Diabetic foot Dr. Cornelia ZETUBucharest, 2013

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).Definition

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 socio-economic 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 disabilitiesEpidemiology

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 diabetesDiabetic 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

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.Diabetic Neuropathy- classification-

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 (1)

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 (2)

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 (3)

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 (4)

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.Somatic neuropathy (5)

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 nerveSCREENING / DIAGNOSTIC FOR SOMATIC NEUROPATHY

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 episodesAutonomic neuropathy (1)

2. extracardiovascular form Gastrointestinal formThe 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 (2)

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 (3)

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.Autonomic neuropathy (4)

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 acid or N-acetyl-carnitine may be 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 acid, natural antioxidant role in reducing oxidative stress, inhibit oxid-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 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- TREATMENT-

Features 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 self-catheterization.Diabetic Neuropathy- TREATMENT-

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 non-enzymatic 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

used 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- Classification Leriche-Fontaine-

Symptoms 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-Symptoms / Clinical exam-

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-Paraclinic Diagnostic -

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; Chronic lower limb peripheral arterial disease-TREATAMENT-

Therapeutic education for diabetic foottherapeutic

Differential diagnosis for ulcers etiology in diabetes

Neuropathic ulcerationIschemic ulcerationLeziuni ntinse dar nedureroaseLeziuni variabile ca extensie, dureroaseLeziuni tip umed sa uscatLeziuni tip uscat sau umedTegumente cianotice, cu temperatur normal sau crescutTegumente palide sau cianotice cu temperatur sczutDeformri ale piciorului i degetelor cu zone hipertrofice, asociate cu atrofia muchilor interosoiLipsa deformrilor osoase, unghii groase, picioare efilateHipoestezie tactil, algic, vibratorieSensibilitate normal sau diminuatROT absenteROT pot fi normaleTurgescen venoas, edemePiele uscatPuls arterial prezentPuls arterial absentTAS glezn/bra > 0,5TAS glezn/bra < 0,5Fotopletismografie: amplitudine normal sau crescutFotopletismografie: amplitudine sczut sau absentPO2 transcutanat > 70 mmHgPO2 transcutanat pe dosul piciorului < 70 mmHg

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