New Diabetic Treatment by Alleviation of Autonomic Nervous System Dysfunction Measured as Periosteal Pressure Sensitivity at Sternum Improves Empowerment, Treatment Satisfaction, and Self-Reported Health of People with Type 2 Diabetes: A Randomized Trial

Abstract

Purpose

Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal pressure sensitivity (PPS) on sternum may be a measure of autonomic nervous system dysfunction (ANSD). We tested if a non-pharmacological PPS-feedback-guided treatment program based on non-noxious sensory nerve stimulation, known to reduce PPS, changed empowerment, treatment satisfaction, and quality of life in people with T2D, compared to usual treatment.

Patients and Methods

Analysis of secondary endpoints in a single center, two-armed, parallel-group, observer-blinded, randomized controlled trial of individuals with T2D. Participants were randomized to non-pharmacological intervention as an add-on to treatment as usual. Endpoints were evaluated by five validated questionnaires: Diabetes specific Empowerment (DES-SF), Diabetes Treatment Satisfaction (DTSQ), quality of life (QOL) (WHO-5), clinical stress signs (CSS), and self-reported health (SF-36). Sample size calculation was based on the primary endpoint HbA1c.

Results

We included 144 participants, 71 allocated to active intervention and 73 to the control group. Active intervention compared to control revealed improved diabetes-specific empowerment (p = 0.004), DTSQ (p = 0.001), and SF-36 self-reported health (p=0.003) and tended to improve quality of life (WHO-5) (p = 0.056). The findings were clinically relevant with a Cohen's effect size of 0.5 to 0.7.

Conclusion

This non-pharmacological intervention, aiming to reduce PPS, and thus ANSD, improved diabetes-specific empowerment, treatment satisfaction, and self-reported health when compared to usual treatment. The proposed intervention may be a supplement to conventional treatment for T2D.

Keywords:

• type 2 diabetes
• empowerment
• autonomic nervous system dysfunction
• periosteal pressure sensitivity

Data Sharing Statement

The data presented in the current study are available from the corresponding author upon request.

Acknowledgments

We would like to thank the employees of the Metabolic Ward O4 at Department of Medicine, Endocrine unit, Herlev University Hospital for their practical contribution: Louise Holmberg Storck, Ulla Kjærulff-Hansen, Marianne Sørensen, Helle R. Christensen, and Syela Azemovski; statistician Tobias Wirenfeldt Klausen for helping with the statistics.

The abstract of this paper was presented at the ‘European Association for the Study of Diabetes’ conference (EASD) in 2023 in Hamburg as a short oral presentation with interim findings. The abstract of this paper was presented at the ‘Annual Meeting of the Diabetic Neuropathy Study Group’ conference (NeuroDiab) in 2023 in Thessaloniki as a poster presentation with interim findings. The abstract was published in “Diabetologia” (as a supplement): https://doi.org/10.1007/s00125-023-05969-6.

Author Contributions

All authors (SKH, JF, CP, NØ, SB, EE, CSH, TWH, GSH, PR, TW, FG) made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Søren Ballegaard developed the PPS measurement device and holds shares in the company that owns the associated patents. To mitigate bias, he was not involved in patient interactions, data collection, or statistical analysis. Consequently, he did not have access to the study site (Herlev University Hospital) throughout the entire study period. In addition, Dr Søren Ballegaard has a patent 8,206,313 and a patent 8,706,213. Dr Peter Rossing reports grants and honoraria to institutions from Astra Zeneca; grants from Bayer and Novo Nordisk; honoraria to institutions from Sanofi, Abbott, Gilead, Novartis, and Boehringer Ingelheim, outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

The work was supported by the Johan Schrøder Erhvervs og Familiefond fund, and Innovation Fund Denmark (Grant Reg. No: 8062-00554B).