Autonomic Reflex Tests Research Articles

A Study of Cardiac Autonomic Neuropathy Among Type-II Diabetic Patients

Background: Though very common, CAN is a least understood complication of diabetes which is often under diagnosed. In diabetes mellitus patients, CAN leads to silent myocardial infarction and sudden death. So by identifying CAN early, which is asymptomatic will help to delay or arrest its progression. AIM: To find out the prevalence and the associated risk factors of Cardiac autonomic neuropathy (CAN) among type-II Diabetes Mellitus patients in a tertiary care hospital. Materials & Methods: A total of 273 type-II diabetic participants were selected after taking into consideration of inclusion & exclusion criteria. The prevalence of CAN was assessed by ewings and clarkesnon invasive cardiac autonomic neuropathy reflex tests. The association of risk factors with the presence of CAN was analysed by using Pearson’s chi square test. Data were analysed by using SPSS 16. The accepted level of significance was set below 0.05 (P<0.05). Results: The prevalence of CAN among type-II diabetic patients in this study was found to be 34%. Prevalence of CAN increased in the participants with male gender, increased age, and increased BMI, increased duration of diabetes, poor glycaemic control,dyslipidimea, smokers and hypertension and it is statistically significant. Conclusion: In this study it is observed that the prevalence of CAN increased with old age, male gender, poor glycemic control, increased duration of diabetes, Dyslipidemia, higher BMI, Hypertension & smoking. So risk factors associated with the CAN be detected and treated at an early stage to further reduce morbidity and mortality.

Noninvasive exploration of Cardiac Autonomic Neuropathy by heart rate and blood pressure variability analysis in Type 2 Diabetic patients

Objectives:To determine the prevalence of asymptomatic cardiac autonomic neuropathy and its association with risk factors among patients with Type-2 diabetes mellitus (T2DM)Methods:The present case-control study was conducted at Department of Medicine, Civil Hospital, Dow University of Health Sciences (DUHS), Karachi, Pakistan during the period September` 2016 to May` 2017. After taking informed consent, subjects from both genders, 72 healthy controls and 72 clinically diagnosed T2DM diabetic patients, age between 30-65 years were selected by non-probability sampling technique. After taking medical history and demographics, Cardiac Autonomic Neuropathy (CAN) was identified by using Ewing`s cardiac autonomic reflex tests (CARTs) and association of risk factors was also investigated.Results:Severe CAN was identified in 13.9% of T2DM patients while in none of the healthy controls. HR response to deep breathing test was most sensitive (sensitivity= 90%) among all tests. The most common symptoms were Numbness (75.9%) and constipation (69%), resting heart rate and diabetes duration was significantly associated with DCAN.Conclusions:CAN was highly prevalent in diabetic population that may lead to nephropathy and retinopathy in future. It is highly recommended to use sensitive and simple CARTs in clinics for early detection and early treatment of CAN.

Effect of HMG-Co-A reductase inhibitors on cardiac autonomic neuropathy in diabetic patients

Objective: To observe the effect of statins on cardiac autonomic neuropathy in patients with diabetes and to study the correlation between cardiac autonomic neuropathy as assessed by cardiac autonomic reflex tests (CARTs) and by Composite Autonomic Symptom Scale (COMPASS)-31. Materials and Methods: A cross-sectional observational study was conducted on 62 patients having Type 2 diabetes mellitus for more than 5 years. Patients were randomized into two groups, one group received standard antidiabetic therapy and other group received standard antidiabetic along with statin medication at least for more than 1 year. Each patient underwent CART and heart rate variability to assess autonomic dysfunction. In addition, COMPASS 31 questionnaire was used to evaluate symptoms subjectively. Statin Experience Assessment Questionnaire was used to note adverse effects of statins. Chi-square test, Spearman correlation test, and Mann–Whitney U-test were used for statistical analysis. Results: A significant difference in severity of cardiac autonomic dysfunction was observed between two groups as measured by CART (P = 0.016) and COMPASS-31 questionnaire (P = 0.008). Moreover, COMPASS score of >16 was observed in patients with advanced cardiac autonomic neuropathy. A significant correlation was found between COMPASS 31 score and CART results (r = 0.29, P = 0.02). Conclusion: Our study highlights the potential utility of statins in curbing progression of cardiac autonomic neuropathy and can be safely administered in patients with Type 2 diabetes mellitus. COMPASS 31 questionnaire can be used as an effective screening tool for CART referral, facilitating the early detection of cardiac autonomic neuropathy.

Abstract 12919: Quantitative Assessment of Cardiovascular Autonomic Impairment in Cancer Survivors: A Single Center Experience

Background: Cardiovascular autonomic dysfunction in cancer survivors is poorly understood. Objectives: To better characterize the clinical characteristics and types of autonomic dysfunction in this population. Methods: A retrospective analysis of cancer survivors within an academic cardio-oncology program referred for suspected autonomic dysfunction was performed. Autonomic reflex testing of adrenergic, cardiovagal, and sudomotor function was done. Patients with pre-existing autonomic dysfunction prior to their cancer diagnosis were excluded. Results: Of approximately 282 patients in the UCLA Cardio-Oncology program, twenty-four patients met the inclusion criteria. Twenty-two had autonomic impairment on autonomic reflex testing. Eight patients were female, and the mean age at time of autonomic testing was 51.3 years. The average duration from cancer diagnosis to autonomic testing was 10.3 years. The reasons for referral included dizziness, tachycardia, palpitations, and syncope. The majority of patients (75%) had hematologic disorders. The most common chemotherapies administered were vinca alkaloids (54.2%), alkylating agents (66.7%), and anthracyclines (54.2%). Most patients received radiation to the thorax (66.7%) and neck (53.3%). Eleven patients had mild autonomic impairment, seven had moderate, and four had severe autonomic impairment. Dysfunction was commonly present in the sympathetic and parasympathetic branches, but most pronounced in the sympathetic system. The majority of patients were diagnosed with orthostatic hypotension (50%), inappropriate sinus tachycardia (20.8%), and postural orthostatic tachycardia syndrome (12.5%) and had subjective improvement with treatment. Conclusion: Cardiovascular autonomic dysfunction occurs in cancer survivors, and commonly affects both the sympathetic and parasympathetic systems. Symptom recognition in patients should prompt autonomic testing and treatment where appropriate.

Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy.

Aim: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). Patients–methods: In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. Results: At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.027, p = 0.031, and p < 0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p < 0.001, p < 0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p < 0.001, p < 0.001, p = 0.031, p < 0.001, and p < 0.001 respectively). Conclusions: The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

Cardiac vagal tone as a novel screening tool to recognize asymptomatic cardiovascular autonomic neuropathy: Aspects of utility in type 1 diabetes

AimsTo test the performance of the cardiac vagal tone (CVT) derived from a 5-minute ECG recording compared with the standardized cardiovascular autonomic reflex tests (CARTs). MethodsCross-sectional study included 56 well-phenotyped adults with type 1 diabetes (19–71 years, 2–54 years disease-duration). Autonomic testing included: standardized CARTs obtained with the VAGUS™, CVT, and indices of heart rate variability (HRV) obtained at 24- and 120-hour, and electrochemical skin conductance assessed with SUDOSCAN®. ROC AUC and cut-off values were calculated for CVT to recognize CAN based on ≥ 2 (established CAN, n = 7) or 1 (borderline CAN, n = 9) abnormal CARTs and compared to HRV indices and electrochemical skin conductance. ResultsEstablished CAN: The cut-off CVT value of 3.2LVS showed 67% sensitivity and 87% specificity (p = 0.01). Indices of HRV at either 24-hour (AUC > 0.90) and 120-hour (AUC > 0.88) performed better than CVT. Borderline CAN: The cut-off CVT value of 5.2LVS indicated 88% sensitivity and 63% specificity (p = 0.07). CVT performed better than HRV indices (AUC < 0.72). Electrochemical skin conductance (AUC:0.63–0.72) had lower sensitivity and specificity compared with CVT. ConclusionsImplementation of CVT with a clinically applicable cut-off value may be considered a quicker and accessible screening tool which could ultimately decrease the number of unrecognized CAN and initiate earlier prevention initiatives.

Resting and post-exercise heart rate variability in type 2 diabetes with and without cardiac autonomic neuropathy: Preliminary results

Cardiac Autonomic Neuropathy (CAN) is a common underdiagnosed complication of type 2 diabetes (DT2). Heart Rate Variability (HRV) at rest, in the time and frequency-domain, has been shown to effectively diagnose CAN. Post-exercise recovery period is associated with changes in parasympathetic and sympathetic control, allowing potential identification of autonomic alterations that are not evident in resting condition. To compare resting and post-exercise recovery HRV frequency variables in DT2 patients with and without CAN and control participants. Thirty-six DT2 patients and 12 control participants (CG) were included. DT2 were divided in DT2 with CAN (CAN+; n = 14) and without CAN (CAN-, n = 22) based on cardiovascular autonomic reflex tests. All subjects performed the six-minutes walking test (6MWT). HRV analysis was assessed during 5 minutes in time and frequency domain (Total Power Spectrum (TP), Low-Frequency (LF), High Frequency (HF), LF/HF ratio) at rest and post-exercise. Statistical comparisons between groups were performed by one-way and repeated measure ANOVA. CAN+ and CAN- performed lower distance to 6WMT than CG (401 ± 98; 449 ± 76; 541 ± 65 m, respectively P < 0.001) despite similar exercise intensity. At rest, TP was lower in CAN+ and CAN- than CG (105 ± 75; 407 ± 290 and 1300 ± 1197ms 2 , respectively P < 0.001) with lower value in CAN+ than CAN-. No significant differences in normalized LF and HF were noted between groups. During recovery, TP decreased in CG whereas it increased in CAN+ and did not change in CAN-. Normalized LF and LF/HF ratio increased significantly while normalized HF decreased in the three groups with no difference between groups. The different TP changes from rest to recovery between groups were not associated with different changes in LF and HF components. Further LF and HF post-exercise kinetics analysis will be necessary to explain the underlying mechanisms.

Glycemic Variability and Diabetic Neuropathy in Young Adults With Type 1 Diabetes.

Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes.Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE).Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models.Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.

Gastrointestinal autonomic neuropathy in diabetes.

Gastrointestinal autonomic neuropathy represents an important and diverse, but poorly appreciated, manifestation of diabetic autonomic neuropathy that impacts negatively on quality of life. There is no test to assess gastrointestinal autonomic nerve damage directly in humans; cardiovascular autonomic reflex tests are often used as a surrogate, but are suboptimal. Gastrointestinal symptoms are common in diabetes, but usually correlate only weakly with disordered motility. Diabetic gastroparesis, or abnormally delayed gastric emptying, occurs frequently and is the best characterized manifestation of gastrointestinal autonomic neuropathy. There is a bi-directional relationship between postprandial glycaemia and the rate of gastric emptying. However, autonomic neuropathy can affect the function of any gut segment from the esophagus to the anus. Current management options for gastrointestinal autonomic neuropathy are, for the main part, empirical and sub-optimal.

Quantitative assessment of cardiovascular autonomic impairment in cancer survivors: a single center case series

BackgroundCardiovascular autonomic dysfunction in cancer survivors is poorly understood.ObjectivesTo better characterize the clinical characteristics and types of autonomic dysfunction in this population.MethodsA retrospective analysis of cancer survivors within an academic cardio-oncology program referred for suspected autonomic dysfunction was performed. Autonomic reflex testing of adrenergic, cardiovagal, and sudomotor function was done. Autonomic impairment was graded on severity based on the Composite Autonomic Severity Score system. Patients with pre-existing autonomic dysfunction prior to their cancer diagnosis were excluded.ResultsOf approximately 282 total patients in the UCLA Cardio-Oncology program, 24 were referred for suspected autonomic dysfunction and met the inclusion criteria. 22 had autonomic impairment on autonomic reflex testing. Eight patients were female, and the mean age at time of autonomic testing was 51.3 years. The average duration from cancer diagnosis to autonomic testing was 10.3 years. The reasons for referral included dizziness, tachycardia, palpitations, and syncope. The majority of patients (75%) had hematologic disorders. The most common chemotherapies administered were vinca alkaloids (54.2%), alkylating agents (66.7%), and anthracyclines (54.2%). Most patients received radiation to the thorax (66.7%) and neck (53.3%). Eleven patients had mild autonomic impairment, 7 had moderate, and 4 had severe autonomic impairment. Dysfunction was commonly present in the sympathetic and parasympathetic branches, but most pronounced in the sympathetic system. The majority of patients were diagnosed with orthostatic hypotension (50%), inappropriate sinus tachycardia (20.8%), and postural orthostatic tachycardia syndrome (12.5%) and had subjective improvement with treatment.ConclusionCardiovascular autonomic dysfunction occurs in cancer survivors, and commonly affects both the sympathetic and parasympathetic systems. Symptom recognition in patients should prompt autonomic testing and treatment where appropriate.

554-P: Dapagliflozin and Measures of Cardiovascular Autonomic Function in Patients with Type 2 Diabetes

Beneficial effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes (T2D) have been reported. We hypothesized that these benefits may be due to modulatory effects on the sympathetic/parasympathetic imbalance through blunting of the expected compensatory increase in heart rate associated with lowering blood pressure. We aimed to evaluate the effect of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN) in patients with T2D. We performed a pilot, randomized, 2-period crossover clinical trial comparing 12 weeks of glucose lowering intervention with DAPA versus glimepiride on measures of CAN [cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV)] assessed at baseline and end of each drug period. Signed rank tests and mixed models were used to evaluate the differences in CARTs and HRV indices from baseline to 12 weeks between each drug period. Preliminary data are presented for forty-one participants with T2D on metformin monotherapy (mean age 57±8 years, mean diabetes duration 7±6 years, mean HbA1c 7.8±1.3%) at baseline. Although there were no significant differences in indices of CAN in each drug period, there was a trend for higher expiration and inspiration ratio on DAPA compared to glimepiride (mean change 0.02±0.10; p=0.07). We found significant or near significant interactions between sex and treatment for the root mean square of the differences of successive RR intervals (rmsSD) (p=0.021) and Valsalva ratio (p=0.06) in women on DAPA versus glimepiride compared with men. In women, the mean 12-week change for both measures on DAPA was larger than the mean change on glimepiride, whereas in men, the mean 12-week change was larger on glimepiride than DAPA. These preliminary short-term data suggest that DAPA may have beneficial effects on measures of CAN particularly in women with T2D. These findings need to be confirmed in larger prospective studies with longer follow-up. Disclosure L. Ang: None. K.M. Kidwell: None. J. Reiss: None. B.R. Dillon: None. K.R. Mizokami-Stout: None. V.A. Leone: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association.

Distal Symmetric and Cardiovascular Autonomic Neuropathies in Brazilian Individuals with Type 2 Diabetes Followed in a Primary Health Care Unit: A Cross-Sectional Study.

The paucity of epidemiological data regarding diabetes complications in Brazil motivated us to evaluate the prevalence rates of distal symmetric polyneuropathy (DSP) and of cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes (T2D) followed in a primary care unit. A total of 551 individuals (59.3% women, 65 years old; diabetes duration of 10 years; HbA1c of 7.2%, medians) were included in this cross-sectional study. DSP was diagnosed by sum of the Neuropathy Symptoms Score (NSS) and Modified Neuropathy Disability Score (NDS) and by the Semmes–Weinstein monofilament. CAN was diagnosed by cardiovascular autonomic reflex tests combined with spectral analysis of heart rate variability. The prevalence rates of DSP were 6.3% and 14.3%, as evaluated by the sum of NSS and NDS and by the Semmes–Weinstein monofilament, respectively. Those with DSP diagnosed by monofilament presented longer diabetes duration, worse glycemic control and a higher stature. The prevalence rates of incipient and definitive CAN were 12.5% and 10%, respectively. Individuals with definitive CAN presented a higher frequency of hypercholesterolemia and of arterial hypertension. The higher prevalence rate of DSP with the use of the monofilament suggests that it may be a more appropriate tool to diagnose DSP in the primary care setting in Brazil.

Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test.

Background Simultaneous pancreas-kidney (SPK) transplantation is a proven option of treatment for patients with type 1 diabetes mellitus (T1DM) and related end-stage renal disease. There is discrepancy between the results of different studies about the impact of prolonged normalization of glucose metabolism achieved by SPK on the course of diabetic complications including severe forms of diabetic neuropathy. The objective of the study was to evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) in patients undergoing SPK transplantation and its evolution 10 years after transplantation. Methods Prospective study of 81 patients transplanted in a single center from year 2002 to 2015. Autonomic function was assessed using cardiovascular autonomic reflex tests (CARTs). CARTs were made before SPK transplantation and during the follow-up. Evolution of tests after SPK transplantation was evaluated by contrasting hypotheses (paired tests). Multiple testing was adjusted with the Benjamini-Hochberg procedure with a false discovery rate of 10%. Results 48 males and 33 females, mean age 37.4 ± 5.7 years, mean BMI 24.0 ± 3.4 kg/m2, and mean duration of diabetes 25.5 ± 6.5 years, received SPK transplantation. Ten years after SPK transplantation, 56 patients re tained the pancreatic graft (42 of them with normofunctioning pancreas and 14 with low doses of insulin therapy). These 42 patients were selected for the autonomic study. Before transplant procedure, all CART results were abnormal. After SPK transplantation, paired test analysis showed an improvement of systolic blood pressure (SBP) response to orthostasis at the 5th year after SPK (p = 0.03), as well as improvement of the Valsalva ratio at the 3rd (p < 0.001) and 5th (p = 0.001) year after SPK. After correcting for the false discovery rate, all the variables of autonomic study reached significance at different time points. Conclusions Prevalence of CAN in patients who are candidates for SPK transplantation is high and is generally advanced. SPK transplantation improves CAN with improved Valsalva ratio as the most precocious test.

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review.

Rigorous glycaemic control-reflected by low HbA1c goals-is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short-term glycaemic variability (GV) is also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM. An electronic database search of Medline (PubMed), Web of Science and Embase was performed up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated using the Newcastle Ottawa Scale for observational studies. Six studies (four cross-sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV), and both found significant negative correlations. Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not, while two other studies did find significant associations between GV parameters and CART scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring-derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN.

Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study.

Background:Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa.Objectives:To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda.Method:We conducted a cross-sectional study among adults with diabetes from November 2018 to April 2019. CAN was assessed using the five autonomic function tests: deep breathing, Valsalva maneuver, postural index on standing, change in blood pressure during standing and diastolic blood pressure response to isometric exercise. We estimated the prevalence of CAN and fit regression models to identify its demographic and clinical correlates.Results:We enrolled 299 individuals. The mean age was 50.1 years (SD ± 9.8), mean HbA1c was 9.7 (SD ± 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 –8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 –9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 –4.34, p = 0.016) were correlated with CAN.Conclusions:Our findings reveal a high prevalence of CAN among individuals in routine outpatient care for diabetes mellitus in Uganda. Older age, longer duration of diabetes and coexistence of retinopathy are associated with CAN. Future work should explore the clinical significance and long term outcomes associated with CAN in this region.

Time in Range, as a Novel Metric of Glycemic Control, Is Reversely Associated with Presence of Diabetic Cardiovascular Autonomic Neuropathy Independent of HbA1c in Chinese Type 2 Diabetes.

Objective The objective of this study is to investigate the relationship between time in range (TIR), a new metric of continuous glucose monitoring (CGM) and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (T2DM). Methods A total of 349 individuals with T2DM were enrolled in this study. Evaluating by the standard cardiac autonomic reflex tests (CARTs), there were 228 diabetic individuals without cardiovascular autonomic neuropathy (without confirmed CAN) including absent CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (Results The total presence of CAN was 34.67% (definite CAN 31.23% and severe CAN 3.44%). Patients with more severe CAN had lower TIR (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (Conclusion TIR is associated with the presence of CAN independent of HbA1c and GV metrics in Chinese type 2 diabetes.

Cardiovascular autonomic reflex tests and serum FGF21 levels in overweight and normal-weight men and women

Objective We evaluated cardiovascular autonomic reflexes and serum fibroblast growth factor 21 (FGF21), a surrogate marker of mitochondrial function, in a cohort of overweight and normal-weight adults (n = 42). Methods Indices of autonomic function were monitored during supine rest, autonomic reflex tests and submaximal clinical exercise test, with heart rate variables and blood pressure measured with an automatic system. Results Markers of sympathetic dominance were accentuated in overweight adults, including elevated resting low-frequency to the high-frequency ratio for heart rate variability (203 ± 227 vs. 96 ± 42; p = .01), and handgrip diastolic blood pressure (36 ± 15 mmHg vs. 25 ± 12 mmHg; p = .01). A weak non-significant trend has been found for a negative correlation between blood pressure responses to isometric handgrip test and FGF21 in the overweight group (r = −0.37; p = .09). Conclusions Excess body weight appears to trigger sympathetic overactivity in overweight adults, yet autonomic dysregulation might not be associated with notable changes in serum FGF21.

Cardiovascular autonomic neuropathy as a cause of fatigue in chronic hypoparathyroidism.

Hypoparathyroidism (hypoPT) results in an impairment of quality of life (QoL), an increase in fatigue and a higher risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system and is associated with increased mortality and fatigability. Patients with hypoPT show an increased risk of CAN. However, no previous studies have investigated the association between CAN and QoL in hypoPT. To test whether CAN is associated with fatigue and impaired QOL in hypoPT patients. We enrolled 48 subjects with postsurgical hypoPT treated with calcium and calcitriol and 38 healthy subjects who underwent thyroidectomy. Subjects completed the RAND 36-Item Short Form (SF-36) Health Survey, evaluating physical (PCS) and mental (MCS) health, and fatigue score. CAN was assessed using cardiovascular autonomic reflex tests (CARTs). Participants were considered to have "early CAN" (EC) if they had one abnormal CART and "definite CAN" (DC) with two or more abnormal CARTs. Compared with controls, hypoPT population had lower fatigue scores (44.5 IQRː9 vs 38.5 IQRː12.3, P = 0.031). In the hypoPT group, only participants with DC had a lower fatigue score than subjects without CAN (DC: β: -9.55, P = 0.005) after adjusting for age, duration of disease, calcium concentration, TSH, calcitriol and calcium supplementation. No differences were found in the PCS and MCS scores in the hypoPT group. CAN may explain fatigue, a common complaint of postsurgical hypoPT patients. Further larger and prospective investigations are needed to confirm our findings.

Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes.

The present study aimed to examine association between inflammatory and endothelial function biomarkers and indices of cardiac autonomic control in T2DM patients. 50 T2DM patients were recruited for this study. For cardiac autonomic function, cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) analysis was performed. Blood samples were collected for evaluating inflammatory and endothelial function biomarkers. Multivariable linear regression analysis adjusted for diabetes duration, glycemic control, waist circumference, hypertension, dyslipidemia, metformin, and statins was performed to examine the association between the biomarkers and cardiac autonomic function parameters. Interleukin-6 was inversely related to total power (p= .009) and low frequency power (p= .04). Interleukin-18 and high sensitivity C-reactive protein inversely correlated with measures of cardiac vagal control (p < .05). Both nitric oxide and endothelial nitric oxide synthase were positively linked with cardiac vagal control indices (p < .05) whereas endothelin-1 did not show any independent association with cardiac autonomic function parameters. Biomarkers of inflammation and endothelial function are associated with measures of cardiac vagal control and global HRV which suggest that there is some pathophysiological link between subclinical inflammation, endothelial dysfunction and cardiac autonomic dysfunction in T2DM.

DIAGNOSIS OF THE CARDIAC AUTONOMIC NEUROPATHY IN DIABETIC PATIENT

Cardiac autonomic neuropathy (CAN) is a very common diabetes-related complication that has a major effect on CVD, mortality and morbidity in patients with DM. Careful and timely testing of CAN with easy standard bedside tests in patients with DM 1 and 2 is critically important for early diagnoses and prophylaxes of further CV complications. Aim of the study was to evaluate the CAN characteristics in DM 1 versus DM 2 patients and to identify the relationship between CAN and typical diabetic complications. Materials and methods. A descriptive and comparative cross-sectional study was developed with 75 patients with Diabetes Mellitus (DM 1 — 30 patients, DM 2 — 45 patients) who were hospitalized to the endocrinology department for treatment. All patients were investigated routinely – complains, anamnestic data, objective examination, lab and instrumental examination. For defining of CAN next five classical tests were done (cardiac autonomic reflex testing (CART)): Evaluating of the Resting tachycardia; Heart rate response to deep breathing; Valsalva maneuver; Systolic blood pressure response to standing; Diastolic blood pressure response to sustained handgrip. Results and discussions. Absence of CAN, according to proposed score, was defined in those patients without clinical features of CVD. 46.8% of all patients presented with early and definitive CAN, while the higher prevalence of definitive CAN was diagnosed in DM 2 patients. Severe CAN was confirmed more often in DM 2 patients also. Coexistence of CAN and peripheral neuropathy was higher in patients with DM 1 than in DM 2 patients. Among DM 1 patients with CAN only 11.8% persons had not sensory peripheral neuropathy, while 29.7% DM 2 patients with CAN, were free of sensory peripheral neuropathy. Positive correlations were found between the duration of the DM and manifestations of CAN in patients with DM II, the development of sensory polyneuropathy, retinopathy and CAN in patients with DM I, and this diabetic complication preceded the clinical manifestations of peripheral neuropathy. Thus, the proposed set of diagnostic measures should be obviously and easily used for the timely diagnosis of CAN in diabetic patients, especially in asymptomatic cases, and objectively assessing the effectiveness of the therapy.