The prevalence of cardiac autonomic neuropathy in prediabetes: a systematic review

Abstract

Aims/hypothesis Cardiac 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. Methods This 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. Results Database 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/interpretation There 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.

Prevalence of peripheral neuropathy in pre-diabetes: a systematic review

“…45 Early microvascular complications have been reported by other authors, and our recently published systematic review has also demonstrated an excess of cardiac autonomic neuropathy in pre-diabetes. 46 Comparisons with previous data Understanding the natural history of DPN and peripheral neuropathy in pre-diabetes is vital to determine the optimal screening approach. A systematic review conducted in 2011 found a significant proportion of participants with IGT have mainly small nerve fiber deficits.…”

“… 45 Early microvascular complications have been reported by other authors, and our recently published systematic review has also demonstrated an excess of cardiac autonomic neuropathy in pre-diabetes. 46 …”

Gender differences in screening for glucose perturbations, cardiovascular risk factor management and prognosis in patients with dysglycaemia and coronary artery disease: results from the ESC-EORP EUROASPIRE surveys

“…This is particularly important considering their higher prevalence of microvascular complications, which at least partially may explain their worse outcome. That microvascular disease is more prevalent in post-menopausal women than men underlines the need to address this in risk stratification of CAD patients by non-invasive measures such as spot albuminuria and cardiac autonomic neuropathy, in addition to OGTT [11,[39][40][41].…”

Dependence of Heart Rate Variability Indices on the Mean Heart Rate in Women with Well-Controlled Type 2 Diabetes

“…However, the maneuver, age, and the presence of diabetes results in independent and significant variables to predict HRV, and they have been also found in other studies in the field. Supine, active standing, and rhythmic breathing are well-known maneuvers proposed by Ewing et al, 1985 [ 51 ], that activate fast and consistent autonomic responses in healthy subjects [ 52 ], and they are widely used in clinical testing of autonomic function in metabolic [ 53 , 54 ], cardiovascular [ 55 , 56 ], psychological [ 57 ], and rheumatic diseases [ 58 ]. We expected a significant correlation with HRV indices, demonstrating the existence of cardiac autonomic activity.…”