Abstract

Bad bedfellows – autonomic dysfunction, inflammation, and diabetes! Are they related? How? Evidence suggests the activation of inflammatory cytokines like IL-6 and TNFα in newly diagnosed type 2 diabetes and that the inflammatory change correlates with abnormalities in sympathovagal balance. Dysfunction of the autonomic system predicts cardiovascular risk and sudden death in patients with type 2 diabetes. It occurs in prediabetes, providing opportunities for early intervention. The importance of recognizing autonomic dysfunction as a predictor of morbidity and mortality with intensification of treatment suggests that all patients with type 2 diabetes at onset, and those with type 1 diabetes after 5 years should be screened for autonomic imbalance. These tests can be performed at the bedside with real time output of information – within the scope of the practicing physician – facilitates diagnosis and allows the application of sound strategies for management. The window of opportunity for aggressive control of all the traditional risk factors for cardiovascular events or sudden death with intensification of therapy is with short duration diabetes, the absence of cardiovascular disease, and a history of severe hypoglycemic events. To this list we can now add autonomic dysfunction and neuropathy, which have become the most powerful predictors of risk for mortality. It seems prudent that practitioners should be encouraged to become familiar with this information and apply risk stratification in clinical practice. After all, how difficult is it to ask patients “do you have numb feet?” and to determine their heart rate variability – it could be lifesaving. Ultimately methods to reset the hypothalamus and the inflammatory cascade are needed if we are to impact the care of patients with this compendium of conditions.

Highlights

  • Bad bedfellows – autonomic dysfunction, inflammation, and diabetes! Are they related? How? Evidence suggests the activation of inflammatory cytokines like IL-6 and TNFα in newly diagnosed type 2 diabetes and that the inflammatory change correlates with abnormalities in sympathovagal balance

  • For instance in the non-obese diabetic (NOD) mouse neurons surrounding the pancreatic beta cells are lost before there is damage to the islet, and the loss of tonic inhibitory signals contributes to the subsequent beta cell destruction (Saravia and Homo-Delarche, 2003)

  • TARGETING INFLAMMATION The treatment of inflammatory diseases including chronic inflammatory demyelinating polyneuropathy (CIDP) and autonomic neuropathy has had a significant boost by the use of immunoglobulin, and biological agents that modulate the activity of TNF-a, IL-1, and IL-6 (Pittenger et al, 1997; Vinik et al, 2006b; Anandacoomaraswamy et al, 2008; Bourcier and Vinik, 2010; Handelsman et al, 2011)

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Summary

The conductor of the autonomic orchestra

Oxygen, glucose, and other metabolites are sensed by specialized glomus cells in the association with the nervous system Upon activation, these cells release dopamine and norepinephrine causing depolarization of the sensory fibers in the vagus which propagate to the brainstem and initiate a motor efferent arc. Shown is the coactivation of the hypothalamic pituitary axis with release of glucocorticoids which modulate the inflammatory response It is unclear how this set point is determined in the body but what is clear is that autonomic modulation of inflammation can be achieved by altering sympathetic/parasympathetic balance.

Femoral neck Greater trochanter Total hip Foot Calcaneal stiffness index
TREATMENT OF AUTONOMIC DYSFUNCTION
Clinical trials
Assessment Modalities
Findings
CONCLUSION
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