Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management

Cardiac autonomic neuropathy (CAN) is a serious complication of type 1 and type 2 diabetes and is independently associated with major cardiovascular events, morbidity, and mortality. This narrative review examines the epidemiology, pathophysiology, and management and identifies areas of future research to address the challenge posed by CAN.

We conducted a comprehensive literature search using a range of sources, including the electronic databases PubMed Central, Google Scholar, OVID, and Open Athens, to search for studies on CAN, diabetes mellitus, lifestyle intervention, and cardiovascular risk. We set inclusion criteria to consider review articles or original research published in peer-reviewed journals that examined CAN in diabetes.

Epidemiologic data indicate a varied prevalence of CAN in type 1 and 2 diabetes, with prevalences of 17% to 73%) depending on clinical and demographic factors. Indeed, duration of diabetes and hyperglycemia are the strongest risk factors for CAN development in type 1 diabetes. However, in type 2 diabetes, multifactorial risk factors, including obesity, hypertension, and hyperlipidemia, are associated with the development of CAN. Insulin resistance, which underpins type 2 diabetes and metabolic syndrome, has a direct role in the pathogenesis of CAN. Lifestyle interventions, including dietary measures and tailored exercise programs, have been beneficial in improving cardiac autonomic function primarily measured through heart rate variability. In addition, weight loss through bariatric surgery also improves heart rate variability and may prevent or reduce CAN progression in people living with obesity and concomitant type 2 diabetes. For optimization in type 2 diabetes, both lifestyle and targeted pharmacologic interventions are required to achieve glycemic/metabolic targets, and weight loss is required to prevent or reverse early CAN or prevent the progression to definite and severe CAN.

The focused use of diagnostic testing for CAN, including cardiac autonomic reflex testing in those at high risk of CAN, will enable earlier diagnosis. This testing will allow timely interventions at a reversible stage. Future research should examine targeted early diagnostic testing with subsequent intervention with a combination of lifestyle measures and newer pharmacotherapeutics (eg, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists), which have produced significant cardiovascular benefit in diabetes.