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      Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses

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          Abstract

          Aims/hypothesis

          Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes.

          Methods

          Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593).

          Results

          Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001).

          Conclusions/interpretation

          Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality.

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          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00125-020-05319-w.

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          Most cited references59

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          Bias in meta-analysis detected by a simple, graphical test

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            Quantifying heterogeneity in a meta-analysis.

            The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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              Meta-analysis in clinical trials

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                Author and article information

                Contributors
                danijela.gasevic@monash.edu
                sophia.zoungas@monash.edu
                Journal
                Diabetologia
                Diabetologia
                Diabetologia
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0012-186X
                1432-0428
                14 December 2020
                14 December 2020
                2021
                : 64
                : 2
                : 275-287
                Affiliations
                [1 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, School Public Health and Preventive Medicine, , Monash University, ; Melbourne, VIC Australia
                [2 ]GRID grid.1051.5, ISNI 0000 0000 9760 5620, Baker Heart and Diabetes Institute, ; Melbourne, VIC Australia
                [3 ]GRID grid.416738.f, ISNI 0000 0001 2163 0069, Centers for Disease Control and Prevention, Division for Diabetes Translation, ; Atlanta, GA USA
                [4 ]GRID grid.9654.e, ISNI 0000 0004 0372 3343, Department of Medicine, , University of Auckland, ; Auckland, New Zealand
                [5 ]GRID grid.4827.9, ISNI 0000 0001 0658 8800, Diabetes Research Group, , Swansea University Medical School, ; Swansea, Wales UK
                [6 ]GRID grid.412937.a, ISNI 0000 0004 0641 5987, Department of Diabetes, , Northern General Hospital, ; Sheffield, UK
                [7 ]GRID grid.413249.9, ISNI 0000 0004 0385 0051, Royal Prince Alfred Hospital, ; Camperdown, NSW Australia
                [8 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Department of Medicine and Therapeutics, , The Chinese University of Hong Kong, Hong Kong Special Administrative Region, ; Shenzhen, People’s Republic of China
                [9 ]GRID grid.144189.1, ISNI 0000 0004 1756 8209, Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, , Azienda Ospedaliero-Universitaria Pisana University of Pisa, ; Pisa, Italy
                [10 ]GRID grid.411634.5, ISNI 0000 0004 0632 4559, Department of Endocrinology, , Peking University People’s Hospital, ; Xicheng District, Beijing, China
                [11 ]GRID grid.429336.9, ISNI 0000 0004 1794 3718, Madras Diabetes Research Foundation & Dr Mohan’s Diabetes Specialities Centre, ; Chennai, India
                [12 ]Hospital Universtario Sant Joan, Reus, Spain
                [13 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Usher Institute, , University of Edinburgh, Old Medical School, ; Teviot Place, Edinburgh, UK
                [14 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Monash Centre for Health Research and Implementation, , Monash University, ; Clayton, VIC Australia
                [15 ]GRID grid.415508.d, ISNI 0000 0001 1964 6010, The George Institute for Global Health, ; Camperdown, NSW Australia
                Author information
                https://orcid.org/0000-0001-9271-9917
                https://orcid.org/0000-0003-2407-770X
                https://orcid.org/0000-0002-3640-079X
                https://orcid.org/0000-0003-3298-4414
                https://orcid.org/0000-0002-6203-1772
                https://orcid.org/0000-0001-6002-4766
                https://orcid.org/0000-0003-1002-1238
                https://orcid.org/0000-0002-2970-6352
                https://orcid.org/0000-0001-5316-1797
                https://orcid.org/0000-0003-0321-9553
                https://orcid.org/0000-0003-1325-1194
                https://orcid.org/0000-0002-5244-6069
                https://orcid.org/0000-0002-2834-4847
                https://orcid.org/0000-0002-3262-2168
                https://orcid.org/0000-0001-5038-6210
                https://orcid.org/0000-0002-9974-889X
                https://orcid.org/0000-0002-7061-8987
                https://orcid.org/0000-0001-5976-4011
                https://orcid.org/0000-0002-9507-6096
                https://orcid.org/0000-0001-7609-577X
                https://orcid.org/0000-0002-9931-0580
                https://orcid.org/0000-0003-2672-0949
                Article
                5319
                10.1007/s00125-020-05319-w
                7801294
                33313987
                558b9944-70fc-40a9-b46d-385b9b0404ee
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 May 2020
                : 2 September 2020
                Funding
                Funded by: University of Edinburgh
                Categories
                Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Endocrinology & Diabetes
                age factors,age of onset,diabetes,diabetes complications,diabetes mellitus, type 2,disease progression,meta-analysis,prognosis,systematic review

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