Diabetic Cardiovascular Autonomic Neuropathy Research Articles

Analysis of the contribution of obstructive sleep apnea/hypopnea syndrome and glycemic level variability to the development and progression of cardiac arrhythmias in patients with type 2 diabetes mellitus

In this review, information is presented within the triad: obstructive sleep apnea/hypopnea syndrome (OSA), glycemic variability, and cardiac arrhythmias in patients with type 2 diabetes mellitus (DM2). Epidemiological aspects, pathogenetic relationships, possible instrumental and laboratory diagnostic methods, as well as approaches to personalized therapy are analyzed. Research is being actively conducted in certain areas of the designated triad, however, no studies have been found that include simultaneous monitoring of indicators reflecting these disorders in patients with DM2. Many issues are still controversial. Sleep disturbances in patients with DM2 are actively studied, but more often questionnaires are used for diagnosis, rather than instrumental methods. There is insufficient data examining the effect of hypoxia on the progression of complications in patients with DM2. Rhythm disturbances are being actively studied in patients with DM2 in combination with various cardiological problems. Of greatest interest is the study of rhythm disturbances in patients with DM2 without concomitant comorbid conditions of the cardiovascular system, in order to identify early signs of diabetic cardiovascular autonomic neuropathy and cardiomyopathy, as well as additional early risk factors for the development and progression of cardiovascular diseases. Most of the studies are devoted to the study of the association of OSA and various arrhythmias in cardiac patients. However, there is no data on the combined effect of glycemic variability and OSA on the development of cardiac arrhythmias in patients with DM2. Additional studies are needed to identify the features of the effect of OSA on cardiac arrhythmias in patients with DM2.

Diabetic cardiovascular autonomic neuropathy: clinical significance, diagnosis and therapy

Diabetic cardiovascular autonomic neuropathy: clinical significance, diagnosis and therapy

Schisandrin B Alleviates Diabetic Cardiac Autonomic neuropathy Induced by P2X7 Receptor in Superior Cervical Ganglion via NLRP3.

Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of diabetes mellitus which brings about high mortality, high morbidity, and large economic burden to the society. Compensatory tachycardia after myocardial ischemia caused by DCAN can increase myocardial injury and result in more damage to the cardiac function. The inflammation induced by hyperglycemia can increase P2X7 receptor expression in the superior cervical ganglion (SCG), resulting in nerve damage. It is proved that inhibiting the expression of P2X7 receptor at the superior cervical ganglion can ameliorate the nociceptive signaling dysregulation induced by DCAN. However, the effective drug used for decreasing P2X7 receptor expression has not been found. Schisandrin B is a traditional Chinese medicine, which has anti-inflammatory and antioxidant effects. Whether Schisandrin B can decrease the expression of P2X7 receptor in diabetic rats to protect the cardiovascular system was investigated in this study. After diabetic model rats were made, Schisandrin B and shRNA of P2X7 receptor were given to different groups to verify the impact of Schisandrin B on the expression of P2X7 receptor. Pathological blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were ameliorated after administration of Schisandrin B. Moreover, the upregulated protein level of P2X7 receptor, NLRP3 inflammasomes, and interleukin-1β in diabetic rats were decreased after treatment, which indicates that Schisandrin B can alleviate the chronic inflammation caused by diabetes and decrease the expression levels of P2X7 via NLRP3. These findings suggest that Schisandrin B can be a potential therapeutical agent for DCAN.

Взаимосвязь показателей вариабельности гликемии и нарушений сердечного ритма у пациентов с сахарным диабетом 1 типа

Objective: To study indicators of glycemic variability (GV) and their relationship with cardiac arrhythmias in patients with type 1 diabetes mellitus according to glucocardiomonitoring data. Design: Cross-sectional study. Materials and methods. The study included 72 patients with type 1 diabetes without previously diagnosed cardiovascular pathology. Of these, 34 patients received insulin pump therapy, 38 received multiple insulin injections. The average age of patients was 39.7 ± 15.9 years, the average duration of type 1 diabetes was 15.4 ± 10.8 years. The level of glycated hemoglobin (HbA1c) was determined in patients, and according to continuous glucose monitoring (CGM), GV indices were calculated: SD (standard deviation), CONGA (continuous overall net glycemic action), LI (lability index), MAGE (mean amplitude of glycemic excursions), MAG (mean absolute glucose). Simultaneously with CGM, Holter monitoring of the electrocardiogram was carried out: heart rate (HR), the presence and time of occurrence of arrhythmias, variability of the corrected QT interval (QTc), and the presence of ischemic changes were assessed. A correlation analysis of the relationships between GV levels and heart rhythm disorders was carried out. Results. Regardless of the type of insulin therapy, GV indicators in patients with type 1 diabetes were higher than the reference values for healthy individuals. Only 19 (26%) patients reached the target HbA1c level. In 62 (86%) people, various heart rhythm disturbances were registered, in 30 (42%) of patients there was a decrease in the circadian index (CI) of heart rate, and in 14 (19%) there was a prolongation of the QTc interval. The results of the correlation analysis showed that with an increase in GV, the HR CI decreased and the frequency of supraventricular and ventricular extrasystoles increased. Conclusion. The detected changes in heart rhythm against the background of increased GV in patients with type 1 diabetes indicate a high risk of developing a cardiovascular process. Strict glycemic control and normalization of GV can better reduce the risk of cardiac arrhythmia and the development of DCAN in patients with type 1 diabetes. Keywords: type 1 diabetes mellitus, glycemic variability, cardiovascular disease, diabetic cardiovascular autonomic neuropathy

ASSESSMENT OF DIASTOLIC FUNCTION IN PATIENTS WITH DIABETIC NEUROPATHY

"Diastolic dysfunction" is thought to be an indication of "diabetic cardiomyopathy" ", and "diabetic cardiovascular autonomic neuropathy" is linked to increased mortality risk. The goal of this study was to see how "diastolic dysfunction" and "cardiovascular autonomic neuropathy" are linked both of which were diagnosed in accordance with the guidelines. Methods: We assessed at seventy three participants Whose elective coronary angiography was referred, Diabetes mellitus was present in twenty-six of them, and twenty four of whom had impaired glucose tolerance, the other twenty-three people had normal "glucose tolerance". To identify "cardiovascular autonomic neuropathy", "autonomic function" tests were done, and "tissue Doppler imaging echocardiography" was employed to confirm "diastolic dysfunction". Results Autonomical cardiovascular neuropathy has been detected with diabetes type 2 diabetes in (28.8%) and with glucose-impaired tolerance in 6 (12.5%) patients. "Diastolic dysfunction" was found in 81 and 33 percent of patients with and without "cardiovascular autonomic neuropathy", respectively (P <0.001). "Early diastolic relaxation velocity" (Em) was considerably less in comparison to the group without cardiovascular autonomic neuropathy. ("5.4 0.9 vs. 7.3 2.1 cm⁄ s;P; P 0.001"), Moreover, the E⁄Em ratio was much higher. ("13.6 4.6 vs. 10.3 3.4 cm⁄ s;P, 0.001"). The significance of these data remained after controlling for "age, gender, coronary artery disease, hypertension, and HbA1c". In individuals with and without "cardiovascular autonomic neuropathy", significant "diastolic dysfunction" was found in 33 and 15% of patients, accordingly (P = 0.001).

Retracted: Association of QT interval indices with cardiac autonomic neuropathy in diabetic patients

Background. Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes mellitus. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of diabetic patients. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. This study was conducted to assess the relationship between Cardiac autonomic neuropathy and QT interval. Material and methods. This was a cross-sectional study conducted in 100 patients attending a tertiary care hospital in India. Deep breathing test, Valsalva ratio, immediate heart rate response to standing 30 : 15, BP rise with sustained hand grip and postural hypotension were evaluated. Scoring was done for cardiac autonomic neuropathy. QT interval and QTc interval were determined and association with CAN was obtained. Results. Out of 100 type 2 diabetic patients, 60% were males and 40% were females. 25 patients having no cardiac autonomic neuropathy and had no prolonged QTc interval. While, 75 patients had QTc prolonged were associated with early and severe CAN cardiac autonomic neuropathy. The prolonged QTc was significantly associated with CAN in diabetic patients when compared without CAN and controls (P < 0.0001). The grading score for CAD showed that 75% cases were having score > 2 were 25% of cases had score < 2. Out of 75 patients 44 were between score 2–4 and 31 were above score 4. A significant association between QTc and Diabetic CAN patients observed when compared non CAN and controls. Conclusions. Diabetic cardiac autonomic neuropathy is associated with increase in prolongation of QTc intervals. Hence, there is need for regular checkup of autonomic nervous system in diabetic patient to prevent further complications.

PHARMACOTHERAPY POSSIBILITIES OF CARDIOVASCULAR AUTONOMOUS NEUROPATHY IN CHILDREN WITH TYPE 1 DIABETES MELLITUS AT THE PRECLINICAL STAGE

The aim of the article is to evaluate the effectiveness of the thioctic acid preparation in the complex therapy of type 1 diabetes mellitus (T1DM) in children with cardiovascular autonomic neuropathy at the preclinical stage.Materials and methods. A design is a prospective randomized study. A clinical and instrumental examination of 64 children with preclinical stage signs of diabetic cardiovascular autonomic neuropathy (DCAN) was carried out. The cohort was divided into 2 groups: in the main and control groups, glycemic control was normalized by adjusting a dose of insulin therapy; in the main group, the children additionally received thioctic acid at the dose of 600 mg/day for 3 months. To control the effectiveness of the therapy, the technique of laser Doppler flowmetry was used.Results. After the pharmacological intervention, there was an improvement in the disease course, normalization of carbohydrate and lipid metabolism, increased vasomotor mechanisms of the regulation of the tissue blood flow due to an increase in endothelial and neurogenic kinds of activity in combination with a decrease in the intravascular tone and an increase in the effective perfusion in tissues. An increase in the heart rate variability was detected, positive dynamics of cardiovascular tests indicators according to D. Ewing, temporal (pNN50%, SDNN) and spectral indicators (VLF) were diagnosed. Achievement and maintenance of the target values of glycemic control indicators, as well as the absence of glycemic variability, turned out to be clinically significant for reducing the manifestations of neuropathy. The non-invasive technique of laser Doppler flowmetry is informative for the early diagnosis of DCAN in T1DM children.Conclusion. The carried out studies have demonstrated the effectiveness of the lipoic acid use at the dose of 600 mg/day for 3 months in the children with DCAN signs at the preclinical stage. The method of laser Doppler flowmetry for determining indications and monitoring the effectiveness of therapy makes it possible to implement a personalized approach to prescribing preventive treatment in T1DM children.

Diabetic Cardiovascular Autonomic Neuropathy: Effects of Simvastatin and Omega-3 Polyunsaturated Fatty Acids on Insulin Resistance and Lipid Profile Parameters

Introduction. Currently, there is no unified treatment algorithm of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to investigate the effects of simvastatin (SIM) and -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) in patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Materials and methods. The study involved 72 patients with T2DM and definite CAN. Patients were divided into four groups: 1st - received standard hypoglycemic therapy - control (n = 15); 2nd (n = 22) – in addition simvastatin (SIM) 20.0 mg/q.d.; 3rd (n = 18) - in addition 1 capsule/q.d. of the ω-3 PUFAs; 4th (n = 17) - in addition SIM 10.0 mg/q.d and 1 capsule/q.d of the ω-3 PUFAs for three months. The concentration of glucose, glycated hemoglobin A1c, immunoreactive insulin (IRI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) in the blood were determined. Homeostasis model assessment IR (HOMA-IR), atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG and glucose index (TyG) were calculated. Results. Prescription of SIM was accompanied by a statistically significant decrease in TC, LDL-C, TG concentrations. In parallel, SIM induced a decrease of AC, TG/HDL-C, increase in HDL-C, and does not affect the IRI, HOMA-IR, TG/LDL-C, TG/TC, TC/LDL-C/HDL-C, TyG. The use of ω-3 PUFAs has contributed to a significant reduction in TG, AC, TG/LDL-C, TG/TC, TG/HDL-C, TyG index, increase in HDL-C, and was not accompanied by changes in IRI content, HOMA-IR, TC, LDL-C, and TC/LDL-C/HDL-C. The combined prescription of SIM and -3 PUFAs was accompanied by more pronounced, statistically significant changes in the blood lipid spectrum, as well as a decrease in the IRI and HOMA-IR. Conclusions. Obtained results justify the appropriateness of combined simvastatin and -3 polyunsaturated fatty acids prescription to patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Keywords: diabetes mellitus, cardiac autonomic neuropathy, treatment.

Actualități despre neuropatia autonomă cardiovasculară la pacienții cu diabet zaharat

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests.

Особливості патогенезу і перебігу цукрового діабету 2 типу та коморбідної з ним кардіоваскулярної патології у пацієнтів літнього віку

The features of the pathogenesis and course of type 2 diabetes mellitus and diseases of the cardiovascular system comorbid with it are considered in patients of elderly and old age – coronary artery disease, arterial hypertension, chronic heart failure. The leading role of insulin resistance, hyperglycemia and dyslipidemia in the development of metabolic, homeostatic disorders, the formation of oxidative stress and endothelial dysfunction, which, together with age-related changes in the body, contribute to the progression of type 2 diabetes mellitus and microvascular complications, primarily diabetic cardiomyopathy. Particular attention is paid to the relationship between cognitive impairment, type 2 diabetes mellitus and chronic heart failure. The main factors that worsen the course and prognosis of type 2 diabetes mellitus in elderly patients, in particular, hypertension, atrial fibrillation, diabetic polyneuropathy, nephropathy, and other concomitant diseases, have been identified. Lack of compensation for type 2 diabetes due to metabolic disorders leads to the development of diabetic cardiovascular autonomic neuropathy, diabetic cardiomyopathy along with the progression of atherosclerotic lesions of different localization. The course of type 2 diabetes in these patients is often complicated by geriatric syndrome, which contains a set of cognitive impairment, senile weakness, depression, functional disorders, polymorbidity. Cognitive disorders negatively affect the course of type 2 diabetes and its complications, significantly disrupting the process of teaching patients the methods of self-control, following the advice of a doctor. It is noted that the management of this category of patients should be individual and include adequate correction of hyperglycemia to prevent microvascular complications and hypoglycemic conditions, as well as reduce cardiovascular mortality and maintain quality of life. Rational selection of drugs, taking into account the factors that determine their impact on the body of elderly patients with type 2 diabetes mellitus and possible adverse drug reactions, will increase the effectiveness and safety of drug therapy in such patients. Optimizing therapeutic approaches for elderly patients with type 2 diabetes requires effective changes in the health care system to provide them with comprehensive medical and social care according to their special needs

Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier, even before diabetes is diagnosed. CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers, which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control. The entire mechanism is still not elucidated, but several aspects of the pathophysiology of CAN have already been described, such as the production of advanced glycation end products, reactive oxygen species, nuclear factor kappa B, and pro-inflammatory cytokines. This microvascular complication is an important risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. It has also been suggested that, compared to other traditional cardiovascular risk factors, CAN progression may have a greater impact on cardiovascular disease development. However, CAN might be subclinical for several years, and a late diagnosis increases the mortality risk. The duration of the transition period from the subclinical to clinical stage remains unknown, but the progression of CAN is associated with a poor prognosis. Several tests can be used for CAN diagnosis, such as heart rate variability (HRV), cardiovascular autonomic reflex tests, and myocardial scintigraphy. Currently, it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV, which is a non-invasive test with a lower operating cost. Therefore, considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes, the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.

Association of Cardiovascular Autonomic Neuropathy and Distal Symmetric Polyneuropathy with All-Cause Mortality: A Retrospective Cohort Study.

Background People with diabetic cardiovascular autonomic neuropathy (CAN) have increased cardiovascular mortality. However, the association between distal symmetric polyneuropathy (DSPN) or CAN with all-cause mortality is much less investigated. Thus, we set out to examine the effect of CAN and DSPN on all-cause mortality in a well-phenotyped cohort. Methods All diabetes cases (n = 1,347) from the catchment area of a secondary diabetes care centre who had medical examination including neuropathy assessment between 1997 and 2016 were followed up for all-cause mortality in the NHS Hungary reimbursement database until 2018. We investigated the association of CAN (Ewing tests) and DSPN (Neurometer) with all-cause mortality using Cox models stratified by diabetes type. Results Altogether, n = 131/1,011 persons with type 1/type 2 diabetes were included. Of the participants, 53%/43% were male, mean age was 46 ± 12/64 ± 10 years, diabetes duration was 13 ± 10/7 ± 8 years, 42%/29% had CAN, and 39%/37% had DSPN. During the 9 ± 5/8 ± 5-year follow-up, n = 28/494 participants died. In fully adjusted models, participants with type 1 diabetes patients with versus without DSPN had an increased mortality (HR 2.99, 95% CI 1.4-8.63), while no association with CAN was observed. In type 2 diabetes, both DSPN and CAN independently increased mortality (HR 1.32, 95% CI: 1.07-1.64, and HR 1.44, 95% CI: 1.17-1.76). Conclusions Our results are compatible with an increased risk of mortality in people with type 1 diabetes and DSPN. Furthermore, we report a similarly strong association between DSPN and CAN and all-cause mortality in type 2 diabetes mellitus.

Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes.

We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study followed for >35 years. Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from CVD, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on electrocardiogram, confirmed angina, or coronary artery revascularization. Cox proportional hazards models assessed the association of microvascular complications with subsequent risk of CVD. A total of 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively), associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER ≥30 mg/24 h occurring alone and/or with eGFR <60 mL/min/1.73 m2 and the presence of both retinal and kidney disease remained associated with CVD. Advanced microvascular disease, especially moderate to severe albuminuria or eGFR <60 mL/min/1.73 m2, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort.

Insulin resistance is independently associated with cardiovascular autonomic neuropathy in type2 diabetes.

Aims/IntroductionDiabetic cardiovascular autonomic neuropathy (DCAN) seriously threatens the prognosis and quality of life of patients with type 2 diabetes mellitus, associated with increased mortality. The present study aimed to investigate the relevant risk factors of DCAN.Materials and MethodsThe present study enrolled a total of 109 patients with type 2 diabetes mellitus. DCAN was defined as a score of at least 2 points in Ewing tests. The updated homeostasis model assessment of insulin resistance (HOMA2‐IR) based on fasting C‐peptide was calculated to reflect insulin resistance. Logistic regression analysis, interaction and stratified analyses were used to investigate the relationship between HOMA2‐IR or other indicators and DCAN. Receiver operating characteristic analysis was carried out to estimate the discriminative value of the variables independently associated with DCAN and to determine the optimal cut‐off point of these models to screen DCAN.ResultsThe HOMA2‐IR levels were significantly higher in patients with DCAN, and tended to be worsened with the progression of the DCAN. Logistic regression analysis showed an independent association between HOMA2‐IR (odds ratio 39.30, 95% confidence interval 7.17–215.47) and DCAN. HOMA2‐IR (area under the curve 0.878, 95% confidence interval 0.810–0.946; cut‐off value 1.735) individually predicted DCAN significantly higher than the other independent risk factors individually used, whereas models combining HOMA2‐IR and other risk factors did not significantly boost the diagnostic power.ConclusionsInsulin resistance is independently associated with DCAN. HOMA2‐IR presents to be a highly accurate and parsimonious indicator for DCAN screening. Patients with HOMA2‐IR >1.735 are at a high risk of DCAN; thus, priority diagnostic tests should be carried out for these patients for timely integrated intervention.

Diabetic cardiovascular autonomic neuropathy in children

Abstract Diabetic cardiovascular autonomic neuropathy (CAN) encompasses damage to the autonomic nerve fibers innervating the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Clinical symptoms associated with CAN include resting tachycardia, postural hypotension, dizziness, syncope, exercise intolerance, silent myocardial infarction. The earliest finding of CAN, even at the subclinical stage, is a decrease in heart rate variability (HRV) Purpose To study CAN prevalence and understand the diagnostic capabilities of HRV - tests of diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes. Methods 100 children with type 1 diabetes were assessed for CAN (age 15.2 yrs [9.0–17.8], duration 6.5 yrs [4.0–10.6], HbA1c 8.1% 6.3–9.7]). The degree of compensation of diabetes was estimated according to criteria ISPAD Consensus Guidelines, 2018. Optimal level (HbA1c &amp;lt;7.0%) of compensation was revealed in 62% of children (group I) and nonoptimal in 38% of children (group II). For evaluation of the CAN we used HRV - tests: RR 30:15 ratio, ΔRR quiet breath, ΔRR deep breath, BP response to standing. Results Diabetic cardiovascular autonomic neuropathy was diagnosed in 41 children: in group I – in 6 (29%) and in group II – 35 (71%) children (p=0.00001). The prevalence of DCN correlated with HbA1c level in children and adolescents (groups I and II): ΔRR quiet breath r=−0.47 &amp; r=−0.9; ΔRR deep breath r=−0.65 &amp; r=−0.85; RR30:15 r=−0.77 &amp; r=−0.88 respectively. Prevalence of CAN increased parallel to type 1 diabetes duration (p&amp;lt;0.01). Conclusions Diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes was diagnosed in 41%. Prevalence of diabetic cardiovascular autonomic neuropathy increases parallel to type 1 diabetes duration (p&amp;lt;0.01). In this study we found an association between HRV indexes and HbA1c level. This provides support for HRV - testing to assess diabetic cardiovascular autonomic neuropathy in children. Funding Acknowledgement Type of funding source: None

Features of course and treatment of chronic heart failure in patients with diabetes mellitus type 2

The epidemiology of chronic heart failure in patients with diabetes mellitus type 2, their general pathophysiological mechanisms, the influence of diabetes mellitus type 2 on the course and prognosis of chronic heart failure are considered. The high prevalence of chronic heart failure of all phenotypes among patients with diabetes mellitus type 2 and the increased risk of developing diabetes mellitus type 2 in patients with chronic heart failure confirm the close relationship and the high degree of comorbidity between these pathological conditions. It is shown that the development and progression of chronic heart failure in patients with diabetes mellitus type 2 is the formation of diabetic cardiomyopathy, which is characterized by disorders of energy metabolism of cardiomyocytes, mitochondrial dysfunction with subsequent apoptosis and myocardial fibrosis. Important links in the pathogenesis of chronic heart failure in diabetes mellitus type 2 are also the accession of diabetic cardiovascular autonomic neuropathy, activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, exposure to atherogenic factors, arterial hypertension, obesity. The features of treatment of chronic heart failure in patients with diabetes mellitus type 2, the results of randomized clinical studies, the choice of target glycemic levels, the effectiveness of different groups of antihyperglycemic agents, drugs for the treatment of chronic heart failure, as well as their impact on the course and prognosis of chronic heart failure. Keywords: chronic heart failure, diabetes mellitus type 2, course, prognosis, treatment.

The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy.

The study investigated the diagnostic performance for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN) of the combined use of composite autonomic symptom score (COMPASS) 31, validated questionnaire for autonomic symptoms of CAN, and electrochemical skin conductance (ESC), proposed for detecting DPN and CAN. One-hundred and two participants with diabetes (age 57 ± 14 years, duration 17 ± 13 years) completed the COMPASS 31 before assessing cardiovascular reflex tests (CARTs), neuropathic symptoms, signs, vibratory perception threshold (VPT), thermal thresholds (TT), and ESC using Sudoscan. Two patterns were evaluated: (a) the combined abnormalities in both tests (COMPASS 31+ESC), and (b) the abnormality in COMPASS 31 and/or ESC (COMPASS 31 and/or ESC). CAN (≥1 abnormal CART) and confirmed CAN (≥2 abnormal CARTs) were present in 28.1% and 12.5%, DPN (two abnormalities among symptoms, signs, VPT, and TT) in 52%, abnormal COMPASS 31 (total weighted score >16.44) in 48% and abnormal ESC (hands ESC <50 μS and/or feet ESC <70 μS) in 47.4%. Both the patterns-COMPASS 31+ESC and COMPASS 31 and/or ESC-were associated with CAN and DPN (P < .01). COMPASS 31 and ESC reached a sensitivity of 75% and 83% for confirmed CAN, and a specificity of 65% and 67% for DPN. When combining the tests, the sensitivity for CAN rose by up to 100% for CAN and the specificity up to 89% for DPN. The combination of the tests can allow a stepwise screening strategy for CAN, by suggesting CAN absence with combined normality, and prompting to CARTs with combined abnormality.

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.

Treatment of Diabetic Cardiovascular Autonomic, Peripheral and Painful Neuropathy. Focus on the Treatment of Cardiovascular Autonomic Neuropathy with ACE Inhibitors.

Neuropathies of the peripheral and autonomic nervous systems affect up to half of all people with diabetes mellitus, and are major risk factors for foot ulceration, amputation and cardiovascular dysfunction. Peripheral neuropathies manifest with either painful or painless symptoms, but many patients experience both. Once diagnosed appropriately, painful diabetic neuropathy management presents a unique challenge for physicians and should be considered as a syndrome, clinically distinct from diabetic peripheral neuropathy. The aetiology is multifactorial: metabolic changes in diabetes may directly affect neural tissue and neurodegenerative changes are precipitated by compromised nerve vascular supply. Metabolic changes include the elevated polyol pathway activity, the increased oxidative stress, the formation of advanced glycation and lipoxidation end products, and various pro-inflammatory changes. These mechanisms work in combination and interact in a mutually facilitatory fashion. This review focuses on the current therapies for the management of peripheral and cardiovascular autonomic neuropathy and of painful neuropathy as a distinct entity, based on the current knowledge of diabetic neuropathy. Moreover, the role of ACE inhibition has been explored in the treatment of Cardiovascular Autonomic Neuropathy.

Correlation between serum bilirubin and cardiovascular autonomic neuropathy in patients with type 2 diabetes

Objective: To investigate the correlation between serum bilirubin and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes mellitus patients. Methods: A total of 369 patients with type 2 diabetes mellitus who were hospitalized at the Department of Endocrinology, Nanjing Jinling Hospital from April 2017 to October 2018 were enrolled, including 226 males and 143 females, with an average age of (54.6±12.1) years. According to cardiovascular reflex tests (CARTs), all the patients were divided into Non CAN group(149 patients without CAN) and CAN group (220 patients complicated with CAN). The difference of serum bilirubin levels between the two groups was compared. The differences of CARTs and the incidence of CAN were compared by tertiles of serum bilirubin levels. The binary logistic regression was used to analyze the risk factors for diabetic cardiovascular autonomic neuropathy. Results: The serum total bilirubin [(9.28±2.74) μmol/L vs (11.08±2.98) μmol/L, P<0.001], direct bilirubin [(3.17±1.20) μmol/L vs (3.71±1.24) μmol/L, P<0.001] and indirect bilirubin levels [(6.11±1.89) μmol/L vs (7.37±2.10) μmol/L, P<0.001] in CAN group were significantly lower than that in Non CAN group. With the increase of serum bilirubin, the incidence of CAN decreased (P<0.01). Multivariate Logistic regression analysis showed that serum total bilirubin (OR=0.819, 95%CI: 0.744-0.901, P<0.001), direct bilirubin (OR=0.739, 95%CI: 0.601-0.908, P=0.004) and indirect bilirubin (OR=0.749, 95%CI: 0.653-0.860, P<0.001) were inversely correlated with the incidence of CAN. Conclusions: Within the physiological range, lower level of serum bilirubin is inversely correlated with the incidence of CAN. It is noteworthy to screen diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus who had a lower serum bilirubin level.