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      Effect of Short-Term rHuEPO Treatment on Insulin Resistance in Haemodialysis Patients

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          Abstract

          Background/Aim: Decreased sensitivity to the hypoglycaemic action of insulin is an almost universal phenomenon in uraemic patients, and it is attributed either to uraemic toxins or to anaemia or even to secondary hyperparathyroidism. Considering the conflicting data of few existing studies, we examined the influence of erythropoietin (EPO) treatment on insulin resistance and tested the probable correlation of this influence with sympathetic nervous system (SNS) activity. Methods: We studied 8 non-obese, non-diabetic, stable dialysis patients using the euglycaemic insulin clamp technique before administration of EPO (phase A), 10 days after (phase B), and after the correction of the haematocrit level, at least 8 weeks later (phase C). We estimated the indices (glucose infusion rate, mg/kg/min), M/G (glucose clearance), and M/I (tissue sensitivity to insulin), and we measured haematocrit, haemoglobin, triglyceride, ferritin, EPO, and fasting insulin levels in each phase. During each phase, we tested the SNS activity using the response of blood pressure to persistent handgrip and the response of blood pressure to the standing position. Results: Our patients appeared to have an increased insulin resistance in phase A (M<sub>A</sub> = 6.24 ± 1.01) which was significantly improved 10 days after the beginning of EPO treatment and before the rise of haematocrit (M<sub>B</sub> = 7.71 ± 1.54, p < 0.05). There was no further improvement in phase C. Indices M/G and M/I behaved similarly. The serum triglyceride levels decreased in response to the increased insulin sensitivity. The patients studied did not demonstrate fasting hyperinsulinaemia, while the SNS activity was abnormal and remained unchanged throughout the study period in spite of some individual improvement. Conclusions: Our study proves the beneficial effect of EPO treatment on insulin resistance in dialysis patients which could be attributed to the EPO itself and not to the correction of anaemia and is accompanied by improvement in triglyceride levels. Amelioration of insulin resistance did not influence the SNS activity, making the association between EPO treatment and SNS-derived changes in blood pressure quite improbable.

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          Insulin resistance and hypertension.

          A common mechanism which may be involved in the development of hypertension in both type I and type II diabetes mellitus is a deficiency of insulin at the cellular level. Observations from a number of laboratories suggest that impaired cellular response to insulin rather than hyperinsulinemia predisposes to increased vascular smooth muscle tone (the hallmark of hypertension in the diabetic state). This review presents some of the data which suggest that there is a relationship between impaired cellular action of insulin, altered cellular calcium metabolism and the development of hypertension.
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            Author and article information

            Journal
            NEF
            Nephron
            10.1159/issn.1660-8151
            Nephron
            S. Karger AG
            1660-8151
            2235-3186
            2000
            April 2000
            30 March 2000
            : 84
            : 4
            : 320-325
            Affiliations
            aRenal Department, Second Hospital of IKA, Thessaloniki, and bSecond Department of Internal Medicine, Papanikolaou Hospital, Thessaloniki, Greece
            Article
            45606 Nephron 2000;84:320–325
            10.1159/000045606
            10754408
            33e2d34e-0bef-4e6a-8859-f9ba9069b4f6
            © 2000 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
            Page count
            Tables: 3, References: 18, Pages: 6
            Categories
            Original Paper

            Cardiovascular Medicine,Nephrology
            Haemodialysis,Insulin resistance,Recombinant human erythropoietin,Sympathetic nervous system activity

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