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  • Review Article
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Cardiovascular autonomic neuropathies as complications of diabetes mellitus

Abstract

Diabetic autonomic neuropathies are a heterogeneous and progressive disease entity and commonly complicate both type 1 and type 2 diabetes mellitus. Although the aetiology is not entirely understood, hyperglycaemia, insulin deficiency, metabolic derangements and potentially autoimmune mechanisms are thought to play an important role. A subgroup of diabetic autonomic neuropathy, cardiovascular autonomic neuropathy (CAN), is one of the most common diabetes-associated complications and is ultimately clinically important because of its correlation with increased mortality. The natural history of CAN is unclear, but is thought to progress from a subclinical stage characterized by impaired baroreflex sensitivity and abnormalities of spectral analysis of heart rate variability to a clinically apparent stage with diverse and disabling symptoms. Early diagnosis of CAN, using spectral analysis of heart rate variability or scintigraphic imaging techniques, might enable identification of patients at highest risk for the development of clinical CAN and, thereby, enable the targeting of intensive therapeutic approaches. This Review discusses methods for diagnosis, epidemiology, natural history and potential causes and consequences of CAN.

Key Points

  • The overall prevalence of confirmed cardiovascular autonomic neuropathy (CAN) among patients with diabetes mellitus is approximately 20%

  • Subclinical CAN precedes clinical symptoms and is associated with abnormal cardiac function

  • Impaired spectral analysis of heart rate variability is one of the early presentations of CAN, followed by resting tachycardia, impaired exercise tolerance and ultimately orthostatic hypotension

  • CAN increases mortality of patients with diabetes mellitus by more than threefold, independently of traditional cardiovascular risk factors

  • Strict glycaemic control, multifactorial risk factor intervention and lifestyle changes are the most effective treatment strategies for CAN

  • Routine CAN assessment is relevant in clinical practice for the diagnosis of clinical CAN, risk stratification of patients for diabetes complications and target setting for metabolic control

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Figure 1: Pathogenesis of DAN.
Figure 2: Progression of cardiac autonomic neuropathy.
Figure 3: Increased cardiac sympathetic tone in a patient with type 1 diabetes mellitus (T1DM).
Figure 4: Progression of cardiac denervation in a female patient with type 1 diabetes mellitus (T1DM) and cardiovascular autonomic neuropathy (CAN) with poor glycaemic control.
Figure 5: Relationship between MPRI and LV torsion.
Figure 6: Cardiac dysfunction in diabetes mellitus.

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M. Kuehl researched data for the article. Both authors wrote the article, provided substantial contributions to discussions of the content and reviewed and/or edited the manuscript before submission.

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Kuehl, M., Stevens, M. Cardiovascular autonomic neuropathies as complications of diabetes mellitus. Nat Rev Endocrinol 8, 405–416 (2012). https://doi.org/10.1038/nrendo.2012.21

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