Treatment options in diabetic sensorimotor and autonomic Neuropathy

At least one of three diabetic patients is affected by polyneuropathy which, on the one hand, presents with partly excruciating neuropathic pain and, on the other hand, is associated with markedly reduced quality of life and poor prognosis. The manifestations of diabetic autonomic neuropathy (DAN) cause multiple symptoms and involve: 1.) cardiovascular system: resting tachycardia, reduced heart rate variability and circadian rhythm of heart rate and blood pressure, painless myocardial ischaemia/infarction, orthostatic hypotension, exercise intolerance, perioperative instability, sudden death 2.) respiratory system: reduced ventilatory drive to hypercapnia/hypoxaemia, sleep apnea: 3,) gastrointestinal tract: oesophageal motor dysfunction, diabetic gastroparesis, gallbladder atony, diabetic enteropathy, colonic hypomotility, anorectal dysfunction: 4.) genitourinary tract: diabetic cystopathy, erectile dysfunction. Treatment is based on four cornerstones: 1.) causal tratment aimed at (near)-normoglycaemia, 2.) treatment based on pathogenetic mechanisms (currently only (-lipoic acid available): 3.) symptomatic treatment, and 1.) avoidance of risk factors and complications. Since treatment of painful neuropathy is frequently difficult and the response to a single agent is not the rule, a stepwise rational evidence-based treatment scheme is proposed. A simple measure of therapeutic efficacy (number needed to treat (NWT). i.e. the number of patients needed to treat with a particular therapy to achieve a clinically meaningful effect or adverse event in one patient) permits to estimate the risk-benefit-ratio for each agent on the basis of the available controlled trials. In recent meta-analyses, the NNTs have been calculated fur several drugs employed in the treatment of painful diabetic neuropathy which may serve the physician in deciding for the individual treatment. These agents include (-lipoic acid, antidepressants. anticonvulsants. opioids, and capsaicin. Pharmacological treatment of symptomatic DAN may be difficult due to limited efficacy and frequent adverse reactions. First line treatments include midodrine for orthostatic hypotension. prokinetic drugs for gastroparesis, broad spectrum antibiotics for diabetic diarrhoea, and Sildenafil for erectile dysfunction. Prior to an adequate symptomatic treatment a thorough risk-benefit estimate aimed at maintaining the patients' quality of life is required. Epidemiological data indicate that not only increased alcohol consumption but also the traditional cardiovascular risk factors such as hypertension, smoking, and cholesterol play a role in development and progression of diabetic neuropathy and, hence, need to be prevented or treated.