Cardiac Autonomic Neuropathy in Diabetes

A clinical perspective

  1. Rodica Pop-Busui, MD, PHD
  1. From the Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan.
  1. Corresponding author: Rodica Pop-Busui, rpbusui{at}

This review covers the epidemiology, pathophysiology, clinical presentation, and diagnosis of cardiac autonomic neuropathy (CAN) in diabetes and discusses current evidence on approaches to prevention and treatment of CAN.


A 26-year-old woman with “brittle” type 1 diabetes and severe CAN experienced sudden cardiac death. She had a 16-year history of poor diabetes control presenting with wide blood glucose fluctuations, recurrent episodes of severe hypoglycemia, and hypoglycemia unawareness. Over time she developed persistent orthostatic hypotension with daily falls in systolic blood pressure ranging from 30–60 mmHg. These episodes had significant impact on her daily activities and required intermittent therapy with the α-1 agonist midodrine. Other complications included severe gastroparesis, refractory diarrhea, and painful diabetic peripheral neuropathy. Her last clinical examination revealed resting tachycardia with a fixed rate of 115 bpm, supine blood pressure of 110/78 mmHg, which dropped to 70/48 mmHg while standing, symmetrical absent pinprick and temperature discrimination in stocking distribution, and left Charcot joint. Her last pertinent laboratory findings were A1C 8.7%, creatinine 1.9 mg/dl, microalbumin/creatinine 496 mg/g, and hemoglobin 10.8 g/dl.

CAN represents a significant cause of morbidity and mortality in diabetic patients and is associated with a high risk of cardiac arrhythmias and sudden death, possibly related to silent myocardial ischemia. Therefore, it has important clinical and prognostic relevance. Recent reports of major clinical trials undermine established thinking concerning glycemic control and cardiac risk. Thus, a review of this topic is both timely and important for physicians to better understand how to assess the complexity of conditions present in patients with diabetes in order to establish safe treatment targets.


Diabetes affects more than 23 million people in the U.S. ( and an estimated 250 million worldwide ( Diabetic neuropathies, including CAN, are a common chronic complication of type 1 and type 2 diabetes and confer high morbidity …

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