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      Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

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          Abstract

          The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as “diabetes.” Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.

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          Most cited references138

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          Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

          Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
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            2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020

            (2019)
            The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee (https://doi.org/10.2337/dc20-SPPC), a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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              Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

              We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                July 2020
                11 June 2020
                : 43
                : 7
                : 1617-1635
                Affiliations
                [1] 1Department of Pediatrics, Columbia University Irving Medical Center, New York, NY
                [2] 2Department of Medicine, Columbia University Irving Medical Center, New York, NY
                [3] 3American Diabetes Association, Arlington, VA
                [4] 4Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA
                [5] 5Diabetes Unit, Massachusetts General Hospital, Boston, MA
                [6] 6Metabolism Program, Broad Institute of MIT and Harvard, Cambridge, MA
                [7] 7Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA
                [8] 8Department of Medicine, Harvard Medical School, Boston, MA
                [9] 9Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, U.K.
                [10] 10Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA
                [11] 11National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
                [12] 12Wellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.
                [13] 13Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
                [14] 14School of Medicine, Trinity College, Dublin, Ireland
                [15] 15Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
                [16] 16Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, Scotland, U.K.
                [17] 17Department of Medicine, University of Chicago, Chicago, IL
                [18] 18Department of Pediatrics, University of Chicago, Chicago, IL
                [19] 19Duke University School of Medicine, Durham, NC
                [20] 20Center for Public Health Genomics, University of Virginia, Charlottesville, VA
                [21] 21Department of Public Health Sciences, University of Virginia, Charlottesville, VA
                [22] 22Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Lund University, Malmo, Sweden
                [23] 23Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
                Author notes
                Corresponding author: Paul W. Franks, paul.franks@ 123456med.lu.se
                Author information
                https://orcid.org/0000-0002-1730-9325
                https://orcid.org/0000-0001-5620-473X
                https://orcid.org/0000-0001-7752-2585
                https://orcid.org/0000-0003-3648-1590
                https://orcid.org/0000-0001-8674-2598
                https://orcid.org/0000-0001-9237-8585
                https://orcid.org/0000-0002-0654-4047
                https://orcid.org/0000-0003-3872-7793
                https://orcid.org/0000-0002-0520-7604
                Article
                i200022
                10.2337/dci20-0022
                7305007
                32561617
                24bb5dc1-9f53-4bc3-926d-f94c977688bf
                © 2020 by the American Diabetes Association and the European Association for the Study of Diabetes

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.

                History
                Page count
                Figures: 5, Tables: 5, Equations: 0, References: 137, Pages: 19
                Categories
                0201
                Consensus Reports

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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