Mamdouh El-Nahas

Professor od Endocrinology and Diabetes

Mansoura University

1. Causes substantial morbidity and increased mortality,particularly if cardiovascular autonomic neuropathy(CAN) is present.

2. Painful DPN: A number of treatment options exist

3. Painless DPN: >80% of amputations follow a foot ulcer orinjury, early recognition of at-risk individuals, provisionof education, and appropriate foot care may result in areduced incidence of ulceration and consequentlyamputation.

4. Autonomic neuropathy may involve every system in thebody

*

*The diabetic neuropathies are heterogeneous with diverse

clinical manifestations.

*Classification: They may be focal or diffuse.

*

*The most prevalent neuropathies are DPN and autonomic

neuropathy.

*Diabetic peripheral neuropathy affects up to 50% of

patients with diabetes (Tesfaye and Selvarajah 2012).

*The prevalence of Cardiovascular Autonomic

Neuropathies in randomly selected cohorts of

asymptomatic individuals with diabetes, ∼20% (Vinik et al

2003).

*Electrophysiological testing or referral to a neurologist is

rarely needed, except in situations where the clinical

features are atypical or the diagnosis is unclear.

Please, Always remember

*

*Tight glycemic control, implemented early in the course of

diabetes, has been shown to effectively prevent or delay

the development of DPN and CAN in patients with type 1

diabetes.

*While the evidence is not as strong for type 2 diabetes,

some studies have demonstrated a modest slowing of

progression without reversal of neuronal loss.

*Several observational studies further suggest that

neuropathic symptoms improve not only with optimization

of glycemic control but also with the avoidance of extreme

blood glucose fluctuations.

Treatment based on pathogenetic

mechanisms

* Alpha Lipoic Acid

* Benfotiamine

Aldose reductase inhibtors Toxicity prevent the use of this group.

Epalrestat is approved in Japan for the

treatment of neuropathy.

Inhibitors of glycation Although new drugs that inhibit the formation of

AGEs , no effective treatment modalities against

AGE-induced nerve injury are currently available.

PKC inhibitors Studies revealed the ability of Ruboxistaurin to

reduce visual loss in patients with DR. But, the

benefit of RBX for peripheral neuropathy has not

been successfully demonstrated in Phase III trials.

Gamma linolenic acid No clear evidence. Many double blind trials have

been performed, some of them have proved

statistically significant efficacy, the others have

led to some doubts.

Nerve growth factors Disappointing

Basic fibroblast growth factor Need further evaluation.

*Pharmacological and nonpharmacological for the relief

of specific symptoms related to painful DPN or autonomic

neuropathy are recommended because they can potentially

reduce pain and improve quality of life.

Pharmacological Interventions

1. TCA

2. Gapabentin and pregabalins

3. SNRI e.g. Duloxetine

Pharmacological interventions: Midodrine, 9-α-

fluorohydrocortisone

Nonpharmacological interventions: compressive socks

over the legs.

Pharmacological interventions: Prokinetic agents used

to treat diabetic gastropathy are metoclopramide,

domperidone, erythromycin, and levosulpiride.

Nonpharmacological interventions: patients should be

advised to eat multiple small meals (four to six per day)

and to reduce the fat content of their diet. They should

also restrict their fiber intake to prevent the formation of

bezoars.

*

Pharmacological interventions: phosphodiesterase type 5

inhibitors, intracorporeal or intraurethral prostaglandins

Nonpharmacological interventions: vacuum devices, or

penile prostheses.

*All patients should be screened for diabetic peripheral

neuropathy (DPN) starting at diagnosis of type 2 diabetes

and 5 years after the diagnosis of type 1 diabetes and at

least annually thereafter, using simple clinical tests, such

as a 10-g monofilament. B

*Screening for signs and symptoms (e.g., orthostasis, resting

tachycardia) of cardiovascular autonomic neuropathy (CAN)

should be considered with more advanced disease. E

*Tight glycemic control is the only strategy convincingly

shown to prevent or delay the development of DPN and

CAN in patients with type 1 diabetes A and to slow the

progression of neuropathy in some patients with type 2

diabetes. B

*Assess and treat patients to reduce pain related to DPN Band symptoms of autonomic neuropathy and to improve

quality of life. E