Cardiovascular Autonomic Neuropathy In Patients Research Articles

Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

AimsVitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients. Methods469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices. ResultsSerum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001).A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI −0.47; −0.03, p=0.025). ConclusionVitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

Cardiovascular autonomic neuropathy in patients with type 2 diabetes.

Aims/IntroductionHeart rate recovery (HRR) after exercise is considered to be a new index of autonomic dysfunction associated with cardiovascular disease and mortality. The present study aimed to investigate the risk factors of HRR and the effects of exercise on the abnormal HRR in type 2 diabetes.Materials and MethodsA total of 123 type 2 diabetes patients were recruited, and the oral glucose tolerance test and exercise test were carried out to analyze the risk factors associated with abnormal HRR. Among these patients, 42 patients with abnormal HRR were further randomized to either the conventional therapy group (CT group; n = 20) or the intensive therapy group (IT group; n = 22). The CT group patients underwent metformin and diet control, whereas the IT group additionally underwent a combined moderate intensity aerobic and resistance training three times per week for 12 weeks. The results of blood sample analysis and HRR were recorded before and after the training.ResultsAbnormal HRR was related to fasting blood glucose, glycosylated hemoglobin, low‐density lipoprotein cholesterol, and resting and maximum heart rates (P < 0.05 for both). After training, the IT group had significantly lower levels of fasting blood glucose, glycosylated hemoglobin and resting heart rate than the CT group (all P < 0.01 or P < 0.005). Significant improvement in HRR and metabolic equivalents was observed in the IT group compared with the CT group (P < 0.05).ConclusionsThese data suggested that combined aerobic and resistance training improved cardiac autonomic dysfunction as measured by HRR in type 2 diabetes patients. This might be due to better improvement of glycemic control, resting heart rate and physical fitness.

Neuropad for the detection of cardiovascular autonomic neuropathy in patients with type 2 diabetes

BackgroundCardiovascular autonomic neuropathy (CAN) is a prevalent and neglected chronic complication of diabetes, with a large impact on morbidity and mortality. Part of the reason why it is not detected and treated opportunely is because of the complexity of the tests required for its diagnosis. We evaluated the Neuropad®, a test based on sudomotor function, as a screening tool for CAN in adult patients with type 2 diabetes in Bogotá, Colombia. MethodsThis was a cross-sectional evaluation of Neuropad® for the detection of CAN. Patients were 20–75years of age and did not suffer from any other type of neuropathy. CAN was diagnosed using the Ewing battery of tests for R-R variability during deep breathing, Valsalva and lying-to-standing maneuvers. Additionally, distal symmetric polyneuropathy (DSP) was diagnosed using a sign-based scale (Michigan Neuropathy Disability Score – NDS) and a symptom-based score (Total Symptom Score – TSS). The primary outcome was the sensitivity and specificity of the Neuropad® for the diagnosis of CAN, and secondary outcomes were the sensitivity and specificity of Neuropad® for DSP. ResultsWe studied 154 patients (74 men and 80 women). Prevalence of CAN was extremely high (68.0% of study participants), but also DSP was prevalent, particularly according to the signs-based definition (45%). The sensitivity of the Neuropad® for any degree of CAN was 70.1%, being slightly higher for the deep breathing and Valsalva tests than for lying-to-standing. The specificity of the Neuropad® for any type of CAN was only 37.0%, as expected for a screening exam. The negative predictive value was higher for the deep breathing and Valsalva tests (69.4 and 81.6%, respectively). Neuropad showed also a good sensitivity and negative predictive value for DSP. The sensitivity and specificity of Neuropad were better among men, and among patients with diabetes duration above the group median. ConclusionsThe Neuropad is a simple and inexpensive device that demonstrated an adequate performance as a screening tool for cardiovascular autonomic neuropathy in Latin American patients with DM2.

Serum Cystatin C Levels are Positively Associated with Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes.

Previous studies have reported that cystatin C is associated with degenerative disorder in the nervous system. However, the relationship between serum cystatin C concentrations and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes is currently unknown. The aim of this study was to assess the relationships between serum cystatin C levels and CAN in patients with type 2 diabetes. A total of 357 patients with type 2 diabetes were studied in this cross-sectional study. CAN was diagnosed by a cardiovascular autonomic reflex test. According to the American Diabetes Association criteria, the degree of cardiovascular autonomic dysfunction was graded as normal, early, definite, or severe. CAN was either definite or severe in the subjects of the present study. Serum cystatin C concentrations were significantly higher in patients with CAN than in those without CAN. The mean cystatin C levels differed significantly according to the degree of cardiovascular autonomic dysfunction (normal, 0.78 mg/l; early, 0.79 mg/l; definite, 0.87 mg/l; severe, 0.90 mg/l; P for trend=0.021) after adjustment for other covariates. In multivariate analysis, serum cystatin C levels were significantly associated with CAN (odds ratio [OR] of each standard deviation increase in the logarithmic value, 5.25; 95% confidence interval [CI], 1.17-23.70, P=0.025). Serum cystatin C levels are positively associated with CAN in patients with type 2 diabetes.

The association between glycemic variability and diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes.

BackgroundIt is presently unclear whether glycemic variability is associated with diabetic cardiovascular autonomic neuropathy (CAN). The aim of this study was to examine whether short- and/or long-term glycemic variability (GV) contribute to CAN.MethodsA total of 110 patients with type 2 diabetes who underwent three-day continuous glucose monitoring (CGM) completed five standardized autonomic neuropathy tests. Short-term GV was measured by the standard deviation (SD), coefficient of variation (CV) of glucose, and the mean amplitude of glycemic excursions (MAGE) in CGM. HbA1c variability was calculated from the intrapersonal SD, adjusted SD, and CV of serial HbA1c over 2-year period. CAN was defined as the presence of at least two abnormal parasympathetic function tests. The severity of CAN was evaluated by total scores of five autonomic function tests.ResultsIn univariate analysis, not only SD and CV in CGM but also all parameters of HbA1c variability were significantly higher in the patients with CAN (n = 47, 42.7 %) than in those without CAN. In multivariate analysis, CV (Odds ratio [OR] 1.07, 95 % confidence interval [CI] 1.01–1.13; p = 0.033), but neither SD nor MAGE in CGM, independently correlated with the presence of CAN. All parameters of HbA1c variability, such as SD of HbA1c (OR 12.10 [95 % CI 2.29–63.94], p = 0.003), adjusted SD of HbA1c (OR 17.02 [95 % CI 2.66–108.86], p = 0.003), and log CV of HbA1c (OR 24.00 [95 % CI 3.09–186.48], p = 0.002), were significantly associated with the presence of CAN. The patients with higher HbA1c variability had an increased risk of advanced CAN.ConclusionCV in CGM and all parameters of HbA1c variability were independently associated with the presence of CAN in patients with inadequately controlled type 2 diabetes requiring CGM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0233-0) contains supplementary material, which is available to authorized users.

Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus and coronary artery disease: Diagnosis and severity assessment

To study the nature and severity of heart rate variability (HRV) and heart rate turbulence (HRT) abnormalities in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) and to assess the prevalence of cardiovascular autonomic neuropathy (CAN) and its severity in patients with T2DM concurrent with CAD. A total of 185 patients with T2DM and/or CAD were examined and divided into 3 groups: 1) 92 patients with CAD and T2DM; 2) 43 patients with CAD without T2DM; 3) 49 patients with T2DM without CAD. All the patients underwent 24-hour ECG monitoring with HRV and HRT analysis. CAN was identified and the severity of CAN was assessed based on the abnormal HRV and HRT parameters. CAN, especially severe one, was more common in Group 1 (the relative risk was 3.3 [95% CI 1.3-8.2]; p<0.05), than in Group 3. In Group 1, CAN was associated with the duration of T2DM and the level of glycated hemoglobin (p<0.05). The patients with severe CAN in Group 1 showed a 4-fold higher risk for multivessel coronary artery lesions than those without CAN (p<0.05). Glycemic control quality, T2DM duration, and obvious coronary atherosclerotic lesions were demonstrated to be associated with the presence and severity of CAN. The developed methods may be used in practice to detect and more accurately determine the severity of CAN and to predict cardiovascular risk in patients with T2DM and CAD.

Predictors of cardiovascular autonomic neuropathy in patients with type 1 diabetes.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 1 diabetes (T1D). The cardiovascular autonomic neuropathy (CAN), although considered as an independent risk factor for CVD, remains underdiagnosed. The aim of this paper was to determine the prevalence, predictors of CAN in patients with T1D and its association with other chronic complications of diabetes. Patients with T1D underwent a clinical-epidemiological survey, had blood and urinary samples collected, performed ophthalmoscopic and clinical neurological examination and cardiovascular reflex tests. One hundred and fifty one patients with T1D, 53.6% female, 45.7% Caucasian, mean age of 33.4 ± 13 years, diabetes duration of 16.3 ± 9.5 years, and glycated hemoglobin levels of 9.1 ± 2% were evaluated. The prevalence of CAN in the studied population was 30.5%. CAN was associated with age (p = 0.01), diabetes duration (p = 0.036), hypertension (p = 0.001), resting heart rate (HR) (p = 0.000), HbA1c (p = 0.048), urea (p = 0.000), creatinine (p = 0.008), glomerular filtration rate (p = 0.000), urinary albumin concentration (p = 0.000), LDL (p = 0.048), free T4 (p = 0.023), hemoglobin (p = 0.01) and presence of retinopathy (p = 0.000), nephropathy (p = 0.000) and diabetic neuropathy (p = 0.000), the following symptoms syncope (p = 0.000), post prandial nausea (p = 0.042), early satiety (p = 0.031), sexual dysfunction (p = 0.049), and gustatory sweating (p = 0.018). In logistic regression model, it was observed that only resting HR, diabetic neuropathy, and retinopathy were independent associated with CAN. In conclusion, CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications. Indicators of CAN included age, diabetes duration, hypertension, resting HR, diabetic neuropathy and retinopathy, and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for CAN.

Physiological serum bilirubin concentrations are inversely associated with the prevalence of cardiovascular autonomic neuropathy in patients with Type 2 diabetes

Although severe hyperbilirubinaemia causes kernicterus in neonates, normal to modestly elevated bilirubin concentrations have been reported to be neuroprotective. However, the relationship between serum bilirubin concentrations and cardiovascular autonomic neuropathy in patients with Type 2 diabetes is currently unknown. This study assessed the relationships between physiological serum total bilirubin concentrations and cardiovascular autonomic neuropathy in patients with Type 2 diabetes. A total of 2991 patients with Type 2 diabetes were investigated in this cross-sectional study. Cardiovascular autonomic neuropathy was diagnosed by a cardiovascular reflex test. According to the American Diabetes Association criteria, the degree of cardiovascular autonomic dysfunction was graded into normal, early, definite and severe. Cardiovascular autonomic neuropathy was either definite or severe in the present study. An analysis of covariance after adjustment for other covariates was performed. A logistic regression model was used to assess an association of cardiovascular autonomic neuropathy with serum total bilirubin tertiles. Serum total bilirubin concentrations were significantly lower in subjects with cardiovascular autonomic neuropathy. The mean total bilirubin values differed significantly according to the severity of cardiovascular autonomic dysfunction (normal 13.0 μmol/l; early 12.3 μmol/l; definite 11.8 μmol/l; severe 10.1 μmol/l; P for trend < 0.001) after adjustment for other covariates. In multivariate analysis, serum total bilirubin levels were significantly associated with cardiovascular autonomic neuropathy (odds ratio 0.36; 95% CI 0.21-0.63 for the highest vs. the lowest bilirubin tertile, P < 0.001). Serum total bilirubin concentrations within the physiologic range are inversely associated with the prevalence of cardiovascular autonomic neuropathy in patients with Type 2 diabetes.

Benfotiamine and alpha-lipoic acid in the treatment of cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus

The aim of this study was to assess the efficiency of benfotiamine and α-lipoic acid (α-LA) in the treatment of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (type 2 DM). We have examined 70 patients with type 2 DM with established CAN. Treatment groups were sex and age-matched, there was no difference in duration of illness, HbA1c levels. Patients with type 2 DM and CAN were divided into four treatment groups: group A received traditional hypoglycemic therapy (n=15, control group), group B (n=12), in addition to traditional therapy received benfotiamine 300 mg/day; patients from group C (n=18) – α-LA 600 mg/day; group D (n=15) – 300 mg/day of benfotiamine in combination with 600 mg/day α-LA. Duration of the study was 3 months. As a result, no significant difference in HbA1c concentrations in the blood of patients with type 2 DM and CAN before and after treatment was found. It was established, that assignment of benfotiamine to patients with type 2 DM and CAN was not associated with significant changes in LDL, HDL, TG, total cholesterol and leptin levels, but contributes significant decrease of IRI, hsCRP and TNF- α concentrations. Usage of α-LA in the complex treatment of patients with type 2 DM and CAN contribute to significant decrease of LDL, total cholesterol, IRI, leptin and TNF-α concentrations. Combined usage of benfotiamine and α-LA in patients with type 2 DM and CAN is accompanied by more significant decrease of LDL, total cholesterol, IRI, hsCRP and TNF-α and increase of HDL concentration. Obtained results suggest that the efficacy of combined treatment with benfotiamine and α-LA has no connection with the improvement of diabetes compensation, but are as result of the direct pharmacological agents effect on the investigated metabolic parameters level.

Screening of cardiovascular autonomic neuropathy in patients with diabetes using non-invasive quick and simple assessment of sudomotor function

AimCardiovascular autonomic neuropathy (CAN) is a common but often overlooked complication of diabetes. Sympathetic C-fibers innervating sweat glands can be impaired early on in patients with diabetes. In this study, SUDOSCAN, a new non-invasive device that assesses sudomotor function was compared to methods generally used for the investigation of CAN. PatientsA total of 232 patients with diabetes were measured for heart rate variability (HRV) at rest and during moderate activity. Time and frequency domain analysis techniques, including measurement of the low-frequency (LF) domain component, were assessed during HRV testing. Ewing tests, as recommended by the French Health Authority, were also done. Electrochemical sweat conductance (ESC) was measured on the hands and feet, and a risk-score was calculated. ResultsUsing two abnormal Ewing tests as a reference for the area under the curve (AUC) of the receiver operating characteristics (ROC) curve for SUDOSCAN, the risk-score was 0.74, with a sensitivity of 92% and specificity of 49% for a risk-score cut-off value of 35%. For the ROC curve analysis using the LF power component during moderate activity at a threshold of 90 ms2 (first quartile) as reference, the AUC was higher for the SUDOSCAN risk-score (0.77) compared with the standard Ewing tests [E:I ratio (0.62), 30:15 ratio (0.76) and blood pressure change on standing (0.55)]. Using a cut-off value of 35%, risk-score sensitivity and specificity were 88 and 54%, respectively. ConclusionSUDOSCAN, which allows quick quantitative assessment of sudomotor function, may be used for early screening of CAN in everyday clinical practice before resorting to the more sophisticated and specific, but ultimately more time-consuming, Ewing tests.

Screening of Cardiovascular Autonomic Neuropathy in Patients with Diabetes by Quick and Simple Assessment of Sudomotor Function

Aims: Cardiovascular Autonomic Neuropathy (CAN) is a common but overlooked complication of diabetes. Sympathetic C-fibers innervating sweat glands can be impaired early in patients with diabetes. SUDOSCAN, a new and non-invasive device that assesses sudomotor function, was compared to Heart Rate Variability (HRV) and to Ewing tests, known to be reliable methods for the investigation of CAN. Methods: 232 patients with diabetes were measured for HRV at rest and during moderate activity (stair climbing). Time and frequency domain analysis techniques, including measurement of Standard Deviation of the average NN intervals over 5 minutes (SDNN), High Frequency domain component (HF) and Low Frequency domain component (LF), were assessed during HRV testing. Heart rate variations during deep breathing and heart rate and blood pressure responses while standing, as described by Ewing were also assessed. Electrochemical Sweat Conductance (ESC) was measured on the hands and feet, and a risk score was calculated. Patients were classified according to their risk score. The classifications were as follow: no sweat dysfunction, moderate sweat dysfunction and high sweat dysfunction. All results are means ± SD. Results: The highest correlation was observed between the risk score based on sudomotor function and the LF component during moderate activity (r = 0.47, p 405 ms 2 (3 rd quartile) (46 ± 13 vs 30 ± 13, p < 0.001). When taking the LF power component during moderate activity < 90 ms 2 as a reference value, the AUC of the ROC curve for the SUDOSCAN risk score was 0.77. Conclusions: SUDOSCAN allowing quick and quantitative assessment of sudomotor function can be used for the early screening of cardiovascular autonomic neuropathy in daily clinical practice before more sophisticated, specific, and time-consuming tests.

Haemodynamic changes during a squat test, pulsatile stress and indices of cardiovascular autonomic neuropathy in patients with long-duration type 1 diabetes

Cardiovascular autonomic neuropathy (CAN) and pulsatile stress are considered to be independent cardiovascular risk factors. This study compared haemodynamic changes during an active orthostatic test in adult patients with type 1 diabetes (T1DM), using low versus high RR E/I ratios as a marker of CAN. A total of 20 T1DM patients with low RR E/I ratios were compared with 20 T1DM patients with normal RR E/I ratios, matched for gender (1/1 ratio), age (mean: 46 years) and diabetes duration (22-26 years); 40 matched healthy subjects served as controls. All subjects were evaluated by continuous monitoring of arterial blood pressure (Finapres(®)) and heart rate using a standardized posture test (1-min standing, 1-min squatting, 1-min standing), thus allowing calculation of baroreflex gain. Compared with controls, T1DM patients showed lower RR E/I ratios, reduced baroreflex gains, higher pulsatile stress (pulse pressure×heart rate), greater squatting-induced pulse pressure rises, orthostatic hypotension and reduced reflex tachycardia. Compared with T1DM patients with preserved RR E/I ratios, T1DM patients with low RR E/I ratios showed reduced post-standing reflex tachycardia and baroreflex gain, and delayed blood pressure recovery, but no markers of increased pulsatile stress. Interestingly, decreased baroreflex gain was significantly associated with both pulsatile stress and microalbuminuria. The use of RR E/I ratios to separate T1DM patients allows the detection of other CAN markers during an orthostatic posture test, but with no significant differences in pulsatile stress or microalbuminuria. In this context, squatting-derived baroreflex gain appears to be more informative.

Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes.Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague–Dawley rats and citrate buffer was injected in 14 control rats. After 4–11weeks, the rats were anesthetized with pentobarbital, ventilated and paralyzed. A laminectomy enabled extracellular recording of T3 spinal cord neuronal activity. Intrapericardial administration of a mixture of algogenic chemicals (bradykinin, serotonin, prostaglandin E2 (all at 10−5M), and adenosine (10−3M)) was applied to activate nociceptors of cardiac afferent nerve endings. Furthermore, somatic receptive properties were examined by applying innocuous (brush and light pressure) and noxious (pinch) cutaneous mechanical stimuli.Diabetes-induced increases in spontaneous activity were observed in subsets of neurons exhibiting long-lasting excitatory responses to administration of the algogenic mixture.Algogenic chemicals altered activity of a larger proportion of neurons from diabetic animals (73/111) than control animals (55/115, P<0.05). Some subtypes of neurons exhibiting long-lasting excitatory responses, elicited prolonged duration and others, had a shortened latency. Some neurons exhibiting short-lasting excitatory responses in diabetic animals elicited a shorter latency and some a decreased excitatory change. The size of the somatic receptive field was increased for cardiosomatic neurons from diabetic animals. Cutaneous somatic mechanical stimulation caused spinal neurons to respond with a mixture of hyper- and hypoexcitability.In conclusion, diabetes induced changes in the spinal processing of cardiac input and these might contribute to cardiovascular autonomic neuropathy in patients with diabetes.

Is erectile dysfunction a sentinel symptom for cardiovascular autonomic neuropathy in patients with type 2 diabetes?

The study investigated whether there is a significant association between erectile dysfunction (ED) secondary to autonomic failure, and cardiovascular autonomic neuropathy (CAN) in male patients suffering from type 2 diabetes. Twenty-two patients suffering from type 2 diabetes were recruited for this study after satisfying the stringent exclusion criteria used in the first stage. They had no evidence of overt cardiovascular disease, hypertension, neurological, renal or thyroid disease. Each subject was assessed for ED and CAN using standardized tests. Six patients were suffering from CAN while 10 patients were suffering from ED. There was no significant association between CAN and autonomic ED (P = 1). Three patients with normal erectile function had CAN, whilst three patients with ED had CAN. Further analysis demonstrates a significant increase in association between ED and CAN with age (P = 0.036). These results show that ED secondary to autonomic neuropathy is not significantly associated with CAN in this specific group of patients. Nonetheless, the study reveals that ED is a sentinel symptom for future development of CAN.

P35.13 Subclinical cardiovascular autonomic neuropathy in patients with diabetic somatic neuropathy

P35.13 Subclinical cardiovascular autonomic neuropathy in patients with diabetic somatic neuropathy

Comparative study of haemodynamic responses to active and passive posture inducing head-ward pooling of blood in man

To study the relative effects of passive head-down tilt and squatting on the cardiovascular dynamics in man. A pre-test/post-test study. Physiology Research Laboratories in the Schools of Medicine at Addis Ababa University and the University of Dundee, UK. Ten normal healthy subjects aged nineteen to twenty two years. Cardiovascular variables measured in Passive body tilt and squatting. Similar responses in forearm blood flow, arterial blood pressure, peripheral vascular resistance, and pulse rate observed in both active and passive postural changes. A change from the sitting to the squatting position resulted in marked changes of forearm blood flow (FBF=1.63ml/100 ml/min, p<0.05), mean arterial blood pressure (BP=9mmHg, p<0.05), mean forearm vascular resistance (PVR=-10 PRU, p<0.05) and mean pulse rate (PR =-5 beats/min, p>0.05). The corresponding changes in the head-down position were: FBF=2.37ml/100 ml/min, p<0.05; BP=11.0 mmHg, p<0.05; VR=-12.85 PRU, p<0.05; PR=-10 beats/min, p>0.05). These results suggest that the movement of blood towards the head is only slightly more marked in the head-down tilt than in the squatting position. The changes in flow and arterial blood pressure are similarly correlated (r=0.6291 in squatting and r=0.553 in 30 degrees head-down tilt). In both positions, blood moves to the thorax, neck and the head thus traversing the same baroreflex regions. This means that changes in cardiovascular variables in the two positions are detected by the same receptors signalling information to integrating centres via the same afferent pathways. Squatting and head-down tilt can, therefore, be used alternately to counteract orthostatic dizziness and to assess the significance of cardiovascular autonomic neuropathy in patients with disease conditions like diabetes mellitus.

Risk for cardiovascular autonomic neuropathy is associated with the HLA-DR3/4 phenotype in type I diabetes mellitus.

To identify risk factors for the development of cardiovascular autonomic neuropathy in patients with juvenile-onset type I diabetes mellitus. Cross-sectional examination of an inception cohort 15 to 21 years after the onset of diabetes. Outpatient diabetes clinic. Seventy-nine patients with type I diabetes who experienced onset of disease before 21 years of age and who were followed for 15 to 21 years. Autonomic nerve function was evaluated in all patients using deep breathing and tilt tests. On the basis of these tests, an index of cardiovascular autonomic neuropathy was derived and patients were classified as having intact, mildly impaired, or significantly impaired autonomic function. The group with significantly impaired function had a higher mean hemoglobin A1 at the time of examination than the group without impairment, yet the groups did not differ regarding glycemic control during the first decade of diabetes. The HLA-DR3/4 phenotype was present in more than 50% of the patients with significant autonomic dysfunction and conferred relative odds of 6.2 (95% CI, 1.7 to 23.3) for the development of autonomic neuropathy when compared with other HLA-DR phenotypes. Sex, percent ideal body weight, and smoking did not have a statistically significant effect on the development of autonomic neuropathy. The development of cardiovascular autonomic neuropathy in type I diabetes mellitus is strongly associated with the HLA-DR3/4 phenotype. Thus, genetic predisposition may play an important role in the development of this complication.