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: autonomic nervous system dysfunction; empowerment; periosteal pressure sensitivity; type 2 diabetes.

Figure 1

Continued.

Figure 1

The proposed link between stress, autonomic nervous system (ANS) function, PPS, and autonomic homeostatic regulation of glucose metabolism. Effect of reversal of ANS dysfunction. (A) Autonomic homeostatic control of glucose metabolism (HbA1c) and warning and defense system sensitivity (PPS). Inspired by Goldstein et al (B) Autonomic homeostatic control by an autonomic reflex arc, regulation of PPS. 1) an afferent signal generated from polymodal sensor cells on periosteum of sternum initiates an afferent signal to hypothalamus for warning and defense system regulation; 2) modulation by the brain in the lateral horn of hypothalamus, and 3) efferent sympathetic neural signals for adaptation, including the periosteal pressure sensitivity measured as PPS.; 4) The reflex arc for regulation of glucose metabolism is structured the same way with afferent signals coming from glucose sensors. (C) Autonomic homeostatic control in transient stress. 1) an afferent signal to hypothalamus in response to the perception of a transient stress condition (e.g, an emotional challenge/physical threat/mental demand); 2) hypothalamus initiates a transient physiological stress response, which leads to 3) transient increase in PPS and transient increase in insulin release from pancreas, transient increase in insulin levels in blood to facilitate transport of glucose into the cells, and transient increase in blood glucose to meet transient increase in demand of glucose in the cells. For simplicity, the figure shows the situation for PPS, only. (D) A persistent perception of stress leading to gradual loss of ANS resilience and ANS homeostatic power bringing forward the situation of autonomic dysfunction. If this condition persists, it may pass the ANS tipping point for internal regulation as shown in (A), which is associated with loss of autonomic homeostatic control of the sensitivity of the warning and defense system, measured as persistently elevated PPS. In addition, autonomic homeostatic control of glucose metabolism is also lost,, resulting in the development of type 2 diabetes. A vicious circle is established as ANSD itself is disease worsening. For simplicity, the figure shows the situation for PPS, only. (E) Regaining autonomic homeostatic control by reversal of ANSD mediated by repetitive activations of the autonomic reflex arc, including the following steps: 1) Non-noxious sensory nerve stimulation for 30–60 seconds of a tender spot on the body surface related to spinal cord thoracic segments T3-T5 (ie, a hypersensitive polymodal sensor cell) and identified by finger-palpation; 2) transmission of the signal through A-delta and C-nerve fibers to the spinal cord and forward to the hypothalamus; 3) the signal is evaluated by hypothalamus as non-hostile, leading to 4) an efferent descending signal to the periosteum of the sternum reducing the elevated sensitivity of the warning and defense system, which is measured acutely as reduced tenderness by the finger and a reduced PPS. 5) the steps 1–4 are repeated twice daily for 6 months and the person experiences this as a gradual decrease of the initially elevated PPS. The normal autonomic homeostatic regulation of glucose metabolism is gradually reestablished, and a concomitant reduction of HbA1c can be measured after 6 months.