Degree Of Autonomic Neuropathy Research Articles

Transcutaneous vagus nerve stimulation has no anti-inflammatory effect in diabetes

Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes.

Autonomic Neuropathy in Healthy Elderly Person

Background: Cardiac autonomic nerve function can be affected in older age. Objective: To find out the degree of autonomic neuropathy by autonomic nerve function scoring system in apparently healthy elderly subjects. Methods: This cross sectional study was conducted in the Department of Physiology, BSMMU, Dhaka between July 2005 and June 2006.For study group, 30 elderly subjects age ranged from 51-60 years were enrolled in one group whereas another 30 elderly subjects age between 61-70 years were enrolled in another group. For comparison sex and BMI matched thirty apparently healthy adults with age from 21-30 years were studied as control. Autonomic nerve function status of all the subjects were examined by five simple non-invasive cardiovascular reflex tests Valsalva maneuver deep breathing test, orthostatic test handgrip test, and sudden standing. Autonomic nerve function (ANF) scoring was done to find out the degree of autonomic neuropathy. Results: 23.34% of subjects of 61-70 years group showed autonomic nerve dysfunctions and 20% had early involvement and 3.34% of them had definite involvement of Autonomic neuropathy. But this percentage was relatively less (10%) in 51-60 years who had early involvement and none had found definite involvement whereas autonomic nerve function was normal in 21-30 years age group.. Conclusion: From this study, it can be concluded that aging process substantially impaired cardiovascular autonomic nerve function. DOI: http://dx.doi.org/10.3329/jbsp.v8i2.18658 Bangladesh Soc Physiol. 2013, December; 8(2): 77-83

A study on autonomic neuropathy scorings in patients of chronic renal failure with and without symptoms

Abstract: Introduction: Chronic renal failure may be asymptomatic or symptomatic. Autonomic neuropathy is commonly associated with chronic renal failure. In recent years, there has been a growing interest in the cardiovascular autonomic neuropathy in chronic renal failure because of its association with an increase in mortality in these patients. So the study of autonomic neuropathy in patients of chronic renal failure with and without symptoms was taken up. Methods: The following clinical tests for autonomic neuropathy were done in 100 patients. Heart rate variability in response to deep breathing, heart rate variability in response to standing heart rate in response to valsalva maneuver, blood pressure response to standing and BP response to sustained hand grip exercise were recorded. Values obtained from the various tests were tabulated into a worksheet and a scoring system was applied to each test as recommended by Bellavere et al. The degree of autonomic neuropathy was assessed using CAN score. Mean CAN scores were compared in patients with and without symptoms using ANOVA test. P value<0.01 was considered to be statistically significant. Result: We found out that autonomic neuropathy autonomic neuropathy scorings is significantly higher in symptomatic chronic renal failure patients. Conclusion: So study of autonomic neuropathy can guide clinicians to prevent early complications in chronic renal failure patients.

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.

Factors determining the 24-h blood pressure profile in normotensive patients with type 1 and type 2 diabetes.

Some controversy still exists about factors involved in the abnormal circadian pattern of blood pressure (BP) in diabetes, while prognostic value of non-dipping condition is being increasingly recognised. This study was aimed at evaluating the relative influence of autonomic neuropathy (AN) and albumin excretion on 24-h BP profile in type 1 and type 2 diabetes. We measured AN cardiovascular tests, 24-h ambulatory BP, and urinary albumin excretion rate (UAE) in 47 type 1 and 34 type 2 normotensive non-proteinuric diabetic patients. In type 1 diabetic patients day-night differences (Delta) in systolic and diastolic BP were lower in those with AN than in those without (3 +/- 9 vs 10 +/- 6%, P < 0.01, and 8 +/- 9 vs 16 +/- 6%, P < 0.001), and in univariate regression analysis they were inversely related to both autonomic score, index of degree of AN (r = -0.61, P < 0.001 and r = -0.65, P < 0.001), and to 24-h UAE (r = -0.39, P < 0.01 and r = -0.46, P < 0.001). In type 1 diabetic patients AN was also associated with lower nocturnal decrease in UAE (patients with AN vs without AN: -37 +/- 214 vs 49 +/- 37%, P < 0.05), and with a stronger relationship between simultaneous 24-h UAE and 24-h BP (for systolic BP patients with AN vs without AN: r = 0.62, P < 0.01 vs r = 0.28, NS). In type 2 diabetic patients Delta systolic BP was reduced in patients with AN compared to those without (4 +/- 7 vs 10 +/- 4%, P < 0.01), and it was related only to autonomic score (r = -0.42, P < 0.01). Using a stepwise regression analysis, in type 1 diabetic patients autonomic score was the variable of primary importance for Delta BP, while in type 2 diabetic patients it was the unique determinant not only of Delta systolic BP but also of 24-h systolic BP. In conclusion, AN is the pivotal factor of blunted nocturnal fall in BP in both type 1 and type 2 diabetic patients. In type 1 diabetic patients AN is associated with attenuated circadian pattern of albuminuria and with a steeper relationship between albuminuria and BP, in type 2 diabetic patients AN is the only factor related to elevated 24-h BP levels. Longitudinal studies are needed to establish the potential role of autonomic dysfunction as a progression promoter for nephropathy and hypertension in type 1 and type 2 diabetes respectively.

Sympathetic function test of vasoconstrictor changes in foot arteries in diabetic patients.

We studied the relationship between vasoconstrictor changes in foot arteries (pedal, metatarsal, and digital arteries) and autonomic neuropathy in diabetic patients to estimate the degrees of sympathetic dysfunction. Sixty-two patients and nineteen age-matched control subjects were studied. The resistance index (RI) and pulsatility index (PI) were measured as vascular hemodynamic parameters using Doppler sonography, and the increases in these hemodynamic parameters (%RI and %PI) from rest to a deep breath were measured as indexes of the degrees of sympathetic vasoconstrictor function. Cardiovascular autonomic function tests (AFTs) were performed and the score was compared to %RI and %PI values obtained. Of the 62 diabetic patients, 51 had various degrees of autonomic neuropathy. Both %RI and %PI in the diabetic patients were significantly less than those in the control subjects for all foot arteries tested (all P < 0.001). There were strongly inverse correlations between the %RI and %PI of foot arteries and the AFT score (r = -0.556 to -0.846, P < 0.0001). The %RI of the digital artery was the most strongly correlated with AFT score (r = -0.846, P < 0.0001) among foot arteries tested. The abnormality of sympathetic vasoconstriction was detectable in the majority of the diabetic patients with the early phase of autonomic neuropathy (%RI: 89.5%; %PI: 94.5%). We conclude that the %RI of the digital artery is a useful and reliable sympathetic function test of early phase in diabetic patients.

Individual factors influencing cardiovascular reflexes in normals and in patients with different degrees of autonomic neuropathy

Individual factors influencing cardiovascular reflexes in normals and in patients with different degrees of autonomic neuropathy

Day and night variation in ambulatory blood pressure in type 1 diabetes mellitus with nephropathy and autonomic neuropathy

The objective was to study ambulatory blood pressure and heart rate variability between day and night in patients with type 1 (insulin-dependent) diabetes mellitus with different degrees of diabetic nephropathy, and to evaluate the influence of autonomic neuropathy and type of antihypertensive treatment. Twenty type 1 diabetic patients with diabetic nephropathy and antihypertensive treatment were studied with 24-h ambulatory blood pressure monitoring using an oscillometric method. They were compared with eight insulin-treated diabetic patients with short duration of diabetes (1-5 years) and with 10 apparently healthy subjects. The degree of autonomic neuropathy was evaluated by measuring the RR-interval during deep breathing and uprising. The 24-h blood pressure was generally higher in patients with diabetic nephropathy compared to those other two groups. These patients also had a lower ratio between day and night in diastolic blood pressure compared to the control subjects (1.15 +/- 0.12 vs. 1.25 +/- 0.76, P < 0.05) and heart rate compared to the diabetic patients without nephropathy, as well as the control subjects (1.15 +/- 0.08 vs. 1.26 +/- 0.09 vs. 1.27 +/- 0.08, P < 0.01, respectively). All patients with diabetic nephropathy had clinical signs of autonomic neuropathy as judged by RR-interval measurements during deep breathing and uprising.

Circadian Rhythm of Blood Pressure in Normotensive NIDDM Subjects: Its Relationship to Microvascular Complications

To investigate the relationship between circadian rhythm of mean blood pressure (MBP) and microvascular complications in non-insulin-dependent diabetes mellitus (NIDDM) subjects. Seventy-six normotensive NIDDM subjects without azotemia were studied under ordinary hospital conditions with a noninvasive ambulatory blood pressure monitoring device. Time series data were analyzed by the cosinor method. Fifty-four subjects had a circadian MBP rhythm similar to that of 34 age-matched nondiabetic control subjects, with a peak value in the afternoon (group 1). In contrast, 22 had a reversed circadian MBP rhythm, with a peak value during the night (group 2). Obvious complications were found in 65% of group 1 and in all of group 2. The prevalence of retinopathy and somatic neuropathy and the degree of retinopathy were similar in the two groups. The prevalence and degree of autonomic neuropathy (postural hypotension and reduced beat-to-beat heart-rate variation) and nephropathy were greater in group 2 than group 1. Linear discriminant analysis revealed a correlation between the reversed circadian MBP rhythm and postural hypotension (F = 32.2, P less than 0.001) and overt nephropathy (F = 5.1, P less than 0.05) but not with beat-to-beat heart-rate variation (F = 0.17, NS). These results suggest that in the hospitalized normotensive NIDDM subjects, there are normal and reversed circadian MBP rhythms and that the reversal of normal circadian MBP rhythm may be related to the degree of postural hypotension and/or nephropathy.

Impaired left-ventricular function in insulin-dependent diabetic patients with increased urinary albumin excretion

Cardiac function was studied in 30 patients with insulin-dependent diabetes mellitus. Three groups, matched for age and diabetes duration, were defined as: group I (n = 10), normal urinary albumin excretion less than 30 mg 24 h-1; group II (n = 10), incipient diabetic nephropathy (urinary albumin excretion in the range of 30-300 mg 24 h-1); and group III (n = 10), clinical diabetic nephropathy (urinary albumin excretion greater than 300 mg 24 h-1). Ten non-diabetic subjects matched for sex and age served as controls. The left-ventricular end-diastolic volume measured by radionuclide cardiography was, at rest and during exercise, lower in group II and III compared with controls (p less than 0.05), while intermediate values were found in group I. The cardiac output was similar in the control group and group I; it was reduced, but not significantly so (p = 0.10), in group III and was significantly lower in group II (p less than 0.05). Stroke volume was also lower in group II and III than in controls (p less than 0.05), but not so in group I. These differences could not be explained by differences in metabolic control, blood pressure, blood volume status, degree of autonomic neuropathy or frequency of coronary heart disease. Our results might suggest that insulin-dependent diabetic patients with slightly but persistently elevated urinary albumin excretion have reduced diastolic compliance of the left-ventricle leading to impaired cardiac performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training in individuals with diabetic retinopathy and blindness.

Limited guidelines exist for rehabilitation programs for individuals with diabetes mellitus, blindness, and associated autonomic neuropathy. Abnormalities in autonomic function have been postulated to interfere with exercise conditioning and may predispose individuals to exercise-induced hypoglycemia. Twenty-nine individuals with diabetes mellitus underwent standardized noninvasive testing for the evaluation of cardiovascular autonomic function and graded exercise before entering a rehabilitation program. Inadequate responses of heart rate to respiratory variation were observed in 28 patients, abnormal heart rate responses to postural maneuvers were seen in 23, and postural hypotension was noted in nine. Individuals with symptomatic postural hypotension were able to exercise using a stationary bicycle, but developed hypotensive episodes on walking or prolonged standing. Blood glucose consistently decreased by a mean of 76 (+/- 9) mg/dl after each exercise session, even though low levels of exercise were performed (2.9 +/- 0.2 metabolic equivalents, for 28 +/- 1 min). There was no relationship between the degree of autonomic neuropathy and the level of blood glucose fall. There was, however, a significant correlation (r = -0.59, p = 0.001) between the decrease in blood glucose level and the amount of regular insulin used in the routine morning dose. Precautions were taken to avoid hypoglycemia, and insulin and diet were adjusted accordingly to prevent severe hypoglycemic reactions.

Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion.

To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal urinary albumin excretion (less than 30 mg/24 h), group 2 comprised 10 with incipient diabetic nephropathy (urinary albumin excretion 30-300 mg/24 h, and group 3 comprised 10 with clinical diabetic nephropathy (urinary albumin excretion greater than 300 mg/24 h). Ten non-diabetic subjects matched for sex, age, and physical activity served as controls. Oxygen uptake was similar in the four groups at rest and during a 75 W workload. Maximal oxygen uptake was also similar in the control subjects and group 1 (median 41.7, (range 29.1-53.0) ml/kg/min v 38.5 (26.6-59.2) ml/kg/min, respectively), but was significantly lower in group 2 (27.7 (13.9-44.3) ml/kg/min) and group 3 (22.6-36.7) ml/kg/min). The difference in maximal oxygen uptake between groups 1 and 2 was 10.8 ml/kg/min (95% confidence interval 3.6 to 23.4 ml/kg/min) and between groups 1 and 3, 11.7 ml/kg/min (4.9 to 22.5 ml/kg/min). These differences were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy or the duration of diabetes. Whether the reduced capacity is due to widespread microangiopathy or another pathological process affecting the myocardium remains to be established.

Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy.

A critical level of diabetic autonomic neuropathy.

Diabetic autonomic neuropathy was expressed quantitatively using the coefficient of variation of R-R intervals (CVR-R) in ECG and its critical level where diabetics were plagued with various symptoms was investigated. The subjects were 58 diabetics under the age of 40 years. ECGs were recorded in the resting supine position and the degree of autonomic neuropathy was expressed as CVR-R by processing 100 consecutive R-R intervals. Symptoms caused by diabetic autonomic neuropathy were determined using a questionnaire. CVR-R were 1.10 +/- 0.34% (mean +/- SD) and 4.31 +/- 2.01% in patients with and without orthostatic hypotension respectively, the former being significantly lower. CVR-R were 1.30 +/- 0.88% and 3.81 +/- 1.31% in those with and without impotence respectively, the former being significantly lower. CVR-R were 0.80 +/- 0.14% and 3.85 +/- 2.17% in those with and without diabetic diarrhea respectively, the former being significantly lower. Concerning sweating abnormality CVR-R were significantly reduced in subjects exhibiting gustatory sweating (1.52 +/- 0.74%) and hypohidrosis (2.26 +/- 1.44%) when compared to those without these symptoms. From the results obtained, a CVR-R of 2% can be considered as the critical level which determines whether symptoms due to diabetic autonomic neuropathy will appear or not.