UNASSIGNED: Cardiac autonomic neuropathy (CAN) is a severe complication of type 1 diabetes mellitus (T1DM). This meta-analysis aimed to synthesize relevant literature on the prevalence of CAN and its risk factors in individuals with T1DM.
UNASSIGNED: We screened relevant literature from databases based on predefined search criteria until June 28, 2022. Data extraction and quality assessment were conducted independently by two reviewers. A meta-analysis was conducted to determine the prevalence of CAN and its risk factors in individuals with T1DM using a random-effects model. A subgroup analysis was conducted to assess variations in CAN prevalence based on diabetes duration, diagnostic criteria, study quality, study design, and geographic region of the participants.
UNASSIGNED: A total of 21 studies provided information on the prevalence of CAN, while 18 studies explored the potential risk factors for CAN. The overall estimated prevalence of CAN in individuals with T1DM was 25.8% (95% confidence interval (95% CI): 0.208-0.307), with no significant differences observed among the five regions. Additionally, smoking, lipid abnormalities, hypertension, duration of diabetes, increased body mass index, elevated glycated haemoglobin concentrations, and presence of chronic complications of diabetes, such as diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy, were associated with a higher prevalence of CAN in individuals with diabetes.
UNASSIGNED: CAN is prevalent in individuals with T1DM worldwide. Efforts should be made to improve early screening and intervention for CAN, as well as to implement strategies aimed at improving or controlling early risk factors associated with CAN.

BACKGROUND: Cardiac autonomic neuropathy (CAN) in diabetes mellitus (DM) is independently associated with cardiovascular (CV) events and CV death. Diagnosis of this complication of DM is time-consuming and not routinely performed in the clinical practice, in contrast to fundus retinal imaging which is accessible and routinely performed. Whether artificial intelligence (AI) utilizing retinal images collected through diabetic eye screening can provide an efficient diagnostic method for CAN is unknown.
METHODS: This was a single center, observational study in a cohort of patients with DM as a part of the Cardiovascular Disease in Patients with Diabetes: The Silesia Diabetes-Heart Project (NCT05626413). To diagnose CAN, we used standard CV autonomic reflex tests. In this analysis we implemented AI-based deep learning techniques with non-mydriatic 5-field color fundus imaging to identify patients with CAN. Two experiments have been developed utilizing Multiple Instance Learning and primarily ResNet 18 as the backbone network. Models underwent training and validation prior to testing on an unseen image set.
RESULTS: In an analysis of 2275 retinal images from 229 patients, the ResNet 18 backbone model demonstrated robust diagnostic capabilities in the binary classification of CAN, correctly identifying 93% of CAN cases and 89% of non-CAN cases within the test set. The model achieved an area under the receiver operating characteristic curve (AUCROC) of 0.87 (95% CI 0.74-0.97). For distinguishing between definite or severe stages of CAN (dsCAN), the ResNet 18 model accurately classified 78% of dsCAN cases and 93% of cases without dsCAN, with an AUCROC of 0.94 (95% CI 0.86-1.00). An alternate backbone model, ResWide 50, showed enhanced sensitivity at 89% for dsCAN, but with a marginally lower AUCROC of 0.91 (95% CI 0.73-1.00).
CONCLUSIONS: AI-based algorithms utilising retinal images can differentiate with high accuracy patients with CAN. AI analysis of fundus images to detect CAN may be implemented in routine clinical practice to identify patients at the highest CV risk.
BACKGROUND: This is a part of the Silesia Diabetes-Heart Project (Clinical-Trials.gov Identifier: NCT05626413).

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.

This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM).
METHODS: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM.
RESULTS: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN.
CONCLUSIONS: The review presents a possible relationship between DPN and CAN, such as in their severity.

OBJECTIVE: Cardiac autonomic neuropathy (CAN) is one of the most serious complications of diabetes. This study aimed to analyze the correlation between neutrophil-to-lymphocyte ratio (NLR) and CAN in patients with type 2 diabetes (T2D) using 24-hour Holter ECG and to assess the relationship between NLR and severity of diabetic peripheral neuropathy (DPN).
METHODS:  This cross-sectional study included 90 T2D patients with DPN confirmed by nerve conduction study (NCS). A 24-hour Holter ECG was done to detect the decrease in heart rate variability (HRV). Laboratory parameters, including fasting blood glucose, creatinine, cholesterol, triglyceride, and glycosylated hemoglobin (HbA1c) levels, as well as CBC, neutrophils, lymphocytes, NLR, and platelet-to-lymphocyte ratio (PLR), were calculated accordingly. An albumin-to-creatinine ratio (ACR) test was done and the estimated glomerular filtration rate (eGFR) was calculated. Chronic kidney disease was diagnosed by the presence of albuminuria (≥30 mg/g creatinine) and/or eGFR less than 60.
RESULTS: Based on the 24-hour Holter ECG, 25 patients out of 90 (27.7%) had CAN. On comparing both the CAN and non-CAN groups, the CAN group had higher HbA1C (p = 0.005), higher NLR (p = 0.014), and higher neutrophils (p = 0.10). Also, PLR was higher in the CAN group than in the non-CAN group, but this was not statistically significant (p = 0.180). Receiver operator characteristic curve analysis revealed that NLR with a cutoff of 1.7 succeeded in detecting patients with CAN.
CONCLUSIONS: NLR can be used as an inexpensive and accessible marker to detect patients with diabetes at risk for developing CAN.

BACKGROUND: Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN).
METHODS: The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m2. Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics.
RESULTS: Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN.
CONCLUSIONS: CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events.
BACKGROUND: http://www.
RESULTS: gov . Unique identifier: NCT00000620.

OBJECTIVE: Hypermetabolic state in Graves\' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To characterize cardiac autonomic neuropathy (CAN) as a possible complication in patients with GD.
METHODS: We evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients.
RESULTS: Sixty GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7% established CAN, while in the control group, it was verified incipient in 8% and established in 6% (P = .7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of CAN.
CONCLUSIONS: The prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.

OBJECTIVE: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM.
METHODS: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared.
RESULTS: Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001).
CONCLUSIONS: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.

Introduction This study aimed to evaluate hemodynamic changes using heart rate variability (HRV) measurements in diabetic and nondiabetic patients who will undergo laparoscopic cholecystectomy and to provide our preoperative measurements to guide us for better perioperative anesthesia management. Materials and methods The study included 143 patients aged 40 years and older who would undergo elective laparoscopic surgery, did not have any comorbidities other than diabetes mellitus (DM) type II, and were in the American Society of Anesthesiologists (ASA) class I-III risk group. Patients were divided into two groups: the control group (n = 77) and the DM group (n = 66). The preoperative glycated hemoglobin (HbA1C) level was measured. Peripheral oxygen saturation (SpO2) and hemodynamic parameters such as systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), and HRV parameters were measured preoperatively, perioperatively, and postoperatively. Intra-abdominal pressure (IAP) was administered at 10-12 mmHg. Results Even though SAP, DAP, MAP, and HR decreased with induction, they increased with insufflation, and an overall decrease was seen at the postoperative 24th hour for all parameters. When the groups were evaluated, no difference was observed except that the DAP was significantly lower in the DM group (p = 0.029) at insufflation and the HR was higher in the DM group at induction, and the difference was significant (p = 0.001). Preoperative HRV parameters were significantly lower in the DM group. According to the HRV parameters, although a decrease was observed after induction and insufflation, conversely, an increase was observed postoperatively. When the postoperative and preoperative values were compared, the standard deviation of the NN (R-R) intervals (SDNN), SDNN index, high frequency (HF), low frequency (LF), and LF/HF parameters were found to be significantly lower in the DM group than in the control group. Conclusion Diabetic patients are more sensitive to increased intra-abdominal pressure (IAP) in laparoscopic surgery, and the effects on cardiac autonomic functions can be determined by HRV measurements without clinically reflecting on hemodynamic data. Additionally, in diabetic patients with preoperative LF and/or HF values less than 100, we believe that careful follow-up in terms of autonomic neuropathy complications and anesthesia management should be done more meticulously in these patients.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes.
METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE \"Medical Center Hospital of the President\'s Affairs Administration of the Republic of Kazakhstan\". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0.
RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively).
CONCLUSIONS: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.