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

Williams, S.; Raheim, Siddig Abdel; Khan, Muhammad Ilyas; Rubab, Umme; Kanagala, Prathap; Zhao, Sizheng Steven; Marshall, Anne; Brown, Emily; Alam, Uazman

doi:10.1016/j.clinthera.2022.09.002

Cited by 30 publications

(23 citation statements)

References 137 publications

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“…This was consistent with the results of a recent meta-analysis [ 7 ] in which there was significant heterogeneity, reflecting a variety of sample sizes, participant sources including people with type 1 diabetes and those with type 2 diabetes selected for clinical trials [ 8 , 31 , 32 ], and methods of diagnosing CAN which ranged from full CARTs to change in heart rate on standing [ 32 ] and heart rate variability (HRV) and QT index on resting electrocardiography [ 8 ]. Our multivariable analysis showed HRs for possible and definite CAN that were close to unity in the presence of other recognised predictors of incident IHD (longer diabetes duration, higher heart rate and increased uACR [ 2 ]). It is possible that relatively intensive CVD risk factor management in FDS2 paralleling trends in other high income countries [ 9 , 10 ] (for example, approximately two-thirds of our participants were taking renin-angiotensin blocking drugs and statins) attenuated both the risk of CAN and its effect on CVD outcomes found in earlier studies, most of which were published before the first FDS2 patient was assessed for CAN [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…The only individual CART test predictive of all-cause death was MCR. Taken together, these findings question the need for screening for CAN, as has been suggested [ 2 , 7 ], as part of routine care of type 2 diabetes, especially since the gold standard CART evaluation is demanding for both patients and staff [ 6 ]. In addition, the present data suggest that around one-third of patients will either be ineligible because of age or they will, for various reasons, be unable to complete a valid CART assessment.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiovascular autonomic neuropathy (CAN) is characterised by orthostatic hypotension, resting tachycardia, impaired exercise tolerance and abnormal blood pressure regulation [ 1 ], but it may also remain asymptomatic and thus elude timely diagnosis [ 2 ]. It is a common chronic complication of type 2 diabetes with a prevalence estimated at between 9 and 78% from studies conducted in primary but mainly secondary care [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although testing for autonomic dysfunction has been recommended as part of routine early screening in diabetes [ 2 , 7 ], its role as an independent predictor of CVD events and mortality needs to be established in contemporary cohorts of people with type 2 diabetes. The aim of this study was, therefore, to assess the prevalence and prognostic significance of CAN in well characterised, representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2).…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II

Davis,

Tan,

Davis

2024

Cardiovasc Diabetol

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Background There is a paucity of contemporary data on the prevalence and prognostic significance of cardiac autonomic neuropathy (CAN) from community-based cohorts with type 2 diabetes assessed using gold standard methods. The aim of this study was to assess these aspects of CAN in the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). Methods FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variation during deep breathing, Valsalva manoeuvre and standing. CAN (no/possible/definite) was assessed from the number of abnormal CARTs. Multinomial regression identified independent associates of CAN status. Cox proportional hazards modelling determined independent baseline predictors of incident heart failure (HF) and ischaemic heart disease (IHD), and all-cause mortality. Results Of 1254 participants assessed for CAN, 86 (6.9%) were outside CART age reference ranges and valid CART data were unavailable for 338 (27.0%). Of the remaining 830 (mean age 62.3 years, 55.3% males, median diabetes duration 7.3 years), 51.0%, 33.7% and 15.3% had no, possible or definite CAN, respectively. Independent associates of definite CAN (longer diabetes duration, higher body mass index and resting pulse rate, antidepressant and antihypertensive therapies, albuminuria, distal sensory polyneuropathy, prior HF) were consistent with those reported previously. In Kaplan–Meier analysis, definite CAN was associated with a lower likelihood of incident IHD and HF versus no/possible CAN (P < 0.001) and there was a graded increase in all-cause mortality risk from no CAN to possible and definite CAN (P < 0.001). When CAN category was added to the most parsimonious models, it was not a significant independent predictor of IHD (P ≥ 0.851) or HF (P ≥ 0.342). Possible CAN (hazard ratio (95% CI) 1.47 (1.01, 2.14), P = 0.046) and definite CAN (2.42 (1.60, 3.67), P < 0.001) increased the risk of all-cause mortality versus no CAN. Conclusions Routine screening for CAN in type 2 diabetes has limited clinical but some prognostic value.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II

Davis,

Tan,

Davis

2024

Cardiovasc Diabetol

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“…Diseases associated with or caused by chronic hyperglycemia, such as diabetes mellitus and metabolic syndrome, have been widely studied for their pathophysiology and complications. Autonomic and cardiovascular complications are well-reported in such cases [1][2][3]. However, the effects of acute relative hyperglycemic states on cardiovascular autonomic functions in healthy subjects have been less explored.…”

Section: Introductionmentioning

confidence: 99%

Blood Pressure Variability is Better Associated with Acute Relative Hyperglycemia Than the Heart Rate Variability in Healthy Young Adults

Prakash,

Ranjan,

Malhotra

2024

Exp Clin Endocrinol Diabetes

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Background: Deranged cardiovascular autonomic functions are well-reported complications of diabetes mellitus where chronic hyperglycemia is one of the important factors. But, the role of acute relative hyperglycemia on cardiovascular autonomic functions in healthy subjects is less explored. Hardly any study has reported the effect of acute hyperglycemia on blood pressure variability. Therefore, the present study was planned to study the effect of acute relative hyperglycemia on cardiovascular autonomic functions in healthy young adults. Methods: Beat-to-beat blood pressure and electrocardiogram were recorded for the assessment of heart rate variability and blood pressure variability in forty-two young, healthy subjects during fasting and relative hyperglycemic states. Recorded cardiovascular parameters were analyzed in time and frequency domains. Correlations among analyzed parameters of cardiovascular autonomic variabilities were explored during fasting and relative hyperglycemic state. Results: We observed significant alteration of few of the systolic, mean and diastolic blood-pressure-variability-parameters during acute relative hyperglycemia when compared to the fasting state. However, no significant changes were observed in any of the heart-rate-variability parameters. Also, we found novel significant correlations among many of the parameters of cardiovascular autonomic variabilities during fasting and relative hyperglycemic states. Conclusions: Present study concludes that the blood pressure variability is affected significantly during acute relative hyperglycemia in healthy young adults, however, the heart rate variability does not show such changes. Also, many of the parameters of blood pressure variability show significant correlations with heart rate variability and baroreflex sensitivity. We may hypothesize that although the heart rate variability and blood pressure variability assess cardiovascular autonomic functions, blood pressure variability is a better indicator of cardiovascular autonomic effects of acute relative hyperglycemia than heart rate variability.

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Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management

Eleftheriadou,

Spallone,

Tahrani

et al. 2024

Diabetologia

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Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. CAN affects approximately 20% of people with diabetes, with recent studies highlighting the presence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose), indicating early involvement of the autonomic nervous system. Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. Recent advancements, such as streamlining CAN detection through wearable devices and monitoring of heart rate variability, present simplified and cost-effective approaches for early CAN detection. Further research on the optimal use of the extensive data provided by such devices is required. Despite the lack of specific pharmacological interventions targeting the underlying pathophysiology of autonomic neuropathy, several studies have suggested a favourable impact of newer glucose-lowering agents, such as sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, where there is a wealth of clinical trial data on the prevention of cardiovascular events. This review delves into recent developments in the area of CAN, with emphasis on practical guidance to recognise and manage this underdiagnosed condition, which significantly increases the risk of cardiovascular events and mortality in diabetes. Graphical Abstract

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

Cited by 30 publications

References 137 publications

Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II

Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II

Blood Pressure Variability is Better Associated with Acute Relative Hyperglycemia Than the Heart Rate Variability in Healthy Young Adults

Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management

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