Diabetic Autonomic Neuropathy

Aaron I. Vinik, MD, PhD.; Roy Freeman, MB, ChB.; Tomris Erbas, MD

Disclosures

Semin Neurol. 2003;23(4) 

In This Article

Abstract and Introduction

Abstract

Diabetic autonomic neuropathy is the most common and troublesome complication of diabetes mellitus. Although involvement of the autonomic nervous system is generally diffuse, symptoms may be confined to a single target organ or organ system. Complications of diabetic autonomic neuropathy contribute greatly to the morbidity, mortality, and reduced quality of life of the person with diabetes and are the major source of increased costs of caring for the diabetic patient. Factors in the pathogenesis of these complications are altered metabolism, vascular insufficiency, loss of growth factor trophism, and autoimmune destruction of nerves in a visceral and cutaneous distribution. The clinical manifestations and the complications of diabetic autonomic neuropathy are reviewed. Future therapeutic strategies that are developed from a better understanding of the pathogenetic processes underlying this disorder can be directed at the cause rather than the manifestations. There are studies in progress that suggest that autonomic nerves can be induced to regenerate, and the future for patients with diabetic autonomic neuropathy is brighter.

Introduction

Diabetic neuropathy is a heterogeneous disorder that encompasses a wide range of abnormalities affecting both proximal and distal peripheral sensory and motor nerves, as well as the autonomic nervous system (ANS). Diabetic autonomic neuropathy is among the least recognized and understood complications of diabetes despite its significant negative impact on survival and quality of life in people with diabetes.[1,2,3] Many organs are dually innervated, receiving fibers from the parasympathetic and sympathetic divisions of the ANS. Diabetic autonomic neuropathy typically occurs as a systemwide disorder affecting all parts of the ANS. Diabetic autonomic neuropathy manifests first in longer nerves. The vagus nerve (the longest of the ANS nerves) accounts for ~75% of all parasympathetic activity; as such, even early affects of diabetic autonomic neuropathy are widespread. The organ systems that most often exhibit prominent clinical autonomic signs and symptoms in diabetes include the pupil, sweat glands, genitourinary system, gastrointestinal tract system, adrenal medullary system, and the cardiovascular system ( Table 1 ).[4] The availability of sensitive, specific, and reproducible noninvasive tests of autonomic function has enhanced our understanding of the prevalence, pathophysiology, and clinical manifestations of this disorder.[1,5,6] Clinical symptoms of autonomic neuropathy generally do not occur until long after the onset of diabetes. Subclinical autonomic dysfunction, however, can occur within a year of diagnosis in type 2 diabetic patients and within 2 years in type 1 diabetic patients.[7]

Estimates of the prevalence of diabetic autonomic neuropathy are dependent on the criteria used for diagnosis and the specific population under study. The prevalence of symptoms of autonomic dysfunction and abnormal tests of autonomic nervous system function in diabetic clinic-based populations and tertiary referral centers is considerably higher than in general clinic-based populations. For example, symptomatic visceral autonomic neuropathy had a prevalence of 5.5% in a population-based study of diabetic patients in Rochester, Minnesota.[8] In a community-based population study of diabetic neuropathy in Oxford, England, the prevalence of autonomic neuropathy as defined by one or more abnormal heart rate variability (HRV) test results was 16.7%.[9] In a study that evaluated the prevalence of cardiovascular autonomic neuropathy in 1171 diabetic patients randomly recruited from 22 diabetic centers in Germany, Austria, and Switzerland, 25.3% of patients with type 1 diabetes and 34.3% of patients with type 2 diabetes had abnormal findings in more than two of six autonomic function tests.[10]

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