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Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis

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Abstract

Purpose

Active acromegaly is associated with impaired glucose metabolism, which improves upon treatment. Treatment options include surgery, medical therapy with somatostatin analogues (SSA) and Pegvisomant (PEG), and irradiation. The objective of the study was to describe the differential effect of various treatment regimens on the secretion of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) in patients with acromegaly.

Methods

23 surgically treated, non-diabetic patients with acromegaly and 12 healthy controls underwent an oral glucose tolerance test (OGTT) and subsequently isoglycaemic intravenous glucose infusion on a separate day. Baseline hormone concentrations, time-to-peak and area under the curve (AUC) on the OGTT-day and incretin effect were compared according to treatment regimens.

Results

The patients treated with SSA (N = 15) had impaired GIP-response (AUC, P = 0.001), and numerical impairment of all other hormone responses (P > 0.3).

Patients co-treated with PEG (SSA + PEG, N = 4) had increased secretion of insulin and glucagon compared to patients only treated with SSA (SSA ÷ PEG, N = 11) (insulinAUC mean ± SEM, SSA + PEG 49 ± 8.3 nmol/l*min vs SSA ÷ PEG 25 ± 3.4, P = 0.007; glucagonAUC, SSA + PEG 823 ± 194 pmol/l*min vs SSA ÷ PEG 332 ± 69, P = 0.009). GIP secretion remained significantly impaired, whereas GLP-1 secretion was numerically increased with PEG (SSA + PEG 3088 ± 366 pmol/l*min vs SSA ÷ PEG 2401 ± 239, P = 0.3).

No difference was found in patients treated with/without radiotherapy nor substituted or not with hydrocortisone.

Conclusion

SSA impaired the insulin, glucagon, and incretin hormone secretions. Co-treatment with PEG seemed to counteract the somatostatinergic inhibition of the glucagon and insulin response to OGTT. We speculate that PEG may exert its action through GH-receptors on pancreatic δ-cells.

Clinical trial registration NCT02005978.

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Acknowledgements

The authors are also grateful to research laboratory technician Casper Kok, the laboratory at Dept Biomedical Sciences, and NNF Centre for Basic Metabolic Research Faculty of Health Science for their kind assistance.

Funding

This work is supported in part by grants from the Danish Council for Independent Research (Grant No. 12-126045), The Foundation of Assisting Medical Science, The Augustinus Foundation, Novo Nordisk’s Fund (Grant No. NNF16OC0022632), The Foundation of the Capital Region of Denmark, Else and Mogens Wedell-Wedellsborg’s Fund (Grant No. 8-17-2), Poul and Ellen Hertz’s Fund (Grant No. 3.17.1), The Foundation of King Christian the Tenth (Grant No. 119) and The Fund of Shipowner Per Henriksen and Wife (Grant No. 10118). Professor Ulla Feldt-Rasmussen’s research salary was sponsored by unrestricted grants from Novo-Nordisk Foundation and from The Kirsten and Freddy Johansen’s Fund.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Nanna Thurmann Jørgensen, Trine Møller Erichsen, Ulla Feldt-Rasmussen & Marianne Klose

  2. Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Morten Buus Jørgensen, Thomas Idorn & Bo Feldt-Rasmussen

  3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Bo Feldt-Rasmussen & Ulla Feldt-Rasmussen

  4. Department of Biomedical Sciences, and NNF Centre for Basic Metabolic Research Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Jens J. Holst

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  1. Nanna Thurmann Jørgensen
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Contributions

UF-R and MK were in charge of the study design. TME was in charge of data gathering in the cohort from 2012 to 2013 with help from TI, while in 2016–2018 NTJ was in charge of the remaining data gathering with help from MBJ and MK, and NTJ performed statistical analysis and prepared the manuscript in collaboration with MK and UF-R. JJH and CD generated data and critically revised the manuscript. BF-R also critically revised the manuscript.

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Correspondence to Marianne Klose.

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Jørgensen, N.T., Erichsen, T.M., Jørgensen, M.B. et al. Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis. Pituitary 26, 152–163 (2023). https://doi.org/10.1007/s11102-022-01297-x

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