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Exp Clin Endocrinol Diabetes 2007; 115(2): 146-150
DOI: 10.1055/s-2007-955096
Case Report

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Preserved GLP-1 Effects in a Diabetic Patient with Cushing's Disease

R. A. Ritzel 1 , 2 , N. Kleine 3 , J. J. Holst 4 , B. Willms 3 , W. Schmiegel 1 , M. A. Nauck 1 , 3
  • 1Department of Internal Medicine, Ruhr-University, Knappschafts-Krankenhaus, Bochum, Germany
  • 2Department of Internal Medicine I, University of Heidelberg, Germany
  • 3Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
  • 4Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark
Further Information

Publication History

received 7. 6. 2006 first decision 11. 8. 2006

accepted 11. 8. 2006

Publication Date:
22 February 2007 (online)

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Abstract

Context:A patient with diabetes mellitus, who participated in a study with intravenous administration of GLP-1, was later found to have Cushing's disease (markedly elevated 24 h urinary cortisol excretion and inadequate suppression of fasting cortisol with 2 mg dexamethasone). His diabetic state disappeared (2 h plasma glucose after 75 g oral glucose 159 mg/dl=IGT) after successful pituitary surgery (normal 24 h urinary cortisol excretion and adequate cortisol suppression with 2 mg dexamethasone).

Objective:The present analysis was undertaken to compare GLP-1 actions on fasting glycemia in diabetes mellitus due to Cushing's disease with GLP-1 actions in typical type 2 diabetes.

Design and Methods:GLP-1 (1.2 pmol/kg/min) and placebo had been infused into ten patients with diabetes mellitus over 4 h in the fasting state. The results from the patient with Cushing's disease (C) were compared to the data from the remaining nine patients with type 2 diabetes (D).

Results:Within 4 h glucose decreased from basal (C: 12.9; D: 12.9±0.7 mmol/l) to normal fasting values (C: 5.0; D: 4.9±0.4 mmol/l). The stimulation of insulin secretion and suppression of glucagon secretion was similar in the patient with Cushing's disease compared to those with type 2 diabetes.

Conclusions:The insulinotropic, glucagonostatic and glucose-lowering actions of GLP-1 in a patient with diabetes mellitus due to cortisol excess were similar to actions in typical type 2 diabetes. Therefore incretin mimetics might be a novel therapeutic strategy for the treatment of glucocorticoid-induced diabetes mellitus.

References

  • 1 Achermann JC, Brook CG, Robinson IC, Matthews DR, Hindmarsh PC. Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor-1 (IGF-1) concentrations in short children.  Clin Endocrinol (Oxf). 1999;  50 301-308
    PubMedSearch in Google Scholar
  • 2 Atkinson AB, McCance DR, Kennedy L, Sheridan B. Cyclical Cushing's syndrome first diagnosed after pituitary surgery: a trap for the unwary.  Clin Endocrinol (Oxf). 1992;  36 297-299
    PubMedSearch in Google Scholar
  • 3 Bierwolf C, Kern W, Molle M, Born J, Fehm HL. Rhythms of pituitary-adrenal activity during sleep in patients with Cushing's disease.  Exp Clin Endocrinol Diabetes. 2000;  108 470-479
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Brubaker PL, Drucker DJ. Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut and central nervous system.  Endocrinology. 2004;  145 2653-2659 , Epub 2004 Mar 2624
    CrossrefPubMedSearch in Google Scholar
  • 5 Buteau J, Roduit R, Susini S, Prentki M. Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)- cells.  Diabetologia. 1999;  42 856-864
    CrossrefPubMedSearch in Google Scholar
  • 6 Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes.  Diabetes Care. 2003;  26 2929-2940
    CrossrefPubMedSearch in Google Scholar
  • 7 Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human.  Endocr Rev. 1998;  19 717-797
    CrossrefPubMedSearch in Google Scholar
  • 8 Gutzwiller JP, Drewe J, Goke B, Schmidt H, Rohrer B, Lareida J, Beglinger C. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2.  Am J Physiol. 1999;  276 R1541-1544
    PubMedSearch in Google Scholar
  • 9 Holst JJ. Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33-69) of glicentin.  Biochem J. 1982;  207 381-388
    PubMedSearch in Google Scholar
  • 10 Holst JJ. Glucagon-like peptide-1: from extract to agent, 2005.  The Claude Bernard Lecture, 2005 Diabetologia. 2006;  1-8
    PubMedSearch in Google Scholar
  • 11 Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 7-36: a physiological incretin in man.  Lancet. 1987;  2 1300-1304
    PubMedSearch in Google Scholar
  • 12 Lambillotte C, Gilon P, Henquin JC. Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets.  J Clin Invest. 1997;  99 414-423
    CrossrefPubMedSearch in Google Scholar
  • 13 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
    Search in Google Scholar
  • 14 Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients.  Diabetologia. 1993;  36 741-744
    CrossrefPubMedSearch in Google Scholar
  • 15 Nauck MA, Meier JJ. Glucagon-like peptide 1 and its derivatives in the treatment of diabetes.  Regul Pept. 2005;  128 135-148
    CrossrefPubMedSearch in Google Scholar
  • 16 Newell-Price J, Trainer P, Perry L, Wass J, Grossman A, Besser M. A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome.  Clin Endocrinol (Oxf). 1995;  43 545-550
    CrossrefPubMedSearch in Google Scholar
  • 17 Orskov C, Holst JJ. Radio-immunoassays for glucagon-like peptides 1 and 2 (GLP- 1 and GLP-2).  Scandinavian Journal of Clinical & Laboratory Investigation. 1987;  47 165-174
    PubMedSearch in Google Scholar
  • 18 Pagano G, Cavallo-Perin P, Cassader M, Bruno A, Ozzello A, Masciola P, Dall'omo AM, Imbimbo B. An in vivo and in vitro study of the mechanism of prednisoneinduced insulin resistance in healthy subjects.  J Clin Invest. 1983;  72 1814-1820
    CrossrefPubMedSearch in Google Scholar
  • 19 Ritzel R, Orskov C, Holst JJ, Nauck MA. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships.  Diabetologia. 1995;  38 720-725
    CrossrefPubMedSearch in Google Scholar
  • 20 Taskinen MR, Nikkila EA, Pelkonen R, Sane T. Plasma lipoproteins, lipolytic enzymes, and very low density lipoprotein triglyceride turnover in Cushing's syndrome.  J Clin Endocrinol Metab. 1983;  57 619-626
    PubMedSearch in Google Scholar
  • 21 Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR. A role for glucagon-like peptide-1 in the central regulation of feeding.  Nature. 1996;  379 69-72
    CrossrefPubMedSearch in Google Scholar
  • 22 Vella A, Shah P, Reed AS, Adkins AS, Basu R, Rizza RA. Lack of effect of exendin-4 and glucagon-like peptide-1-(7,36)-amide on insulin action in non-diabetic humans.  Diabetologia. 2002;  45 1410-1415 , Epub 2002 Sep 1415
    PubMedSearch in Google Scholar
  • 23 Willms B, Werner J, Holst JJ, Orskov C, Creutzfeldt W, Nauck MA. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients.  J Clin Endocrinol Metab. 1996;  81 327-332
    CrossrefPubMedSearch in Google Scholar

1 This study was supported in part by the respective institutions.

Correspondence

R. A. Ritzel

Department of Internal Medicine I

University of Heidelberg

Im Neuenheimer Feld 410

69120 Heidelberg

Germany

Phone: +49/6221/56 87 92

Fax: +49/6221/56 42 33

Email: Robert.Ritzel@med.uni-heidelberg.de