Diabetic autonomic neuropathy is one of the commonest complications of diabetes. Although it can involve the autonomic nervous system diffusely, symptoms are confined to a single organ system and are responsible for increased incidence of morbidity, reduced quality of life and mortality.
Diabetic neuropathy affects the peripheral sensory and motor nerves as well as the autonomic nervous system while diabetic autonomic neuropathy (DAN) involves all organ systems [1] but manifests initially in the longer nerves such as the vagus nerve. Although DAN is known to occur at any time in patients with type 1 and type 2 diabetes, it typically develops in patients with long-standing diabetes with poor blood glucose control. Subclinical DAN, however, can appear within a year of detecting type 2 diabetes and up to 2 years after the diagnosis of type 1 diabetes [2]. The prevalence of DAN varies amongst published studies [3] depending upon the measures used to assess the condition.
The overt clinical manifestations due to autonomic dysfunction and microvascular complications can occur concurrently but without a specific pattern [4] and can be classified according to the involved organ system as follows:
The diagnosis of DAN focuses on symptoms linked to a specific organ system. The patient history will elicit symptoms of DAN, review history of diabetes management, family history of diabetes, medication history and exclude other etiologies of neuropathy like alcoholism, vitamin B12 deficiency, malignancy and autoimmune diseases. Physical examination is likely to indicate variability in heart rate (resting tachycardia followed by bradycardia and later a fixed heart rate). Examination of the skin may reveal areas of alopecia with changes in the skin and nails and callus formation. There may also be erythematous "peritrophic" intertriginous areas between the toes. Neurological examination is essential to evaluate the ability for mental arithmetics which can be diminished in DAN. An ophthalmic evaluation is also required to detect effects of DAN on the eyes.
Laboratory tests include complete blood count, fasting and post-meal blood glucose levels, hemoglobin A1c levels as well as lipid profile, serum blood urea nitrogen and serum creatinine (to exclude concomitant diabetic nephropathy). Serial blood glucose testing may be required to monitor DAN.
Since the cardiovascular system is most commonly affected with life-threatening problems and as several tests are available to evaluate it, DAN is tested first. Five noninvasive tests for DAN include the Valsalva maneuver, the response of heart rate to deep breathing and standing; and blood pressure response to standing and sustained handgrip [5]. Orthostatic hypotension with a decrease in systolic blood pressure of more than 30 mm Hg on standing up is noted in DAN. An electrocardiogram (ECG) may show prolonged corrected QT interval and QT dispersion indicating an imbalance between the sympathetic innervation on the two sides of the heart [6]. Power spectral analysis of short R-R intervals or a 24 hour ECG is a sensitive and early test for identification of DAN [7] [8]. Exercise stress test is likely to reveal limited or decreased tolerance while echocardiography may show decreased cardiac ejection fraction with systolic dysfunction and poor diastolic filling [9].
Gastric scintigraphy can be employed to evaluate gastric emptying although its results do not correlate with the symptom severity in DAN patients. Other imaging tests are usually not helpful in the diagnosis of DAN.