Diabetic Autonomic Neuropathy Research Articles

Efficacy of Neuro-muscular Electrical Stimulation for Orthostatic Hypotension Associated with Long-term Disuse and Diabetic Autonomic Neuropathy: A Case Report

Efficacy of Neuro-muscular Electrical Stimulation for Orthostatic Hypotension Associated with Long-term Disuse and Diabetic Autonomic Neuropathy: A Case Report

The vagus nerve cross-sectional area on ultrasound in patients with type 2 diabetes.

Diabetic neuropathy, including autonomic neuropathy is a serious complication related to type 2 diabetes mellitus (T2D). The vagus nerve (VN) is the longest nerve in the autonomic nervous system, and since diabetic neuropathy manifests first in longer nerves, the VN is commonly affected in early diabetic autonomic neuropathy. The use of high-resolution ultrasound for peripheral and cranial nerve imaging has significantly increased over the past 2 decades. The aim of the study is to compare the cross-sectional area of the VN in patients with T2D to that of a control cohort without T2D. A total of 52 VN cross-sectional areas were recorded from patients with T2D. A total of 56 VN cross-sectional areas were also recorded from asymptomatic subjects without T2D. In each subject, high-resolution ultrasound imaging of the bilateral VNs was performed in the short-axis between the common carotid artery and the internal jugular vein. The VN cross-sectional areas were recorded and compared. In the patients with T2D, HbA1c and fasting blood glucose levels were obtained as well as the duration of T2D in years and correlated with the cross-sectional areas. The bilateral VN cross-sectional areas were similar in both cohorts. Additionally, no correlation was seen between the VN cross-sectional areas, demographics, or clinical data of T2D. Our study demonstrated normal VN cross-sectional areas in patients with T2D without any significant relation with the patients' demographic or clinical data.

Autonomic diabetic neuropathies: A brief overview

This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for screening and diagnosis in research and clinical settings, the latest evidence on effective management, and novel perspectives on the impacts of social determinants of health in development and management of DAN. Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy, are by far the most studied. However, emerging data highlight the impact of other forms of autonomic neuropathies such as gastrointestinal and urogenital autonomic neuropathies, on healthcare and patients’ reported outcomes [1].

Association of Long-Term HbA1c Variability with Anxiety and Depression in Patients with Type 2 Diabetes: A Cross-Sectional Retrospective Study.

To explore the relationship between long-term glycemic variability and anxiety and depression in patients with type 2 diabetes. A cohort comprising 214 individuals diagnosed with type 2 diabetes participated in this study. Comprehensive demographic and laboratory information was gathered for them. The evaluation of anxiety relied on the 7-item Generalized Anxiety Disorder Scale (GAD-7), while depression was assessed utilizing the 9-item Health Questionnaire (PHQ-9). Based on the presence or absence of anxiety and depression, participants were categorized into either the mood disorder or control groups. Subsequently, univariate and stepwise multiple binary logistic regression analyses were conducted to investigate the potential correlations between factors and the presence of anxiety and depression. The prevalence of anxiety disorders is 23%, and depression is 32%. The prevalence of smoking, diabetic autonomic neuropathy, stroke, and osteoporosis in the mood disorder group was significantly higher than that in the control group (P < 0.05), the glycated hemoglobin A1c variability score (HVS), mean hemoglobin A1c value, total cholesterol, urinary albumin/creatinine and systemic immune-inflammatory index (SII) were significantly higher in the control group (P < 0.05). The level of high-density lipoprotein in the mood disorder group was significantly lower than the control group (P < 0.05). In stepwise multiple binary logistic regression analyses, the main factors associated with anxiety were depression (P < 0.001, OR=117.581) and gender (P < 0.001, OR=9.466), and the main factors related to depression included anxiety (P < 0.001, OR=49.424), smoking (P=0.042, OR=2.728), HVS (P=0.004, OR=8.664), and SII (P=0.014, OR=1.002). Persistent fluctuations in blood glucose levels have been linked to anxiety and depression. Consequently, maintaining an optimal level of glycemic control and minimizing fluctuations becomes imperative in the comprehensive management of diabetes.

Ceftriaxone-associated Biliary Pseudolithiasis with Elderly Type 1 Diabetes Mellitus: Two Case Reports.

Biliary pseudolithiasis is a ceftriaxone (CTRX)-induced complication, but the risk in cases of elderly type 1 diabetes mellitus (T1DM) is unclear. Case 1: A 78-year-old woman with T1DM complicated by diabetic autonomic neuropathy was admitted with pneumonia and treated with CTRX. On day 8, biliary pseudolithiasis and cholecystitis were observed. Case 2: an 80-year-old woman with T1DM was suspected of having a urinary tract infection and treated with CTRX. After a week, she developed asymptomatic biliary pseudolithiasis with gastroparesis. CTRX-associated biliary pseudolithiasis was thus noted in these cases of elderly T1DM. CTRX should be cautiously administered, especially in elderly T1DM patients with diabetic autonomic neuropathy.

Sudoscan as substitute for quantitative sudomotor axon reflex test in composite autonomic scoring scale and its correlation with composite autonomic symptom scale 31 in type 2 diabetes

ObjectiveThis study aims to evaluate the feasibility of substituting electrochemical skin conductance measurement using SUDOSCAN for sudomotor function testing in the Composite Autonomic Scoring Scale (CASS) and to correlate the results with the Composite Autonomic Symptom Scale 31 (COMPASS 31) among patients with type 2 diabetes mellitus (T2DM). MethodsFifty patients with T2DM underwent cardiovascular autonomic function testing and the SUDOSCAN test and completed the COMPASS 31 questionnaire. We developed a SUDOSCAN-based sudomotor subscore as a substitute for the original sudomotor subscore (based on the quantitative sudomotor axon reflex test [QSART]). The modified CASS score (SUDOSCAN-based sudomotor subscore combined with the adrenergic and cardiovagal subscores) and the original CASS score without suomotor assessment (sum of the adrenergic and cardiovagal subscores) were obtained according to the results of the cardiovascular autonomic function and SUDOSCAN tests. ResultsThe total COMPASS 31 score was significantly correlated with the modified CASS score (p = 0.019 and 0.037 for the raw and weighted scores, respectively) but not with the CASS score without sudomotor assessment. After adding the SUDOSCAN-based sudomotor subscore, the number of patients identified as having diabetic autonomic neuropathy (DAN) increased from 24 (48 %, based on the CASS score without sudomotor assessment) to 35 (70 %, based on the modified CASS score). The modified CASS score enhances the accuracy of assessing autonomic function and improves the diagnosis of diabetic autonomic neuropathy (DAN) among patients with T2DM. In medical settings where QSART is not accessible, SUDOSCAN testing offers a practical and efficient alternative.

CADD Studies in the Discovery of Potential ARI (Aldose Reductase Inhibitors) Agents for the Treatment of Diabetic Complications.

The lack of currently available drugs for treating diabetes complications has stimulated our interest in finding new Aldose Reductase inhibitors (ARIs) with more beneficial biological properties. One metabolic method uses aldose reductase inhibitors in the first step of the polyol pathway to control excess glucose flux in diabetic tissues. Computer-aided drug discovery (CADD) is key in finding and optimizing potential lead substances. AR inhibitors (ARI) have been widely discussed in the literature. For example, Epalrestat is currently the only ARI used to treat patients with diabetic neuropathy in Japan, India, and China. Inhibiting R in patients with severe to moderate diabetic autonomic neuropathy benefits heart rate variability. AT-001, an AR inhibitor, is now being tested in COVID-19 to see how safe and effective it reduces inflammation and cardiac damage. In summary, these results from animal and human studies strongly indicate that AR can cause cardiovascular complications in diabetes. The current multi-center, large-scale randomized human study of the newly developed powerful ARI may prove its role in diabetic cardiovascular disease to establish therapeutic potential. During the recent coronavirus disease (COVID-19) outbreak in 2019, diabetes and cardiovascular disease were risk factors for severely negative clinical outcomes in patients with COVID19. New data shows that diabetes and obesity are among the strongest predictors of COVID-19 hospitalization. Patients and risk factors for severe morbidity and mortality of COVID- 19.

Chronic kidney disease in a patient with type 1 diabetes mellitus: expectations and reality based on a case report

Decompensation of diabetes mellitus leads to serious consequences due to the presence of vascular complications: microangiopathy (retinopathy and nephropathy), macroangiopathy (myocardial infarction, stroke, peripheral arterial disease), neuropathy (diabetic peripheral and autonomic neuropathy). The professional approach of a specialist and a patient to the treatment of diabetes leads to a favorable course of the disease and the achievement of compensation. The presented clinical case clearly shows the connection between the decompensation of diabetes mellitus and the development of severe consequences.

Influence of Fibrinogen/Albumin Ratio and Fibrinogen/Pre-Albumin Ratio on Cardiac Autonomic Neuropathy in Type 2 Diabetes.

Subclinical inflammation may be involved in the pathogenesis of diabetic cardiac autonomic neuropathy (DCAN). The purpose of the study is to explore the relationship between novel inflammation biomarkers fibrinogen-albumin ratio (FAR), fibrinogen-prealbumin ratio (FPR), and DCAN in type 2 diabetes mellitus (T2DM). A total of 715 T2DM patients were enrolled in this retrospective study, divided into non-DCAN (n=565) and DCAN (n=150) groups by Ewing's test. Serum fibrinogen, albumin, prealbumin, routine inflammatory and other biochemical markers were measured. Patients with versus without DCAN had higher FAR (10.29 ± 4.83 vs 7.22 ± 2.56 g/g, P < 0.001) and FPR (2.19 ± 1.85 vs 1.43 ± 0.93 g/mg, P < 0.001). As FAR and FPR quartiles increased, the incidence of DCAN increased (Quartile 1 vs Quartile 4: 8.4 vs 42.7%, 9.6 vs 39.2%, respectively, P < 0.001), heart rate variability parameters decreased (P < 0.001); the incidence of diabetic nephropathy, retinopathy and peripheral neuropathy tended to be higher and inflammation factors were more active (P < 0.01). FAR (OR, 95% CI: 1.16, 1.08-1.25, P < 0.001) and FPR (OR, 95% CI: 1.22, 1.03-1.44, P = 0.021) were independent determinants of DCAN; the risk of DCAN increased by approximately 65% and 27% with each increase in the standard deviation (SD) of FAR (OR per SD, 95% CI: 1.65, 1.29-2.11, P < 0.001) and FPR (OR per SD, 95% CI: 1.27, 1.04-1.56, P = 0.021). FAR and FPR are independent risk factors and may influence DCAN development through inflammation.

Autonomic Neuropathy in Ambulatory Type 2 Diabetes Mellitus Patients: A Single-arm Prospective, Observational Study

Abstract Introduction: Diabetic autonomic neuropathy (DAN), a serious complication of diabetes, is a significant contributor to increased morbidity and mortality. Although DAN often coexists with different peripheral neuropathies and other complications, it may also present in isolation. The present study aimed to understand the DAN status of a cohort of ambulatory type 2 diabetics in a tertiary care setting. Methods: A single-arm prospective observational study was carried out, where enrolled patients were interviewed for basic demographics and comorbidities, screened for symptoms of autonomic dysregulation, and other risk factors such as smoking and alcoholism. Based on the presence of overt symptoms, they were divided into two groups with or without any overt symptoms of autonomic neuropathy. Both groups were subjected to a battery of autonomic neuropathy tests, and their DAN status was characterized based on the observed scores. Results: The overall prevalence of DAN, as observed in our study, was 36%. Of 108 patients, 97 presented with one or more symptoms of autonomic dysregulation, whereas the rest, 10.1%, were without any symptoms. Among heart rate-based tests, a significant (P &lt; 0.001) decrease followed by an increase in the Valsalva ratio was observed in 6 months and 12 months, respectively. A significant decrease (P &lt; 0.001) in deep breathing test (E: I) values was observed in the 12th month. Most of the DAN patients presented with moderate autonomic dysfunction, followed by mild and severe, respectively. However, no significant change in DAN severity was noted with time. Conclusion: Using simple cardiovascular tests, DAN can be detected during the asymptomatic phase of the disease.

Ultrasound characteristics of the cervical vagus nerve in patients with type 2 diabetes and diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) and autonomic neuropathy are commonly coexistent in patients with type 2 diabetes mellitus (T2DM). Current assessment tools for diabetic neuropathy remain complicated and limited. We aimed to investigate the sonographic changes of the cervical vagus nerve in DPN patients with T2DM. Patients with T2DM were divided into a DPN group (DPN, n = 44) and non-DPN controls (NDPN, n = 43) based on electromyogram results. Another 43 healthy controls (CON) were included. High-frequency ultrasound (HFU) of the vagus nerve was performed in all participants. Compared with controls, the honeycomb structure of the vagus nerve in patients with T2DM decreased, p < 0.001. The DPN group had higher cross-sectional area (CSA) of the right vagus nerve than the NDPN group (1.60 ± 0.52 vs. 2.00 ± 0.57 mm2, p =0.001). Logistic regression showed that right vagus nerve CSA was a risk factor of DPN (odds ratio [OR] = 3.924, p = 0.002). Right vagus nerve CSA was positively correlated with diabetes duration (p = 0.003), and negatively correlated with the motor conduction velocity (MCV) of the ulnar, median, and common peroneal nerves (p < 0.001 for all), as well as the sensor conduction velocity (SCV) of the ulnar and median nerve (both p < 0.005). HFU shows thickening of the cervical vagus nerve in patients with DPN, which is a potential diagnostic feature of diabetic neuropathy.

Omega-3 polyunsaturated fatty acids: Effects on the arterial stiffness and heart rate variability in patients with diabetic cardiac autonomic neuropathy

Omega-3 polyunsaturated fatty acids: Effects on the arterial stiffness and heart rate variability in patients with diabetic cardiac autonomic neuropathy

Diabetic cardiac autonomic neuropathy: insulin resistance, lipid profile, and omega-3 polyunsaturated fatty acids

The significance of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM) has been not fully appreciated and there is no unified treatment algorithm. Aim: The aim of study was to investigate the effects of -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) parameters in patients with T2DM and definite CAN. The study involved 33 patients with T2DM and definite CAN. Patients were allocated into two treatment groups: 1st group - 15 patients received standard hypoglycaemic therapy - control (n = 15); 2nd group (n = 18) - standard hypoglycaemic therapy and 1 capsule/day of the ω-3 PUFAs (1 g, including 90 % ω-3 PUFAs) for three months. The concentrations of glucose, glycated haemoglobin A1c, immunoreactive insulin in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The insulin resistance Homeostasis model assessment, atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG glucose (TyG) index were calculated. Obtained results of our study could witness that the prescription of -3 PUFAs was accompanied by a statistically significant decrease in TG concentration; AC, TG/LDL-C, TG/TC, TG/LDL-C, TyG index parameters and increase in HDL-C levels (compared to control). Conclusions. Obtained results justify the appropriateness of -3 PUFAs prescriptions to patients with T2DM and definite CAN.

Clinical characteristics and influencing factors of hypoglycemia in hospitalized patients with type 2 diabetes mellitus: A cross-sectional study.

Analysed clinical characteristics and influencing factors for hypoglycemia in hospitalized patients with type 2 diabetes mellitus (T2DM), and providing a scientific reference for precision nursing care of hypoglycemia in hospitalized patients with T2DM. A cross-sectional study. This study involved 378 hospitalized patients diagnosed with T2DM who have suffered hypoglycemia. Through questionnaires and electronic medical records to obtain the data concerning the general information, clinical symptoms, all recorded blood glucose information, and the diabetes knowledge and self-management level of the patients. The clinical characteristics and influencing factors for hypoglycemia were analysed on the basis of the classification of hypoglycemia published by the American Diabetes Association in 2020. Among 378 patients, 207 patients (54.76%) were experiencing Grade 1 hypoglycemia and 171 patients (45.24%) were experiencing Grade 2 hypoglycemia. Hypoglycemia and Grade 2 hypoglycemia in patients with T2DM occurred predominantly within the first 3 days of hospitalization. Hypoglycemia occurred most frequently after breakfast (74 cases, 19.6%), of which Grade 1 hypoglycemia and Grade 2 hypoglycemia accounted for 50%, respectively. Multivariable logistic regression identified risk factors for Grade 2 hypoglycemia in hospitalized patients with type 2 diabetes: older age, longer duration of diabetes, low body weight, diabetic nephropathy stages 4-5, diabetic autonomic neuropathy, inadequate self-management ability and diabetes knowledge, and lower educational background. Hypoglycemia in type 2 diabetes occurs in the first 3 days during the hospitalization and most often after breakfast during the full day. Identifying high-risk individuals and providing a scientific reference for precision nursing care of hypoglycemia in hospitalized patients with T2DM.

Autonomic Nerve Function Tests in Patients with Diabetes

The autonomic nervous system (ANS) regulates the internal functions of the body organs, such as heart rate, digestion, respiratory rate, pupil response, urination, and sexual arousal. The ANS is divided into two parts: the sympathetic and parasympathetic nervous systems. However, the ANS can be damaged or degenerated by metabolic problems including hyperglycemia, leading to diabetic autonomic neuropathy (DAN), which is a prevalent complication among diabetic patients. Cardiac autonomic neuropathy is an important form of DAN that results from an imbalance between the sympathetic and parasympathetic nerve responses. This imbalance can lead to symptoms such as resting tachycardia, postural hypotension, and orthostatic tachycardia along with other types of autonomic neuropathy. Special tests can be performed to evaluate and diagnose this condition, including cardiovascular autonomic function tests. The aim of this review is to discuss the various tests used to diagnose and monitor autonomic neuropathy in diabetic patients and how to use and interpret them effectively.

Cardiac autonomic neuropathy as risk factor of diabetic complications progression

Introduction. Diabetes mellitus (DM) is the most common and incapacitating endocrine disorder. Diabetic foot syndrome (DFS) is one of the most serious complications of DM, which is the main cause of nontraumatic lower-extremity amputations. Despite the efforts of the entire medical community, the survival rate of DFS patients with non-healing ulcers and after foot surgery does not exceed 50% over 5 years and is comparable to the survival rates of patients with colorectal cancer.Aim. It has been demonstrated that postsurgical diabetic foot wounds tend to chronization of inflammatory process. The diabetic autonomic neuropathy can be involved in diabetic foot damages. We hypothesized that progression of cardiovascular autonomic neuropathy (CAN) leads to aggressive microvascular complications of diabetes and delay the postsurgical wound healing in diabetic foot patients during 2 years of observation.Materials and methods. We examined 94 outpatients with postsurgical diabetic foot wounds and observation period of two years. The clinical neurological examination and standard cardiovascular autonomic reflex tests with identification of severe/advanced abnormalities were performed at baseline and after 2 years. The progression of CAN was diagnosed in cases of an increase in the amount of cardiovascular autonomic reflex tests by 1 score and more. The unsatisfactory result of wound treatment was detected in patients with wound healing delay and new cases of surgery debridement, foot amputations and Charcot foot during 2 years of observation.Results. The mean duration of diabetes was 10.7 year, HbA1c 8.3%, LDL-Chol 3.3 mmol/l, TG 1.8 mmol/l. The 51.1% patients had been amputated in the level of foot, 48.9% patients had surgery debridement. All patients had CAN, confirmed/severe forms in 57.4% cases. The progression of CAN was found in 22.3% patients, the most of them with functional stage at baseline. The aggressive course of CAN increased the risk of progression of diabetic sensomotor neuropathy (OR = 14.6; 95% CI 3.0–70.5; p = 0.0006), nephropathy (OR = 22.4; 95% CI 3.4–147.4; p = 0.0009) and unsatisfactory result of wound treatment (OR = 40; 95% CI 6.0–268.5; p = 0.0001).Conclusions. The patients with diabetic foot surgery wounds has high risk of confirmed/severe CAN and its progression during 2 years. The aggressive course of CAN associates with unsatisfactory result of wound treatment and progression of microvascular diabetic complications.

323-OR: Association of Silent Myocardial Infarction with Cardiac Autonomic Neuropathy among Asymptomatic Patients with Type 2 Diabetes

Background: Silent myocardial infarction (SMI) is a severe cardiovascular disease among patients with DM. Nowadays, the mechanism of SMI is not clear, but diabetic cardiac autonomic neuropathy (CAN) is assumed to be the most probable reason. However, whether SMI is associated with CAN remains controversial. Therefore, we aimed to evaluate the relationship between SMI and CAN in asymptomatic patients with T2DM. Methods: This is a hospital-based observational study. 4055 T2DM patients who were screened for CAN by Holter monitoring were investigated. Q-waves SMI was detected by ECG. The sensitivity and specificity of ECG-detected SMI by computed tomography-coronary angiography (CTA). Results: A total of 4055 patients were screened. At last, we included 1015 patients with T2DM. In the included population, 508 cases (50%) had CAN. Patients with CAN were more likely to be older and have higher levels of TC, LDL-c, Cr, UA, and Hcy (p&amp;lt;0.05). A total of 466 cases of SMI were detected by ECG, and the prevalence of SMI was 45.9% in 1015 patients. Compared with T2DM patients without CAN, patients with CAN had a higher prevalence of SMI (73.4% vs 26.6%, p&amp;lt;0.001). Multivariate logistic regression analysis confirmed that concomitant CAN was an independent predictor of the risk of SMI in T2DM patients (OR=7.53, 95%CI:2.98-19.02, p&amp;lt;0.001). Among the 133 patients who underwent coronary CTA, 55 (41.0%) cases had SMI, and 36 of them had Q-waves on ECG. The sensitivity and specificity of SMI detected by ECG were 65.5% and 91.0%, respectively. In 133 T2DM patients, patients with CAN also had a higher risk of occurring SMI than those without CAN (65.5% vs 34.5%, p&amp;lt;0.001). Conclusion: In asymptomatic T2DM patients, the occurrence of SMI was independently associated with CAN. Therefore, we should pay attention to the possibility of SMI in asymptomatic T2DM patients clinically. In particular, the monitoring should be strengthened when patients combined with diabetic CAN. Disclosure Y.Fu: None. L.Wu: None. Y.Yang: None. B.Qin: None. Q.Luo: None. Y.Chen: None. Y.Zhu: None.

The potential role of CpG oligodeoxynucleotides on diabetic cardiac autonomic neuropathy mediated by P2Y12 receptor in rat stellate ganglia.

Cardiac autonomic neuropathy has a high prevalence in type 2 diabetes, which increases the risk of cardiovascular system disorders. CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to have cardioprotection and cellular protection. Our previous work showed that P2Y12 in stellate ganglia (SG) is involved in the process of diabetic cardiac autonomic neuropathy (DCAN). Here, we aim to investigate whether CpG-ODN 1826 plays a protective role in DCAN and whether this beneficial protection involves regulation of the P2Y12-mediated cardiac sympathetic injury. Our results revealed that CpG-ODN 1826 activated TLR9 receptor, improved the abnormal blood pressure (BP), heart rate (HR), heart rate variability (HRV) and sympathetic nerve discharge (SND) activity in diabetic rats and reduced the up-regulated NF-κB, P2Y12 receptor, TNF-α and IL-1β in SG. Meanwhile, CpG-ODN 1826 significantly decreased the elevated ATP, nuclear receptor coactivator 4 (NCOA4), iron, ROS and MDA levels and increased GPX4 and GSH levels. In addition, CpG-ODN 1826 contributes to maintain normalization of mitochondrial structure in SG. Overall, CpG-ODN 1826 alleviates the sympathetic excitation and abnormal neuron-glial signal communication via activating TLR9 receptors to achieve a balance of autonomic activity and relieve the DCAN in rats. The mechanism may involve the regulation of P2Y12 receptor in SG by reducing ATP release and NF-κB expression, which counteract neuroinflammation and ferroptosis mediated by activated P2Y12 in SG.

Highlights from the 82nd ADA Scientific Sessions and the 58th EASD Meeting on Diabetic Neuropathy.

Diabetic neuropathy is one of the commonest diabetic complications. It affects 30-50% of people with diabetes mellitus (DM) and may cause severe pain and foot ulcers. Distal symmetric polyneuropathy and diabetic autonomic neuropathy are the main manifestations of diabetic neuropathy. The American Diabetes Association's (ADA) 82nd Scientific Sessions took place in June 2022 in New Orleans, Louisiana, and the 58th European Association for the Study of Diabetes (EASD) Annual Meeting was held in September 2022 in Stockholm, Sweden. Herein, we describe interesting studies in the field of diabetic neuropathy presented in these two meetings.

Lianmei Qiwu Decoction relieves diabetic cardiac autonomic neuropathy by regulating AMPK/TrkA/TRPM7 signaling pathway

This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.