Autonomic neuropathy in diabetes

Abstract

Diabetic autonomic neuropathy (DAN) is a serious and often under-recognized complication of diabetes that can affect any division of the autonomic nervous system (ANS), presenting with a wide range of signs and symptoms. The pathophysiology of DAN involves a complex interplay of hyperglycemia-driven metabolic and vascular pathways, oxidative stress, inflammation, and autonomic imbalance, ultimately leading to progressive nerve dysfunction. Cardiovascular autonomic neuropathy (CAN) has emerged as a particularly severe condition, associated with heightened risk of arrhythmia, silent myocardial ischemia, heart failure, and mortality. DAN, however, extends beyond the cardiovascular system, encompassing gastrointestinal (GI), genitourinary (GU), and sudomotor dysfunctions, that strongly impair quality of life. Despite its impact, DAN remains largely overlooked in clinical practice due to its subclinical onset, non-specific symptoms, and limited routine screening. This review integrates basic, epidemiological, and clinical data to provide a practical understanding of DAN with the aim of helping clinicians to suspect, investigate and manage DAN, with particular attention to its cardiovascular (CV), GI, and GU manifestations.

Keywords: Diabetic neuropathy; cardiovascular autonomic neuropathy; diabetes mellitus; diabetic autonomic neuropathy; heart rate variability.

Figure 1

Clinical spectrum of diabetic autonomic neuropathy.Diabetic autonomic neuropathy may affect multiple systems, including cardiovascular, gastrointestinal, genitourinary, and sudomotor pathways, as well as pupillary function and hypoglycemia awareness. Each subtype presents with characteristic symptoms that reflect widespread autonomic dysfunction in diabetes.

Figure 2

Stages of cardiovascular autonomic neuropathy.

Figure 3

Example of spectral analysis study of HRV and CART in individuals with and without cardiovascular autonomic neuropathy.