Diabetic Neuropathy

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Anwar Wardy W
Departemen Neurologi FKK-UMJ

anwarwardy@gmail.com
anwar wardy@yahoo.co.id

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Diabetic Neuropathy
About 60-70% of people with diabetes
have mild to severe forms of nervous
system damage, including:
Impaired sensation or pain in the feet or
hands
Slowed digestion of food in the stomach
Carpal tunnel syndrome
Other nerve problems
More than 60% of nontraumatic lower-
limb amputations in the United States
occur among people with diabetes.



Risk Factors
Glucose control
Duration of diabetes
Damage to blood vessels
Mechanical injury to nerves
Autoimmune factors
Genetic susceptibility
Lifestyle factors
Smoking
Diet

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Pathogenesis of Diabetic
Neuropathy
Metabolic factors
High blood glucose
Advanced glycation end products
Sorbitol
Abnormal blood fat levels
Ischemia
Nerve fiber repair mechanisms
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Diagnostic Tests
Assess symptoms - muscle weakness, muscle
cramps, prickling, numbness or pain, vomiting,
diarrhea, poor bladder control and sexual
dysfunction
Comprehensive foot exam
Skin sensation and skin integrity
Quantitative Sensory Testing (QST)
X-ray
Nerve conduction studies
Electromyographic examination (EMG)
Ultrasound
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Classification of Diabetic Neuropathy
Symmetric polyneuropathy
Autonomic neuropathy
Polyradiculopathy
Mononeuropathy
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Classification Of DN
(Dyck 1993)
Polyneuropathy Sensory
Focal & Multifocal ..Motor

Distal Sensory DN
The commonest type of DN (80%)
Symmetric & distal distribution
Mainly sensory & painless:
Numbness, tingling, tightness
walking on cotton-wooletc.
Painful in 10%:
Burningachingsharp quality
Distal Sensory DN

Risk factors for developing
distal DN :
Age
Duration of DM
Diabetic control
Male & height (DCCT 90)

Distal Sensory DN
Complications

Diabetic Foot
Neurogenic Arthropathy
Autonomic Neuropathy

Diabetic Foot
Clinical Features

Numbness, hair loss, dry skin
Painless ulcers
Osteomyelitis, cellulitis, &
abcess
Gangrene & Amputation
Diabetic Foot
Pathophysiology

Sensory loss & autonomic changes
Small vessel disease-Ischemia
Trauma (foreign body)
Infection
Neurogenic Arthropathy
Severe loss of pain sensation &
painless ulcers
Enhanced by trauma & abnormal
posture
XR : painless fractures-
disorganization of ANKLES
Autonomic Neuropathy

Correlates with severity of distal
sensory DN
Associated with poor prognosis
50 % reduction of 5 yrs survival
Incraesed sudden death & silent MI

Autonomic Neuropathy
Clinical Manifestations
Postural hypotension:
BP drop >20 mmHg
Bladder atony (Overflow
incontinence)
Gastro-intestinal paresis
(Fullness & diabetic diarrhea)
Impotence
Autonomic Neuropathy
..Clinical Manifestations
Heat intolerance
Unawareness of hypoglycemia
Impaired hypoglycemia counter-
regulation
Focal & Multifocal neuropathies
Acute or Subacute onset
Predominantly Motor
Spontaneous recovery
(Improve control)

Focal & Multifocal neuropathies
Cranial Neuropathies
Entrapment Neuropathies
(Carpal Tunnel Syndrome)
Diabetic amyotrophy
DN Pathogenesis
Multifactorial

Metabolic
Vascular
Others
DN Pathogenesis
Metabolic Hypothesis
Sorbitol accumulation
Non-enzymatic glycation
Oxidative stress
Others
DN Pathogenesis
Vascular Hypothesis
Early endoneural hypoxia
Nerve hypoxia Metabolic changes
& Microangiopathy & Ischemia
Symmetric Polyneuropathy
Most common form of diabetic neuropathy
Affects distal lower extremities and hands
(stocking-glove sensory loss)
Symptoms/Signs
Pain
Paresthesia/dysesthesia
Loss of vibratory sensation

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Complications of Polyneuropathy
Ulcers
Charcot arthropathy
Dislocation and stress fractures
Amputation - Risk factors include:
Peripheral neuropathy with loss of protective
sensation
Altered biomechanics (with neuropathy)
Evidence of increased pressure (callus)
Peripheral vascular disease
History of ulcers or amputation
Severe nail pathology


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Treatment of Symmetric
Polyneuropathy
Glucose control
Pain control
Tricyclic antidepressants
Topical creams
Anticonvulsants
Foot care

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Autonomic neuropathy
Affects the autonomic nerves controlling
internal organs
Peripheral
Genitourinary
Gastrointestinal
Cardiovascular
Is classified as clinical or subclinical based on
the presence or absence of symptoms
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Peripheral Autonomic Dysfunction
Contributes to the following symptoms/signs:
Neuropathic arthropathy (Charcot foot)
Aching, pulsation, tightness, cramping, dry skin, pruritus,
edema, sweating abnormalities
Weakening of the bones in the foot leading to fractures
Testing
Direct microelectrode recording of postglanglionic C fibers
Galvanic skin responses
Measurement of vascular responses



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Peripheral Autonomic Dysfunction,
cont.
Treatment
Foot care/elevate feet when sitting
Eliminate aggravating drugs
Reduce edema
midodrine
diuretics
Support stockings
Screen for CVD
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Genitourinary Autonomic
Neuropathy
Sign/Symptom Treatment
Bladder dysfunction Voluntary urination;
catheterization
Retrograde ejaculation Antihistamine
Erectile dysfunction Sildenafil, tadalafil
Dyspareunia Lubricants; estrogen
creams
Gastrointestinal Autonomic
Neuropathy
Symptoms/Signs
Gastroparesis resulting in anorexia, nausea, vomiting,
and early satiety
Diabetic enteropathy resulting in diarrhea and
constipation
Treatment
Other causes of gastroparesis or enteropathy should
first be ruled out
Gastroparesis - Small, frequent meals, metoclopramide,
erythromycin
Enteropathy - loperamide, antibiotics, stool softeners or
dietary fiber
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Cardiovascular Autonomic
Neuropathy
Symptoms/Signs
Exercise intolerance
Postural hypotension
Treatment
Discontinue aggravating drugs
Change posture (make postural changes slowly,
elevate bed)
Increase plasma volume
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Polyradiculopathy
Lumbar polyradiculopathy (diabetic
amyotrophy)
Thigh pain followed by muscle weakness and
atrophy
Thoracic polyradiculopathy
Severe pain on one or both sides of the abdomen,
possibly in a band-like pattern
Diabetic neuropathic cachexia
Polyradiculopathy + peripheral neuropathy
Associated with weight loss and depression


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Polyradiculopathy, cont.
Polyradiculopathies are diagnosed by
electromyographic (EMG) studies
Treatment
Foot care
Glucose control
Pain control

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Mononeuropathy
Peripheral mononeuropathy
Single nerve damage due to compression or
ischemia
Occurs in wrist (carpal tunnel syndrome), elbow, or
foot (unilateral foot drop)
Symptoms/Signs
numbness
edema
pain
prickling
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Mononeuropathy, cont.
Cranial mononeuropathy
Affects the 12 pairs of nerves that are connected
with the brain and control sight, eye movement,
hearing, and taste
Symptoms/Signs
unilateral pain near the affected eye
paralysis of the eye muscle
double vision
Mononeuropathy multiplex


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Mononeuropathy, cont.
Treatment
Foot care
Glucose control
Pain control



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Other Treatment Options
Aldose reductase inhibitors
ACE inhibitors
Weight control
Exercise

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Complications:
Short term Complications: (metabolic)
Hypoglycemia
Diabetic Ketoacidosis
Non Ketotic hyperosmolar diabetic coma
Lactic acidosis
Long term Complications:(Angiopathy)
Microngiopathy - Retinopathy, Nephropathy,
Neurophathy, dermatopathy.
Macroangiopathy Atherosclerosis.

Neuropathy
Sensory Motor (myelin)
Peripheral Neuropathy
Bilateral, symmetric
Progressive, irreversible
Paraesthesia, pain, muscle
atrophy
Visceral neuropathy
Cranial nerve diplopia, Bell
palsy
GIT- constipation, diarrhoea
CVS orthostatic hypotension
Diabetic Microangiopathy
Normal
Diabetic
Glucose
Glycosylation
BM damage leak
AGE deposition
AGE = advanced glication
end products
Narrow lumen
Ischemic Organ damage...
Chronic Polyneuropathy
Claw foot Dermopathy & Neuropathy
Diabetic Amyotrophy
Painful muscle wasting
Neuropathic ulcer
Etiology:
peripheral sensory
neuropathy, Trauma &
deformity.
Factors:
Ischemia, callus formation,
and edema.
Neuropathic ulcers
FEATURES:
Painless, surrounded by callus
At pressure points.
associated with good foot pulses
May not be associated with gangrene
Essentials of Foot Care
Examination
Annually for all patients
Patients with neuropathy - visual inspection of feet at
every visit with a health care professional
Advise patients to:
Use lotion to prevent dryness and cracking
File calluses with a pumice stone
Cut toenails weekly or as needed
Always wear socks and well-fitting shoes
Notify their health care provider immediately if any foot
problems occur
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Retinopathy
Non Proliferative
Microaneurysms,
Dot- blot hemorrhages
Hard and soft exudates
Cotton wool infarcts
Macular edema.
Proliferative.
Neovascularization
Large hemorrhages
Retinal detachment.
Normal Retina
Retinal H.ages
Neovascularization
Large hemorrhages
Retinal detachment.
Retinal detachment
Diabetic Retinopathy
Cataract
Atherosclerosis:
Diabetic Gangrene
Macrosomia = large birth weight
more than 3.5kg (7.7 lb)
suspect mother with DM
Acanthosis Nigricans
Nephropathy
Diabetic Nephropathy

Microangiopathy, atherosclerosis &
infections:
Diffuse or nodular diabetic
glomerulosclerosis (Kimmelstiel
Wilson Sy)
Renal arteriolosclerosis &
atherosclerosis
Necrotizing renal papillitis.
Pyelonephritis.
End stage kidney.
Infections in Diabetes:
Decreased metabolism low immunity.
Decreased function of lymphocytes & neutrophils
glycosylation/ glycation.
Glycosylation of immune mediators. Ab ( glycation of
proteins)
Capillary thickening impaired inflammation.
Ischemia & infarctions.
Increased glucose (alone is not the cause*)
Diabetes State of immunosuppression.
References
American Diabetes Association: Preventive Foot Care in Diabetes
(Position Statement). Diabetes Care 27 (Suppl.1): S63-S64, 2004

Feldman, EL: Classification of diabetic neuropathy. In UpToDate.
Wellesley, MA, UpToDate, 2003

National Diabetes Information Clearinghouse. Diabetic Neuropathies:
The Nerve Damage of Diabetes. Bethesda, MD: National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (NIH), DHHS; 2002

National Diabetes Information Clearinghouse. Prevent Diabetes
Problems: Keep Your Feet and Skin Healthy. Bethesda, MD: National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health (NIH), DHHS; 2003








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References, cont.
Feldman, EL: Pathogenesis and prevention of diabetic
polyneuropathy. In UpToDate. Wellesley, MA, UpToDate, 2003.

Feldman, EL, McCulloch, DK: Treatment of diabetic neuropathy. In
UpToDate. Wellesley, MA, UpToDate, 2003.

Stevens, MJ: Diabetic autonomic neuropathy. In UpToDate.
Wellesley, MA, UpToDate, 2003.

Feldman, EL: Clinical manifestations and diagnosis of diabetic
polyneuropathy. In UpToDate. Wellesley, MA, UpToDate, 2003.




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