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      Contribution of type 2 diabetes to all-cause mortality, cardiovascular disease incidence and cancer incidence in white Europeans and South Asians: findings from the UK Biobank population-based cohort study

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          Abstract

          Objective

          To investigate whether the health implications of having type 2 diabetes (T2D) were different in South Asian compared with white European participants.

          Research design and methods

          Prospective data from UK Biobank were used, and 457 935 participants of white European and 7102 of South Asian background were included. Cox proportional regression was performed to investigate the association between T2D and health outcome by ethnicity.

          Results

          Over a mean of 7.0 years (IQR 6.3–7.6) of follow-up, 12 974 participants had died, and 30 347 and 27 159 developed cardiovascular disease (CVD) and cancer, respectively. South Asians had a higher risk for CVD mortality (HR: 1.42, 95% CI 1.07 to 1.89) and incidence (HR: 1.78, 95% CI 1.63 to 1.94), but a decreased risk for cancer mortality (HR: 0.59, 95% CI 0.41 to 0.85) and incidence (HR: 0.80, 95% CI 0.70 to 0.92) compared with white Europeans. Compared with individuals without T2D, both white Europeans and South Asians with T2D had a higher risk for all-cause mortality (1.59 (1.48 to 1.71) vs 2.83 (1.76 to 4.53)), CVD mortality (2.04 (1.82 to 2.28) vs 4.40 (2.37 to 8.16)) and CVD incidence (1.37 (1.31 to 1.44) vs 1.60 (1.31 to 1.95)), respectively. However, the magnitude of the risk was higher for South Asians than white Europeans.

          Conclusions

          Although T2D was associated with a higher risk for all-cause mortality and CVD incidence and mortality, in both white Europeans and South Asians, the risk experienced by South Asians with T2D was higher than their white European counterparts.

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          Most cited references20

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          Algorithms for the Capture and Adjudication of Prevalent and Incident Diabetes in UK Biobank

          Objectives UK Biobank is a UK-wide cohort of 502,655 people aged 40–69, recruited from National Health Service registrants between 2006–10, with healthcare data linkage. Type 2 diabetes is a key exposure and outcome. We developed algorithms to define prevalent and incident diabetes for UK Biobank. The algorithms will be implemented by UK Biobank and their results made available to researchers on request. Methods We used UK Biobank self-reported medical history and medication to assign prevalent diabetes and type, and tested this against linked primary and secondary care data in Welsh UK Biobank participants. Additionally, we derived and tested algorithms for incident diabetes using linked primary and secondary care data in the English Clinical Practice Research Datalink, and ran these on secondary care data in UK Biobank. Results and Significance For prevalent diabetes, 0.001% and 0.002% of people classified as “diabetes unlikely” in UK Biobank had evidence of diabetes in their primary or secondary care record respectively. Of those classified as “probable” type 2 diabetes, 75% and 96% had specific type 2 diabetes codes in their primary and secondary care records. For incidence, 95% of people with the type 2 diabetes-specific C10F Read code in primary care had corroborative evidence of diabetes from medications, blood testing or diabetes specific process of care codes. Only 41% of people identified with type 2 diabetes in primary care had secondary care evidence of type 2 diabetes. In contrast, of incident cases using ICD-10 type 2 diabetes specific codes in secondary care, 77% had corroborative evidence of diabetes in primary care. We suggest our definition of prevalent diabetes from UK Biobank baseline data has external validity, and recommend that specific primary care Read codes should be used for incident diabetes to ensure precision. Secondary care data should be used for incident diabetes with caution, as around half of all cases are missed, and a quarter have no corroborative evidence of diabetes in primary care.
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            Type 2 diabetes in South Asians: similarities and differences with white Caucasian and other populations

            Type 2 diabetes mellitus (T2DM) is one of the leading causes of morbidity and mortality. While all ethnic groups are affected, the prevalence of T2DM in South Asians, both in their home countries and abroad, is extremely high and is continuing to rise rapidly. Innate biological susceptibilities coupled with rapid changes in physical activity, diet, and other lifestyle behaviors are contributing factors propelling the increased burden of disease in this population. The large scope of this problem calls for investigations into the cause of increased susceptibility and preventative efforts at both the individual and population level that are aggressive, culturally sensitive, and start early. In this review, we outline the biological and environmental factors that place South Asians at elevated risk for T2DM, compared with Caucasian and other ethnic groups.
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              Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

              Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.
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                Author and article information

                Journal
                BMJ Open Diabetes Res Care
                BMJ Open Diabetes Res Care
                bmjdrc
                bmjdrc
                BMJ Open Diabetes Research & Care
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2052-4897
                2019
                17 December 2019
                : 7
                : 1
                : e000765
                Affiliations
                [1 ] departmentDepartment of Public Health, Amsterdam Public Health Research Institute , Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                [2 ] departmentBHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences , University of Glasgow , Glasgow, UK
                [3 ] departmentInstitute of Health and Wellbeing , University of Glasgow , Glasgow, UK
                [4 ] departmentCentre for Research in Exercise Physiology (CIFE) , Universidad Mayor , Santiago, Chile
                Author notes
                [Correspondence to ] Dr Mirthe Muilwijk; m.muilwijk@ 123456amsterdamumc.nl

                JMRG, NS and CC-M are joint senior authors.

                Author information
                http://orcid.org/0000-0002-3686-5116
                http://orcid.org/0000-0001-5845-4804
                http://orcid.org/0000-0002-7970-3643
                http://orcid.org/0000-0001-6453-6654
                http://orcid.org/0000-0001-8969-9636
                http://orcid.org/0000-0003-2612-3917
                Article
                bmjdrc-2019-000765
                10.1136/bmjdrc-2019-000765
                6936483
                31908795
                5e8809a6-9d74-4147-982b-9c05361059a1
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 18 July 2019
                : 14 November 2019
                : 22 November 2019
                Funding
                Funded by: Health Behaviours & Chronic Diseases, Amsterdam Public Health;
                Award ID: Travel grant
                Categories
                Epidemiology/Health Services Research
                1506
                1867
                Custom metadata
                unlocked

                type 2 diabetes,mortality,ethnic differences
                type 2 diabetes, mortality, ethnic differences

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