Diabetic Autonomic Neuropathy

Abstract

ABSTRACT-Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, ϳ20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brittle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal [GI], genitourinary, and cardiovascular). GI disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal incontinence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; measurement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve function; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations ...

Usefulness of ambulatory blood pressure monitoring in predicting the presence of autonomic neuropathy in type I diabetic patients

“…Moreover, there are defined recommendations to perform ABPM, as stated by official bodies. 2,34 However, given the rather widespread use of ABPM in the general and diabetic population 4 and conversely the still limited application of routine diagnosis of diabetic autonomic neuropathy, 35 it is helpful to know that nondipping status suggests a high probability of the presence of autonomic neuropathy. Thus, a nondipper diabetic patient should be considered at high risk of autonomic neuropathy and should undergo, by way of confirmation, a standard diagnostic approach with cardiovascular tests and an intensive therapeutic strategy, aimed at providing good glycaemic control, correcting cardiovascular risk factors, and guaranteeing good BP control for the whole 24-h period.…”

Levels of three distinct p75 neurotrophin receptor forms found in human plasma are altered in type 2 diabetic patients

“…Since the diagnosis of CAN relies on the detection of variability in the R-R interval under haemodynamic stress (i.e. deep breathing, Valsalva manoeuvre, lying to standing) [20], a variety of external factors, such as medication, circadian rhythm and age, can cause bias [20]. In a nerve crush model in diabetic mice, p75NTR appears in plasma [1] and plays a role in the switch from adrenergic stimulation of cardiomyocytes to inhibitory cholinergic transmission [21].…”

Disparity of autonomic control in type 2 diabetes mellitus

“…By design, our findings were obtained in patients with type 2 diabetes who had no evidence of neuropathy, because this could interfere with autonomic neural control and its effects [33][34][35][36]. We used previously accepted criteria [19,20], as well as clinical examination and vasopressor responses, to exclude somatic and autonomic neuropathy.…”