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      Glucocorticoid treatment and impaired mood, memory and metabolism in people with diabetes: the Edinburgh Type 2 Diabetes Study

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          Abstract

          Objective

          Both type 2 diabetes and glucocorticoid therapy are highly prevalent. Although people with type 2 diabetes may be more susceptible to adverse effects of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided for fear of worsening glycaemic control, the extent to which this advice is followed and the consequences when glucocorticoids are prescribed are poorly documented. The aim was to assess the characteristics of people with type 2 diabetes prescribed glucocorticoids in a real-world setting and to quantify resulting adverse effects.

          Design

          Cross-sectional cohort study.

          Methods

          Cardiometabolic variables, body fat distribution, cognitive function and mood were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids.

          Results

          Glucocorticoid therapy was more common in women and in smokers but was not avoided in patients with diabetic complications or cardiovascular risk factors. People taking glucocorticoids were more centrally obese with slightly higher HbA1c and total serum cholesterol but were no more likely to have hepatic steatosis or hypertension. Glucocorticoid treatment was associated with substantially lower mood and greater anxiety. Women taking glucocorticoid therapy were twice as likely to report depressive symptoms compared with those not taking treatment. Glucocorticoid therapy was also associated with poorer cognitive function among those with subclinical atherosclerosis, as indicated by low ankle–brachial pressure index.

          Conclusions

          Glucocorticoids are prescribed commonly for people with type 2 diabetes despite being associated with adverse indices of glycaemic control, cardiovascular risk factors, mood and cognitive function.

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          Most cited references23

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          Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease.

          Glucocorticoids have adverse systemic effects, including obesity, hypertension, and hyperglycemia, that may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been quantified. To test the hypothesis that users of exogenous glucocorticoids have an increased risk for cardiovascular disease. A cohort study using a record linkage database. Tayside, Scotland, United Kingdom. 68,781 glucocorticoid users and 82,202 nonusers without previous hospitalization for cardiovascular disease who were studied between 1993 and 1996. The average daily dose of glucocorticoid exposure during follow-up was categorized as low (inhaled, nasal, and topical only), medium (oral, rectal, or parenteral or =7.5 mg of prednisolone equivalent). Poisson regression model, sensitivity analysis, and propensity score methods were used to investigate the association between glucocorticoid exposure and cardiovascular outcome. 4383 cardiovascular events occurred in 257,487 person-years of follow-up for a rate of 17.0 (95% CI, 16.5 to 17.5) per 1000 person-years in the comparator group, and 5068 events occurred in 212,287 person-years for a rate of 23.9 (CI, 23.2 to 24.5) per 1000 person-years in the group exposed to glucocorticoids (22.1, 27.2, and 76.5 in low, medium, and high groups, respectively). The absolute risk difference was 6.9 (CI, 6.0 to 7.7) per 1000 person-years (5.1, 10.1, and 59.4, respectively). After adjustment for known covariates, the relative risk for a cardiovascular event in patients receiving high-dose glucocorticoids was 2.56 (CI, 2.18 to 2.99). Because the data were observational, residual confounding cannot be excluded. Treatment with high-dose glucocorticoids seemed to be associated with increased risk for cardiovascular disease.
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            The diagnosis of ischaemic heart pain and intermittent claudication in field surveys.

            G Rose (1961)
            Hospital studies were used to identify those characteristics of angina pectoris, cardiac infarction and intermittent claudication which most effectively distinguish these conditions from other causes of chest or leg pain. These are used to formulate precise definitions for epidemiological use and to form the basis of a standardized questionnaire.Agreement on the use of such a questionnaire would permit international comparisons of the prevalence of these conditions, as defined. This would not hinder the collection of additional information, as required in particular studies.As compared with physicians' diagnoses, the questionnaire had high specificity and reasonably good sensitivity. Interpretation of subjects' answers presents no serious difficulties. There is evidence that the diagnosis of angina pectoris presents special problems in populations with a high prevalence of chronic bronchitis.
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              Glucocorticoids and cardiovascular disease.

              Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitary-adrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11beta-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intra-vascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.

                Author and article information

                Contributors
                On behalf of : on behalf of the Edinburgh Type 2 Diabetes study investigators
                Journal
                Eur J Endocrinol
                Eur. J. Endocrinol
                EJE
                European Journal of Endocrinology
                BioScientifica (Bristol )
                0804-4643
                1479-683X
                May 2012
                : 166
                : 5
                : 861-868
                Affiliations
                [1 ]simpleEndocrinology Unit simpleUniversity/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh 47 Little France Crescent, Edinburgh, EH16 4TJUK
                [2 ]simpleHospital Psiquiatric Universitari Institut Pere Mata, IISPV simpleUniversitat Rovira i Virgili ReusSpain
                [3 ]simpleMetabolic Unit simpleWestern General Hospital EdinburghUK
                [4 ]simpleDepartment of Psychology simpleUniversity of Edinburgh EdinburghUK
                [5 ]simpleCentre for Cognitive Ageing and Cognitive Epidemiology simpleUniversity of Edinburgh EdinburghUK
                [6 ]simpleDivision of Cardiovascular and Medical Sciences simpleUniversity of Glasgow ScotlandUK
                [7 ]simpleCentre for Population Health Sciences simpleUniversity of Edinburgh EdinburghUK
                Author notes
                (Correspondence should be addressed to R M Reynolds; Email: r.reynolds@ 123456ed.ac.uk )
                Article
                EJE120041
                10.1530/EJE-12-0041
                3341665
                22408122
                8ca7c3a5-ea33-48d0-a2e8-4957793038f6
                © 2012 European Society of Endocrinology

                This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 January 2012
                : 25 February 2012
                : 9 March 2012
                Funding
                Funded by: Medical Research Council
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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