Displaying publications 1 - 20 of 148 in total

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  1. Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  2. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  3. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  4. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al.
    Lancet, 2014 Sep 13;384(9947):980-1004.
    PMID: 24797575 DOI: 10.1016/S0140-6736(14)60696-6
    BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.

    METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.

    FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.

    INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

    FUNDING: Bill & Melinda Gates Foundation.

  5. Page DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, et al.
    J Pathol, 2023 Aug;260(5):514-532.
    PMID: 37608771 DOI: 10.1002/path.6165
    Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
  6. Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.
    J Pathol, 2023 Aug;260(5):498-513.
    PMID: 37608772 DOI: 10.1002/path.6155
    The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
  7. Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, et al.
    J Pathol, 2024 Mar;262(3):271-288.
    PMID: 38230434 DOI: 10.1002/path.6238
    Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
  8. Zhong Y, Chu C, Myers JA, Gilbert GS, Lutz JA, Stillhard J, et al.
    Nat Commun, 2021 May 25;12(1):3137.
    PMID: 34035260 DOI: 10.1038/s41467-021-23236-3
    Arbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) associations are critical for host-tree performance. However, how mycorrhizal associations correlate with the latitudinal tree beta-diversity remains untested. Using a global dataset of 45 forest plots representing 2,804,270 trees across 3840 species, we test how AM and EcM trees contribute to total beta-diversity and its components (turnover and nestedness) of all trees. We find AM rather than EcM trees predominantly contribute to decreasing total beta-diversity and turnover and increasing nestedness with increasing latitude, probably because wide distributions of EcM trees do not generate strong compositional differences among localities. Environmental variables, especially temperature and precipitation, are strongly correlated with beta-diversity patterns for both AM trees and all trees rather than EcM trees. Results support our hypotheses that latitudinal beta-diversity patterns and environmental effects on these patterns are highly dependent on mycorrhizal types. Our findings highlight the importance of AM-dominated forests for conserving global forest biodiversity.
  9. Chu C, Lutz JA, Král K, Vrška T, Yin X, Myers JA, et al.
    Ecol Lett, 2019 Feb;22(2):245-255.
    PMID: 30548766 DOI: 10.1111/ele.13175
    Climate is widely recognised as an important determinant of the latitudinal diversity gradient. However, most existing studies make no distinction between direct and indirect effects of climate, which substantially hinders our understanding of how climate constrains biodiversity globally. Using data from 35 large forest plots, we test hypothesised relationships amongst climate, topography, forest structural attributes (stem abundance, tree size variation and stand basal area) and tree species richness to better understand drivers of latitudinal tree diversity patterns. Climate influences tree richness both directly, with more species in warm, moist, aseasonal climates and indirectly, with more species at higher stem abundance. These results imply direct limitation of species diversity by climatic stress and more rapid (co-)evolution and narrower niche partitioning in warm climates. They also support the idea that increased numbers of individuals associated with high primary productivity are partitioned to support a greater number of species.
  10. Cui Y, Hada K, Kawashima T, Kino M, Lin W, Mizuno Y, et al.
    Nature, 2023 Sep;621(7980):711-715.
    PMID: 37758892 DOI: 10.1038/s41586-023-06479-6
    The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.
  11. Porwal P, Pachade S, Kokare M, Deshmukh G, Son J, Bae W, et al.
    Med Image Anal, 2020 01;59:101561.
    PMID: 31671320 DOI: 10.1016/j.media.2019.101561
    Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.
  12. Rohner K, Marlais M, Ahn YH, Ali A, Alsharief A, Novak AB, et al.
    PMID: 38211969 DOI: 10.1093/ndt/gfae009
    BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy.

    METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up.

    RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR 

  13. Tang BH, Guan Z, Allegaert K, Wu YE, Manolis E, Leroux S, et al.
    Clin Pharmacokinet, 2021 11;60(11):1435-1448.
    PMID: 34041714 DOI: 10.1007/s40262-021-01033-x
    BACKGROUND: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data.

    OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates.

    METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods.

    RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods.

    CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.

  14. Wills C, Wang B, Fang S, Wang Y, Jin Y, Lutz J, et al.
    PLoS Comput Biol, 2021 Apr;17(4):e1008853.
    PMID: 33914731 DOI: 10.1371/journal.pcbi.1008853
    When Darwin visited the Galapagos archipelago, he observed that, in spite of the islands' physical similarity, members of species that had dispersed to them recently were beginning to diverge from each other. He postulated that these divergences must have resulted primarily from interactions with sets of other species that had also diverged across these otherwise similar islands. By extrapolation, if Darwin is correct, such complex interactions must be driving species divergences across all ecosystems. However, many current general ecological theories that predict observed distributions of species in ecosystems do not take the details of between-species interactions into account. Here we quantify, in sixteen forest diversity plots (FDPs) worldwide, highly significant negative density-dependent (NDD) components of both conspecific and heterospecific between-tree interactions that affect the trees' distributions, growth, recruitment, and mortality. These interactions decline smoothly in significance with increasing physical distance between trees. They also tend to decline in significance with increasing phylogenetic distance between the trees, but each FDP exhibits its own unique pattern of exceptions to this overall decline. Unique patterns of between-species interactions in ecosystems, of the general type that Darwin postulated, are likely to have contributed to the exceptions. We test the power of our null-model method by using a deliberately modified data set, and show that the method easily identifies the modifications. We examine how some of the exceptions, at the Wind River (USA) FDP, reveal new details of a known allelopathic effect of one of the Wind River gymnosperm species. Finally, we explore how similar analyses can be used to investigate details of many types of interactions in these complex ecosystems, and can provide clues to the evolution of these interactions.
  15. Mi C, Ma L, Yang M, Li X, Meiri S, Roll U, et al.
    Nat Commun, 2023 Mar 13;14(1):1389.
    PMID: 36914628 DOI: 10.1038/s41467-023-36987-y
    Protected Areas (PAs) are the cornerstone of biodiversity conservation. Here, we collated distributional data for >14,000 (~70% of) species of amphibians and reptiles (herpetofauna) to perform a global assessment of the conservation effectiveness of PAs using species distribution models. Our analyses reveal that >91% of herpetofauna species are currently distributed in PAs, and that this proportion will remain unaltered under future climate change. Indeed, loss of species' distributional ranges will be lower inside PAs than outside them. Therefore, the proportion of effectively protected species is predicted to increase. However, over 7.8% of species currently occur outside PAs, and large spatial conservation gaps remain, mainly across tropical and subtropical moist broadleaf forests, and across non-high-income countries. We also predict that more than 300 amphibian and 500 reptile species may go extinct under climate change over the course of the ongoing century. Our study highlights the importance of PAs in providing herpetofauna with refuge from climate change, and suggests ways to optimize PAs to better conserve biodiversity worldwide.
  16. Chen C, Granados A, Brodie JF, Kays R, Davies TJ, Liu R, et al.
    Conserv Biol, 2023 Nov 08.
    PMID: 37937455 DOI: 10.1111/cobi.14221
    Reliable maps of species distributions are fundamental for biodiversity research and conservation. The International Union for Conservation of Nature (IUCN) range maps are widely recognized as authoritative representations of species' geographic limits, yet they might not always align with actual occurrence data. In recent area of habitat (AOH) maps, areas that are not habitat have been removed from IUCN ranges to reduce commission errors, but their concordance with actual species occurrence also remains untested. We tested concordance between occurrences recorded in camera trap surveys and predicted occurrences from the IUCN and AOH maps for 510 medium- to large-bodied mammalian species in 80 camera trap sampling areas. Across all areas, cameras detected only 39% of species expected to occur based on IUCN ranges and AOH maps; 85% of the IUCN only mismatches occurred within 200 km of range edges. Only 4% of species occurrences were detected by cameras outside IUCN ranges. The probability of mismatches between cameras and the IUCN range was significantly higher for smaller-bodied mammals and habitat specialists in the Neotropics and Indomalaya and in areas with shorter canopy forests. Our findings suggest that range and AOH maps rarely underrepresent areas where species occur, but they may more often overrepresent ranges by including areas where a species may be absent, particularly at range edges. We suggest that combining range maps with data from ground-based biodiversity sensors, such as camera traps, provides a richer knowledge base for conservation mapping and planning.
  17. Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al.
    Nature, 2020 07;583(7815):286-289.
    PMID: 32380510 DOI: 10.1038/s41586-020-2313-x
    The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
  18. Sreekar R, Katabuchi M, Nakamura A, Corlett RT, Slik JWF, Fletcher C, et al.
    R Soc Open Sci, 2018 Sep;5(9):181168.
    PMID: 30839691 DOI: 10.1098/rsos.181168
    The relationship between β-diversity and latitude still remains to be a core question in ecology because of the lack of consensus between studies. One hypothesis for the lack of consensus between studies is that spatial scale changes the relationship between latitude and β-diversity. Here, we test this hypothesis using tree data from 15 large-scale forest plots (greater than or equal to 15 ha, diameter at breast height ≥ 1 cm) across a latitudinal gradient (3-30o) in the Asia-Pacific region. We found that the observed β-diversity decreased with increasing latitude when sampling local tree communities at small spatial scale (grain size ≤0.1 ha), but the observed β-diversity did not change with latitude when sampling at large spatial scales (greater than or equal to 0.25 ha). Differences in latitudinal β-diversity gradients across spatial scales were caused by pooled species richness (γ-diversity), which influenced observed β-diversity values at small spatial scales, but not at large spatial scales. Therefore, spatial scale changes the relationship between β-diversity, γ-diversity and latitude, and improving sample representativeness avoids the γ-dependence of β-diversity.
  19. Miller V, Jenkins DA, Dehghan M, Srichaikul K, Rangarajan S, Mente A, et al.
    PMID: 38588684 DOI: 10.1016/S2213-8587(24)00069-X
    BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets.

    METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs).

    FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030).

    INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes.

    FUNDING: Full funding sources are listed at the end of the Article.

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