Distinct osmoregulatory responses to sodium loading in patients with altered glycosaminoglycan structure: a randomized cross-over trial

Eliane F. E. Wenstedt, Jetta J. Oppelaar, Stijn Besseling, Nienke M. G. Rorije, Rik H. G. Olde Engberink, Arie Oosterhof, Toin H. van Kuppevelt, Bert-Jan H. van den Born, Jan Aten, Liffert Vogt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: By binding to negatively charged polysaccharides called glycosaminoglycans, sodium can be stored in the body—particularly in the skin—without concurrent water retention. Concordantly, individuals with changed glycosaminoglycan structure (e.g. type 1 diabetes (DM1) and hereditary multiple exostosis (HME) patients) may have altered sodium and water homeostasis. Methods: We investigated responses to acute (30-min infusion) and chronic (1-week diet) sodium loading in 8 DM1 patients and 7 HME patients in comparison to 12 healthy controls. Blood samples, urine samples, and skin biopsies were taken to investigate glycosaminoglycan sulfation patterns and both systemic and cellular osmoregulatory responses. Results: Hypertonic sodium infusion increased plasma sodium in all groups, but more in DM1 patients than in controls. High sodium diet increased expression of nuclear factor of activated t-cells 5 (NFAT5)—a transcription factor responsive to changes in osmolarity—and moderately sulfated heparan sulfate in skin of healthy controls. In HME patients, skin dermatan sulfate, rather than heparan sulfate, increased in response to high sodium diet, while in DM1 patients, no changes were observed. Conclusion: DM1 and HME patients show distinct osmoregulatory responses to sodium loading when comparing to controls with indications for reduced sodium storage capacity in DM1 patients, suggesting that intact glycosaminoglycan biosynthesis is important in sodium and water homeostasis. Trial registration These trials were registered with the Netherlands trial register with registration numbers: NTR4095 (https://www.trialregister.nl/trial/3933 at 2013-07-29) and NTR4788 (https://www.trialregister.nl/trial/4645 at 2014-09-12).
Original languageEnglish
Article number38
JournalJournal of Translational Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Dec 2021

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