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      Hyperglycemia Induced by Glucocorticoids in Nondiabetic Patients: A Meta-Analysis

      meta-analysis

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          Abstract

          Background/Aims: Glucocorticoids are associated with a number of side effects including the development of new-onset hyperglycemia or diabetes. The diagnosis and treatment of glucocorticoid-induced hyperglycemia are surprisingly undervalued by many health-care professionals, probably due to the lack of quality studies that assess specific reasons for and prevention of hyperglycemia. The aim of this meta-analysis was to evaluate the long-term incidence of glucocorticoid-induced hyperglycemia and diabetes in nondiabetic patients who received glucocorticoid treatment. Methods: We searched Medline, Embase, and the Cochrane Library (Central) until January 2014 for studies in which subjects received systematic glucocorticoid treatment and which evaluated whether subjects developed hyperglycemia or were diagnosed with diabetes following treatment. The primary outcome for this analysis was the incidence of hyperglycemia and the secondary outcome was the frequency of diabetes. Results: We identified 13 studies that met our inclusion criteria; 12 of the studies were retrospective or observational in design. We found that the rate at which patients developed glucocorticoid-induced hyperglycemia or diabetes was 32.3% (p = 0.003) and 18.6% (p = 0.002), respectively. Conclusions: Our meta-analysis indicated that glucocorticoid-induced hyperglycemia occurs fairly frequently and points to the need for the design of prospective, randomized, controlled studies to further investigate and better understand this medical problem.

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          Most cited references18

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          Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor detect of insulin action.

          The present studies were undertaken to assess the mechanisms responsible for cortisol-induced insulin resistance in man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in six normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 microgram kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 +/- 3 vs. 14 +/- 1 microgram/dl; P less than 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased postabsorptive plasma glucose (126 +/- 2 vs. 97 +/- 2 mg/dl; P less than 0.01) and plasma insulin (16 +/- 2 vs. 10 +/- 2 microU/ml; P less than 0.01) concentrations and rates of glucose production (2.4 +/- 0.1 vs. 2.1 +/- -0.1 mg kg-1 min-1; P less than 0.01) and utilization (2.5 +/- 0.1 vs. 2.1 +/- 0.1 mg kg-1 min -1; P less than 0.01). Insulin dose-response curves for both suppression of glucose production (half-maximal response at 81 +/- 19 vs. 31 +/ 5 microU/ml; P less than 0.05) and stimulation of glucose utilization (half-maximal response at 104 +/- 9 vs. 64 +/- 7 microU/ml; P less than 0.01) were shifted to the right, with preservation of normal maximal responses to insulin. Neither monocyte nor erythrocyte insulin binding was decreased. However, except at near-maximal insulin receptor occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte insulin receptors occupied was decreased. These results indicate that the cortisol-induced insulin resistance in man is due to the decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be explained on the basis of a postreceptor defect.
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            Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients.

            To investigate the prevalence of and risk factors for hyperglycemia in hospitalized patients receiving corticosteroids, which have been identified as an independent predictor of hyperglycemia. We conducted a retrospective review of electronic medical records of patients admitted to the general medicine service at a university hospital during a 1-month period. Pharmacy charges were used to identify patients receiving high doses (> or = 40 mg/day of prednisone or the equivalent) of corticosteroids for at least 2 days. Occurrence of hyperglycemia and the presence of risk factors, including history of diabetes, duration of corticosteroid therapy, concurrent parenteral nutrition, antibiotic therapy, use of medications associated with hyperglycemia, severity of illness scores, and hospital length of stay, were determined. Patients experiencing multiple episodes of hyperglycemia (glucose levels > or = 200 mg/dL) were compared with those who had < or = 1 hyperglycemic episode. Patients without a history of diabetes were assessed separately. During the 1-month study period, 66 of 617 patients received high doses of corticosteroids, but only 50 of the 66 had glucose measurements. Hyperglycemia was documented in 32 of these 50 patients (64%), and multiple hyperglycemic episodes occurred in 26 (52%). A history of diabetes was documented in 12 of 26 patients who experienced multiple episodes, in comparison with 4 of 24 patients with < or = 1 episode of hyperglycemia (P = 0.035). Among patients without a history of diabetes, 19 of 34 (56%) had hyperglycemia at least once. Patients with multiple episodes of hyperglycemia had more comorbid diseases, longer duration of corticosteroid therapy, and longer duration of hospital stay. Hyperglycemia occurs in a majority of hospitalized patients receiving high doses of corticosteroids. In light of the poor outcomes associated with hyperglycemia, protocols targeting its detection and management should be available for patients who receive corticosteroid therapy.
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              Glucocorticoid-induced hyperglycemia.

              Provide treatment guidelines for glucocorticoid-induced hyperglycemia and to understand the clinical implications of glucocorticoid-induced hyperglycemia.
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                Author and article information

                Journal
                ANM
                Ann Nutr Metab
                10.1159/issn.0250-6807
                Annals of Nutrition and Metabolism
                S. Karger AG
                0250-6807
                1421-9697
                2014
                December 2014
                14 November 2014
                : 65
                : 4
                : 324-332
                Affiliations
                aDepartment of Endocrinology and Metabolism, Northern Branch of Huashan Hospital, and bDepartment of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China
                Author notes
                *Yi-ming Li, PhD, Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, 0 Building, 2nd floor, 12 Wulumuqi Middle Road, Shanghai 200040 (China), E-Mail yimingli@fudan.edu.cn
                Article
                365892 Ann Nutr Metab 2014;65:324-332
                10.1159/000365892
                25402408
                7c6f502f-13b3-4102-a136-d0ccaf34fc83
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 20 March 2014
                : 13 July 2014
                Page count
                Figures: 4, Tables: 2, Pages: 9
                Categories
                Original Paper

                Nutrition & Dietetics,Health & Social care,Public health
                Hyperglycemia,Glucocorticoid,Steroids,Glucocorticoid-induced hyperglycemia,Diabetes

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