Parasympathetic Autonomic Dysfunction Research Articles

Evaluation of Cardiovascular Autonomic Dysfunction According to Heart Rate Turbulence and Variability in Patients with Benign Paroxysmal Positional Vertigo

Introduction: The relationship between benign paroxysmal positional vertigo (BPPV) and cardiovascular autonomic dysfunction is not clear. Disruption of the balance between the sympathetic and parasympathetic systems causes various diseases. It is believed that disorders of the parasympathetic system, particularly, may be responsible for causing BPPV. Heart rate variability (HRV) and HRT (heart rate turbulence), which show autonomic dysfunction, are two non-invasive tests that show the relationship of the heart rate with the autonomic nervous system. The purpose of the present study was to evaluate the relationship between autonomic dysfunction and BPPV in patients with BPPV by using HRV and HRT, which are non-invasive laboratory parameters. Patients and Methods: A total of 100 age- and gender-matched volunteers and 100 patients with BPPV were selected for the study between January 2015 and January 2020. We obtained HRT and HRV parameters from 24-hour ECG Holter recordings. We considered a TO above 0 and a TS above 2.5 to be abnormal. We compared the parameters between groups. Results: A significant difference was observed between the BPPV and control groups in the HRV parameters SDNNI (p= 0.036), SDANN (p= 0.045), and HRT parameter TS (p= 0.048). We showed that abnormal TO (p= 0.025) and TS (p= 0.038) values were significantly higher in the patient group. Conclusion: Parasympathetic autonomic dysfunction was demonstrated by the lower HRV and HRT values observed in the patients with BPPV compared to the control group in the present study. The present findings must be confirmed with a much larger number of patients and multi-center studies.

Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients

Several disabling symptoms potentially related to dysautonomia have been reported in “long-COVID” patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31–43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0–16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

N°45 – Fluctuating and polymorphic symptoms in [LDQUO]Long-COVID[RDQUO] may hide parasympathetic autonomic dysfunction

N°45 – Fluctuating and polymorphic symptoms in [LDQUO]Long-COVID[RDQUO] may hide parasympathetic autonomic dysfunction

Association of Cardiac Autonomic Function Derangement with Obesity and Glycated Haemoglobin: A Cross-sectional Study

Introduction: Hyperglycaemia (as assessed by Glycated haemoglobin (HbA1c)) and obesity lead to the production of advanced glycation end products in blood, which are responsible for damage to the microvasculature, slowly leading to cardiac autonomic dysfunction. Thus, chronic prediabetic hyperglycaemia, as measured by HbA1c may affect cardiac autonomic function in different ranges of obesity (overweight and obese). Aim: To study the association of cardiac autonomic dysfunction with Body Mass Index (BMI) and HbA1c. Materials and Methods: The cross-sectional study was conducted at BPS Government Medical College, Sonepat, Haryana, India, from June to December 2019. This study included age and sex-matched 50 healthy, 50 overweight, and 50 obese subjects aged 18-50 years. Serum HbA1c, lipid profile and cardiac autonomic function tests for the parasympathetic system (Resting heart rate, Expiration-inspiration difference on deep breathing, Heart rate response to standing/30:15 stand ratio, Valsalva ratio) and sympathetic system {postural hypotension/fall in Systolic Blood Pressure (SBP) and change in Diastolic Blood Pressure (DBP) on sustained hand grip test} were performed. Chi-square test and Mann-Whitney test were used for statistical analysis. Results: The prevalence of sympathetic autonomic dysfunction was highest in the obese group (36% in males n=25, and 32% in females, n=25) followed by overweight group (12% in males, n=25 and 12% in females, n=25). The prevalence of parasympathetic autonomic dysfunction was highest in the obese group (40% in males, n=25 and 32% in females, n=25), followed by the overweight group (24% in males, n=25 and 16% in females, n=25). Further, HbA1c was highest in obese males (6.27±1.54) and females (5.94±0.45), followed by overweight males (5.89±0.92) and females (5.46±1.84). Males and females with autonomic dysfunction had significantly higher HbA1c (Males 6.4±0.42 and Females 6.2±0.38) than those without it (Males 5.4±0.86 and Females 5.2±0.75) in the obese and overweight groups taken together. Conclusion: The prevalence of parasympathetic and sympathetic dysfunction is incrementally increased with higher obesity (BMI) and HbA1c. Overweight and obese subjects with cardiac autonomic dysfunction had higher HbA1c and worse lipid profiles than overweight and obese subjects without autonomic dysfunction.

Renal Transplantation in Pure Autonomic Failure.

Renal Transplantation in Pure Autonomic Failure.

Association of Postural Instability with Autonomic Dysfunction in Early Parkinson’s Disease

Background: There have been several pathologic data that support an association between postural instability (PI) and autonomic dysfunction in Parkinson’s disease (PD). The purpose of this study was to investigate the correlation of PI and autonomic deficits in early PD. Methods: We collected 17 patients with a diagnosis of early PD. PI was assessed by computerized dynamic posturography (CDP). Standardized autonomic function test (AFT) and time and frequency domain spectral analysis of heart rate variability (HRV) were performed. CDP data obtained from the 21 patients were compared to that from age- and sex-matched healthy controls. We collected HRV data from 18 other age- and sex-matched controls. All patients were evaluated in the “OFF” state. We used Mann–Whitney U-test to compare parameters of CDP between the early PD and control groups. Spearman correlation was used for correlation analysis between parameters of CDP and autonomic function test in PD patients. Results: Most patients (76.5%) showed mild or moderate autonomic dysfunction in the standardized AFT. In CDP, sensory ratios of equilibrium score (e.g., visual and vestibular) and composite scores were significantly lower in PD patients than in controls. In HRV, the low-frequency/high-frequency ratio during the tilt and the gap of low- frequency/high-frequency ratio from supine to tilt were significantly different in both groups. The parameters of time and frequency domains of HRV reflecting parasympathetic function were correlated with equilibrium scores for somatosensory organization test in CDP. Discussion: PI was associated with parasympathetic autonomic dysfunction in early PD. This result was in accordance with a previous assumption that PI in PD is related to parasympathetic cholinergic neuron loss in the brainstem.

Autonomic dysfunction in patients with essential tremor

Essential tremor (ET) is henceforth considered as multi-systemic neurodegenerative disorder characterized by a combination of motor and non-motor symptoms including autonomic dysfunction. Our aim was to explore neurophysiologic autonomic dysfunction in patients with ET. A prospective study was conducted in the department of Neurology in Razi Hospital (January2018-April 2019) including consecutive patients with ET according to the Tremor Investigation Group (TRIG) criteria. The sympathetic autonomic system (AS) was assessed with the sympathetic skin response (SSR) evaluated at the four limbs. Absent SSR at either one or more extremities was regarded as abnormal. Parasympathetic AS was assessed according to Ewing’s battery (Heart rate variation to deep breathing, to Valsalva, heart rate response to standing). Fifty ET patients were included with a sex-ratio of 1,08 (26 men and 24 women) and a mean age of 64.5years [20–86]. Neurophysiologic dysautonomia was found in 74% of ET. Heart rate variability was reduced in 60% of ET, mostly to standing in third of the patients. Parasympathetic dysfunction was early in 86,7% and definite in 13,3%. Sympathetic dysautonomia was found in 30%. Only 9 patients (18%) had both sympathetic and parasympathetic autonomic dysfunction. Our study showed the high prevalence of autonomic dysfunction on electrophysiological assessment in ET affecting mostly parasympathetic but also sympathetic autonomic system.

Infectious diseases causing autonomic dysfunction.

To review infectious diseases that may cause autonomic dysfunction. Review of published papers indexed in medline/embase. Autonomic dysfunction has been reported in retrovirus (human immunodeficiency virus (HIV), human T-lymphotropic virus), herpes viruses, flavivirus, enterovirus 71 and lyssavirus infections. Autonomic dysfunction is relatively common in HIV-infected patients and heart rate variability is reduced even in early stages of infection. Orthostatic hypotension, urinary dysfunction and hypohidrosis have been described in tropical spastic paraparesis patients. Varicella zoster reactivation from autonomic ganglia may be involved in visceral disease and chronic intestinal pseudo-obstruction. Autonomic and peripheral nervous system dysfunction may happen in acute tick-borne encephalitis virus infections. Hydrophobia, hypersalivation, dyspnea, photophobia, and piloerection are frequently observed in human rabies. Autonomic dysfunction and vagal denervation is common in Chagas disease. Neuronal depopulation occurs mainly in chagasic heart disease and myenteric plexus, and megacolon, megaesophagus and cardiomyopathy are common complications in the chronic stage of Chagas disease. Parasympathetic autonomic dysfunction precedes left ventricle systolic dysfunction in Chagas disease. A high prevalence of subclinical autonomic neuropathy in leprosy patients has been reported, and autonomic nerve dysfunction may be an early manifestation of the disease. Autonomic dysfunction features in leprosy include anhidrosis, impaired sweating function, localised alopecia ,and reduced heart rate variability. Urinary retention and intestinal pseudo-obstruction have been described in Lyme disease. Diphtheritic polyneuropathy, tetanus and botulism are examples of bacterial infections releasing toxins that affect the autonomic nervous system. Autonomic dysfunction may be responsible for additional morbidity in some infectious diseases.

Disease-modifying antirheumatic drugs improve cardiovascular autonomic neuropathy in psoriatic arthritis.

Cardiovascular autonomic neuropathy (CAN) is a significant risk predictor for sudden cardiac death in autoimmune rheumatic diseases. As yet, there is no therapeutic treatment of CAN in psoriatic arthritis (PsA). Even now, the impact of the most commonly employed disease-modifying antirheumatic drug (DMARD) therapy on CAN in PsA is not known. Hence, we investigated the impact of DMARDs on CAN in PsA. In this prospective, cross-sectional study, 20 patients of PsA and 20 age- and sex-matched healthy controls were recruited. CAN was diagnosed by applying the five cardiovascular reflex tests according to Ewing. Parasympathetic dysfunction was established by performing three tests: heart-rate response to deep breathing, standing, and Valsalva tests. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing, and handgrip tests. Disease severity was assessed by the 28-joint-count disease activity score (DAS-28) and the disease activity score in psoriatic arthritis (DAPSA). Cardiovascular reflex tests were impaired significantly among the PsA patients compared with well-matched healthy subjects (p < 0.05). Parasympathetic dysfunction was more prominent than sympathetic dysfunction. After 12 weeks treatment, parasympathetic dysfunction (heart rate response to deep breath and standing) significantly (p < 0.05) improved in patients with PsA, while there was no significant improvement in sympathetic function. These study results suggests parasympathetic autonomic dysfunction is more prominent than sympathetic dysfunction in PsA. Synthetic DMARDs improved parasympathetic dysfunction in PsA.

PP13.5 – 2902: Acute pandysautonomia case treated with intravenous immunoglobulin

Objective Acute pandysautonomia is a rarely seen acquired disorder with acute or subacute development of systemic sympathetic and parasympatheticautonomic dysfunction. Patients may suffer from orthostatic hypotension, bradycardia, anhidrosis, unreactive pupils, ptosis, decreased lacrimation and salivation, gastrointestinal paresis, and impaired genitourinary function. Methods Herein, we present a 15 year-old male patient who underwent laparotomy due to acute abdomen, and suffered from autonomic dysfunction postoperatively. Results The patient had no significant medical history except the laparotomy he underwent a month ago, due to acute appendicitis and ileus. Patient was consulted to neurology because of repetitive syncopes, occurring when he was trying to stand up, and ptosis. A urinary catheter was placed in order to treat globe vesical. Bradycardia (ongoing at sleep) was detected in physical examination, in addition to bilateral ptosis, and absence of deep tendon reflexes. His pupillary reflexes were normal. Blood count, chemical tests, and cardiac sonography didn't reveal any pathologic findings. Electroencephalography and cranial magnetic resonance were also normal. Acetylcholine receptor antibody result was negative, and cerebrospinal fluid protein level was 31.9 mg/dl. 400 mg/kg/day of intravenous immunoglobulin was administered for five days with the diagnosis of acute pandysautonomia. Deep tendon reflexes were reactive, and ptosis, bradycardia and syncopes vanished after treatment. Conclusion Acute pandysautonomia is a rare form of Guillain Barre Syndrome and it is usually seen after an infectious disease or a surgical trauma. Some of these cases may recover spontaneously in childhood. In more severe cases, corticosteroids and intravenous immunoglobulin are effective agents in treatment.

Autonomic Dysfunction in Cancer Cachexia Coincides With Large Fiber Polyneuropathy

ContextCancer cachexia occurs in most patients suffering from solid malignancies. Recent works suggest paraneoplastic mechanisms. Empirical studies also found autonomic dysfunction in cancer patients, but comprehensive evaluation of the peripheral nervous system is lacking. ObjectivesTo further understand the role of the autonomic and peripheral nervous system in cancer cachexia to guide treatment. MethodsWe prospectively investigated cachectic cancer patients for parasympathetic autonomic dysfunction with a time-domain–based analysis of heart rate variability (breathing at rest, deep breath, and in response to the Valsalva maneuver). Blood pressure changes after the Valsalva maneuver were used as a marker of the sympathetic noradrenergic system. Orthostatic hypertension was investigated in response to active standing. We used a noninvasive continuous beat-to-beat heart rate assessment and blood pressure monitoring. The sympathetic cholinergic nervous system was evaluated with the sympathetic skin response. A detailed neurological examination, nerve conduction studies, and electromyography also were conducted. ResultsA total of 13 patients were enrolled (median age 66 years). Median time from inclusion until death was 3.5 months. About 12 of the 13 patients showed abnormal results in at least one autonomic test. Sympathetic noradrenergic and cholinergic abnormalities were discovered in six patients each and five patients had orthostatic hypotension. Only one patient showed abnormal results in parasympathetic cholinergic tests. Asymptomatic large fiber polyneuropathy was detected in eight patients. ConclusionLarge fiber polyneuropathy coincides with autonomic dysfunction in cachectic cancer patients. Our findings suggest a relevant role of sympathetic impairment in cancer cachexia.

Parasympathetic autonomic dysfunction is common in mild cognitive impairment

Components of the central autonomic network attract the greatest neurofibrillary degeneration and related cell death during the course of Alzheimer's disease (AD). The insular cortex and brainstem are affected from the early stages of disease. Acetylcholine, the main neurotransmitter of the parasympathetic system may be deficient in mild cognitive impairment (MCI). Hence, autonomic dysfunction may be a novel biomarker of neurodegeneration. Autonomic function was examined in 97 MCI participants and 36 controls using beside cardiovascular reflex tests and heart rate variability. The association between dysautonomia and neuropsychiatric deficits was examined. This observational study was conducted in a clinical setting. MCI participants showed significant parasympathetic deficits in bedside cardiovascular reflex tests and heart rate variability compared with controls. Those with more significant autonomic dysfunction had more severe neuropsychological deficits. MCI participants were 5.60 (95% confidence interval, 1.6–27.2) times more likely than a control to have autonomic dysfunction. Autonomic dysfunction, particularly parasympathetic dysfunction is prevalent in MCI. This may be due to early neuroanatomical and neurochemical changes in the central autonomic network in Alzheimer's disease. This may accelerate cognitive decline via proinflammatory mechanisms and/or hypotension-induced cerebral hypoperfusion. This provides insight into the pathophysiological mechanisms that contribute to cognitive decline, and may lead to the development of effective therapeutic interventions.

The subclinic autonomic dysfunction in patients with Behçet disease: an electrophysiological study

Studies that have evaluated autonomic nervous system (ANS) function in Behçet disease (BD) are rare and have indicated conflicting results with different degrees of involvement. The aim of this study was to investigate ANS function by using electrophysiological tests in patients with BD and to determine the relationship between the disease activity parameters and the indicators of autonomic activity. We included 70 BD patients and 50 healthy controls. Demographic characteristics including age, sex, and disease duration were recorded. A detailed neurological examination was performed, and clinical autonomic symptoms were recorded. The Behçet Disease Current Activity Form (BDCAF) was used to determine the disease activity. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were determined for laboratory activity. The electrophysiological assessments of ANS function were performed by sympathetic skin response (SSR) and R-R interval variation (RRIV) tests. The mean values of sympathetic (SSR latency and amplitude) and parasympathetic (RRIV at rest [R%] and deep breathing [D%], D% - R%, and D%/R%) parameters were compared, and any correlations between ANS parameters and clinical disease characteristics were determined. Seventy BD patients (23 males, 47 females) with a mean age of 41.2 ± 10.01years and 50 control subjects (18 males, 32 females) with a mean age of 39.5 ± 8.94years were included in the study. All the subjects were totally symptom free with respect to ANS involvement, and the subjects in both groups had normal neurological examination findings. The demographic characteristics were similar between the groups. The mean latency of SSR was increased (1.4 ± 0.4 vs 0.7 ± 0.8), and R% (0.3 ± 0.3 vs 0.5 ± 0.4) and D% (0.3 ± 0.3 vs 0.6 ± 0.5) values were decreased in BD patients compared to control subjects. No correlation was found between BDCAF scores and ANS variables. However, there was a significant correlation between SSR latency and ESR and CRP values (p < 0.01, r = -0.25, r = -0.31, respectively) in the patient group, indicating a more sympathetic dysautonomia in patients with active laboratory parameters. In conclusion, our study indicates a subclinical sympathetic and parasympathetic autonomic dysfunction in patients with BD, which may be related with disease activity. As the early recognition of abnormalities in ANS may be very important in order to prevent excessive morbidity, simple electrophysiological methods are suggested to identify Behçet patients at high risk for symptomatic dysautonomia.

Valsalva manoeuvre in patients with different Parkinsonian disorders

The valsalva manoeuvre (VM), used as an autonomic function test, can detect sympathetic and/or parasympathetic autonomic dysfunction. This study investigated the value of VM in patients with different Parkinsonian syndromes (PS). We continuously recorded blood pressure, ECG and respiration among 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson's disease (PD) and in 27 healthy subjects matched in age and sex (Con). VM was performed in addition to metronomic breathing and tilt-table testing. VM could not be analysed in 26% of the ES patients. Valsalva ratio (VR), as a parameter of cardiovagal function, was pathologically decreased in all patient groups. Valsalva ratio (VR) was not able to discriminate parasympathetic dysfunction between patients and controls as well as E/I ratio of metronomic breathing. As a parameter of sympathetic dysfunction during VM, the physiological increase of blood pressure was more often missing during phase IV than phase II especially in PD and MSA patients. Correlation with orthostatic hypotension during tilt-table testing was only moderate. Although VM can demonstrate sympathetic and parasympathetic autonomic dysfunction, we cannot recommend VM as a first line autonomic test in PS patients. Metronomic breathing and tilt-table test seem more capable as parasympathetic resp. and sympathetic function tests to identify cardiovascular abnormalities in PS patients.

A 41-year-old man with polyarthritis and severe autonomic neuropathy

Orthostasis due to autonomic neuropathy can cause severe debilitation and prove refractory to treatment. This report describes a case of severe sympathetic and parasympathetic autonomic dysfunction as a consequence of acetylcholine receptor antibodies and Sjogren's syndrome. Symptomatic management, plasma fluid expanders, and IVIG therapy failed to offer a salutary response to the condition. Etanercept therapy provided improvement of the orthostasis and autonomic function measured as high and low frequency respiratory effects on heart rate variability as well as enhancement of skin blood flow using Laser Doppler. It would be of considerable interest to determine the effectiveness of etanercept in other autoimmune neuropathies.

Autonomic dysfunction in primary biliary cirrhosis correlates with fatigue severity

Autonomic dysfunction has previously been described in primary biliary cirrhosis patients. In nonhepatic diseases, fatigue is associated with autonomic dysfunction and impaired baroreflex sensitivity. Here, we investigate the prevalence of autonomic dysfunction using highly sensitive detection modalities and its relationship with fatigue in both noncirrhotic and cirrhotic primary biliary cirrhosis patients. Autonomic reflex tests were performed, using continuous blood pressure and electrocardiograph measurement in 47 primary biliary cirrhosis patients and age and sex-matched controls. Fatigue was measured using the primary biliary cirrhosis-40. In all, 100% of precirrhotic and 81% of cirrhotic primary biliary cirrhosis patients exhibited autonomic dysfunction. Valsalva ratio and 30 : 15 ratio (measures of parasympathetic autonomic dysfunction) were significantly lower in primary biliary cirrhosis patients than in controls (valsalva ratio: 1.42 vs. 1.57; P=0.01, 30 : 15: 1.1 vs. 1.2; P=0.01). Blood pressure drop on standing (sympathetic autonomic dysfunction) was greater in the primary biliary cirrhosis group (31+/-22 vs. 23+/-15 mmHg; P=0.03). Valsalva phase IV size was similar between primary biliary cirrhosis patients and controls, however, time to phase IV was significantly longer (P=0.01), suggesting adrenergic failure. Increasing fatigue was associated with impaired baroreflex sensitivity and an earlier, bigger phase IV (sympathetic overactivity). No significant differences were seen, between cirrhotic and noncirrhotic patients. The prevalence of autonomic dysfunction in primary biliary cirrhosis patients is significantly higher than has previously been thought to be the case. Indeed, when sensitive detection modalities are used, it is found to be almost universal at all stages of the disease process. Fatigue in primary biliary cirrhosis is associated with abnormalities of autonomic function.

Frequency and predictors of autonomic dysfunction in Parkinson′s disease: a study of African patients in Lagos, Nigeria

The degenerative changes in PD also affect the autonomic nervous system. The frequency and predictors of such involvement in Africans with PD has not been reported. i) To determine the frequency and type of autonomic dysfunction in Nigerians with idiopathic Parkinson's disease (PD). ii) To determine the predictors of autonomic dysfunction in PD. Cardiovascular autonomic function assessed in 33 study subjects with PD and 33 age-matched controls, utilising heart rate variability to deep breathing, standing and the Valsalva manoeuvre, and the blood pressure (BP) response to standing. The results were compared based on treatment category, grade of severity on the Columbia scale of Hoehn and Yahr, duration of PD, age at onset of PD, present age and occurrence of autonomic symptoms. Parasympathetic function was abnormal in 51.5% of PD subjects, significantly higher than controls (P<0.001). Of these, 76.5% had early parasympathetic involvement and 23.5% definite parasympathetic involvement. Age above 65 years (at time of study or onset of PD) was the only clinical variable associated with parasympathetic autonomic dysfunction (p<0.05). Symptoms dysfunction occurred in 60.6% of PD patients and only 6.1% of controls (p<0. 001). There was however no demonstrable relationship between the occurrence of symptoms and objective evidence of autonomic dysfunction: 41.2% of PD patients with parasympathetic dysfunction had no symptoms. Autonomic dysfunction was found to be common in Africans with PD, particularly those above 65 years and tends to affect the parasympathetic system. However, the abnormality may be detectable even before symptoms appear. As such, we recommend that cardiovascular tests of autonomic function be a routine aspect of the evaluation of PD patients, especially with advancing age.

Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation.

The purpose of pancreatic transplantation in insulin-dependent diabetic patients is to restore normoglycemia and thereby prevent the secondary complications of diabetes. However, uncertainty remains as to whether the mortality rate in diabetic patients can be affected by this procedure. We followed 14 patients with insulin-dependent diabetes mellitus (IDDM) and end-stage diabetic nephropathy for 10 years after successful combined kidney and pancreas transplantation. Fifteen diabetic patients subjected to kidney transplantation alone have served as controls. The glycemic control has been studied annually for 10 years and diabetic polyneuropathy has been assessed in both groups after 2, 4, and 8 years. In recipients of pancreas-kidney grafts, metabolic control was maintained throughout the observation period, with values of glycated hemoglobin in the normal range. In contrast, glucose metabolism was impaired in the control group, with glycated hemoglobin values around 10%. Nerve conduction and parasympathetic autonomic dysfunction improved in both groups after 2 years; there was no difference between the groups. After 4 years, we found a significant difference between the study group and the control group, and after 8 years it had widened. At the 4-year evaluation, there was no difference in mortality between the groups. At 8 years, however, a significant difference was noted, which was further substantiated at 10 years with a 20% mortality rate in the pancreas-kidney group versus an 80% mortality in the kidney alone group. We found a substantial reduction in mortality in IDDM patients 10 years after successful combined pancreas and kidney transplantation. We speculate that the decrease in mortality was due to the beneficial effect of long-term normoglycemia on diabetic late complications and suggest therefore that combined pancreas and kidney transplantation, rather than kidney transplantation alone, should be offered to IDDM patients with end-stage diabetic nephropathy.

Improvement of Uremic Autonomic Dysfunction after Renal Transplantation: A Heart Rate Variability Study

Autonomic dysfunction in hemodialysis patients is one of the components of uremic neuropathy. In this prospective study, we investigated the effect of renal transplantation on uremic autonomic dysfunction with long-term time-domain and frequency-domain heart rate variability. Fourteen hemodialysis patients (10 male, 4 female; mean age 33 ± 11 (range 16–50) years) were examined before and at the early after transplantation period (mean 4.6 ± 1.5 (range 3–7.5) months). The mean time spent on hemodialysis was 16.7 ± 15.6 (range 6–65) months. In time-domain analysis, significant increases in all parameters except pNN50 (SD, SDANN, SDNN, rMSSD) were observed after renal transplantation (p < 0.01). In frequency-domain analysis, low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.40 Hz) spectral power were found to be significantly increased after renal transplantation (4.54 ± 1.04 vs. 12.58 ± 8.69 for LF (p = 0.005), 2.80 ± 1.0 vs. 6.50 ± 3.55 for HF (p = 0.005)), but the LF/HF ratio was not different from a pretransplant period (1.71 ± 0.349 vs. 1.85 ± 0.49, p = 0.26). It was concluded that autonomic dysfunction in hemodialysis patients is reversible and renal transplantation reverses the sympathetic and parasympathetic autonomic dysfunction simultaneously and at a relatively early stage.

Predicting cardiac autonomic neuropathy in type I (insulin-dependent) diabetes mellitus.

A total of 24 subjects with type I insulin-dependent diabetes mellitus were studied. Cardiac parasympathetic function was measured by supine heart rate variability (HRV) in the respiratory frequency 0.10-0.50 Hz and the sympathetic index was measured as the ratio of HRV between 0.055 and 0.098 Hz to that between 0.004 and 0.5 Hz. Factors assessing diabetic control and complications, and factors unrelated to diabetes but possibly influencing HRV, were recorded. Association with depressed HRV was assessed with correlation, and prediction of depressed HRV was determined with multiple regression. Factors associated with depressed HRV but not independently predictive were renal dysfunction and elevated thyroid stimulating hormone. Elevated glycosylated haemoglobin was not significantly correlated with depressed HRV. Four factors (presence of diabetic retinopathy, male gender, duration of diabetes and increasing age) were significant in the regression and sufficed to predict 81% of the sample variance. The relative weights (beta) were -0.65, 0.40, -0.40 and 0.26, respectively. Supine sympathetic index was not sufficient to demonstrate sympathetic dysfunction. It is proposed that the regression model may be used to identify patients likely to have cardiac parasympathetic autonomic dysfunction.