Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution...
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Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.
Background: Asthma and atopic dermatitis are common allergic conditions that contribute to substantial health loss, economic burden, and pain across individuals of all ages worldwide. Therefore, as a component of the ...
Background: Asthma and atopic dermatitis are common allergic conditions that contribute to substantial health loss, economic burden, and pain across individuals of all ages worldwide. Therefore, as a component of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we present updated estimates of the prevalence, disability-adjusted life-years (DALYs), incidence, and deaths due to asthma and atopic dermatitis and the burden attributable to modifiable risk factors, with forecasted prevalence up to 2050. Methods: Asthma and atopic dermatitis prevalence, incidence, DALYs, and mortality, with corresponding 95% uncertainty intervals (UIs), were estimated for 204 countries and territories from 1990 to 2021. A systematic review identified data from 389 sources for asthma and 316 for atopic dermatitis, which were further pooled using the Bayesian meta-regression tool. We also described the age-standardised DALY rates of asthma attributable to four modifiable risk factors: high BMI, occupational asthmagens, smoking, and nitrogen dioxide pollution. Furthermore, as a secondary analysis, prevalence was forecasted to 2050 using the Socio-demographic Index (SDI), air pollution, and smoking as predictors for asthma and atopic dermatitis. To assess trends in the burden of asthma and atopic dermatitis before (2010–19) and during (2019–21) the COVID-19 pandemic, we compared their average annual percentage changes (AAPCs). Findings: In 2021, there were an estimated 260 million (95% UI 227–298) individuals with asthma and 129 million (124–134) individuals with atopic dermatitis worldwide. Asthma cases declined from 287 million (250–331) in 1990 to 238 million (209–272) in 2005 but increased to 260 million in 2021. Atopic dermatitis cases consistently rose from 107 million (103–112) in 1990 to 129 million (124–134) in 2021. However, age-standardised prevalence rates decreased—by 40·0% (from 5568·3 per 100 000 to 3340·1 per 100 000) for asthma and 8·3% (from 1885·4
作者:
Danaei, G.Farzadfar, F.Kelishadi, R.[a]Department of Global Health and Population and Department of Epidemiology
Harvard T H Chan School of Public Health Boston MA USA Department of Global Health and Population and Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA [b]Scientific Association for Public Health in Iran
Boston MA USA Scientific Association for Public Health in Iran Boston MA USA [c]Non-Communicable Diseases Research Center
Endocrinology and Metabolism Population Sciences Institute Tehran University of Medical Sciences Tehran Iran Non-Communicable Diseases Research Center Endocrinology and Metabolism Population Sciences Institute Tehran University of Medical Sciences Tehran Iran [d]Endocrinology and Metabolism Research Center
Tehran University of Medical Sciences Tehran Iran Endocrinology and Metabolism Research Center Tehran University of Medical Sciences Tehran Iran [e]Diabetes Research Center
Tehran University of Medical Sciences Tehran Iran Diabetes Research Center Tehran University of Medical Sciences Tehran Iran [f]Endocrinology and Metabolism Clinical Sciences Institute
Department of Health Management and Economics Tehran University of Medical Sciences Tehran Iran Endocrinology and Metabolism Clinical Sciences Institute Department of Health Management and Economics Tehran University of Medical Sciences Tehran Iran [g]Department of Global Health and Public Policy
Tehran University of Medical Sciences Tehran Iran Department of Global Health and Public Policy Tehran University of Medical Sciences Tehran Iran [h]Department of Epidemiology and Biostatistics
Tehran University of Medical Sciences Tehran Iran Department of Epidemiology and Biostatistics Tehran University of Medical Sciences Tehran Iran [i]School of Public Health
Tehran University of Medical Sciences Tehran Iran School of Public Health Tehran University of Medical Sciences Tehran Iran [j]Faculty of Medicine
Tehran University of Medical Sciences Tehran Iran Faculty of Medicine Te
Summary Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorgani...
Summary Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.
Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalen...
Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution. Methods: We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals. Findings: In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South Am
Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (un...
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Background: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factor...
Background: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. Methods: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990–2011, 2011–19, and 2019–21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. Findings: All countries showed mean annual improvements in life expectancy in both 1990–2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011–19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011–19 than in 1990–2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990–2011 to 0·23 years (0·21 to 0·26) in 2011–19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from –0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to –0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019–21, there was an overall decrease in mean annual life expectancy a
Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of ...
Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic;characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic;and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019;293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided
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