Chronic stress adversely affects intestinal health, but the specific neural pathways linking the brain to intestinal tissue are not fully understood. Here, we show that chronic stress-induced activation of the central amygdala-dorsal motor nucleus of the vagus (CeA-DMV) pathway accelerates premature aging and impairs the stemness of intestinal stem cells (ISCs). This pathway influences ISC function independently of the microbiota, the hypothalamic-pituitary-adrenal (HPA) axis, the immune response, and the sympathetic nervous system (SNS). Under chronic stress, DMV-mediated vagal activation prompts cholinergic enteric neurons to release acetylcholine (ACh), which engages ISCs via the M3 muscarinic acetylcholine receptor (CHRM3). This interaction activates the p38 mitogen-activated protein kinase (MAPK) pathway, triggering growth arrest and mitochondrial fragmentation, thereby accelerating an aging-like decline in ISCs. Together, our findings provide insights into an alternative neural mechanism that links stress to intestinal dysfunction. Strategies targeting the DMV-associated vagal pathway represent potential therapeutic approaches for stress-induced intestinal diseases.

Cardiac autonomic neuropathy (CAN) is a progressive condition associated with chronic diseases like diabetes, requiring regular reviews. Current CAN diagnostic methods are often time-consuming and lack precision. This study presents a novel, two-stage classification model designed to improve CAN diagnostic efficiency. Using a dataset of 1335 patient entries, including inflammatory markers and autonomic function tests (CARTs), the model first classifies patients based on six inflammatory markers- Interleukin-6 (IL-6), C-reactive protein (CRP), Interleukin-1 beta (IL-1beta), Interleukin-10 (IL-10), Monocyte Chemoattractant Protein-1 (MCP-1), and Insulin-like growth factor-1 (IGF-1). In this initial stage, the model achieves 0.893 accuracy for 31.46% of cases in the three-class CAN model at a 0.80 threshold. For cases requiring further assessment, the second stage incorporates CARTs, improving overall accuracy to 0.933. Notably, 98.87% of cases are accurately classified using only a subset of CARTs, with just 1.12% needing all five tests. Additionally, we developed a web application that utilizes Shapley plots to visualize and explain the contribution of each marker, facilitating interpretation for clinical use. This two-stage approach underscores the diagnostic relevance of inflammatory markers, providing clinicians with a streamlined, resource-efficient tool for timely CAN diagnosis and intervention.

Diabetes is a major risk factor for cardiovascular diseases. However, some reports have shown that diabetes has a low prevalence and is associated with favorable outcomes in takotsubo syndrome (TTS). This phenomenon, known as the "diabetes paradox," in which diabetes plays a protective role in the development of TTS, remains controversial. Therefore, we investigated the prevalence of diabetes and the prognostic impact of diabetes and glycemic control in patients with TTS. Using the Tokyo Cardiovascular Care Unit Network registry between 2015 and 2021, we identified 1,226 eligible patients with TTS (median age 77 years, male proportion 21%). The prevalence of diabetes, its clinical characteristics, and its association with in-hospital mortality were assessed. The prevalence of diabetes was 17.0% in TTS and 15.8% in the general population, with no significant difference (p = 0.445). Patients with diabetes were older and had higher body mass index, brain natriuretic peptide, and C-reactive protein levels than patients without diabetes. Patients with diabetes tended to have a higher in-hospital mortality rate than those without (6.3% vs 3.4%, p = 0.057). The multivariable analysis revealed that neither diabetes (odds ratio 1.83, 95% confidence interval 0.88 to 3.80, p = 0.106) nor hemoglobin A1c level was significantly associated with in-hospital mortality. In conclusion, diabetes is not uncommon and not a good prognostic factor in this multicenter registry. Our observations do not support a protective effect of diabetes on the emergence and outcomes of TTS.

Autonomic neuropathy assessment is needed for the diagnosis and prognostication of different clinical disorders. Heart rate variability (HRV) and autonomic reactivity assessment by Ewing's battery of tests form the cornerstones of laboratory assessment of cardiac autonomic neuropathy evaluation.

While these tests are routinely used, there are conflicting reports regarding the visit-to-visit repeatability of these tests. Therefore, we assessed autonomic measures derived using aforementioned tests on multiple visits in healthy subjects.

We enrolled 31 healthy subjects and performed autonomic function evaluation on five visits by assessment of HRV and autonomic reactivity on day 1 forenoon and afternoon, next day, one week later and one month later. Repeatability assessment was evaluated using Intraclass correlation coefficients. Values were defined as moderate, good and excellent based on previously reported criteria.

Thirty-one subjects completed all five visits (17 males, 14 females; mean age = 29 ± 5.44 years). While time-domain measures demonstrated good to excellent repeatability, frequency-domain measures were only moderately repeatable. Autonomic reactivity indices also displayed good to excellent repeatability with the exception of blood pressure response to orthostatic challenge which was moderately repeatable.

We recommend that sole reliance on frequency domain metrics for HRV assessment should be avoided. HRV indices and autonomic reactivity measures may continue to be used for cardiac autonomic neuropathy assessment.

To investigate the correlation of advanced glycation end products (AGEs) with diabetic cardiovascular autonomic neuropathy (DCAN). Factors affecting DCAN and those related to skin AGE accumulation in patients with DCAN were analyzed.

A total of 192 patients with type 2 diabetes mellitus (T2DM) who were hospitalized in the Department of Endocrinology of Hefei Second People's Hospital from November 2020 to December 2022 were included and divided into DCAN (n=121) and No_DCAN (n=71) groups based on the results of Ewing test. All patients completed the detection of skin AGEs accumulation. The clinical features of the two groups were analyzed; the factors affecting DCAN were analyzed by multiple logistic regression analysis, and those related to skin AGE accumulation in patients with DCAN were analyzed by Spearman correlation analysis and Pearson correlation analysis.

Compared with the No_DCAN group, the combined DR ratio, fasting plasma glucose (FPG), and skin AGEs were increased in the DCAN group (all P<0.05). Multivariate logistic regression analysis showed that FPG, combined DR, and skin AGEs all affected DCAN (P<0.05). Spearman correlation analysis showed that skin AGE accumulation in patients with DCAN was correlated with sex (male or female) and the presence of vascular plaques (All P<0.05). Pearson correlation analysis showed that skin AGE accumulation in patients with DCAN was correlated with age, diabetes course, diastolic blood pressure, uric acid, creatinine and UACR levels (All P<0.05).

Skin AGEs, combined DR and FPG affected DCAN, and skin AGEs, combined DR and FPG were closely related to the incidence of DCAN. Sex (male or female), presence of vascular plaques, age, diabetes course, diastolic blood pressure, uric acid levels, creatinine levels and UCAR levels were correlated with skin AGE accumulation in patients with DCAN.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms. Study participants had an established diagnosis of HF with NYHA Class I-III and LVEF ≤ 45%. Patients were required to have an implanted cardiac defibrillator (ICD) or cardiac resynchronization therapy (CRT) device because of the potential for bradycardia or AV conduction delay, which may be induced by BAY 2413555. The study period included a screening and run-in period, followed by a treatment period of over 28 days, consisting of two parts, A and B, comprising 14 days each. Participants were randomized into 1 of 3 arms: a placebo arm and two BAY 2413555 arms-one receiving 1.25 mg in both Part A and Part B (BAY 1.25 mg-1.25 mg) and the other receiving 1.25 mg in Part A followed by 5 mg in Part B (BAY 1.25 mg-5 mg). The primary safety endpoint was the number of participants with treatment-emergent adverse events (TEAEs). Secondary endpoints included number of participants with high degree AV block or symptomatic pauses/ bradycardia and changes from baseline in resting heart rate after 2 and 4 weeks of dosing with BAY 2413555. Changes from baseline in heart rate recovery (HRR) at 1 and 2 min after exercise testing and chronotropic reserve (CR) were also assessed. Of the anticipated 129 participants, 22 participants were randomized: 7 to placebo, 8 to BAY 1.25 mg-1.25 mg, and 7 to BAY 1.25 mg-5 mg. The study was terminated early based on new and unexpected preclinical findings from a chronic animal toxicology study in monkeys in which evidence of increased vascular inflammation was observed, leading to a no longer favorable risk-benefit balance for the intended long-term (i.e., life-long) treatment of heart failure patients. Comparable adverse events were not encountered in REMOTE-HF. Overall, until the termination of the study, BAY 2413555 was safe and well tolerated, with no deaths or TEAEs leading to discontinuation, and no symptomatic bradycardia or AV blocks observed. There was a larger change in the mean HRR at 60 s in the pooled BAY 2413555 treatment arms in Part A (1.25 mg) compared to the placebo (+ 7.3 vs. -6.7 bpm), indicating enhanced cardiac parasympathetic activity. Administration of 1.25 mg and 5 mg BAY 2413555 was safe and well tolerated in both active treatment arms, with no concerning safety findings observed. However, due to the limited number of subjects resulting from early termination, the results should be considered with caution and viewed as exploratory. There were promising signs of target engagement, providing grounds for further exploration of the mechanism.

Cardiovascular autonomic neuropathy (CAN) is a chronic complication of diabetes. As obesity is a major risk factor for CAN, we hypothesized that metabolic bariatric surgery (MBS) could improve CAN indices in Korean patients with obesity.

Patients who underwent bariatric surgery between February 2020 and June 2022 were prospectively recruited. CAN was conducted once before surgery and again after surgery, using the Ewing method and heart rate variability (HRV) analysis (standard deviation of the NN interval [SDNN], root mean square of successive RR interval difference [RMSSD], and spectral analysis).

A total of 47 patients were included. The mean age was 39.8 ± 8.7 years, 15 (31.9%) were male, and 26 (55.3%) had diabetes. Resting HR before surgery was 81.0 ± 12.3 bpm, which decreased significantly to 68.0 ± 9.3 bpm after surgery (P < 0.001). Changes in HR and BP according to the Valsalva maneuver, postural changes, and handgrip were not significantly different before and after surgery. However, SDNN significantly increased from 25.2 [15.1, 33.5] to 38.0 [25.4, 45.0] ms (P < 0.001), and RMSSD also significantly increased from 17.0 [9.2, 31.8] to 28.2 [15.3, 45.6] ms (P = 0.001). Both low-frequency power (LF) and high-frequency power (HF) increased significantly, and the LF/HF ratio significantly decreased from 2.1 ± 1.6 to 1.3 ± 1.3 (P = 0.010). Loss of weight, fat mass, and lean body mass were independently associated with improving the HRV variables.

MBS improved HRV variables, and these changes were mainly associated with postoperative weight loss.

The association between diabetes mellitus (DM) and masked hypertension (MH) in ambulatory blood pressure (BP) monitoring is established, but its relationship with home BP monitoring (HBPM) remains uncertain. This web-based database study compared BP phenotypes in individuals using (n = 51,194; 6.05% with DM) and not using (n = 55,320; 0.63% with DM) antihypertensive medications (AH) undergoing HBPM. Multivariable logistic regression analysis revealed similar MH and white-coat hypertension (WCH) prevalence in individuals with or without DM, irrespective of AH use. However, among AH non-users, DM was associated with a higher likelihood of normotension (OR 1.35, 95%CI 1.09-1.66; p = 0.006) and a lower likelihood of sustained hypertension (OR 0.77, 95%CI 0.60-0.99; p = 0.039) compared to individuals without DM. These findings suggest that while DM does not significantly impact MH and WCH in HBPM, it may influence normotension and sustained hypertension rates in AH non-users. Likelihood of diabetes mellitus according to blood pressure phenotypes. AH - antihypertensive medications; CH - controlled hypertension; MH - masked hypertension; MUCH - masked uncontrolled hypertension; NT - normotension; SH - sustained hypertension; SUCH - sustained uncontrolled hypertension; WCH - white-coat hypertension; WUCH - white-coat uncontrolled hypertension.

Diabetes mellitus (DM) affects 537 million people as of 2021, and is projected to rise to 783 million by 2045. This positions DM as the ninth leading cause of death globally. Among DM patients, cardiovascular disease (CVD) is the primary cause of morbidity and mortality. Notably, the prevalence rates of CVD is alarmingly high among diabetic individuals, particularly in North America and the Caribbean (46.0%), and Southeast Asia (42.5%). The predominant form of CVD among diabetic patients is coronary artery disease (CAD), accounting for 29.4% of cases. The pathophysiology of DM is complex, involving insulin resistance, β-cell dysfunction, and associated cardiovascular complications including diabetic cardiomyopathy (DCM) and cardiovascular autonomic neuropathy (CAN). These conditions exacerbate CVD risks underscoring the importance of managing key risk factors including hypertension, dyslipidemia, obesity, and genetic predisposition. Understanding the genetic networks and molecular processes that link diabetes and cardiovascular disease can lead to new diagnostics and therapeutic interventions. Imeglimin, a novel mitochondrial bioenergetic enhancer, represents a promising medication for diabetes with the potential to address both insulin resistance and secretion difficulties. Effective diabetes management through oral hypoglycemic agents (OHAs) can protect the cardiovascular system. Additionally, certain antihypertensive medications can significantly reduce the risk of diabetes-related CVD. Additionally, lifestyle changes, including diet and exercise are vital in managing diabesity and reducing CVD risks. These interventions, along with emerging therapeutic agents and ongoing clinical trials, offer hope for improved patient outcomes and long-term DM remission. This study highlights the urgent need for management strategies to address the overlapping epidemics of DM and CVD. By elucidating the underlying mechanisms and risk factors, this study aims to guide future perspectives and enhance understanding of the pathogenesis of CVD complications in patients with DM, thereby guiding more effective treatment strategies.

Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients.

Background Cardiac autonomic neuropathy (CAN) is the most underdiagnosed consequence of diabetes because standard hospital settings do not provide consistent diagnostic criteria or testing resources. It is still unclear how diabetic peripheral neuropathy (DPN) and CAN are related. Therefore, this study aimed to determine the prevalence of CAN in individuals with type 2 diabetes mellitus who had isolated DPN without other microvascular or macrovascular complications. Methodology A total of 35 type 2 diabetes mellitus patients with isolated DPN (group 1) and an equal number of sex- and age-matched patients without DPN (group 2) underwent CAN testing. Results were compared between the two groups. Results A significantly higher prevalence of isolated parasympathetic (28.57 vs. 11.42%), isolated sympathetic (22.85 vs. 8.57%), and combined autonomic dysfunction (37.14 vs. 2.85%) was found in the neuropathic group compared to the non-neuropathic group. Group 1 exhibited more abnormal parasympathetic nervous system test results and increased diastolic pressure during sustained handgrip compared to group 2 (all p-values <0.05). Conclusions A significantly higher prevalence of cardiac autonomic dysfunction is seen in patients with DPN without other microvascular or macrovascular complications, irrespective of age, sex, or duration of diabetes mellitus. Patients with a higher body mass index were found to have significantly increased cardiac autonomic dysfunction.

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.

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.

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).

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.

We examined heart rate variability (HRV) and baroreflex sensitivity (BRS) disease- and age-related response at 10-and 60-min after an acute high-intensity interval (HIIE) and moderate continuous exercise (MICE) in older adults with and without type 2 diabetes mellitus (T2DM) and healthy young adults.

Twelve older male adults with (57-84 years) and without T2DM (57-76 years) and 12 healthy young male adults (20-40 years) completed an isocaloric acute bout of HIIE, MICE, and a non-exercise condition in a randomized order. Time and Wavelets-derived frequency domain indices of HRV and BRS were obtained in a supine position and offline over 2-min time-bins using Matlab.

HIIE but not MICE reduced natural logarithm root mean square of successive differences (Ln-RMSSD) (d = - 0.85; 95% CI - 1.15 to - 0.55 ms, p < 0.001), Ln-high-frequency power (d = - 1.60; 95% CI - 2.24 to - 0.97 ms2; p < 0.001), and BRS (d = - 6.32; 95% CI - 9.35 to - 3.29 ms/mmHg, p < 0.001) in adults without T2DM (averaged over young and older adults without T2DM), returning to baseline 60 min into recovery. These indices remained unchanged in older adults with T2DM after HIIE and MICE. Older adults with T2DM had lower resting Ln-RMSSD and BRS than aged-matched controls (Ln-RMSSD, d = - 0.71, 95% CI - 1.16 to - 0.262 ms, p = 0.001; BRS d = - 3.83 ms/mmHg), 95% CI - 6.90 to - 0.76, p = 0.01).

Cardiovagal modulation following acute aerobic exercise is intensity-dependent only in adults without T2DM, and appears age-independent. These findings provide evidence of cardiac autonomic impairments in older adults with T2DM at rest and following aerobic exercise.

Background Cardiovascular autonomic dysregulation is a known complication of Type 2 diabetes mellitus (T2DM), characterized by dysregulation in heart rate (HR) and blood pressure (BP). These disruptions in cardiovascular autonomic control can significantly influence the morbidity and mortality associated with the disease. Objectives This study aims to investigate how T2DM affects cardiovascular autonomic functions by comparing responses in HR, BP, and specific autonomic function tests between a control group without diabetes and a study group with diabetes. The research questions focus on assessing HR variability, baroreflex sensitivity, and other autonomic parameters to determine the extent of cardiovascular autonomic dysregulation in diabetic patients.  Methods This cross-sectional study involved 200 adults, divided equally between a control group (n = 100) and a T2DM study group (n = 100). The exclusion criteria included cardiovascular diseases and renal impairment. Data collection involved assessing baseline characteristics such as age and BMI. Cardiovascular measures, including HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were recorded after a five-minute rest. Autonomic function tests assessed sympathetic and parasympathetic responses, including the cold pressor test and the isometric hand grip exercise test. The statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States), focusing on independent t-tests to compare between groups, considering p-values <0.05 as significant. Potential confounding variables like age and BMI were accounted for in the analysis to ensure robust findings  Results The study group showed a higher average BMI (28.95 ± 5.60) compared to the control group (26.50 ± 5.70) and an increased resting HR (74.20 ± 8.60 bpm vs. 69.30 ± 9.10 bpm). The SBP was slightly higher in the study group (115.00 ± 19.00 mmHg vs. 114.50 ± 8.90 mmHg), while the DBP was lower (71.50 ± 10.70 mmHg vs. 72.80 ± 6.70 mmHg). The autonomic function tests showed a smaller increase in SBP (106.80 ± 11.00 mmHg) and a larger increase in DBP (75.90 ± 8.30 mmHg) upon standing in the study group compared to controls. The cold pressor test indicated increased sympathetic activity in the study group, with significant rises in SBP (133.70 ± 10.30 mmHg) and DBP (83.40 ± 9.00 mmHg) compared to the control group (SBP: 114.31 ± 11.87 mmHg, DBP: 71.85 ± 8.67 mmHg). These findings demonstrate marked differences in cardiovascular autonomic responses between the groups. Conclusions This study demonstrates that T2DM significantly impacts cardiovascular autonomic functions, with diabetic patients showing altered HR and BP indicative of increased sympathetic and decreased parasympathetic activity. These autonomic dysfunctions may heighten cardiovascular risk in diabetic individuals. Our findings highlight the importance of monitoring and managing cardiovascular autonomic functions in diabetic patients to reduce their risk of cardiovascular complications. Further research should investigate the underlying mechanisms and the effectiveness of interventions to improve autonomic function in this population.

Transient global amnesia (TGA) often involves precipitating events associated with changes in autonomic nervous system (ANS), and heart rate variability (HRV) reflects the ANS state. This study aimed to investigate HRV changes after TGA. A retrospective analysis of HRV included patients diagnosed with TGA between January 2015 and May 2020. The time and frequency domains of HRV were compared among three groups: early (< 1 week after TGA, n = 19), late (1-4 weeks after TGA, n = 38), and healthy control (HC, n = 19). The Pearson's correlation between time and time-domain HRV was also examined. The standard deviation of NN intervals (SDNN) (early, 47.2; late, 35.5; HC, 41.5; p = 0.033) and root mean square of successive RR interval differences (RMSSD) (early, 38.5; late, 21.3; HC, 31.0; p = 0.006) differed significantly among the three groups. Post-hoc analysis showed statistically significant differences only in the early and late groups in both SDNN (p = 0.032) and RMSSD (p = 0.006) values. However, the frequency domain with total power, low-frequency and high-frequency powers, and low-frequency/high-frequency ratio did not differ. SDNN (Pearson correlation coefficient =- 0.396, p = 0.002) and RMSSD (Pearson correlation coefficient =- 0.406, p = 0.002) were negatively correlated with time after TGA. Changes in HRV occurred over time after the onset of TGA, with the pattern showing an increase in the first week and then a decrease within 4 weeks.

Cardiac Autonomic Dysfunction (CAD) is an overlooked cardiovascular risk factor in individuals with obesity-related hypertension. Despite its clinical significance, there is a notable lack of clarity regarding the pathophysiological correlates involved in its onset and progression.

The present study aimed to identify potential predictors of CAD in obesity-related hypertension.

A total of 72 participants (34 men and 38 women) were enrolled. Comprehensive evaluations were conducted, including cardiac autonomic function assessments, body composition estimation and biochemical analysis. Participants were categorized as CAD-positive or CAD-negative based on Ewing's criteria for autonomic dysfunction. Univariate logistic regression analysis was performed to identify potential predictors for CAD. Multivariate logistic regression models were further constructed by adjusting clinically relevant covariates to identify independent predictors of CAD.

Multivariate logistic regression analysis revealed that resting heart rate (HRrest), (odds ratio, confidence interval: 0.85, 0.78-0.93; p = 0.001) and percentage body fat (BF%), (odds ratio, confidence interval: 0.78, 0.64-0.96; p = 0.018) were significant independent predictors of CAD. Receiver Operating Characteristic curve analysis depicted optimal cut-off values for HRrest and BF% as > 74.1 bpm and > 33.6%, respectively. Multicolinearity analysis showed variance inflation factors (VIF) below the cautionary threshold of 3.

The HRrest and BF% emerged as significant independent predictors of CAD in obesity-related hypertension. Therapeutic strategies should target HRrest < 74.1 bpm and BF% < 33.6% to mitigate CAD risk in this population. Future trials are required to establish causal relationships and may consider additional confounding variables in obesity-related hypertension.

Diabetes mellitus is a complex disorder that requires continuous management to control blood sugar levels and prevent complications. Diabetic foot ulcers (DFU) are the most common complication in diabetic patients. A popular therapy modality with considerable advantages in the management of diabetic foot ulcers today is negative pressure wound therapy (NPWT).

This study aimed to review related articles about the efficacy as well as the complications or adverse effects of using NPWT on the healing of DFUs.

Searching English databases from PubMed, Ebscohost, Proquest and Science Direct was done to identify relevant citations published between January 2017 and January 2022. A combination of terms was used with the boolean formulation of "negative pressure wound therapy OR NPWT" OR "vacuum-assisted closure or VAC" AND "diabetic foot ulcers OR diabetic foot wound" AND "wound healing" AND "Conventional dressings" and map terms were also used for the subject heading. Some potentially relevant citations of articles from the bibliographies are also reviewed.

This study included 8 related articles consisting of 6 RCTs, 1 cohort study and 1 Quasy experimental study. There were various methodological techniques for using NPWT and outcome measures among studies. The results of this literature review showed that NPWT was more efficacious than the other conventional or advanced moist dressings. This therapy revealed a faster healing time with complete wound healing and formation of granulation tissue and reduction in wound size. The complications or adverse effects of NPWT, such as amputation rate, bleeding and pain, were not different from conventional or advanced moist dressings, though.

NPWT was more efficacious than other conventional or advanced moist dressings for the healing of DFUs. However, complications or adverse effects of using this therapy showed no significant difference with other conventional or advanced moist dressings.

Autonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM.

A total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR).

There were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR < 70%) compared with well controlled glucose levels (TIR > 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P < 0.001).

Poorly controlled glucose levels were independently associated with lower HRV in patients with DM. This was further substantiated by the independent continuous association between real-time measurements of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is caused by elevated blood sugar levels.

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.

Metabolic disorders such as obesity and type 2 diabetes (T2D) are increasingly prevalent worldwide, necessitating a deeper comprehension of their underlying mechanisms. However, translating findings from animal research to human patients remains challenging. This study aimed to investigate the long-term effects of Streptozotocin (STZ) on metabolic, cardiac, and somatosensory function in mice fed a Western diet (WD) of high fat, sucrose, and cholesterol with low doses of STZ administration compared to mice fed WD alone. In our research, we thoroughly characterized energy balance and glucose homeostasis, as well as allodynia and cardiac function, all of which have been previously shown to be altered by WD feeding. Notably, our findings revealed that the treatment of WD-fed mice with STZ exacerbated dysfunction in glucose homeostasis via reduced insulin secretion in addition to impaired peripheral insulin signaling. Furthermore, both WD and WD + STZ mice exhibited the same degree of cardiac autonomic neuropathy, such as reduced heart rate variability and decreased protein levels of cardiac autonomic markers. Furthermore, both groups developed the same symptoms of neuropathic pain, accompanied by elevated levels of activating transcription factor 3 (Atf3) in the dorsal root ganglia. These discoveries enhance our understanding of metabolic activity, insulin resistance, neuropathy, and cardiac dysfunction of diet-induced models of obesity and diabetes. The exacerbation of impaired insulin signaling pathways by STZ did not lead to or worsen cardiac and somatosensory dysfunction. Additionally, they offer valuable insights into suitable diet induced translational mouse models, thereby advancing the development of potential interventions for associated conditions.

Using supervised machine learning to classify the severity of cardiovascular autonomic neuropathy (CAN). The aims were 1) to investigate which features contribute to characterising CAN 2) to generate an ensembled set of features that best describes the variation in CAN classification.

Eighty-two features from demographic, beat-to-beat, biochemical, and inflammation were obtained from 204 people with diabetes and used in three machine-learning-classifiers, these are: support vector machine, decision tree, and random forest. All data were ensembled using a weighted mean of the features from each classifier.

The 10 most important features derived from the domains: Beat-to-beat, inflammation markers, disease-duration, and age.

Beat-to-beat measures associate with CAN as diagnosis is mainly based on cardiac reflex responses, disease-duration and age are also related to CAN development throughout disease progression. The inflammation markers may reflect the underlying disease process, and therefore, new treatment modalities targeting systemic low-grade inflammation should potentially be tested to prevent the development of CAN.

Cardiac reflex responses should be monitored closely to diagnose and classify severity levels of CAN accurately. Standard clinical biochemical analytes, such as glycaemic level, lipidic level, or kidney function were not included in the ten most important features. Beat-to-beat measures accounted for approximately 60% of the features in the ensembled data.

The purpose of this research is to investigate the effect of High Intensity Interval Training and Resistance training (HIITR) on heart rate variability (HRV), blood glucose, and plasma biomarkers levels in adolescents with type 1 diabetes (T1D).

24 boys with T1D (FBS: 274.66 ± 52.99, age: 15.2 ± 1.78 years, and BMI = 19.61 ± 1.11) and 12 healthy boys (FBS: 92.75 ± 5.22, age: 15.08 ± 1.67 years, and BMI = 20.26 ± 2.66) were divided into three groups: Diabetes Training (DT, n = 12), Diabetes Control (DC, n = 12), and Healthy Control (HC, n = 12). HRV (24 h) was computed in time and frequency domains, anthropometric, biochemical parameters at rest, and aerobic capacity (VO2peak) obtained during a graded exercise testing (GXT). All variables were evaluated at the baseline and following 12 weeks of exercise training, done 3 days weekly. The statistical method used for data analysis was analysis of covariance (ANCOVA) test.

HRV, Hemoglobin A1c (HbA1c) and Fasting blood sugar (FBS), VO2peak, norepinephrine (NEP), and HDL-C indicated significant differences between both T1D groups compared to HC at baseline (p < 0.001). BMI, LDL-C, TC, and TG parameters were similar in all groups. HRV parameters, VO2peak and HDL-C, and NEP were significantly improved by exercise training, and HbA1c and FBS levels were significantly reduced (p < 0.001). There is a negative and significant correlation between LF/HF Ratio Difference (post-test minus pre-test) and VO2Peak Difference variables (post-test minus pre-test) (p < 0.001).

The present study suggests the importance of early screening for CVD risk factors in adolescent males with T1D. Also, it was revealed HIITR training compared to other training patterns, and cardiovascular health improves via enhancement of autonomic modulation, VO2peak, plasma lipids, and catecholamine levels.

Neurological disorders and type 2 diabetes mellitus (T2DM) are deeply intertwined. For example, autonomic neuropathy contributes to the development of T2DM and continued unmanaged T2DM causes further progression of nerve damage. Increasing glycemic control has been shown to prevent the onset and progression of diabetic autonomic neuropathies. Neuromodulation consisting of combined stimulation of celiac vagal fibers innervating the pancreas with concurrent electrical blockade of neuronal hepatic vagal fibers innervating the liver has been shown to increase glycemic control in animal models of T2DM. The present study demonstrated that the neuromodulation reversed glucose intolerance in alloxan-treated swine in both pre- and overt stages of T2DM. This was demonstrated by improved performance on oral glucose tolerance tests (OGTTs), as assessed by area under the curve (AUC). In prediabetic swine (fasting plasma glucose (FPG) range: 101-119 mg/dL) the median AUC decreased from 31.9 AUs (IQR = 28.6, 35.5) to 15.9 AUs (IQR = 15.1, 18.3) p = 0.004. In diabetic swine (FPG range: 133-207 mg/dL) the median AUC decreased from 54.2 AUs (IQR = 41.5, 56.6) to 16.0 AUs (IQR = 15.4, 21.5) p = 0.003. This neuromodulation technique may offer a new treatment for T2DM and reverse glycemic dysregulation at multiple states of T2DM involved in diabetic neuropathy including at its development and during progression.

The extensive innervations of the heart include a complex network of sympathetic, parasympathetic, and sensory nerves connected in loops that serve to regulate cardiac output. Metabolic dysfunction in diabetes affects many different organ systems, including the cardiovascular system; it causes cardiac arrhythmias, silent myocardial ischemia, and sudden cardiac death, among others. These conditions are associated with damage to the nerves that innervate the heart, cardiac autonomic neuropathy (CAN), which is caused by various pathophysiological mechanisms. In this review, the main facts about the anatomy of cardiac innervations and the current knowledge of CAN, its pathophysiological mechanisms, and its diagnostic approach are discussed. In addition, anatomical evidence for CAN from human and animal studies has been summarized.

Cardiac autonomic neuropathy (CAN), widely assessed by heart rate variability (HRV), is a common complication of long-term diabetes. We hypothesized that HRV dynamics during tonic cold pain in individuals with type 1 diabetes mellitus (T1DM) could potentially demask CAN. Forty-eight individuals with long-term T1DM and distal symmetrical polyneuropathy and 21 healthy controls were included. HRV measures were retrieved from 24-h electrocardiograms. Moreover, ultra-short-term HRV recordings were used to assess the dynamic response to the immersion of the hand into 2 °C cold water for 120 s. Compared to healthy, the T1DM group had expectedly lower 24-h HRV measures for most components (p < 0.01), indicating dysautonomia. In the T1DM group, exposure to cold pain caused diminished sympathetic (p < 0.001) and adynamic parasympathetic (p < 0.01) HRV responses. Furthermore, compared to healthy, cold pain exposure caused lower parasympathetic (RMSSD: 4% vs. 20%; p = 0.002) and sympathetic responses (LF: 11% vs. 73%; p = 0.044) in the T1MD group. QRISK3-scores are negatively correlated with HRV measures in 24-h and ultra-short-term recordings. In T1DM, an attenuated sympathovagal response was shown as convincingly adynamic parasympathetic responses and diminished sympathetic adaptability, causing chronometric heart rhythm and rigid neurocardiac regulation threatening homeostasis. The findings associate with an increased risk of cardiovascular disease, emphasizing clinical relevance.

Background Cardiac autonomic neuropathy (CAN) is a major complication of type 2 diabetes mellitus (T2DM). Hyperglycaemia and hypertriglyceridemia are known risk factors in the development of CAN with T2DM. The triglyceride glucose (TyG) index is calculated using both the fasting blood glucose (FBG) and fasting triglyceride levels (FTG). There is a paucity of literature revealing a direct relationship between the TyG index and CAN in T2DM patients of the south Indian population. Objective To assess the TyG index levels in T2DM with and without CAN. Methods A cross-sectional study was performed, involving 100 T2DM patients (58 males and 42 females) aged between 30 and 60 years, who attended medicine OPD, Sri Venkateswaraa Medical College, Hospital and Research Centre (SVMCH & RC) during the study period. Age, duration of illness, height, weight, waist circumference (WC), hip circumference (HC), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Glycated hemoglobin (HbA1C) and lipid profile values were taken from patients' recent medical records. Ewing autonomic function tests were used to diagnose CAN, which included heart rate response to standing, heart rate response to deep breathing, heart rate response to Valsalva maneuver, blood pressure response to standing and blood pressure response to isometric handgrip. FBG and FTG were measured and the TyG index was calculated from these parameters. Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 20.0, Armonk, NY) was used for the statistical analysis and a 'P' value < 0.05 was considered statistically significant. Results In our study, out of 100 T2DM patients, 42 patients were diagnosed with CAN. The mean levels of TyG Index, HbA1C, FBG, FTG, BMI and WC were significantly (p<0.05) higher in T2DM patients with CAN when compared to T2DM without CAN. We couldn't find any significant difference (p<0.05) in age, duration of illness, blood pressure and lipid profile parameters between the groups. Conclusion We found that abdominal obesity, hyperglycemia, and hypertriglyceridemia are the risk factors for developing CAN in T2DM patients. Our study results also showed that the TyG index can be used to predict CAN in T2DM patients.

Cardiovascular autonomic neuropathy (CAN) is a debilitating complication of diabetes mellitus. To date, there is no systematic review on all the available drug treatments for CAN in diabetic patients, except for one review focusing on aldose reductase inhibitors.

To evaluate available drug treatment options for CAN in diabetic patients.

A systematic review was conducted with a search of CENTRAL, Embase, PubMed and Scopus from database inception till 14th May 2022. Randomised controlled trials (RCTs) of diabetic patients with CAN that investigated the effect of treatment on blood pressure, heart rate variability, heart rate or QT interval were included.

Thirteen RCTs with a total of 724 diabetic patients with CAN were selected. There was a significant improvement in the autonomic indices of diabetic patients with CAN given angiotensin-converting enzyme inhibitor (ACEI) for 24 weeks (p<0.05) to two years (p<0.001), angiotensin-receptor blocker (ARB) for one year (p<0.05), single dose of beta blocker (BB) (p<0.05), omega-3 polyunsaturated fatty acids (PUFAs) for three months (p<0.05), alpha-lipoic acid (ALA) for four months (p < 0.05) to six months (p=0.048), vitamin B12 in combination with ALA, acetyl L‑carnitine (ALC), superoxide dismutase (SOD) for one year (p=0.001)  and near significant improvement in the autonomic indices of diabetic patients with CAN given vitamin E for four months (p = 0.05) compared to the control group. However, there was no significant improvement in the autonomic indices of patients given vitamin B12 monotherapy (p ≥ 0.05).

ACEI, ARB, BB, ALA, omega-3 PUFAs, vitamin E, vitamin B12 in combination with ALA, ALC and SOD could be effective treatment options for CAN, while vitamin B12 monotherapy might be unlikely to be recommended for the treatment of CAN due to its lack of efficacy.

The online version contains supplementary material available at 10.1007/s13340-023-00629-x.

Diabetes-aggravated myocardial ischemia-reperfusion (MI/R) injury remains an urgent medical issue, and the molecular mechanisms involved with diabetes and MI/R injury remain largely unknown. Previous studies have shown that inflammation and P2X7 signaling participate in the pathogenesis of the heart under individual conditions. It remains to be explored if P2X7 signaling is exacerbated or alleviated under double insults. We established a high-fat diet and streptozotocin-induced diabetic mouse model, and we compared the differences in immune cell infiltration and P2X7 expression between diabetic and nondiabetic mice after 24 h of reperfusion. The antagonist and agonist of P2X7 were administered before and after MI/R. Our study showed that the MI/R injury of diabetic mice was characterized by increased infarct area, impaired ventricular contractility, more apoptosis, aggravated immune cell infiltration, and overactive P2X7 signaling compared with nondiabetic mice. The major trigger of increased P2X7 was the MI/R-induced recruitment of monocytes and macrophages, and diabetes can be a synergistic factor in this process. Administration of P2X7 agonist eliminated the differences in MI/R injury between nondiabetic mice and diabetic mice. Both 2 wk of brilliant blue G injection before MI/R and acutely administered A438079 at the time of MI/R injury attenuated the role of diabetes in exacerbating MI/R injury, as evidenced by decreased infarct size, improved cardiac function, and inhibition of apoptosis. Additionally, brilliant blue G blockade decreased the heart rate after MI/R, which was accompanied by downregulation of tyrosine hydroxylase expression and nerve growth factor transcription. In conclusion, targeting P2X7 may be a promising strategy for reducing the risk of MI/R injury in diabetes.

HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans Affair Cohort Study index. In addition, it is known that cardiovascular autonomic neuropathy due to diabetes is associated with poor cardiovascular outcomes. This study aimed to evaluate whether HIV-AN is predictive of important adverse clinical outcomes.

The electronic medical records of HIV-infected participants who underwent autonomic function tests at the Mount Sinai Hospital between April 2011 and August 2012 were reviewed. The cohort was stratified into those who had no or mild autonomic neuropathy (HIV-AN [-], CASS ≤3) and those with moderate or severe autonomic neuropathy (HIV-AN [+], CASS >3). The primary outcome was a composite of the incidence of death from any cause, new major cardiovascular or cerebrovascular event, or development of severe renal or hepatic disease. Time-to-event analysis was performed using Kaplan-Meier analysis and multivariate Cox proportional hazards regression models.

One hundred eleven of 114 participants had follow-up data (median follow-up for HIV-AN (-) was 94.00 months, and HIV-AN (+) was 81.29 months) and were included in the analysis. Participants were followed until March 1, 2020. The HIV-AN (+) group (N = 42) was significantly associated with the presence of hypertension, higher HIV-1 viral load, and more abnormal liver function. Seventeen (40.48%) events occurred in the HIV-AN (+) group, and 11 (15.94%) occurred in the HIV-AN (-) group. Six (14.29%) cardiac events occurred in the HIV-AN (+) group, whereas 1 (1.45%) occurred in the HIV-AN (-) group. The other subgroups of the composite outcome had a similar trend. The adjusted Cox proportional hazards model showed that the presence of HIV-AN predicted our composite outcome (HR 3.85, CI 1.61-9.20).

These findings suggest that HIV-AN is associated with the development of severe morbidity and mortality in people living with HIV. People living with HIV with autonomic neuropathy may benefit from closer cardiac, renal, and hepatic surveillance.

Frailty is the incremental accumulation of minute defects that progressively impair health and performance. Frailty is commonly observed in older adults; however, secondary frailty may also occur in patients with metabolic disorders or major organ failure. In addition to physical frailty, several distinct types of frailty have been identified, including oral, cognitive, and social frailty, each of which is of practical importance. This nomenclature suggests that detailed descriptions of frailty can potentially advance relevant researches. In this narrative review, we first summarize the clinical value and plausible biological origin of frailty, as well as how to appropriately assess it using physical frailty phenotypes and frailty indexes. In the second part, we discuss the issue of vascular tissue as a relatively underappreciated organ whose pathologies contribute to the development of physical frailty. Moreover, when vascular tissue undergoes degeneration, it exhibits vulnerability to subtle injuries and manifests a unique phenotype amenable to clinical assessment prior to or accompanying physical frailty development. Finally, we propose that vascular frailty, based on an extensive set of experimental and clinical evidence, can be considered a new frailty type that requires our attention. We also outline potential methods for the operationalization of vascular frailty. Further studies are required to validate our claim and sharpen the spectrum of this degenerative phenotype.

Cardiac innervation by the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS) modulates the heart rate (HR) (chronotropic activity) and the contraction of the cardiac muscle (inotropic activity). The peripheral vasculature is controlled only by the SNS, which is responsible for peripheral vascular resistance. This also mediates the baroreceptor reflex (BR), which in turn mediates blood pressure (BP). Hypertension (HTN) and the autonomic nervous system (ANS) are closely related, such that derangements can lead to vasomotor impairments and several comorbidities, including obesity, hypertension, resistant hypertension, and chronic kidney disease. Autonomic dysfunction is also associated with functional and structural changes in target organs (heart, brain, kidneys, and blood vessels), increasing cardiovascular risk. Heart rate variability (HRV) is a method of assessing cardiac autonomic modulation. This tool has been used for clinical evaluation and to address the effect of therapeutic interventions. The present review aims (a) to approach the heart rate (HR) as a CV risk factor in hypertensive patients; (b) to analyze the heart rate variability (HRV) as a "tool" to estimate the individual risk stratum for Pre-HTN (P-HTN), Controlled-HTN (C-HTN), Resistant and Refractory HTN (R-HTN and Rf-HTN, respectively), and hypertensive patients with chronic renal disease (HTN+CKD).

Diabetes mellitus (DM) and heart failure (HF) are frequently encountered afflictions that are linked by a common pathophysiologic background. According to landmark studies, those conditions frequently coexist, and this interaction represents a poor prognostic indicator. Based on mechanistic studies, HF can be propagated by multiple pathophysiologic pathways, such as inflammation, oxidative stress, endothelial dysfunction, fibrosis, cardiac autonomic neuropathy, and alterations in substrate utilization. In this regard, DM may augment myocardial inflammation, fibrosis, autonomic dysfunction, and lipotoxicity. As the interaction between DM and HF appears critical, the new cornerstone in DM and HF treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i), may be able to revert the pathophysiology of those conditions and lead to beneficial HF outcomes. In this review, we aim to highlight the deleterious pathophysiologic interaction between DM and HF, as well as demonstrate the beneficial role of SGLT2i in this field.

In today's world, science has progressed significantly, yet most people are still unaware of diabetes. Lack of obesity, physical work, and lifestyle changes are the main factors. Diabetes is becoming more common all around the globe. Type 2 diabetes may go unnoticed for years, resulting in serious consequences and high healthcare expenses. The goal of this study is to look at a wide range of studies in which the autonomic function of diabetic people has been studied with the help of various autonomic function tests (AFTs). AFT is a non-invasive approach to assessing patients for testing sympathetic and parasympathetic responses to stimuli. AFT findings give us comprehensive knowledge of the autonomic physiology reactions in normal and in autonomic diseases like diabetes. This review will concentrate on AFTs that are scientifically valid, trustworthy, and clinically beneficial, according to experts.

Diabetes mellitus has reached global epidemic proportions, with type 2 diabetes (T2DM) comprising more than 90% of all subjects with diabetes. Cardiovascular autonomic neuropathy (CAN) frequently occurs in T2DM. Heart rate variability (HRV) reflects a neural balance between the sympathetic and parasympathetic autonomic nervous systems (ANS) and a marker of CAN. Reduced HRV has been shown in T2DM and improved by physical activity and exercise. External addition of pulses to the circulation, as accomplished by a passive simulated jogging device (JD), restores HRV in nondiseased sedentary subjects after a single session. We hypothesized that application of JD for a longer period (7 days) might improve HRV in T2DM participants.

We performed a nonrandomized study on ten T2DM subjects (age range 44-73 yrs) who were recruited and asked to use a physical activity intervention, a passive simulated jogging device (JD) for 7 days. JD moves the feet in a repetitive and alternating manner; the upward movement of the pedal is followed by a downward movement of the forefoot tapping against a semirigid bumper to simulate the tapping of feet against the ground during jogging. Heart rate variability (HRV) analysis was performed using an electrocardiogram in each subject in seated posture on day 1 (baseline, BL), after seven days of JD (JD7), and seven days after discontinuation of JD (Post-JD). Time domain variables were computed, viz., standard deviation of all normal RR intervals (SDNN), standard deviation of the delta of all RR intervals (SDΔNN), and the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD). Frequency domain measures were determined using a standard Fast Fourier spectral analysis, as well as the parameters of the Poincaré plots (SD1 and SD2).

Seven days of JD significantly increased SDNN, SDΔNN, RMSSD, and both SD1 and SD2 from baseline values. The latter parameters remained increased Post-JD. JD did not modify the frequency domain measures of HRV.

A passive simulated jogging device increased the time domain and Poincaré variables of HRV in T2DM. This intervention provided effortless physical activity as a novel method to harness the beneficial effects of passive physical activity for improving HRV in T2DM subjects.

High-intensity interval training (HIIT) has been suggested as an alternative for continuous training (CT) in people with diabetes mellitus (DM) due to its short duration and potential to improve adherence to exercise. However, data on its impact on heart rate variability (HRV) are scarce.

To assess and compare the effects of HIIT and CT on exercise capacity, HRV and isolated hearts in diabetic rats.

DM (intravenous streptozotocin, 45 mg.kg -1 ) and control (C) animals performed 20 sessions (5 days/week, 50 min, for 4 weeks) of CT on a treadmill (70% of maximal exercise capacity) or HIIT (cycles of 1:1min at 50% and 90% of maximal exercise capacity). HRV was assessed by continuous electrocardiogram, and cardiac function assessed in isolated perfused hearts. For data analysis, we used the framework of the multivariate covariance generalized linear model or one-way ANOVA followed by Tukey's test, considering p<0.05 as significant.

Higher exercise capacity (m/min) was achieved in HIIT (DM-HIIT: 36.5 [IQR 30.0-41.3]; C-HIIT: 41.5 [37.8-44.5], both n=10) compared to CT (DM-CT: 29.0 [23.8-33.0]; C-CT: 32.0 [29.5-37.0], both n=10) (p<0.001). Heart rate (bpm) was lower in DM compared to controls (p<0.001) both in vivo (DM-HIIT:348±51, C-HIIT:441±66, DM-CT:361±70, C-CT:437±38) and in isolated hearts. There were no differences in HRV between the groups. Maximum and minimal dP/dt were reduced in DM, except +dP/dt in DM-HIIT vs. C-HIIT (mean difference: 595.5±250.3, p=0.190).

Short-term HIIT promotes greater improvement in exercise performance compared to CT, including in DM, without causing significant changes in HRV.

The review presents modern ideas about peripheral microhemodynamics, approaches to the ana-lysis of skin blood flow oscillations and their diagnostic significance. Disorders of skin microhemodynamics in type 2 diabetes mellitus (DM) and the possibility of their interpretation from the standpoint of external and internal interactions between systems of skin blood flow regulation, based on a comparison of couplings in normal and pathological conditions, including models of pathologies on animals, are considered. The factors and mechanisms of vasomotor regulation, among them receptors and signaling events in endothelial and smooth muscle cells considered as models of microvessels are discussed. Attention was drawn to the disturbance of Ca2+-dependent regulation of coupling between vascular cells and NO-dependent regulation of vasodilation in diabetes mellitus. The main mechanisms of insulin resistance in type 2 DM are considered to be a defect in the number of insulin receptors and impaired signal transduction from the receptor to phosphatidylinositol-3-kinase and downstream targets. Reactive oxygen species plays an important role in vascular dysfunction in hyperglycemia. It is assumed that the considered molecular and cellular mechanisms of microhemodynamics regulation are involved in the formation of skin blood flow oscillations. Parameters of skin blood microcirculation can be used as diagnostic and prognostic markers for assessing the state of the body.

Diabetes mellitus (DM) is a major independent risk factor for cardiovascular disease. Patients who present with the metabolic emergency of diabetic ketoacidosis (DKA) have similar symptoms of diaphoresis, nausea, emesis, and abdominal pain, which can conceal acute coronary syndrome (ACS). We present a unique case where computed tomography (CT) of the abdomen and pelvis with IV contrast played an integral role in diagnosing an acute myocardial infarction in a patient with no typical ischemic symptoms. A 56-year-old female presented to the emergency department with abdominal pain, nausea, and vomiting. She was suspected of having DKA. Aggressive management was started, including weight-based appropriate IV regular insulin. A CT abdomen and pelvis with IV contrast was performed due to persistent abdomen pain. This demonstrated severe hypoattenuation of the posteroinferior aspect of the left ventricular wall. An EKG was immediately performed and was consistent with an inferior STEMI. The patient was taken to the interventional cardiology suite where they found the culprit lesion to be mid-circumflex with 100% stenosis. This case highlights many important lessons in approaching diabetic patients who are presenting with DKA. DM is associated with cardiac autonomic neuropathy (CAN), a condition that greatly influences perceived chest pain. While little is known about this condition, some manifestations include resting tachycardia, exercise intolerance, orthostatic hypotension, and an increased risk of silent myocardial infarction. Critically, providers must maintain a low threshold to assess for cardiac ischemia in diabetic patients and more readily obtain EKGs in triage as well as during the patient's course in the ED to prevent complications from delayed ACS care.

Exercise prescription based on a population-specific physiological response can help ensure safe and effective physical interventions. However, as a facile approach for exercise prescription in hemodialysis population that is based on their exercise capacity has not yet been established, the aim of our study was to develop a unique prediction formula for peak heart rate (HR) that can be used in this population.

This cross-sectional study measured physical function and HR at peak exercise and anaerobic threshold (AT) during cardiopulmonary exercise tests in 126 individuals. Participants were randomly assigned to the development group (n = 78), whose data were used to calculate the prediction equation, or the validation group (n = 48).

The HR reserve in this population was significantly lower (0.44 ± 0.20%) and there was a large discrepancy between conventional age-predicted maximal HR and measured peak-HR values (R = 0.36). The average of the ratio between HR at AT point and peak HR was 85% (95% CI, 83.5%-86.4%). The peak-HR prediction equation was based on resting HR, presence of diabetes, physical dysfunction (gait speed < 1.0 m/s), and hypoalbuminemia (< 3.5 g/dL). It showed high prediction accuracy (R² [95%CI] = 0.71 [0.70-0.71]) with similar correlation coefficients between the development and validation groups (R = 0.82).

Aerobic exercise based on estimated peak HR < 85% obtained from the equation in this study may enable safe and effective physical intervention in this population.

Purpose: Studies have shown that subjects with psoriasis (PsO) are associated with an increased risk of developing metabolic syndrome (MetS), diabetes, and cardiovascular disease. In addition, MetS and diabetes are associated with autonomic dysfunction (AD). The aim of this study was to investigate cardiac and sudomotor autonomic function in subjects with PsO and without diabetes. Methods: A cross-sectional study was performed in 20 subjects with PsO, compared with age- and sex-matched 21 healthy controls, and 20 subjects with MetS. Subjects underwent skin evaluation by dermatologist, glycated hemoglobin (HbA1c), insulin, glucose, and lipid levels, sudomotor function testing with Sudoscan^™ device (Impeto Medical, Paris, France), and cardiac autonomic function testing with ANSAR device (ANX 3.0; ANSAR Group, Inc., Philadelphia, PA). Quality of Life (QOL) and peripheral neurologic function were also assessed. Results: Participants with PsO were significantly more obese, had higher levels of fasting insulin and triglycerides, and were more insulin resistant when compared to controls. Subjects with PsO showed significantly worse cardiac autonomic function when compared to control and MetS groups. Sudomotor function and QOL scores were similar between the groups. Subgroup analysis of PsO subjects without MetS criteria (n = 15) showed persistent significantly deteriorated cardiac autonomic function when compared to the other two groups. Conclusion: This study suggests an association between PsO and cardiac AD, independent of the presence of overt dysglycemia and MetS. Additional larger studies are needed to clarify the significance of these findings and the relationship between PsO, AD, and metabolic disease.

Type 1 diabetes (T1D) is associated with increased arterial stiffness and cardiac autonomic neuropathy. We tested whether those variables are acutely affected by a high fat meal (HFM).

Responses to a HFM were measured in adolescents with T1D (N = 14) or without T1D (Control, N = 21). Heart rate variability (HRV), arterial stiffness, blood pressure (BP), and energy expenditure (EE) were measured before (baseline) and four times over 180 min postprandially.

T1D had higher blood glucose and insulin, but the suppression of fatty acids (~40%) and rise in triglycerides (~60%) were similar between groups. T1D had 9% higher EE, but postprandial increase in EE was similar to Controls. T1D had ~7 to 24% lower baseline HRV but a similar postprandial decline of ~8 to 25% as Controls. Both groups had a similar 2 to 5% increase in BP after the meal. Rate pressure product increased postprandially in both groups and was higher in T1D. Pulsewave velocity and augmentation index did not differ between groups or change postprandially.

Adolescents with T1D have evidence of cardiac autonomic dysfunction and increased EE, but those variables, along with arterial stiffness, are not acutely made worse by a HFM.