**3. Current standards of medical care in diabetes**

Up to 70% of people with diabetes experience nervous system damage in their lifetime. Dia‐ betic neuropathy compromises quality of life being a major contributing cause of lower limb amputation (http://www.diabetes.org/diabetes-basics/diabetes-statistics/) [11, 21-22].

Diabetic neuropathy is considered to be a multifactorial process whose contributing factors, yet not completely understood, are metabolic, vascular, autoimmune, oxidative and nitrosa‐ tive stress, and neuro-hormonal growth factor deficiency [20-21].

The classification of diabetic neuropathy that was originally proposed by Thomas [23] has been recently adapted by Vinik [22, 24] (Table 2).


**Table 2.** Classification of diabetic neuropathy proposed by Vinik et al. [22].

Diabetic autonomic neuropathy is the least recognised and understood diabetic complica‐ tion: clinical symptoms generally do not appear until long after the onset of diabetes, but subclinical autonomic dysfunction can occur within one year of diagnosis in type 2 diabetes and within two years of diagnosis in type 1 diabetes [24]. Diabetic autonomic neuropathy can involve the entire autonomic nervous system leading to a wide range of symptoms [21-22, 24]. Cardiac autonomic neuropathy can manifest as tachycardia (heart rate > 100 bpm), decreased exercise tolerance, orthostatic hypotension (a fall in systolic blood pressure > 20 mmHg upon standing without appropriate heart rate response), cardiac denervation syndrome with silent myocardial infarction, paradoxical supine or nocturnal hypertension, intra- and peri-operative cardiovascular instability, left ventricular diastolic dysfunction.

Peripheral diabetic autonomic neuropathy can manifest as decreased thermoregulation, de‐ creased sweating, altered blood flow, impaired vasomotion, and oedema. From the metabol‐ ic point of view, there may be hypoglycaemia unawareness with decreased counterregulatory catecholamine responses as well as hypoglycaemia unresponsiveness with reduction in glucagon and epinephrine secretion in response to hypoglycaemia. Gastrointes‐ tinal diabetic autonomic neuropathy can manifest as oesophageal dysmotility, gastro-paresis diabeticorum, diarrhoea or constipation, faecal incontinence. Genitourinary symptoms in‐ clude erectile dysfunction, retrograde ejaculation, neurogenic bladder and cystopathy, fe‐ male sexual dysfunction. Sudomotor diabetic autonomic neuropathy may manifest as anhidrosis, hyperhidrosis, heat intolerance, gustatory sweating, and dry skin. Pupillomotor function impairment and pseudo-Argyll-Robertson pupil have also been described.

The American Diabetes Association [11] recommends that:

mechanical (mechanoreflex) and metabolic (metaboreflex) stimuli. However, the receptors activating muscle afferent fibres as well as the factors contributing to a decrease in reflex ac‐

Up to 70% of people with diabetes experience nervous system damage in their lifetime. Dia‐ betic neuropathy compromises quality of life being a major contributing cause of lower limb

Diabetic neuropathy is considered to be a multifactorial process whose contributing factors, yet not completely understood, are metabolic, vascular, autoimmune, oxidative and nitrosa‐

The classification of diabetic neuropathy that was originally proposed by Thomas [23] has

amputation (http://www.diabetes.org/diabetes-basics/diabetes-statistics/) [11, 21-22].

Diffuse neuropathies Proximal motor (amyothrophy) Co-existing chronic inflammatory demyelinating

polyneuropathy

Inflammatory vasculitis

cells

Diabetic autonomic neuropathy is the least recognised and understood diabetic complica‐ tion: clinical symptoms generally do not appear until long after the onset of diabetes, but subclinical autonomic dysfunction can occur within one year of diagnosis in type 2 diabetes and within two years of diagnosis in type 1 diabetes [24]. Diabetic autonomic neuropathy can involve the entire autonomic nervous system leading to a wide range of symptoms

Monoclonal gammopathy of undetermined significance Circulating GM1 antibodies and antibodies to neuronal

tivity in oxidative muscle are still not precisely characterised [20].

tive stress, and neuro-hormonal growth factor deficiency [20-21].

**Clinical Presentation and Diagnosis Differential Diagnosis**

Entrapment syndromes

been recently adapted by Vinik [22, 24] (Table 2).

Acute sensory


Chronic sensorimotor

**Table 2.** Classification of diabetic neuropathy proposed by Vinik et al. [22].

Focal neuropathies Mononeuritis

362 Type 1 Diabetes

Generalised symmetric polyneuropathies

**3. Current standards of medical care in diabetes**

