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      Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people

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          Summary

          Background

          The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.

          Methods

          We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439).

          Findings

          Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1–10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76–3·22]), ischaemic stroke (1·72 [1·52–1·95]), stable angina (1·62 [1·49–1·77]), heart failure (1·56 [1·45–1·69]), and non-fatal myocardial infarction (1·54 [1·42–1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35–0·59]) and subarachnoid haemorrhage (0·48 [0·26–0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76–1·19]).

          Interpretation

          Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design.

          Funding

          Wellcome Trust, National Institute for Health Research, and Medical Research Council.

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          Most cited references34

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          Diagnosis and Classification of Diabetes Mellitus

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            Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

            Summary Background Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. Methods We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. Findings Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8·49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2·00 (95% CI 1·83–2·19) for coronary heart disease; 2·27 (1·95–2·65) for ischaemic stroke; 1·56 (1·19–2·05) for haemorrhagic stroke; 1·84 (1·59–2·13) for unclassified stroke; and 1·73 (1·51–1·98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40–59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10–12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3·90 mmol/L and 5·59 mmol/L. Compared with fasting blood glucose concentrations of 3·90–5·59 mmol/L, HRs for coronary heart disease were: 1·07 (0·97–1·18) for lower than 3·90 mmol/L; 1·11 (1·04–1·18) for 5·60–6·09 mmol/L; and 1·17 (1·08–1·26) for 6·10–6·99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. Interpretation Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. Funding British Heart Foundation, UK Medical Research Council, and Pfizer.
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              Diabetes and cardiovascular disease. The Framingham study.

              Based on 20 years of surveillance of the Framingham cohort relating subsequent cardiovascular events to prior evidence of diabetes, a twofold to threefold increased risk of clinical atherosclerotic disease was reported. The relative impact was greatest for intermittent claudication (IC) and congestive heart failure (CHF) and least for coronary heart disease (CHD), which was, nevertheless, on an absolute scale the chief sequela. The relative impact was substantially greater for women than for men. For each of the cardiovascular diseases (CVD), morbidity and mortality were higher for diabetic women than for nondiabetic men. After adjustment for other associated risk factors, the relative impact of diabetes on CHD, IC, or stroke incidence was the same for women as for men; for CVD death and CHF, it was greater for women. Cardiovascular mortality was actually about as great for diabetic women as for diabetic men.
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                Author and article information

                Contributors
                Journal
                Lancet Diabetes Endocrinol
                Lancet Diabetes Endocrinol
                The Lancet. Diabetes & Endocrinology
                The Lancet, Diabetes & Endocrinology
                2213-8587
                2213-8595
                1 February 2015
                February 2015
                : 3
                : 2
                : 105-113
                Affiliations
                [a ]Farr Institute of Health Informatics Research at London, London, UK
                [b ]Department of Epidemiology and Public Health, University College London, London, UK
                [c ]MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
                [d ]Faculty of Medicine and Health, University of Leeds, Leeds, UK
                [e ]National Institute of Cardiovascular Outcomes Research, University College London, London, UK
                [f ]Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
                [g ]Barts and the London National Institute for Health Research Cardiovascular Biomedical Research Unit, Queen Mary, University of London, London, UK
                Author notes
                [* ]Correspondence to: Dr Anoop Dinesh Shah, Farr Institute of Health Informatics Research at London, University College London, London NW1 2DA, UK anoop@ 123456doctors.org.uk
                Article
                S2213-8587(14)70219-0
                10.1016/S2213-8587(14)70219-0
                4303913
                25466521
                9128adfa-e6bc-48da-916d-8f18ec308c75
                © 2015 Shah et al. Open Access article distributed under the terms of CC BY

                This document may be redistributed and reused, subject to certain conditions.

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