The core physiological issue underlying
diabetes and insulin resistance has been linked to impaired afferent
vagal function.1 Disruption of vagal afferent fibers by toxicity
or surgical activates the glucocorticoid induction of diabetes and
hypertension.2 Other researchers have shown that intact vagal afferent
fibers are required for glucocorticoid-induced glucose intolerance.2-4
The vagus nerve derives its name from the Latin word for wanderer,
to explain the meandering anatomic distribution of the vagus nerve,
which has been documented to suppress inflammation,5 inhibit seizure
activity6 and depression,7 and establish a regulatory circuit between
the liver and central nervous system that can have a positive effect
in insulin metabolismand blood pressure.4
Diabetes and metabolic syndrome due to insulin resistance cause
aberrations in visceral-abdominal fat that generate a cluster of
physiological abnormalities: high triglycerides, high blood pressure,
high fasting blood sugar, and low HDL cholesterol. While insulin
injections help control diabetes, they do not address the afferent
vagal deficit and this leads to elevated risks of severe neurological
and vascular complications, primarily due to autoimmune destruction
of the insulin-producing beta cells. When the body lacks insulin,
cells starve and glucose levels soar, causing blindness, kidney
failure, and a wide spectrum of other diseases. No treatment on
the market has been proven to correct insulin resistance by addressing
neural mechanisms underlying the death of pancreatic beta cells.
Excessive abdominal fat is a strong predictor of heart attacks in
young men, chronic heart failure in older people, and high blood
pressure, and is even implicated in the development of Alzheimer's
disease, colon cancer, gallstones, ovarian cystic disease, breast
cancer, and sleep apnea. Unlike other kinds of body fat, visceral-abdominal
fat can become dysfunctional and produce a stew of menacing molecules
that can expand to the point of rupturing. Ruptured fat cells trigger
immune cells (macrophages), interleukin-6 (IL-6) and tumor necrosis
factor-alpha, which adhere to the endothelium of the blood vessels
causing atherosclerosis. Indeed, elevated levels of IL-6 and C-reactive
protein (CRP) predict the development of type 2 diabetes and support
the role for inflammation in diabetogenesis. Baseline levels of
CRP and IL-6 were significantly higher in 188 diabetic women versus
362 matched "normal" controls. And large-scale studies
(the Physician's Health Study and the Women's Health Study) revealed
high CRP levels to be a risk predictor of myocardial infarction
or stroke in men,8 cardiovascular events in women,9 and cardiovascular
events in patients with the metabolic syndrome.10,11 A cross-sectional
study revealed that CRP levels were related to insulin resistance,
obesity, endothelial dysfunction, hypertension and diabetes,12-15
and excessive visceral-abdominal fat,16,17 all of which have been
linked to impaired afferent vagal function.1-7 These studies raise
the prospect that doctors might forestall autoimmune disease by
restoring afferent vagal function, which in turn will restore immune
function and glucose metabolism.
The vagus afferent-efferent physiology provides a two-way highway
of communication between the brain and the liver, duodenum, stomach,
and pancreas that regulates digestion, detoxification, steroidogenesis,
glucose metabolism, and immunological function. Studies have shown
that the afferent-specific neurotoxin capsaicin increased the levels
of circulating glucose and triglycerides and negated the actions
of insulin on these and free fatty acids and ketone bodies.18-19
In summary, alternative medicine needs to address the efferent cholinergic
anti-inflammatory pathway and the afferent vagus, as these are central
mechanisms behind excessive inflammatory responses and diabetes.
The involvement of vagus efferent neurons in neuroimmunomodulation
provides a protective role against prolonged inflammation via the
cholinergic anti-inflammatory pathway.20,21 Thus, being "holistic"
requires that we nourish and support the reciprocal afferent-efferent
vagus function, as this is undoubtedly is a missing link in current
natural protocols for diabetes, which, for the first time, fully
explains the aberrant physiology underlying diabetes.
1. Tougas G et al. Evidence of impaired afferent vagal function
in patients with diabetes gastroparesis. Pacing
Clin Electrophysiol. 1992;15:1597–1602.
2. Carlos Bernal-Mizrachi et al. An afferent vagal nerve pathway
links hepatic PPARa activation to glucocorticoid-induced insulin
resistance and hypertension. Cell Metab.
3. Walls EK et al. Selective vagal rhizotomies: a new dorsal surgical
approach used for intestinal deafferentations. Am
J Physiol Regulatory Integrative Comp Physiol. 1995;269:1279–1288.
4. Uno K et al. Neuronal pathway from the liver modulates energy
expenditure and systemic insulin sensitivity. Science.
5. Borovikova LV et al. Vagus nerve stimulation attenuates the systemic
inflammatory response to endotoxin. Nature.
6. Uthman, BM et al. Effectiveness of vagus nerve stimulation in
epilepsy patients: a 12-year observation. Neurology.
7. Nahas Z et al. Two-year outcome of vagus nerve stimulation (VNS)
for treatment of major depressive episodes.
J Clin Psych. 2005;66:1097–1104.
8. Ridker PM et al. Inflammation, aspirin, and the risk of cardiovascular
disease in apparently healthy men. NEJM.
9. Ridker PM et al. C-reactive protein and other markers of inflammation
in the prediction of cardiovascular disease in women. NEJM.
10. Ridker PM et al. Comparison of C-reactive protein and low-density
lipoprotein cholesterol levels in the prediction of first cardiovascular
events. NEJM. 2002;347: 1557–1565.
11. Ridker PM et al. C-reactive protein, the metabolic syndrome,
and risk of incident cardiovascular events. Circulation.
12. Yudkin JS et al. C-reactive protein in healthy subjects: associations
with obesity, insulin resistance, and endothelial dysfunction. ATVG.
13. Aruna D et al. C-reactive protein, interleukin 6, and risk of
developing type 2 diabetes mellitus. JAMA.
14. Hu FB, Meigs JB, Li TY, Nader R, Manson JE. Inflammatory markers
and risk of developing type 2 diabetes in women. Diabetes.
15. Sesso HD et al. C-reactive protein and the risk of developing
hypertension JAMA. 2003;290:2945–2951.
16. Pitombo C et al. Amelioration of diet-induced diabetes mellitus
by removal of visceral fat J. Endocrinol.
17. Goodpaster BH et al. Obesity, regional body fat distribution,
and the metabolic syndrome in older men and women. Arch
Int Med. April 11, 2005;165(7):777–783.
18. Warne JP et al. Afferent signalling through the common hepatic
branch of the vagus inhibits voluntary lard intake and modifies
plasma metabolite levels in rats. J Physiol.
19. Warne JP, Foster MT, Horneman HF, et al. Hepatic branch vagotomy,
like insulin replacement, promotes voluntary lard intake in streptozotocin-diabetic
rats. Endocrinology. 2007, 148,
20. Blalock JE. Harnessing a neural-immune circuit to control inflammation
and shock. J Exp Med. 2002;195:F25–28.
21. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic
anti-inflammatory pathway: a missing link in neuroimmunomodulation.
Mol Med. 2003;May–Aug;9(5–8):125–134.
Paul Yanick Jr., PhD