Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Davis TME

PROVIDER: S-EPMC10949593 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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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 Timothy M E TME Tan Eva E Davis Wendy A WA

Cardiovascular diabetology 20240318 1

<h4>Background</h4>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).<h4>Methods</h4>FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variatio ...[more]

PMID: 38500197

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Project description:Aims/hypothesisCardiac autonomic neuropathy (CAN) is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular mortality. Several studies have highlighted the increased prevalence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose). Considering the exponential rise of prediabetes, we aimed to determine the prevalence of CAN through a systematic literature review.MethodsThis systematic review was registered with PROSPERO (CRD42019125447). An electronic literature search was performed using MEDLINE, EMBASE, PubMed, Web of Science, Scopus and Cochrane databases. Published full text, English language articles that provide CAN prevalence data of studies in individuals with prediabetes and aged over 18 years were included. Prevalence data for normal glucose tolerance and diabetes were also extracted from the selected articles, if present. All articles were screened by two independent reviewers using a priori criteria. Methodological quality and risk of bias were evaluated using a critical appraisal tool.ResultsDatabase searches found 4500 articles; subsequently, 199 full text articles were screened, 11 of which fulfilled the inclusion criteria (4431 total participants, 1730 people with prediabetes, 1999 people with normal glucose tolerance [NGT] and 702 people with predominantly type 2 diabetes). Six of the selected studies reported definite CAN prevalence data (9-39%). Only a single large population-based study by Ziegler et al (KORA S4 study, 1332 participants) determined definite CAN based on two or more positive autonomic function tests (AFTs), with a mean prevalence of 9% in all prediabetes groups (isolated impaired glucose tolerance 5.9%; isolated impaired fasting glucose 8.1%; impaired fasting glucose plus impaired glucose tolerance 11.4%), which was higher than NGT (4.5%). This study is most likely to provide a reliable population-specific estimate of CAN in prediabetes. There was a higher than expected prevalence of CAN in prediabetes (9-38%) when compared with normal glucose tolerance (0-18%) within the same studies (n = 8). There was a wide prevalence of possible CAN based on one positive AFT (n = 5). There was heterogeneity between the studies with variations in the definition of CAN, methodology and characteristics of the populations, which likely contributed to the diversity of prevalence estimates. The overall risk of bias was low.Conclusions/interpretationThere is a higher than expected prevalence of CAN in prediabetes. Early detection of CAN in prediabetes through population screening needs careful consideration in view of the excess morbidity and mortality risk associated with this condition. Graphical abstract.

Project description:Aims/hypothesisWe examined the effect of a standardised sympathetic stimulus, incremental adrenaline (epinephrine) infusion on cardiac repolarisation in individuals with type 1 diabetes with normal autonomic function, subclinical autonomic neuropathy and established autonomic neuropathy.MethodsTen individuals with normal autonomic function and baroreceptor sensitivity tests (NAF), seven with subclinical autonomic neuropathy (SAN; normal standard autonomic function tests and abnormal baroreceptor sensitivity tests); and five with established cardiac autonomic neuropathy (CAN; abnormal standard autonomic function and baroreceptor tests) underwent an incremental adrenaline infusion. Saline (0.9% NaCl) was infused for the first hour followed by 0.01 μg kg-1 min-1 and 0.03 μg kg-1 min-1 adrenaline for the second and third hours, respectively, and 0.06 μg kg-1 min-1 for the final 30 min. High resolution ECG monitoring for QTc duration, ventricular repolarisation parameters (T wave amplitude, T wave area symmetry ratio) and blood sampling for potassium and catecholamines was performed every 30 min.ResultsBaseline heart rate was 68 (95% CI 60, 76) bpm for the NAF group, 73 (59, 87) bpm for the SAN group and 84 (78, 91) bpm for the CAN group. During adrenaline infusion the heart rate increased differently across the groups (p = 0.01). The maximum increase from baseline (95% CI) in the CAN group was 22 (13, 32) bpm compared with 11 (7, 15) bpm in the NAF and 10 (3, 18) bpm in the SAN groups. Baseline QTc was 382 (95% CI 374, 390) ms in the NAF, 378 (363, 393) ms in the SAN and 392 (367, 417) ms in the CAN groups (p = 0.31). QTc in all groups lengthened comparably with adrenaline infusion. The longest QTc was 444 (422, 463) ms (NAF), 422 (402, 437) ms (SAN) and 470 (402, 519) ms (CAN) (p = 0.09). T wave amplitude and T wave symmetry ratio decreased and the maximum decrease occurred earlier, at lower infused adrenaline concentrations in the CAN group compared with NAF and SAN groups. AUC for the symmetry ratio was different across the groups and was lowest in the CAN group (p = 0.04). Plasma adrenaline rose and potassium fell comparably in all groups.Conclusions/interpretationParticipants with CAN showed abnormal repolarisation in some measures at lower adrenaline concentrations. This may be due to denervation adrenergic hypersensitivity. Such individuals may be at greater risk of cardiac arrhythmias in response to physiological sympathoadrenal challenges such as stress or hypoglycaemia.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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