Diagnostic principles:

— Symptoms: abnormal sensation, numbness, burn-ing, tinglburn-ing, spontaneous pain, muscle jerks and cramps, mostly involving feet and calves, persist-ing for several months (worsened or occurrpersist-ing mostly during the night; exercise does not cause or worsen symptoms);

— Signs: reduced muscle power, reduced or absent tendon reflexes (knee, ankle), reduced or absent

vibration, pressure, pain and temperature sensa-tion;

— Peripheral diabetic neuropathy is considered most likely based on the presence of 2 out of the fol-lowing 3 components of the clinical examinations:

symptoms, reduced or absent sensation (touch, vibration, pain, and/or temperature) and/or absent tendon reflexes;

— Nerve conduction studies (electroneurography) may be also necessary to make a definite diagnosis of neuropathy in selected patients;

— Evaluation of corneal nerve fiber density by confo-cal microscopy may also used for the diagnosis of thin fiber neuropathy.

Autonomic neuropathy

Autonomic nervous system function is evaluated indi-rectly based on the analysis of effector organ function in response to specific stimuli. Due to a non-specific nature of clinical symptoms and signs, the diagnosis should be supported by specific tests. It is necessary to exclude other disease of the effector organ, take into account other organic and functional abnormalities, and exclude an effect of the treatment used.

1. Cardiovascular system:

Autonomic neuropathy may be suspected when the results of two of the tests listed below are positive, and it may be diagnosed when the results of three tests are positive:

— Tests evaluating the parasympathetic nervous sys-tem:

• Heart rate change during deep breathing,

• Heart rate change in response to the upright posture,

• Heart rate change in response to the Valsalva manoeuver;

— Tests evaluating the sympathetic nervous system:

• Systolic blood pressure change in response to the upright posture,

• Diastolic blood pressure change;

— Other tests:

• Evaluation of heart rate variability during a 5-min ute resting ECG recording or 24-hour Holter monitoring.

2. Gastrointestinal system:

— Gastric dysfunction — barium radiography, ra-dioisotope scanning, electrogastrography (EGG), insulin challenge test, manometry;

— Small intestine dysfunction — no specific diagnos-tic tests, manometry to identify abnormal intesti-nal motility;

20. Prevention, diagnosis, and management of diabetic neuropathy

— Large intestine dysfunction — barium follow--through, manometry;

— Gall bladder dysfunction — functional ultrasound.

3. Genitourinary system

— Bladder dysfunction — cystometry (evaluation of bladder volume before and after micturition);

bladder sphincter electromyography, uroflow-metry and urethral pressure profile;

— Erectile dysfunction — questionnaires [Interna-tional Index of Erectile Function (IIEF) and its ab-breviated 5-item version (IIEF-5)], vascular studies (Doppler ultrasound), cavernosography, functional testing (nocturnal penile tumescence tests).

4. Dysfunctional sudomotor function — simple perspi-ration tests, testing using sophisticated equipment (evaluation of sudomotor function using Sudoscan).

5. Pupil dysfunction — pupillometry.

V. Management

1. Causal treatment of diabetic neuropathy:

— Optimal metabolic control of diabetes, with par-ticular attention to avoiding hypoglycemia;

— Blood pressure and lipid control, smoking cessa-tion, avoiding alcohol use;

— Drug therapy: alpha-lipoic acid, benfotiamine, ACEI.

2. Symptomatic treatment of somatic diabetic neuropa-thy:

— Pregabalin;

— Gabapentin;

— Carbamazepine;

— Tricyclic antidepressants (amitryptiline);

— Serotonin and norepinephrine reuptake inhibitors:

duloxetine, venlafaxine;

— Tramadol and opioid analgesics;

— Topical agents: capsaicin, nitroglycerin;

— Non-steroidal anti-inflammatory drugs and acet-aminophen;

— Non-drug treatments: physical therapy, acupuncture.

3. Symptomatic treatment of autonomic diabetic neu-ropathy:

— Cardiovascular system:

• Cardiac arrhythmia — controlled graded exer-cise, ACEI, beta-blockers (without intrinsic sym-pathomimetic activity),

• Orthostatic hypotension — compression cloth-ing to increase venous return (e.g. compression stockings), mineralocorticoids (fludrocortisone);

— Gastrointestinal system:

• Gastroparesis — diet modification (frequent small meals, semiliquid or liquid diet in severe dysfunction), prokinetic drugs (domperidone, cisapride, erythromycin), acid reducers (H2 re-ceptor antagonists, proton pump inhibitors), antiemetics, nasoduodenal tube, surgical treat-ment, gastric electrical stimulation therapy,

• Intestinal dysfunction — diet modifications (consider gluten- or lactose-free diet), chole-styramine, clonidine, octreotide, antidiarrheals (loperamide), pancreatic enzymes, antibiotics;

— Genitourinary system:

• Bladder dysfunction — avoiding urinary reten-tion, regular micturireten-tion, anticholinergic drugs (bethanechol), external bladder massage be-fore micturition, bladder catheterization (tem-porary or permanent);

• Erectile dysfunction — phosphodiesterase type 5 inhibitors (sildenafil, vardenafil, tadalafil), central erection stimulants (apomorphine), vacuum penile pump devices, intracavernosal prostaglandin E1 injections, penile prostheses,

• Female sexual dysfunction — mechanical stimu-lating devices, topic moisturizers;

— Dysfunctional perspiration:

• Botulinum toxin, vasodilators, moisturizing creams.

21. Diagnosis and management of diabetic foot syndrome

Multidisciplinary (reference) diabetes foot clinics should be created in regional (voivodship, university) dia-betologic centers, and basic diabetes foot clinics should be created at diabetology clinics to continue care initia-ted in a multidisciplinary clinic.

Organizational structure and responsibilities in accor-dance with the Diabetes Foot Outpatient Treatment Sup-port Program by the Ministry of Health (http://www.

mz.gov.pl/zdrowie-i-profilaktyka/programy-zdrowotne/

wykaz-programow/program-wsparcia-ambulatoryjnego--leczenia-zespolu-stopy-cukrzycowej/).

I. Definition. Diabetic foot is a foot infection and/or ulceration and/or deep tissue (e.g., bone) destruc-tion caused by a varying degree of damage to pe-ripheral nerves and/or pedal vessels. Implied in the definition is further categorization of this condition into neuropathic, vascular, and mixed diabetic foot.

Investigations in the diabetic foot syndrome in-clude evaluation for peripheral polyneuropathy, leg isch-emia, deformations, and other risk factors for foot dam-age. It is recommended that physicians directly inspect patients’ feet during each visit.

II. Risk factors for diabetic foot syndrome:

— Peripheral neuropathy and/or vascular ischemic changes within lower limbs;

— Low patient knowledge;

— Long-lasting, poorly controlled diabetes;

— Inappropriate foot hygiene;

— Inappropriate footwear;

— Presence of corns and calluses;

— Foot deformations;

— Increased sole pressure.

Factors contributing to disease recurrences:

— Previous amputations;

— History of ulcerations;

— Neuropathic arthropathy (Charcot foot).

III. Clinical classification of diabetic foot syndrome The Perfusion, Extent, Depth, Infection, Sensation classification (PEDIS) is recommended, taking into ac-count both infections and the ischemic factor (Table 21.1).

IV. Prevention:

— Systematic foot examination; yearly evaluation for abnormal sensation (physical examination) and ischemia [assessment of dorsalis pedis and poste-rior tibial artery pulses; consider measurement of the ankle-brachial index (ABI)] in all patients;

— Regular podiatric care (removal of calluses and hyperkeratosis);

— Use of recommended footwear, orthopedic in-soles, and socks;

— Systematic patient education regarding foot hy-giene and consequences of absent protective pain sensation;

— Education and systematic treatment of other risk factors such as smoking, overweight, hyperten-sion, and dyslipidemia, along with good metabolic control of diabetes;

— Early identification and treatment of limb isch-emia.

V. Infections in the course of diabetic foot

1. The diagnosis is mostly based on the clinical picture (the presence of at least two typical symptoms and signs of infection) and not only microbiological test-ing results.

2. Evaluation of the severity of infection (see the PEDIS classification).

3. Microbiological testing (including antibiotic suscepti-bility) and its interpretation (colonization, contamina-tion, infection):

— It is recommended to collect tissue samples, as-pirate, or scrapings for culture following wound debridement;

— Testing is recommended if a clinically infected wound is present;

— When evaluating infection, interpretation of the culture result is difficult, and it is recommended that this evaluation is primarily based on the clini-cal picture;

— Blood culture is recommended only in case of systemic evidence of an infection (grade 4 by the PEDIS classification);

— If there is no or mild clinical wound infection, and no antibiotics were used previously, it is accept-able not to perform culture.

4. Evaluation for osteomyelitis (should be performed in all cases of an infected ulceration, particularly if chronic):

Table 21.1. The PEDIS classification

Degree of severity

1 2 3 4

Perfusion Normal: palpable pedal pulses

or ABI > 0.9 Clinical evidence of impaired perfusion: intermittent

Extent Ulceration size in square centimeters

Depth Superficial ulceration within

the dermis Ulceration may involve all soft

tissues Penetration to bone:

osteo lysis in X-ray or posi-tive probe-to-bone test Increase of

infection No clinical evidence

of infection Infection involving the skin and subcutaneous tissue, inflam-mation within 2 cm from the

margin of the ulceration

Locally severe inflamma-tion, beyond 2 cm from the margin of the ulcer-ation, but no evidence of

a systemic infection

Evidence of a systemic infection: fever > 38°C,

heart rate > 90 bpm, breath rate > 20/min, leukocyte count > 12,000/mm³

or < 4000/mm³ Sensation No evidence of sensory

neuro pathy in basic tests (using a monofilament and

tuning forks or Neurotip)

Sensory neuropathy present

ABI — ankle-brachial index; TcpO2 — transcutaneous oxygen pressure

— Probe-to-bone test;

— Foot radiography (every 3–6 weeks);

— Magnetic resonance imaging (indicated);

— Bone biopsy or bone sample culture (indicated);

— Laboratory tests — erythrocyte sedimentation rate

> 70 mm at one hour indicates an increased likeli-hood of osteomyelitis, and lower rates indicate a lower risk. Evaluation of C-reactive protein (CRP) level and leukocyte count may also be use-ful. A possibility of bone inflammation cannot be definitely excluded based on normal laboratory test results.

5. The nature of the wound (dry or exudative) is the primary criterion for the choice of dressing.