Diabetic foot

Dr. Cornelia ZETU

Bucharest, 2013

Definition
infection, ulceration and / or deep tissue destruction associated
with neurological abnormalities and peripheral vascular disease in
varying degrees to the lower limbs in people with diabetes.
Is a "concept" and not a diagnosis itself, as it involves the
diagnosis and management of each element (diabetic
polyneuropathy, peripheral arterial disease and so on).

Epidemiology
1. Predisposing factors:
Diabetic sensory neuropathy, motor and autonomic
Chronic obliterative arteriopathy of the lower limbs
Reduced joint mobility
Other diabetes complications (infection, etc.).
Delayed diagnosis and specific treatment due to low socioeconomic status and limiting access to medical care (assigned
patient and / or healthcare system).

2. Precipitating factors:
Skin lesions
Trauma (cutting nails incorrectly inappropriate shoes, aggressive
treatment of hyperkeratosis areas, eg.)
Low patient compliance due to physical disabilities

Diabetic Neuropathy
Is defined as "the presence of symptoms and / or signs of peripheral nerve
dysfunction in people with diabetes after other causes have been excluded."
Although it is difficult to determine the prevalence of this complication in diabetic
population, it is generally accepted that is the most common complication
encountered in this population.
Pathogenesis (1)
1. Chronic hyperglycemia causes:
-increased polyol pathway activity with secondary accumulation of sorbitol
(aldozoreductaz mediated) and fructose (sorbitol dehydrogenase mediated) nerve,
leading to disruption of intracellular through an unknown mechanism.
-intraneuronal takeover mioinozitol decrease by inhibiting Na / K of ATP-ase, leading
to Na retention with secondary edema, axoglial disjunction and nerve degeneration.
2. Immune mechanisms:
-are responsible for the clinical signs especially in patients with proximal neuropathy
and those from motor component is present
-have revealed the presence of anti-neuronal antibodies (antigangliozidici-GM1,
antiphospholipid-PLA etc.) in serum of patients with diabetes

Diabetic Neuropathy
Pathogenesis (2)
3. Microvascular insufficiency is secondary alteration of epineurial
and endoneurial function associated with occlusion (increase
free radical production).
4. Deficiency of growth factors:
-deficit neural growth factor (NGF) is involved in the pathogenesis
of neuropathy by inducing functional deficits of short fibers (with a
role in painful and thermal sensitivity)
-deficit neurotropina 3 (3NT) may lead to dysfunction of long
nerve fibers, involved in vibratory and mioartrokinetic sensitivity
5. Reduced production of nitric oxide (NO)

Diabetic Neuropathy
- classification-

Somatic neuropathy
1. acute, "rapidly reversible" hyperglycaemic neuropathy
2. chronic, irreversible
2.1.polineuropatia symmetric 2-forms:
-common, respectively,
-particularly (hiperalgic or with loss of protective sensibility)
2.2. focal and multifocal neuropathies with 2 subformas:
-moneuropatia simplex (cranial and peripheral - carpal tunnel syndrome,
tarsus channel at the elbow, peroneal proximal epiphysis)
-moneuropatia multiplex (proximal motor neuropathy and neuropathic
thoraco-abdominal)
Autonomic neuropathy (autonomic)
1. cardiovascular form
2. form extracardiac: gastrointestinal, bladder, pupil, abnormal sexual
dynamics eg.

Somatic neuropathy (1)

Acute hyperglycaemic neuropathy
Is rare and occurs after periods of poor metabolic control (in metabolic
acidosis) or rapid improvement in glucose to initiate insulin therapy
(neuritis insulin") or sulfonylureas.
Sensory symptoms are transient, typically being diffuse symmetric
polyneuropathy, which resolved spontaneously;
Pathogenesis is given by a transient decrease in nerve conduction
velocity in nerve fibers shorter.
It is more common in males, and can occur at any time during the
development of diabetes type 1 or 2.

Somatic neuropathy (2)

Chronic neuropathy
Somatic sensory symmetric polyneuropathy
1. Common form
Is the most common. Clinical onset is insiduos, deficit is predominantly
sensory, with limited involvement of motor fibers. Accustomed long nerve
fibers are most severely affected, impaired vibratory and mioartrokinetic
sensitivity and reduction / loss of tendon reflexes.
Sensory symptoms:
-starts in the periphery, are variable (numbness, tingling, burning, etc.).
-have a centripetal evolution "in socks" progressing from ankle to calves,
thighs, and rarely to the abdominal region
-upper limbs are more rarely affected
- excessive tenderness is sometimes triggered by minimal stimuli,
commonly unpainless (dysesthesia).
-symptoms get worse at night (due to predominance of parasympathetic
tone, painful perception modulator) and can lead to sleep disorders,
depression.
-may be present in varying degrees to hypotonia muscular and atrophy in
severe cases, sensory ataxia.
-signs of autonomic dysfunction are commonly associated (anhydrosis
distal skin, sweating plot etc.)

Somatic neuropathy (3)

Symmetric somatosensory polyneuropathy
2. Hyperalgic form
Clinically manifested by acute pain, frequent character of "burning"
sensation and perception of pain for commonly unpainless stimuli
(allodynia); often is associated with a rapid and marked weight
loss, insomnia, depression and impotence (in men).
Painful symptoms resolves completely in most cases within 12-24
months, while weight gain.
Nerve biopsy shows axonal regeneration typically anarchic.

Somatic neuropathy (4)

Mononeuropathies focal
Are rare, acute onset, predominantly motor touch, often asymmetrical.
Pathogenesis of vascular ischemia is given.
This type of neuropathy is encountered more frequently in the elderly and in
patients with multiple complications of diabetes.
Spontaneous evolution is favorable, full recovery is in 6-8 weeks, and does
not seem to be influenced by glycemic control.
Cranial nerves are affected predominantly, in order of frequency: oculomotor,
abducens, trochlear and facial.
Peripheral mononeuropathies mainly affects nerves: median, ulnar, radial
and common peroneal.
Carpal tunnel syndrome is 2 times more common in patients with diabetes
than in the general population.

Somatic neuropathy (5)

Proximal motor neuropathy (diabetic amyotrophy)
-Frequent in elderly patients with acute or gradual onset of
neuropathic pain typically accompanied by "weak" muscle
-Symptoms are unilateral or bilateral asymmetric
-Distal symmetric sensory polyneuropathy coexist
-Lumbosacral plexopathy outlined electrophysiological and femoral
nerve.
-Clinic is found "weakness" proximal muscle atrophy associated
with local pain at muscles: quadriceps, ileopsoas, obturator,
adductor.

SCREENING / DIAGNOSTIC FOR SOMATIC NEUROPATHY

It is recommended that screening for diabetic neuropathy to be made:
- annually since diagnosis in type 2 diabetes
- 5 years from the onset of diabetes in type 1.
Most guidelines recommend that screening for neuropathic somatic ways:
a) history (neuropathic symptoms - which can be calculated based on neuropathy symptom score - NSS);
b) clinical examination (on which we can calculate the neuropathy disability score - NDS);
c) use at least two methods of assessment instrument sensitivity (monofilament, tuning fork Riedel-Seiffer and so on).
Positive diagnosis
-signs and symptoms of somato-sensory
-surface sensitivity:
-subjective: paresthesia / disestezii, stinging, tingling, etc..
Objective: hyper / hypo / anesthesia: exaggeration / reduction / lack sensitivity to specific stimuli
hypo / hyper-algezie
allodynia (perception of a stimulus as pain painless)
hiperpatie: hyperesthesia + + allodynia hyperalgesia
Deep sensitivity :mioartrokinetic and vibratory
Sensory ataxia: abnormal balance + difficulty making fine movements + unsteady walking
reduction / abolition of tendon reflexes
reducing vibration sensitivity (predictor of developing ulcers)
Quantitative sensory evaluation methods and neurophysiological investigations
-vibratory perception (Riedel-Seiffer tuning fork, biotensiometru)
-thermal perception (device-type thermR)
-nerve conduction velocity (EMG)
-amplitude and action potential duration of sensory and motor fibers
-study axonal excitability
-exploration morphopathological (biopsy skin / nerve) but benefit / risk ratio disadvantageous
-microelectrodes implanted in nerve

Autonomic neuropathy (1)

Cardiovascular form:
1.occurs most often by altering heart rate and vasomotricitii
2. tachycardia "fixed" rest and Valsalva maneuver, decreased heart rate
variability during sleep, the early clinical signs.
3. orthostatic hypotension (defined as decrease SBP by 20 mmHg / DBP
decreased more than 10 mmHg standing in ortostatism), frequently
symptomatic (dizziness at position changing )
4. perioperative cardiovascular instability increased anesthetic risk due to
altered respiratory response to stimuli like hypoxia, risk of hypothermia.
5. silent myocardial ischemia, myocardial infarction unpainless, sudden
death, arrhythmia (increased QTc interval over 440 ms)
6. circulatory disorders of the extremities (edema)
7. lack of symptoms in hypoglycaemic episodes

Autonomic neuropathy (2)

2. extracardiovascular form
Gastrointestinal form
The most common manifestations are:
-oesophageal motor dysfunction involving: abnormal peristaltic and / or
decrease esophageal sphincter pressure, diagnostic tests: scintigraphy,
oesophageal manometry
-gastroparesis (difficulty exhaust pilorospasm) secondary damage to the
stomach and vagal (glycosylation) smooth muscle at this level; clinical
manifestations include: vomiting, early satiety to postprandial bloating,
difficulty in obtaining a satisfactory metabolic control. Diagnostic tests:
barium X-ray examination, upper gastrointestinal endoscopy (presence of
food in the stomach at 8-12 hours postprandial)
-diarrhea, relatively nonspecific and rarely severe consequence of
autonomous deenervrii bowel intestinal and bacterial overpopulation is
often nocturnal, explosive, has a variable evolution remission and
recurrence. Requires a diagnosis of exclusion (celiac disease, exocrine
pancreas insufficiency etc.)
-constipation is commonly encountered, and may alternate with diarrhea.

Autonomic neuropathy (3)

Genitourinary form
1.neuropathic bladder (diabetic cistopatie) is secondary to sacral nerve
damage;
-patients are usually asymptomatic, but may present clinically urinary
incontinence, urine retention partial / complete;
-possible complications: recurrent urinary infections, hidroureter,
hydronephrosis;
-diagnostic test: cystometric, sphincter electromyogram, uroflometrie,
ultrasound postmicional;
2. erectile dysfunction is progressive loss of stiffness initially, but
maintaining libido.
-pathogenic mechanisms involved are: autonomic neuropathy, angiopathy;
-sexual dysfunction in women is manifested clinically by decreased libido;
-retrograde ejaculation, sympathetic efferent nerve-sparing consequence of
damage.

Autonomic neuropathy (4)

other manifestations:
- Skin microcirculatory dysfunction is reflected by delaying cure of
clinical lesions, abnormal thermoregulation;
- Welders dysfunction is sweating in the upper half and the anhydrosis
in lower body and increased risk of lesions in the legs that can lead to
ulceration;
- Pupillary motor dysfunction with paradoxical miosis in the dark.

Diabetic Neuropathy
- TREATMENT

optimizing glycemic control

Numerous clinical trial sites (DCCT, UKPDS etc.) showed the relationship between the degree of metabolic
imbalance and the development / severity of clinical symptoms of diabetic neuropathy.

nutritional factors
Dietary supplementation with 3.2 g inositol and 500mg of -linolenic
-linolenic acid or N-acetyl-carnitine may be beneficial
beneficial

symptomatic treatment
aldozo-reductase inhibitors, polyol pathway leading to discontinuation were reported numerous side effects or
ineffectiveness clinic is still in clinical trials;
mioinozitol administration at a dose of 800-3200 mg / day for at least 6 months may result in a clinically
significant;
-lipoic
-lipoic acid, natural antioxidant role in reducing oxidative stress, inhibit oxidoxid-nitric synthase (by improving blood
flow endoneural), normalized glutathione levels and prevents activation of transcription factor NF-kB
vasodilator which enhances neuronal hypoxia: 1-adrenergic
1-adrenergic antagonists, ACE inhibitors, synthetic analogues of
prostaglandins.
vitaminoterapia is widely used fat-soluble derivative of vitamin B1, B12 can be administered both orally and
parenterally;
pain: clonidine (at the risk of exacerbation of orthostatic hypotension cooexistente) derived opioids, tricyclic
antidepressants, selective serotonin regaining, anticonvulsants, local applications (capsaicin, lidocaine,
isosorbit-dinitrate), anticonvulsants (gabapentin, pregabalin, carbamazepine and so on).

Diabetic Neuropathy
- TREATMENTFeatures of autonomic neuropathy treatment
- For orthostatic hypotension is recommended primarily nonpharmacological
measures (elestic stockings legs, physical activity), and in symptomatic
cases, administration of short-acting vasoconstictoare or cortisone
(preferably type fludrocortizon)
- In symptomatic tachycardias: may be given cardioselective -blockers
- In gastroparesis: prokinetic treatment is indicated (eg, metoclopramide),
macrolides (eg, erythromycin), and in severe cases can practice
jejunostomia.
- Constipation can be treated with increased intake of fiber in the diet,
prokinetic, osmotic laxatives (eg Lactulose).
- Cistopatia diabetes can be treated parasimpaticomimetic (distigmin,
carbacol), 1-adrenergic blockers, and severe intermittent selfcatheterization.

Chronic lower limb peripheral arterial disease

In patients with diabetes clinical lesion location and great vessels are the same as in

atherosclerotic lesions.
The peculiarity lies in the appearance of early and extend higher than the general
population due to the presence of several vascular risk factors (especially type 2
diabetes) dyslipidemia, obesity, hypertension and hyperinsulinism. In addition, an
impairment coexist supporting tissue around vessel secondary enzymatic and nonenzymatic glycosylation of collagen.
In patients with diabetes are two types of pathological lesions encountered:
-medial sclerosis (mediocalcoza Monkenberg), often associated with autonomic
neuropathy, is calcification of the media tunica and leads to stiffness without vascular
lumen narrowing, so that does not cause ischemia, but interferes with the measurement
of blood pressure and induce false appearance of the index ankle/ arm.
-atherosclerosis, atheromatous plate.
Mechanisms involved in the pathogenesis of vascular disease are:
-lipoprotein abnormalities: presence of small dense LDL, low HDL;
-stimulation of protein glycosylation causing platelet aggregation and migration of
monocytes transendoteliale, accumulation of lipoproteins in the extracellular matrix,
formation of advanced glycation end products (AGE);
-endothelial dysfunction by activating protein kinase C in endothelin-dependent
vasodilatation reduction;
-abnormalities in reheological, haemostasis, coagulation and fibrinolysis;
-albuminuria.

Chronic lower limb peripheral arterial disease

- Classification Leriche-Fontaineused for staging arterial leg can be imprecise because symptoms may be
absent as a result of association with diabetic neuropathy.
Stage 1 - Lack of clinical symptoms, chronic ischemia as detected by
laboratory investigations;
Stage 2 - intermittent claudication;
Stage 2a - intermittent claudication walk away greater than 200 m;
Stage 2b - intermittent claudication distance walk less than 200 m;
Stage 3 - Pain at rest;
Stage 4 - Trophic disorders - ulcer / gangrene.

Chronic lower limb peripheral arterial disease

-Symptoms / Clinical examSymptoms may begin as numbness, feeling cold / hot, may occur after
intermittent pain (claudication effort) ; pain at rest and spontaneous sudden.
On examination it is found:
-trophic skin disorders (skin glossy, thin);
-decreased subcutaneous tissue;
-reduced hairiness plot;
-nail bed changes (bold nails, brittle, cracked, ulcers);
-skin "cold";
-peripheral pulse decreased / absent;
-ischemic ulcers can sometimes be the first sign of this damage: frequently at
your fingertips and over the projections bone is surrounded by callus is well
defined.

Chronic lower limb peripheral arterial disease

-Paraclinic Diagnostic Noninvasive investigations:
-pressure index ankle / arm (Winsor index), calculated by dividing the leg
artery systolic brachial pressure (measured bilateral arm pressure and is
used for calculating the highest value) is most widely used in practice;
normal values are 0.9 to 1,
a value below 0.6 is the criterion for defining critical ischemia.
a higher value of 1.3 is typical for the presence of medial sclerosis;
-determination of transcutaneous partial pressure of oxygen: normal values
being above 60 mmHg is predictive method for identifying patients at high
risk of ulceration;
-echo-Doppler examination.

Invasive investigations:
-arteriography with or without magnetic resonance imaging, is the most
accurate to determine the location and extent of lesions and to determine
whether is necessary vascular reconstruction.

Chronic lower limb peripheral arterial disease

-TREATAMENT-

education and proper protective footwear;

control of vascular risk factors: smoking, dyslipidemia, hypertension, metabolic

imbalance;
running programs in patients with claudication, adapted to coexisting

comorbidities; contraindicated in the presence of ulceration or gangrene;

usually recommended brisk walk up to pain, the pain is in remission after at
least three sessions walking per week , lasting 30-60 minutes;
use of vasodilators is controversial due to the phenomenon of vascular

"robbery";
Agents hemoreologici (pentoxifylline, citostazolul, acetylsalicylic acid): relatively

recent studies have shown that sulodexidul (trade name Vessel Due F) has a
positive effect by stimulating fibrinolysis and inhibition of thrombogenesis;

arterial reconstruction - bypass or percutaneous transluminal angioplasty highly recommended for symptomatic patients (disabling intermittent
claudication, rest and night pain) in critical limb ischemia and ulceration train
legs;

local treatment of the wound and possibly antibiotics in the presence of

ulceration;

Therapeutic education for diabetic foot

therapeutic

Differential diagnosis for ulcers etiology in diabetes

Neuropathic ulceration

Ischemic ulceration

Leziuni ntinse dar nedureroase

Leziuni variabile ca extensie, dureroase

Leziuni tip umed sa uscat

Leziuni tip uscat sau umed

Tegumente cianotice, cu temperatur normal sau

crescut

Tegumente palide sau cianotice cu temperatur

sczut

Deformri ale piciorului i degetelor cu zone

hipertrofice, asociate cu atrofia mu chilor
interosoi

Lipsa deformrilor osoase, unghii groase, picioare

efilate

Hipoestezie tactil, algic, vibratorie

Sensibilitate normal sau diminuat

ROT absente

ROT pot fi normale

Turgescen venoas, edeme

Piele uscat

Puls arterial prezent

Puls arterial absent

TAS glezn/bra > 0,5

TAS glezn/bra < 0,5

Fotopletismografie:
crescut

amplitudine

PO2 transcutanat > 70 mmHg

normal

sau

Fotopletismografie:
absent

amplitudine

sczut

sau

PO2 transcutanat pe dosul piciorului < 70 mmHg