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      Evaluation of the Pituitary Function with Insulin Tolerance (Hypoglycaemia) Testing: Are There Any Differences Using Insulin Lispro Compared to Regular Insulin?

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          Background/Aim: The insulin tolerance test (ITT) remains the gold standard for evaluating the pituitary function, but has potential risks when hypoglycaemia is induced. There are scarce data using short-acting insulin analogs for ITTs. This pilot study compares the effects of insulin lispro (LPI) with regular insulin (RGI) during an ITT. Methods: Patients with suspected hypopituitarism (n = 103) randomly received either LPI (n = 51) or RGI (n = 52). Results: All patients reported signs and symptoms when hypoglycaemia was induced. In the LPI group, hypoglycaemia occurred sooner (23.6 ± 1.6 vs. 28.3 ± 1.4 min, p < 0.05), and duration of hypoglycaemia (25.0 ± 1.7 vs. 31.9 ± 1.9 min, p < 0.05) and time for blood glucose levels to return to a ‘safe’ level (>3.3 mmol/l; 56.5 ± 2.3 vs. 76.0 ± 2.1 min, p < 0.001) were shorter as compared with the RGI group. No differences in peak growth hormone and cortisol levels were observed between the two groups. Conclusions: Our data suggest that despite inducing similar symptomatology, LPI exerted a quicker onset and a shorter duration of hypoglycaemia as compared with RGI. Thus, using LPI might reduce the potential risks associated with an ITT by shortening the hypoglycaemic phase of the test.

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          Most cited references 28

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          Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use.

          In recent years, analogs of human insulin have been engineered with the aim of improving therapy for people with diabetes. To ensure that the safety profile of the human hormone is not compromised by the molecular modifications, the toxico-pharmacological properties of insulin analogs should be carefully monitored. In this study, we compared the insulin and IGF-I receptor binding properties and metabolic and mitogenic potencies of insulin aspart (B28Asp human insulin), insulin lispro (B28Lys,B29Pro human insulin), insulin glargine (A21Gly,B31Arg,B32Arg human insulin), insulin detemir (NN304) [B29Lys(epsilon-tetradecanoyl), desB30 human insulin], and reference insulin analogs. Receptor affinities were measured using purified human receptors, insulin receptor dissociation rates were determined using Chinese hamster ovary cells overexpressing the human insulin receptor, metabolic potencies were evaluated using primary mouse adipocytes, and mitogenic potencies were determined in human osteosarcoma cells. Metabolic potencies correlated well with insulin receptor affinities. Mitogenic potencies in general correlated better with IGF-I receptor affinities than with insulin receptor off-rates. The 2 rapid-acting insulin analogs aspart and lispro resembled human insulin on all parameters, except for a slightly elevated IGF-I receptor affinity of lispro. In contrast, the 2 long-acting insulin analogs, glargine and detemir, differed significantly from human insulin. The combination of the B31B32diArg and A21Gly substitutions provided insulin glargine with a 6- to 8-fold increased IGF-I receptor affinity and mitogenic potency compared with human insulin. The attachment of a fatty acid chain to LysB29 provided insulin detemir with reduced receptor affinities and metabolic and mitogenic potencies but did not change the balance between mitogenic and metabolic potencies. The safety implications of the increased growth-stimulating potential of insulin glargine are unclear. The reduced in vitro potency of insulin detemir might explain why this analog is not as effective on a molar basis as human insulin in humans.
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                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                April 2008
                21 January 2008
                : 69
                : 4
                : 233-239
                aDepartment of Endocrinology, Oregon Health and Science University, Portland, Oreg., USA; bDepartment of Endocrinology, Royal Manchester Children’s Hospital, Manchester, UK
                113024 Horm Res 2008;69:233–239
                © 2008 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.

                Page count
                Figures: 1, Tables: 2, References: 36, Pages: 7
                Original Paper


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