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Diabetes and polyneuropathy of the lower limbs in the perspective of diabetologists
(Portuguese PDF version)

Helena Schmid¹, Cristina Neumann², Laura Brugnara³

1. Physician, Division of Endocrinology and Center for Diabetes of Santa Casa de Porto Alegre. Member of the Brazilian Society of Endocrinology, Brazilian Society of Diabetes, and American Diabetes Association and Diabetic Neuropathy Study Group of the EASD.
2. Physician, Division of Endocrinology and Center for Diabetes of Santa Casa de Porto Alegre. Member of the Brazilian Society of Endocrinology, Brazilian Society of Diabetes, and American Diabetes Association.
3. Physician, Division of Endocrinology and Center for Diabetes of Santa Casa de Porto Alegre. Member of the Brazilian Society of Endocrinology.

Correspondence:
Dra. Helena Schmid
Rua Felipe Neri, 296/301
CEP 90440-150 - Porto Alegre - RS
Tel.: +55 51 3330 3075
E-mail: hschmid@terra.com.br

J Vasc Br 2003;2(1):37-48

INTRODUCTION

Of all severe and costly complications that affect diabetes mellitus (DM) patients, foot ulcers and amputations of lower extremities are the major ones. Over 70% of these amputations are related to DM, and in some geographic regions, rates of approximately 90% have been described. According to Levin¹ and to a North-American publication on disease control,² foot disorders account for 20% of hospital admissions of individuals with DM. In comparison with the nondiabetic, these individuals have an increased risk of lower limb amputation estimated at 15 to 40%.³ In Rio de Janeiro, this prevalence is higher.⁴ In 80% of diabetic patients, polyneuropathy is the cause of foot ulcers,⁵ often associated with vascular disease.

For diabetologists, both vascular and neurological complications of diabetes mellitus result from the excessive uptake of glucose by cells of the neuronal, endothelial and mesangial tissues, where glucose transport is controlled by carriers that do not respond to total or relative insulin shortage with the reduction of intracellular glucose levels. Several of these tissues are susceptible to earlier aging and/or to pathognomic manifestations of microvascular complications in response to inappropriate metabolic control, high arterial blood pressure and genetic factors, as we have found and as reported in several other studies.^6-9 Some evidence shows that diabetic patients should be diagnosed as soon as possible and told to control their blood sugar levels for as long as possible, in order to prevent such complications. Given these aspects, we will review some basic concepts for understanding and preventing complications, especially those that involve the lower extremities in this clinical syndrome.

DEFINITION, CLASSIFICATION AND DIAGNOSIS OF DM

Diabetes mellitus is a term used to describe a clinical syndrome in which there are disorders in the metabolism of carbohydrates, lipids and proteins, caused by total or relative insulin deficiency, which leads to microvascular, macrovascular and neuropathic complications in the long run.

In 1979, the National Diabetes Data Group established criteria for the diagnosis of diabetes mellitus to be adopted by the United States. DM was then categorized into two major groups: insulin-dependent or type I diabetes mellitus and noninsulin-dependent or type II diabetes mellitus. Aside from these two groups, the classification also included secondary DM and gestational DM. As new evidence elucidated the etiology and pathogenesis of diabetes mellitus, this classification became inefficient.¹⁰

In 1997,¹¹ the committee of ADA experts recommended a new classification, supported by the World Health Organization (WHO). The terms insulin-dependent and noninsulin-dependent were abolished, and the terms type 1 and type 2 were maintained (now in Arabic numerals).

DM type 1 characterizes the disease in which beta cells of the pancreas are destroyed, and in which severe insulin deficiency is present. In this type, 95% of the cases are autoimmune and 55% are idiopathic. Patients usually have a propensity for ketoacidosis and require insulin treatment. DM type 2 is the most prevalent form (90%) and is a heterogeneous disease that is frequently related to problems with insulin activity and secondarily to cell dysfunction. The rare cases of DM caused by monogenic defects, regarding insulin action and function of cells, and those cases originating from primary pancreatic endocrine disease, as well as drug-induced DM, were classified as "other specific types." Gestational DM is a separate group.

A pathognomic complication of DM, such as retinopathy, has been used to characterize the cutoff point that defines the presence of DM when measuring serum glucose levels. By way of several studies that correlated this complication with fasting sugar levels, the American Diabetes Association established that a patient can be considered to have DM when his/her serum glucose after a 12-to-16-hour fasting is greater than or equal to 126 mg%. According to WHO, patients submitted to a tolerance test with 75 g of oral glucose whose results are greater than or equal to 200 mg/dl can also be considered to have DM.¹²

As the incidence and prevalence of DM type 2 has been increasing all over the world, it has become a public health problem. The disease becomes more severe as it may go unnoticed (due to the absence of symptoms), and may expose individuals to the risk of chronic complications before diagnosis. These complications may be macrovascular (vascular occlusion due to atherosclerosis of the heart, lower limbs, and central nervous system), microvascular (especially in the retina and kidneys) and neuropathic.

PREVENTION OF CHRONIC DM COMPLICATIONS

Given the possibility that individuals with DM remain undiagnosed for a long time and are therefore exposed to a metabolic environment that predisposes to chronic complications, the screening of diabetes mellitus is essential in populations at risk. Some estimates suggest that diabetes mellitus type 2 does not produce symptoms in 35 to 40% of the patients, and that this presentation of DM usually persists for four to seven years before the disease is clinically diagnosed.¹³

The primary therapeutic objectives for the treatment of diabetes mellitus type 2 are to guarantee that the patient's quality of life will be minimally impaired, including the prevention of acute complications, symptoms of hyperglycemia, adverse drug effects, excessive cardiovascular morbidity and mortality, blindness, nephropathy and lower limb complications that characterize the diabetic foot and result in amputations.¹⁴

Two studies (UKPDS and Kumamoto) properly delineated and conducted showed the effects of the reduction of sugar levels on chronic complications in patients with DM type 2; another study, with similar characteristics, revealed the same effects on the progression of complications in patients with DM type 1.^15-17

Diabetologists recommend that patients recently diagnosed with DM be intensively treated from the moment of diagnosis, with the aim of obtaining normal levels of fasting sugar levels lower than 140 mg% two hours postprandially. Also, arterial blood pressure lower than 130/80 mmHg, triglycerides lower than 150 mg%, LDL cholesterol lower than 100 mg/dl, HDL cholesterol greater than 45 mg/dl in men and 55 mg/dl in women are desirable.¹⁷ In order that all of these aims can be achieved, continued education programs should be implemented, in addition to following regular prescriptions: the patient should learn how to measure his/her capillary glucose, learn about diet, and learn about foot and eye care, etc. In some situations, the patient should get acquainted with the use of insulin syringes, pens or infusion pumps.

In a minority of patients, the aims are only achieved when changes in lifestyle are recommended. However, for most patients, the use of one or the combination of several medications is necessary to control the disease. Among these medications are biguanides, glitazones, glinides, sulfonylureas, glucose-oxidase inhibitors and several insulin preparations.

By using the described methods, we should not forget that up to now we diabetologists only delay chronic complications of diabetes mellitus. Most patients, although they follow the proposed treatment, will develop complications such as vasculopathy and neuropathy, which favors ulceration of lower limbs. Simple clinical methods for the detection of neuropathy and of the foot at risk for ulceration, learnt at the University of Michigan and which broadened our experience through the years by their application in daily clinical practice and in studies conducted both at Hospital de Clínicas and at Santa Casa de Porto Alegre, are presented in this chapter. Their use by physicians who attend to DM patients is recommended.^18-21 The diabetologist should prepare a team that meets all these requirements: prevention of neuropathy and vasculopathy and prevention of ulcers on feet that already present such complications.

DIABETIC NEUROPATHY: DEFINITION AND MECHANISMS

Diabetic neuropathy refers to a disorder that can be detected clinically or by diagnostic methods and which affects DM patients without any other causes of neuropathy (San Antonio Conference on Diabetic Neuropathy, 1988). Neuropathic disorders include somatic disorders and/or autonomous nervous system disorders.²²

Diabetic neuropathy is subclinical if nervous dysfunction (e.g.: reduced sensory or motor nerve conduction or elevated sensory threshold) is evident, and if clinical signs and symptoms of diabetic neuropathy are absent. Clinical diabetic neuropathy is characterized by overlapping of symptoms and/or clinically detectable neurological deficiencies.²²

Symmetric peripheral sensory-motor polyneuropathy or distal polyneuropathy (DP) is the most frequent form of diabetic neuropathy.^23,24 For that reason and since it is often an important mechanism that determines the development of foot ulcers (occurs in 80% of the patients), and results from intolerance of glucose and sugar levels that are diagnostic of diabetes, even without symptoms, it should be prevented by the patient's metabolic control.

Diabetic neuropathies are a heterogeneous group of circumstances that may be subdivided into clinical bases, as shown in Table 1. There is no evidence suggesting that some of the mononeuropathies are associated with ulceration of lower limbs,²⁴ but sensory and autonomic polyneuropathies have been associated with ulceration and amputation.

Table 1 - Clinical classification of neuropathies

Polyneuropathies	Mononeuropathies
Sensory Acute sensory Chronic sensory-motor	Isolated peripheral
Autonomic	Cranial
Proximal motor (amyotrophy)	Mononeuropathy multiplex
Truncal	Truncal

 

Sensory neuropathies are undoubtedly the most common forms of diabetic neuropathies and occur frequently in the major types of diabetes. An important study conducted, in 1993, about the prevalence of diabetes in 6,500 patients that are treated at British diabetic clinics revealed a prevalence of 28.5% for chronic sensory-motor neuropathy.²⁵

The reduction in the velocity of nerve conduction, which clinically characterizes polyneuropathy, is always associated with the reduced activity of sodium-potassium ATPase of the nerve. This change is associated with metabolic disorders and ischemia. The possible pathophysiological mechanisms involved and the relationship between them are shown in Figure 1. The points for which therapeutic interventions have been considered or where there is some evidence of effects on experimental animal studies have also been indicated.²⁶

Figure 1 - Pathophysiological mechanisms of polyneuropathies as proposed by Norman Cameron (PGAs - advanced glycosylation products; PGI2: prostaglandin I2).

CLINICAL COURSE OF DIFFUSE NEUROPATHIES

Neurological deficit is classically distributed through all sensory and motor nerves, but has a predilection for more distal innervation sites in a more or less symmetric fashion. Similar distributions occur in other metabolic neuropathies, including uremic and nutritional neuropathies.²⁷

This group of neuropathies may be divided into two subgroups, of which the chronic sensory-motor type is more common. Acute sensory neuropathy often appears after acute metabolic decompensation or another stressful event. Patients show a relatively acute onset of severe neuropathic symptoms, such as paresthesia, burning pain and hyperesthesia, all of which are usually exacerbated at night.

Differently from severe symptoms, the objective signs of neuropathy are usually absent on examination, although mild sensory peripheral disorders might be present;^28,29 weight loss and depression may also be found. The natural history of this type of neuropathy is spontaneous resolution, which occurs up to one year after symptom onset, often following metabolic control.³⁰

The onset of chronic sensory-motor neuropathy is insidious and the initial minor symptoms may go unnoticed to the patient. The symptoms, albeit less severe, are similar to those described above. Neurological dysfunction initially affects the most distal segments of the peripheral nervous system (usually at the feet), stretching proximally along both lower and upper extremities. Signs and symptoms vary according to the spectrum of nerve fibers involved. Injury to thick sensory fibers reduces the sensation to light and positional touch, whereas injury to thin fibers reduces the sensation to pain and temperature. In general, both thick and thin fibers are involved in the neuropathic process of DM.³¹ Motor weakness is usually mild, occurs later, and initially involves the most distal intrinsic muscles of the hands and feet. If predominance of involvement of thick sensory fibers is present, the patients show reduced proprioception and sensitivity to position, in addition to absent or reduced sensitivity to vibration. Subjective symptoms of pain and/or paresthesia or numbness are often absent, and neuropathy may be characterized only by late neuropathic complication, such as Charcot joint or a neuropathic ulcer. With a more severe involvement of thick fibers, the loss of sense of position may result in sensory ataxia, known as the pseudodiabetic form of diabetic neuropathy.

If neuropathy primarily involves thin sensory fibers, the patient may present with undetected trauma of the extremities (cigarette-burnt fingers, or feet burned in hot water, ulcers caused by objects in the shoes not perceived due to pain insensitivity). Thin fiber injuries may also cause numbness or sensation of cold feet, as well as several types of spontaneous pain.³² More often than not, the patients show paresthesia or hyperesthesia. Sometimes, the pain is described as superficial and similar to a burning sensation, or as osseous, deep and tearing. The pain is usually more intense at night, causing insomnia. Muscle cramps, which begin distally and may move up slowly, are similar to those that occur in other disorders related to loss of muscle innervation.³² As the involvement in these muscle innervation disorders may be primarily restricted to thin nerve fibers that are poorly myelinated, conduction velocity might not be dramatically impaired, sensitivity to vibration might be intact, and motor weakness might be absent, that is, if symptoms make the patient seek medical advice early, sensory loss assessed by traditional methods might not be remarkable. The presence of painful symptoms in the absence of marked neurological deficit seems to be paradoxical; however, pain may mean nerve regeneration,³² which might begin before significant degeneration.

Most patients with diabetic neuropathy show mild symptoms or no symptoms at all, revealing neurological deficits on physical examination or complications caused by asymptomatic neurological disorders.³³ The clinical examination usually reveals sensory deficit with the distribution of stockings. The signs of motor dysfunction are typically present, with reduced muscle fatigue and absent ankle reflexes. An especially dangerous situation is that which was described by Ward³⁴ as "painless aching leg," in which the patient shows painful neuropathic symptoms or paresthesia, but shows severe insensitivity to pain and to proprioception on examination: such patients are at risk for large and painless foot injuries.

We should know that the spectrum of severity of the symptoms is quite broad in chronic symptomatic sensory-motor neuropathy: some patients show severe symptoms while others do not have any symptoms or only mild and occasional ones. Therefore, given the fact that the history of symptoms strongly suggests the diagnosis of neuropathy, the absence of symptoms does not exclude neuropathy and should never be compared to the absence of risk for foot ulcers. Consequently, the assessment of foot ulceration risk should include a careful examination of the feet, regardless of the history of symptoms.³⁵ In addition to controlling and trying to obtain an optimally stable blood sugar level, some drugs, such as gabapentin, imipramine, amitriptyline and carbamazepine, help relieve the symptoms.³⁶

Unfortunately up to now, aside from metabolic control, no commercially available drug affects the natural history of the circumstances that determine the gradual deterioration of nerve function. Nevertheless, protein kinase C inhibitors are under study and have shown encouraging results.³⁷

Autonomic involvement may be responsible for symptoms that affect almost all systems. Frequently, the symptoms are vague and remain undetected for some time. However, severe autonomic neuropathy may have a variable combination of postural hypotension, nocturnal diarrhea, gastric disorders, urinary symptoms, abnormal sweating, male sexual impotence and difficulty in recognizing hypoglycemia. Most patients with severe autonomic neuropathy also show severe nephropathy, retinopathy and somatic neuropathy.

ASSESSMENT OF DIABETIC NEUROPATHY

For the diagnostic assessment of diabetic neuropathy, it is initially necessary to rule out other secondary causes of polyneuropathy, such as alcoholism, decompensated hypothyroidism, dysproteinemia, anemia, use of potentially neurotoxic drugs and signs of medullary compression. This assessment may be made through case history and lab exams.

DIAGNOSIS OF DIABETIC PERIPHERAL POLYNEUROPATHY

Neurophysiological diagnosis

Electrophysiological tests play a crucial role in the detection, characterization and assessment of the progression of different forms of diabetic neuropathy. In studies on nerve conduction, sensory or motor nerves are stimulated, with the subsequent registry of the potential of sensory or motor action. The neurophysiological study properly evaluates the thick fibers (myelinated), and among the several parameters for assessment of neuropathy, latency, conduction velocity and range are often used.³⁸

The involvement of thin and non-myelinated fibers, as occurs in neuropathies characterized by pain, is not clearly shown by this method. Notably, the disorders observed in peripheral polyneuropathies are initially seen in the lower limb nerves, especially in their sensory fibers and, with the progression of the disease, these disorders spread to the upper limbs.³⁹

At electromyography, diabetic polyneuropathy is considered in patients who show conduction disorders (velocity, range or latency) in at least two nerves.³⁹

Vibratory sensation tests

Evaluations have been made by way of a 128-Hz tuning fork (Figure 2) and through several devices, such as Biothesiometer, Vibraton II and Neuroesthesiometer.

Figure 2 - Assessment of vibratory perception threshold (tuning fork).

The 128-Hz tuning fork is used (immediately after being submitted to vibration) at the second distal phalanx, and dorsally, at the first toe of one of the feet, with the patient in the supine position. An individual without relevant involvement of vibratory sensitivity will perceive the vibration - and will be asked to inform when he/she ceases to perceive it. At this moment, the examiner changes the position of the tuning fork, placing it at the second phalanx of the first finger, dorsal, of his/her hand and counts the time until he/she perceives the absence of vibration. The examiner will usually perceive the vibrations for approximately 10 seconds; if the time interval is longer; the vibratory sensitivity of the patient is compromised. Due to the simplicity of this test, it may be used in combination with other measures for assessing the presence of neuropathy, as recommended by the University of Michigan.

Biothesiometer (Figure 3) (the most frequently used according to the literature) is an electromechanical tool that vibrates in accordance with its own scale, allowing the quantitative assessment of thick, myelinated sensory fibers. Although it assesses the vibratory sensitivity just as the tuning fork, it allows quantifying the threshold of vibratory perception. In addition, it can detect sensitivity disorders earlier than the tuning fork and it has better reproducibility (the tuning fork has a great variability from one examiner to another.⁴⁰) Test values are expressed in volts. Armstrong and Young observed that 25 volts is the cutoff point for the presence of foot at risk for neuropathic ulceration. Between 11 and 25 volts, the vibratory sensitivity is reduced, but the risk of neuropathic ulceration is lower.⁴¹

Figure 3 - Assessment of vibratory perception threshold (plastic stent).

Tactile sensation tests

Sensitivity may be evaluated by Semmes-Weinstein monofilament (esthesiometry). Esthesiometry is an efficient method for the detection of diabetic feet at risk for ulceration, according to Kumar et al.⁴² The test is based on the principle that the force necessary to bend a certain filament is the same at all attempts, which allows good reproducibility of the method. Semmes-Weinstein monofilaments (Figure 4) have been recommended to assess whether the foot of diabetic patients is at risk of ulceration and amputation. The test has been recommended with this purpose by the Brazilian Society of Diabetes.

Figure 4 -Assessment of pressure sensitvity to 10 grams (monofilament).

In a study carried out by Armstrong et al., the monofilament was applied to sites of higher pressure in the plantar region of the foot and at one point of the dorsum of the foot. It was observed that more than three errors in ten points are characteristic of the foot at risk of neuropathic ulceration.⁴³

In the instrument for the assessment of neuropathy proposed by the University of Michigan, the monofilament is applied at the same site of the tuning fork, with the foot propped up.⁴⁴ Other points are tested in other literature studies.^45,46

In a study carried out in our laboratory, it was possible to assess the level of neurological involvement caused by diabetes by using Semmes-Weinstein monofilament. We observed that, when nine sites of the plantar region of the foot were assessed, the number of times patients were unable to identify the pressure of 10 grams was correlated with the results obtained from measuring the velocity of nerve conduction.⁴⁵ With the cutoff point of two errors in 54 (nine areas, with six touches in each area), the sensitivity to the presence of neuropathy assessed by nerve conduction was 85.7%, and the specificity was 77.5%,⁴⁷ which indicates that the monofilament is a useful tool for assessing the presence of the foot at risk of neuropathic ulceration and for defining the presence of neuropathy that is already well-established clinically.

Thermal sensitivity tests

These tests assess the involvement of thin fibers, which is probably the earliest disorder caused by DM. The Thermal Sensitivity Tester (Sensortek Inc, Clifton, NJ, EUA) assesses a person's capacity of differentiating temperatures by using a Celsius scale. Comparatively to the measurement of the vibration sensory threshold, this technique has a better performance.⁴⁸ The results correlate with the variability of the heart rate.⁴⁹

Electric current sensitivity tests

These tests assess the involvement of thick and thin fibers. The results correlate with the velocity of motor and sensory nerve conduction and with the thresholds of temperature and pain perception.^50-52

Autonomic neuropathy evaluation tests

Autonomic involvement may be evident in several systems and organs, such as the cardiovascular, gastrointestinal, pupillary and genitourinary systems.

In the cardiovascular system, the loss of sympathetic control may predispose to postural hypotension, which is characterized by dizziness, visual disorders or syncope. These complaints may be found in up to 30% of the patients with diabetic autonomic neuropathy.⁵³

Gastrointestinal symptoms were observed in 15% of the patients studied by Rundles⁵⁴ and in 73% of those analyzed by Feldman et al.,⁵⁵ and are often intermittent. The most commonly reported symptoms are dysphagia, pyrosis (due to esophageal dysfunction), vomiting, anorexia, abdominal fullness, frequent hypoglycemias (due to gastric atony), diarrhea (due to intestinal stasis, which, in its turn, leads to excessive bacterial proliferation; these bacteria at the initial segment of the small intestine may deconjugate bile salts, causing malabsorption and steatorrhea),⁵⁵ intestinal constipation and sphincter incontinence (associated with loss of sphincter control).

Genitourinary disorders are one of the most frequent and earliest. Impotence may affect 35 to 75% of diabetics, depending on selection criteria,^56-60 The real incidence of neuropathy-related impotence is unknown, due to the multifactorial nature of this complication. Female sexual dysfunction seems to be less frequent and less important.⁶¹ Neurogenic bladder is a well-known dysfunction of autonomic neuropathy of diabetes, and is associated with recurrent urinary tract infection and urinary retention.⁶²

Sweating disorders are classically described as excessive sweating of the face and of the upper part of the trunk and sweat loss in lower limbs. However, other combinations (e.g.: gustatory sweating) have been observed.⁶³ These disorders are correlated with cardiovascular tests and with the threshold of skin sensitivity⁶⁴ and favor the occurrence of cracks and ulcers on the lower limbs.

The reduced autonomic response to hypoglycemia,^65,66 and to adrenergic symptoms,^67,68 have also been ascribed to autonomic involvement. Autonomic injury does not allow local microvascular reflexes that are mediated by vasoconstrictor and vasodilator fibers.

Loss of innervation and opening of arteriovenous anastomoses may cause an increase in the flow of blood towards the skin, which explains the high temperature of the skin and the presence of venous dilations on the feet of some neuropathic patients.^69,70 In diabetic patients with autonomic neuropathy, peripheral edema is frequent and may be attributed to enlarged arteriovenous shunts.^71,72

Cardiovascular involvement may be assessed by a series of simple and noninvasive tests. These tests, developed by Ewing et al., are based on heart rate and arterial blood pressure variability under physiological stimuli, such as deep breathing, Valsalva maneuver and change of decubitus. The American Association of Diabetes (Consensus Statement, 1992) has proposed that at least three cardiovascular tests be used for the diagnosis of autonomic neuropathy (for instance: variation of RR in deep breathing, Valsalva maneuver, variation of blood pressure in the supine position). These tests should be standardized and performed under the same conditions, since the responses vary according to time, metabolic condition, consumption of coffee, insulin or tobacco, cardiovascular drugs, etc.⁷³

The rate of cardiac frequency, monitored by electrocardiography, is assessed after deep breathing, Valsalva maneuver and orthostatism.

The response of arterial blood pressure to sustained manual force or to orthostatism is measured with an aneroid sphygmomanometer.

A detailed description of these tests may be obtained from studies previously published by our group.^18-21 The patients are classified as having autonomic neuropathy if they present two or more abnormal test results.

Other methods have been used to assess the occurrence of autonomic neuropathy. Among these methods, we have variation of cardiac frequency within 24 hours and use of radiotracers that are captured by sympathetic fibers, viewed by way of scintigraphy or positron emission tomography (PET-SCAN). In studies conducted in collaboration with the University of Michigan, we observed that cardiac sympathetic fibers can be properly mapped^74,75 by using marked carbon-11 hydroxyephedrine as a radiotracer; in addition, the technique clearly showed the areas that become denervated due to neuropathy.

End-stage kidney disease, macrovascular disease and sudden death are the causes of death in cardiovascular autonomic neuropathy. The association of autonomic neuropathy with nephropathy could partly explain the higher mortality caused by renal insufficiency.

However, even in the absence of nephropathy, the reduced variability of cardiac frequency and the decreased activity of the sympathetic system are associated with autonomic neuropathy and increased cardiovascular mortality. At least to some extent, the large number of cardiovascular deaths may result from the altered neural control of the cardiovascular system. Nevertheless, further studies are necessary to elucidate this.

Autonomic neuropathy may increase the risk of cardiac arrhythmia, especially in patients with propensity for arrhythmia, such as those with ischemic heart disease.

STAGING OF NEUROPATHY

To assess the progression of neuropathy and follow the therapeutic interventions it is necessary to develop a staging system for neuropathy. Studies carried out by Dick et al. proposed four stages: stage 0, no neuropathy; stage 1, asymptomatic neuropathy; stage 2, symptomatic neuropathy; and stage 3, incapacitating neuropathy. At each of these stages, neuropathy is subdivided into motor (M), sensory (S) or autonomic (A). The minimal criteria for diagnosis are two or more abnormal results in one or more of the following tests: lower limb symptom score, electrophysiological assay, quantitative assessment of sensitivity (vibratory and thermal), cardiovascular autonomic study (at least one of the tests with abnormal results: nerve conduction or autonomic test). Motor loss, characterized by the inability of walking on one's heels, is used at stage 2 to distinguish between mild and severe involvement.

Another staging method was devised by the University of Michigan. In this case, the patient is initially submitted to a simple questionnaire and physical examination, performed by a clinician or nurse. The patient with a high score is assessed later by a tool known as Michigan Score, in which symptoms, electrophysical disorders, sensitivity and motor function are evaluated. Based on this score, the patient is classified into four stages: 0, no neuropathy; 1, mild neuropathy; 2, moderate neuropathy; and 3, severe neuropathy. Michigan Score relates to that proposed by Dick, although it does not assess autonomic neuropathy.

Experience acquired with the use of the screening part of the Michigan neuropathy score has shown that the tests are reproducible.

Moreover, our studies have shown that these tests can be easily applied. The method to be used is presented in figure 5: when the patient has a score greater than or equal to 4, the sensitivity and the specificity for the presence of polyneuropathy are higher than 70%.

Figure 5 -Michigan tool for screening of neuropathy.

The identification of the patient with foot at risk of neuropathic injury should be a constant concern from the first medical appointment since the patient already presents with chronic complications, including unnoticed foot ulcer. This concern should also be passed on to the patient, his/her family and each member of the health team that treats diabetic patients. The identification should be as early as possible to be preventive as intended. The whole health team should be aware of the importance of preventing diabetic foot and know the signs, symptoms and conduct. The examination of the feet should be continued with regular monitoring of angioneurotrophic conditions of the feet and legs. The patient should be informed about the complications of diabetic neuropathy, especially about the morbidity and mortality caused by it. The identification and reduction of risk factors, improved foot care, use of protective shoes, shock-absorbing inner soles, removal of calluses and skin moisturization are conducts that should accompany risk identification and information to the patient.^76-78

Despite the substantial advances after the São Vicente Statement, the aim of reducing amputations by 50% was not achieved. In the opinion of the first author of this article, the aim will only be easily achieved if patients with foot at risk for neuropathic ulceration are awarded a prize when they succeed in preventing foot ulcers. The awards would make those patients who are concerned with their arterial blood pressure and high sugar levels perform self-examination and ask the medical team to assess their foot conditions on every appointment. If we pay attention to the factors that make a patient seek medical advice, we can understand why most foot lesions are only identified when the physician has no alternatives to offer the patient other than amputation.

According to Boulton, touching and pain are crucial sensations, which develop before the senses of sight and hearing: a newborn baby cannot focus on or interpret complex sounds and, consequently, he/she relies on touching and pain for survival. If an object produces pain when touched, he/she will pull away his/her hand. Later on, pain will be the cause for several medical appointments: our training as health professionals is targeted at the cause and improvement of pain.²² Patients with neuropathy due to diabetes often evolve into a stage of denervation of their lower limbs that nearly determines anesthesia. The care of a patient who feels no pain is a new challenge that physicians have not been prepared to deal with, and which is difficult to understand. It is not easy for a doctor to understand why an intelligent patient buys a pair of shoes whose size is smaller than recommended and turns up for the appointment with extensive ulcers produced by wearing inappropriate shoes. The explanation, however, is simple: with reduced sensation, viable nerve terminations are stimulated only by higher pressures, that is, when the shoes are too tight, this is interpreted as normal adjustment. Therefore, the usual complaint when we offer patients appropriate shoes is: "These shoes are too loose". This means that, if we want to be successful, we should understand that pain loss reduces patient's motivation to prevent and allow the healing of lesions. Arterial disease certainly increases the susceptibility of the foot that is insensitive to injury.⁷⁹ In addition, diabetic foot lesions barely heal if circulation is greatly compromised.

ROLE OF THE DIABETOLOGIST DURING SITUATIONS THAT REQUIRE HOSPITALIZATION OF DIABETIC FOOT PATIENTS

The necessity to use insulin in patients who have to be submitted to surgical procedures or who should receive contrast medium for arteriography seems to be a common agreement among surgeons and clinicians. Old textbooks already show therapeutic schemes aimed at preventing acute decompensation of diabetes with possible secondary dehydration.⁸⁰ Recent studies, however, have suggested that hospitalized patients with acute debilitating disease who receive insulin therapy and intravenous glucose in order to favor anabolism, thus maintaining sugar levels at or below 110 mg/dl, are patients who revealed lesser morbidity and mortality in a study when compared to individuals who did not receive this support: in-hospital mortality decreased by 34%, bacteremia by 46%, acute renal insufficiency by 41%, blood transfusions by 50% and acute polyneuropathy by 55%. As most patients hospitalized for surgical procedure of the lower limbs are acutely ill, we suppose that the conduct presented in this study should be recommended to diabetic foot patients.

FINAL REMARKS

Polyneuropathy is a common complication of diabetes and, at late stages, when it is significantly associated with the risk for neuropathic ulceration, it can be easily diagnosed by way of simple tools, such as Semmes-Weinstein monofilament or Biothesiometer.

In patients with pain or other clinical signs that occur both in diabetic neuropathy and in other clinical syndromes, it is necessary to confirm the diagnosis of somatic polyneuropathy with clinical tests, as proposed by the University of Michigan, and, whenever possible, with electrophysiological tests.

In patients with signs that suggest autonomic neuropathy, cardiovascular tests and specific tests that rule out other diseases are useful for differential diagnosis.

Once identified, patients whose feet are not so competent in terms of sensitivity (assessed by Biothesiometer or Semmes-Weinstein monofilament) should receive instructions so as to implement additional measures with the aim of protecting their feet from trauma, infections and subsequent amputation. It is recommended that diabetic patients be submitted to this kind of evaluation (which tries to identify the foot at risk) at least once a year. In those patients with risk of neuropathic ulceration (insensitivity), the evaluation as to the possibility of ulcerations should be performed every day by the patient or family or every two hours when new shoes are being worn, and also by the physician on every appointment. These measures allow the proposed treatment (revascularization) to be effective in cases of vascular occlusion.

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