**5. Relationship between type 2 diabetes and ANS**

A global approach of the responsibility of a dysfunction of the ANS in the genesis or the aggravation of the 3 main pathophysiological mechanisms of type 2 diabetes, which are insulin resistance, decrease in insulin secretion and hyperglucagonemia, has been attempted, by several studies all over the world especially during the last decades.

a.ANS and insulinoresistance

• Currently there is evidence that sympathetic hyperactivity is responsible for resistance to the action of insulin. Indeed, it can even precede the installation of this insulin resistance [7]. Activation of adrenergic receptors, in particular β-adrenergic receptors, has been shown to transform the phenotype of muscle cells into insulin-resistant cells [8].


#### **Figure 1.**

*Schematic representation of the association between sympathic hyperactivity and the different metabolic and cardiovascular pathologies [8]. Sympathetic overactivity is implicated in various symptoms or pathologies such as essential hypertension, obesity, permanent resting tachycardia, hyperlipidemia, type 2 diabetes, sleep apnea.*

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*Type 2 Diabetes and Dysautonomy*

*DOI: http://dx.doi.org/10.5772/intechopen.95043*

b.ANS and insulinosecretion:

• These results provide new information on the pathophysiological mechanisms of insulin resistance, suggesting that sympathetic overactivity may be a predis-

There are hormones that are part of the metabolic extension of the sympathetic while others are the metabolic extension of the parasympathetic. Insulin

The vagal deficiency secondary to T2DM is added to the depletion of the beta cells of the islets of Langerhans in the pancreas, thus exacerbating the insulin

There is a microcirculation within the islets of Langerhans. Arterial blood first passes through "β" cells and "δ" cells (somatostatin) before reaching "α" cells which therefore do not respond directly to hyperglycemia. Hyperglucagonemia is secondary on the one hand to a direct stimulatory sympathetic action on "α" cells; and on the other hand, to a vagal deficiency responsible for the lifting of the inhibition on the "α" cells and a decrease in the stimulation of the "β" cells responsible for a decrease in GABA and molecules contained in the granules

To date, little therapeutic benefit has been gained from this information, since centrally acting sympatho-inhibitory drugs and alpha and beta blockers are used in

Beta blockers are known to make diabetes worse. On the other hand, quite interestingly, drugs having a central sympatho-inhibitory action, such as clonidine and rilmenidine, are neutral or even slightly beneficial in diabetes and the metabolic

Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) can be extremely effective in regulating the autonomic nervous system and blood pressure. At the same time, some studies indicate that serotonin-norepinephrine

These data may also lead to the proposal of sympathetically inhibiting drugs of central action in patients with metabolic syndrome in order to reduce the cardiovascular and metabolic consequences and perhaps even better in the unincorporated phases of the MS hoping to reduce the probability of evolution towards the consti-

The responsibility of sympathetic dysfunction in the genesis or aggravation of

The consequences could vary depending on the genotypic and phenotypic characteristics of individuals and their environment, this encourages us to always

cardiovascular and/or metabolic disorders is currently confirmed.

posing factor for future insulin resistance (**Figure 1**).

is part of the parasympathetic-vagal tendency.

deficiency of type 2 diabetics [14].

c.ANS and hyperglucagonemia:

the treatment of arterial hypertension.

reuptake inhibitors (a SNRI) are even more effective.

(Zinc) [15].

**6. Outlook**

syndrome.

tuted SM.

**7. Conclusion**

*Lifestyle and Epidemiology - The Double Burden of Poverty and Cardiovascular Diseases...*

muscle cells into insulin-resistant cells [8].

C-peptide concentrations).

of this insulin resistance [7]. Activation of adrenergic receptors, in particular β-adrenergic receptors, has been shown to transform the phenotype of

• Variation of adrenaline and noradrenaline may also reduce insulin-induced glucose uptake. The aforementioned metabolic abnormalities are associated with a depletion of capillaries which reduces the supply of nutrients to the muscles which are therefore largely involved in insulin resistance [9, 10].

• In a recent longitudinal study, Flaa A. et al. studied the relationship between sympathetic activity and future insulin resistance in healthy Caucasian subjects with 18 years of follow-up [11]. They found that sympathetic activity was a predictor of insulin resistance as measured by HOMA-IR (Homeostasis model assessement- Insulin resistance: is a method for **assessing** β-cell function and **insulin resistance** (IR) from basal (fasting) glucose and **insulin** or

• In addition, there is a strong inflammatory activity in abdominal obesity with macrophage infiltration of visceral adipose tissue. These macrophages will be responsible for the secretion of pro-inflammatory factors such as interleukin 6 (IL6) or tumor necrosis factor alpha (TNF alpha) [12]. The secretion of these two cytokines by the visceral adipose tissue in obesity may play a specific role in the development of insulin resistance. Indeed, these factors can activate inhibitory pathways of the insulin cascade which will therefore have less effect on sensitive peripheral tissues (skeletal muscle and liver for

example) and therefore induce insulin resistance [13].

*Schematic representation of the association between sympathic hyperactivity and the different metabolic and cardiovascular pathologies [8]. Sympathetic overactivity is implicated in various symptoms or pathologies such as essential hypertension, obesity, permanent resting tachycardia, hyperlipidemia, type 2 diabetes, sleep apnea.*

**220**

**Figure 1.**


There are hormones that are part of the metabolic extension of the sympathetic while others are the metabolic extension of the parasympathetic. Insulin is part of the parasympathetic-vagal tendency.

The vagal deficiency secondary to T2DM is added to the depletion of the beta cells of the islets of Langerhans in the pancreas, thus exacerbating the insulin deficiency of type 2 diabetics [14].

c.ANS and hyperglucagonemia:

There is a microcirculation within the islets of Langerhans. Arterial blood first passes through "β" cells and "δ" cells (somatostatin) before reaching "α" cells which therefore do not respond directly to hyperglycemia. Hyperglucagonemia is secondary on the one hand to a direct stimulatory sympathetic action on "α" cells; and on the other hand, to a vagal deficiency responsible for the lifting of the inhibition on the "α" cells and a decrease in the stimulation of the "β" cells responsible for a decrease in GABA and molecules contained in the granules (Zinc) [15].
