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Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson’s disease?

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Abstract

Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson’s disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)––a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni’s method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.

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Acknowledgments

This work was supported by a grant from the Michael J. Fox Foundation for Parkinson’s Research, USA (to M.M.U. and W.H.O.) and by resources of the BMBF-founded “Competence Network Parkinson”, Germany (to K.M.E. and W.H.O.).

Conflict of interest

All authors declare that there are no financial or personal relationships with other people or organisations that could inappropriately influence this work. The authors declare that there is no conflict of interest regarding this work.

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Authors and Affiliations

  1. Department of Neurology, Philipps-Universität Marburg, Rudolf-Bultmann-Strasse 8, 35033, Marburg, Germany

    Marcus M. Unger, Jens C. Möller, Katharina Mankel, Karla M. Eggert, Maren Bodden, Karin Stiasny-Kolster & Wolfgang H. Oertel

  2. Neurocentro della Svizzera Italiana, Clinical Trials Unit, Ospedale Regionale di Lugano, Via Tesserete 46, 6903, Lugano, Switzerland

    Jens C. Möller

  3. Division of Gastroenterology, Philipps-University Marburg, Marburg, Germany

    Katharina Bohne & Johannes J. Tebbe

  4. Division of Endocrinology and Diabetology, Philipps-University Marburg, Marburg, Germany

    Peter H. Kann

  5. Department of Neurology, Hephata-Clinic Schwalmstadt-Treysa, Schwalmstadt-Treysa, Germany

    Geert Mayer

  6. Deparment of Internal Medicine, Division of Gastroenterology, Klinikum Lippe, Detmold, Germany

    Johannes J. Tebbe

Authors
  1. Marcus M. Unger
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  2. Jens C. Möller
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  7. Karin Stiasny-Kolster
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  8. Peter H. Kann
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  9. Geert Mayer
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  10. Johannes J. Tebbe
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  11. Wolfgang H. Oertel
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Corresponding author

Correspondence to Marcus M. Unger.

Additional information

J. J. Tebbe and W. H. Oertel contributed equally to this work.

Electronic supplementary material

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415_2010_5864_MOESM1_ESM.docx

Blood glucose levels in mg/dl over the time of assessment. Mean total blood glucose levels (in mg/dl) and the respective 95%-confidence intervals for each time point of assessment are given for healthy controls, PD patients and iRBD patients. (DOCX 53 kb)

415_2010_5864_MOESM2_ESM.docx

Habitual breakfast times of enrolled subjects. Fig. S2 shows the mean habitual breakfast time and the respective 95% confidence intervals for healthy controls, iRBD patients as well as for drug-naïve and treated PD patients that could be retrospectively contacted by telephone. The percentage and the absolute number of subjects in each group that could be re-contacted by telephone to obtain this information are given in brackets. Habitual breakfast times were similarly distributed between the groups and the majority of enrolled subjects in each group reported their habitual breakfast time to be around the time of the test meal. (DOCX 73 kb)

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Unger, M.M., Möller, J.C., Mankel, K. et al. Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson’s disease?. J Neurol 258, 982–990 (2011). https://doi.org/10.1007/s00415-010-5864-1

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  • DOI: https://doi.org/10.1007/s00415-010-5864-1

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