). These patterns were similar across all 4 cohorts analyzed and were relatively stable over 15 years.ConclusionsOur study shows little variation in the prevalence of the multimorbidity of chronic diseases in Brazil over time, but there are differences in the prevalence of multimorbidity across different social groups. It is hoped that the analysis of multimorbidity from the two latest Brazil national surveys will support policy making on epidemic prevention and management.
| S-EPMC8663437 | biostudies-literature
Project description:BackgroundThe burden of non-communicable disease (NCDs) has grown rapidly in low- and middle-income countries (LMICs), where populations are ageing, with rising prevalence of multimorbidity (more than two co-existing chronic conditions) that will significantly increase pressure on already stretched health systems. We assess the impact of NCD multimorbidity on healthcare utilisation and out-of-pocket expenditures in six middle-income countries: China, Ghana, India, Mexico, Russia and South Africa.MethodsSecondary analyses of cross-sectional data from adult participants (>18 years) in the WHO Study on Global Ageing and Adult Health (SAGE) 2007-2010. We used multiple logistic regression to determine socio-demographic correlates of multimorbidity. Association between the number of NCDs and healthcare utilisation as well as out-of-pocket spending was assessed using logistic, negative binominal and log-linear models.ResultsThe prevalence of multimorbidity in the adult population varied from 3.9% in Ghana to 33.6% in Russia. Number of visits to doctors in primary and secondary care rose substantially for persons with increasing numbers of co-existing NCDs. Multimorbidity was associated with more outpatient visits in China (coefficient for number of NCD = 0.56, 95% CI = 0.46, 0.66), a higher likelihood of being hospitalised in India (AOR = 1.59, 95% CI = 1.45, 1.75), higher out-of-pocket expenditures for outpatient visits in India and China, and higher expenditures for hospital visits in Russia. Medicines constituted the largest proportion of out-of-pocket expenditures in persons with multimorbidity (88.3% for outpatient, 55.9% for inpatient visit in China) in most countries.ConclusionMultimorbidity is associated with higher levels of healthcare utilisation and greater financial burden for individuals in middle-income countries. Our study supports the WHO call for universal health insurance and health service coverage in LMICs, particularly for vulnerable groups such as the elderly with multimorbidity.
| S-EPMC4496037 | biostudies-literature
Project description:The plasma profile of subjects with nonalcoholic fatty liver disease (NAFLD), steatosis, and steatohepatitis (NASH) was examined using an untargeted global metabolomic analysis to identify specific disease-related patterns and to identify potential noninvasive biomarkers. Plasma samples were obtained after an overnight fast from histologically confirmed nondiabetic subjects with hepatic steatosis (n = 11) or NASH (n = 24) and were compared with healthy, age- and sex-matched controls (n = 25). Subjects with NAFLD were obese, were insulin resistant, and had higher plasma concentrations of homocysteine and total cysteine and lower plasma concentrations of total glutathione. Metabolomic analysis showed markedly higher levels of glycocholate, taurocholate, and glycochenodeoxycholate in subjects with NAFLD. Plasma concentrations of long-chain fatty acids were lower and concentrations of free carnitine, butyrylcarnitine, and methylbutyrylcarnitine were higher in NASH. Several glutamyl dipeptides were higher whereas cysteine-glutathione levels were lower in NASH and steatosis. Other changes included higher branched-chain amino acids, phosphocholine, carbohydrates (glucose, mannose), lactate, pyruvate, and several unknown metabolites. Random forest analysis and recursive partitioning of the metabolomic data could separate healthy subjects from NAFLD with an error rate of approximately 8% and separate NASH from healthy controls with an error rate of 4%. Hepatic steatosis and steatohepatitis could not be separated using the metabolomic profile. Plasma metabolomic analysis revealed marked changes in bile salts and in biochemicals related to glutathione in subjects with NAFLD. Statistical analysis identified a panel of biomarkers that could effectively separate healthy controls from NAFLD and healthy controls from NASH. These biomarkers can potentially be used to follow response to therapeutic interventions.
| S-EPMC2950914 | biostudies-literature
Project description:Peripheral artery disease (PAD) is a common disease affecting 20-25% of population over 60 years old. Early diagnosis is difficult because symptoms only become evident in advanced stages of the disease. Inflammation, impaired metabolism, and mitochondrial dysfunction predispose to PAD, which is normally associated with other highly prevalent and related conditions, such as diabetes, dyslipidemia, and hypertension. We have measured energy-balance-associated metabolite concentrations in the plasma of PAD patients segregated by the severity of the disease and in plasma of healthy volunteers using a quantitative and targeted metabolomic approach. We found relevant associations between several metabolites (3-hydroxybutirate, aconitate, (iso)citrate, glutamate, and serine) with markers of oxidative stress and inflammation. Metabolomic profiling also revealed that (iso)citrate and glutamate are metabolites with high ability to discriminate between healthy participants and PAD patients without symptoms. Collectively, our data suggest that metabolomics provide significant information on the pathogenesis of PAD and useful biomarkers for the diagnosis and assessment of progression.
| S-EPMC6171256 | biostudies-other
Project description:BackgroundWe aim to discover whether HbA1c affects incident cardiovascular disease (CVD) through regulating endogenous metabolites.Methods and resultsTotally, 2019 plasma samples were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Logistic regression and linear regression were used to screen metabolites which were associated with both CVD and HbA1c. The VanderWeele's mediation approach was performed to assess the direct effect and indirect effect (IE) in the counterfactual model. Forty-eight metabolites showed an association with both HbA1c and CVD risk. Forty-four of the 48 metabolites worked as mediators mediated in HbA1c's effect on CVD (odds ratio [OR]IE from 0.997 to 6.098, false discovery rate q < 0.05, mediated proportion from 0.4% to 85.4%). Pathway enrichment analysis indicated that different metabolic pathway showed significant IE (butanoate metabolism ORIE = 1.058, mediated proportion = 16.0%; alanine, aspartate and glutamate metabolism ORIE = 1.082, mediated proportion = 21.8%; TCA (citric acid) cycle metabolism ORIE = 1.048, mediated proportion = 13.8%; phenylalanine metabolism ORIE = 1.067, mediated proportion = 18.4%; glycerophospholipid metabolism ORIE = 3.007, mediated proportion = 82.2%; all the P <?.01).ConclusionsOur findings suggest that metabolites mediate the effect of HbA1c on incident CVD and provide a new study sight into pathogenesis of CVD.
| S-EPMC6788485 | biostudies-literature
Project description:IntroductionTo examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults.MethodsThis population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models.ResultsThe number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05).DiscussionMultimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults.HighlightsWe used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.
| S-EPMC10984420 | biostudies-literature
Project description:Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY.
| S-EPMC4143229 | biostudies-literature
Project description:Nutrient profile (NP) models, tools used to rate or evaluate the nutritional quality of foods, are increasingly used by government bodies worldwide to underpin nutrition-related policies. An up-to-date and accessible list of existing NP models is currently unavailable to support their adoption or adaptation in different jurisdictions. This study used a systematic approach to develop a global resource that summarizes key characteristics of NP models with applications in government-led nutrition policies. NP models were identified from an unpublished WHO catalog of NP models last updated in 2012 and from searches conducted in different databases of the peer-reviewed (n = 3; e.g., PubMed) and gray literature (n = 15). Included models had to meet the following inclusion criteria (selected) as of 22 December 2016: 1) developed or endorsed by governmental or intergovernmental organizations, 2) allow for the evaluation of individual food items, and 3) have publicly available nutritional criteria. A total of 387 potential NP models were identified, including n = 361 from the full-text assessment of >600 publications and n = 26 exclusively from the catalog. Seventy-eight models were included. Most (73%) were introduced within the past 10 y, and 44% represent adaptations of ≥1 previously built model. Models were primarily built for school food standards or guidelines (n = 27), food labeling (e.g., front-of-pack; n = 12), and restriction of the marketing of food products to children (n = 10). All models consider nutrients to limit, with sodium, saturated fatty acids, and total sugars being included most frequently; and 86% also consider ≥1 nutrient to encourage (e.g., fiber). No information on validity testing could be identified for 58% of the models. Given the proliferation of NP models worldwide, this new resource will be highly valuable for assisting health professionals and policymakers in the selection of an appropriate model when the establishment of nutrition-related policies requires the use of nutrient profiling.
| S-EPMC6247226 | biostudies-literature
Project description:Despite the rising burden of noncommunicable diseases, access to quality decentralized noncommunicable disease services remain limited in many low- and middle-income countries. Here we describe the strategies we employed to drive the process from adaptation to national endorsement and implementation of the 2016 Botswana primary healthcare guidelines for adults. The strategies included detailed multilevel assessment with broad stakeholder inputs and in-depth analysis of local data; leveraging academic partnerships; facilitating development of supporting policy instruments; and embedding noncommunicable disease guidelines within broader primary health-care guidelines in keeping with the health ministry strategic direction. At facility level, strategies included developing a multimethod training programme for health-care providers, leveraging on the experience of provision of human immunodeficiency virus care and engaging health-care implementers early in the process. Through the strategies employed, the country's first national primary health-care guidelines were endorsed in 2016 and a phased three-year implementation started in August 2017. In addition, provision of primary health-care delivery of noncommunicable disease services was included in the country's 11th national development plan (2017-2023). During the guideline development process, we learnt that strong interdisciplinary skills in communication, organization, coalition building and systems thinking, and technical grasp of best-practices in low- and middle-income countries were important. Furthermore, misaligned agendas of stakeholders, exaggerated by a siloed approach to guideline development, underestimation of the importance of having policy instruments in place and coordination of the processes initially being led outside the health ministry caused delays. Our experience is relevant to other countries interested in developing and implementing guidelines for evidence-based noncommunicable disease services.
| S-EPMC6357568 | biostudies-literature
Project description:Noncommunicable diseases (NCDs) are the leading cause of death and disability worldwide. They exact a disproportionate toll in low and middle-income countries, and the world is not on-track to meet international targets for reductions in premature NCD mortality. Largely, we know which policies work for tackling NCDs, and the World Health Organization (WHO) has developed a package of 'best buy' policies that are highly cost effective. However, we don't necessarily know how to adapt and implement these policies in new populations and cultures. Implementation Research (IR) is emerging as a potent tool for gearing the international response, providing a scientific approach to study the processes used to implement policies and interventions and the contextual factors that affect these processes. Amidst growing interest from policymakers, we identify four main areas for action: high-level engagement with IR among international NCD leaders; domestic investment in technical capacity-building; the creation of new financing streams for IR research; and the development of multi-stakeholder engagement mechanisms that can convene and leverage the perspectives and resources of multiple actors with overlapping aims.
| S-EPMC8785572 | biostudies-literature