Predicting cardiac autonomic neuropathy category for diabetic data with missing values

Cardiovascular autonomic neuropathy (CAN) is a serious and well known complication of diabetes. Previous articles circumvented the problem of missing values in CAN data by deleting all records and fields with missing values and applying classifiers trained on different sets of features that were complete. Most of them also added alternative features to compensate for the deleted ones. Here we introduce and investigate a new method for classifying CAN data with missing values. In contrast to all previous papers, our new method does not delete attributes with missing values, does not use classifiers, and does not add features. Instead it is based on regression and meta-regression combined with the Ewing formula for identifying the classes of CAN. This is the first article using the Ewing formula and regression to classify CAN. We carried out extensive experiments to determine the best combination of regression and meta-regression techniques for classifying CAN data with missing values. The best outcomes have been obtained by the additive regression meta-learner based on M5Rules and combined with the Ewing formula. It has achieved the best accuracy of 99.78% for two classes of CAN, and 98.98% for three classes of CAN. These outcomes are substantially better than previous results obtained in the literature by deleting all missing attributes and applying traditional classifiers to different sets of features without regression. Another advantage of our method is that it does not require practitioners to perform more tests collecting additional alternative features.     

依帕司他治疗糖尿病心脏自主神经病变疗效分析

目的评价依帕司他治疗糖尿痛心脏自主神经病变疗效。方法糖尿痛心脏痛心脏自主神经病变患者接受依帕司他50mg，每日3次治疗，服用4周，运用24小时动态心电图检测患者在服用依帕司他前后心率变异性指标的变化，明确依帕司他治疗糖尿病心脏自主神经病变的疗效。结果心率变异性各项指标治疗4周后较治疗前有显著提高。自主神经症状明显好转。结论依帕司他治疗糖尿病心脏自主神经病变的疗效显著，可以改善患者心率变异性。     

Evaluation of autonomic neuropathy in diabetes mellitus

Summary Quantitative assessment of signs or symptoms of neuropathy, and the beat-to-beat variation, valsalva, orthostasis, handgrip and cold pressor tests, and measurements of plasma renin and catecholamine excretion rate were performed in 23 diabetic patients and 10 age-matched normal subjects.Significant inverse correlations were found between the clinical score and the beat-to-beat variation (a test of efferent vagus function) (r=-0.72,P<0.0005) or the pressor response to handgrip (possible test of efferent sympathetic integrity (r=-0.55,P<0.005) or the values of both tests combined (r=-0.79,P«0.0005); but not with the other measured parameters. Beat-to-beat variation was abnormal in all 9 diabetics with increased and in 9 of 14 with normal clinical score, whereas only seven and one patient from these subgroups, respectively, had an abnormal Valsalva ratio. The pressor response to handgrip was only slightly reduced in the diabetic patients, with greater tendency in those with abnormal clincal score. Additional possible indices of adrenergic dysfunction such as the pressor response to cold stimulus, plasma renin levels and noradrenaline or adrenaline excretion rates did not differ significantly between normal subjects and diabetics.These findings demonstrate a greater prevalence of parasympathetic as compared to sympathetic impairment in diabetic autonomic neuropathy; the beat-to-beat variation was the most sensitive among the tests used. An assessment of clinical evidence combined with non-invasive functional procedures such as the beat-to-beat variation and handgrip tests provide a valuable and easy to perform tool in the evaluation of diabetic neuropathy.     

皮肤交感反应对糖尿病自主神经病的诊断价值

目的：探讨皮肤交感反应（SSR）检查对诊断糖尿病自主神经病的价值。方法：将122例2型糖尿病患者分为有自主神经症状组（71例）和无自主神经症状组（51例）,每位患者进行神经传导检查及SSR检查。分析比较两组患者SSR与神经传导检查结果的差异。结果：两组间SSR、神经传导的检查结果比较差异无统计学意义（P〉0．05）。43例SSR正常的患者中有29例（65．9％）有自主神经症状,22例（51。2％）病程短于5年;79例SSR异常的患者中有43例（54．4％）有自主神经症状,37例（46．8％）糖化血红蛋白（HbA1C）高于8．5％。结论：SSR与自主神经症状无明显相关性;糖尿病控制情况及病程对SSR结果均有影响。     

糖尿病在糖尿病大鼠心肌梗死后心力衰竭形成中的效应

目的： 评估糖尿病在链脲霉素（STZ）诱导的血糖不加控制的糖尿病大鼠急性心肌梗死（AMI）后心力衰竭(HF)形成中的效应。方法：所有SD大鼠随机分组,糖尿病组经腹腔内注射STZ（65mg/kg）诱导糖尿病,70 d后所有AMI组结扎冠状动脉左前降支建立AMI模型。确定AMI前后各时点观察大鼠的生存率,心肌超微结构的变化,进行血流动力学分析、心肌纤维化测定及左心肥厚的评估。结果：结扎左冠状动脉前降支后,糖尿病大鼠的左心功能恶化及左室重构的速度均较非糖尿病大鼠显著。在早期阶段,糖尿病与非糖尿病大鼠心肌纤维化相似,而1月后却出现显著差别。结论：糖尿病大鼠AMI后心力衰竭进展明显加速。     

2型糖尿病患者尿白蛋白排泄率与心自主神经病变的关系

目的 观察2型糖尿病心自主神经病变的患病率及其与尿白蛋白排泄率的相关性.方法 选取T2DM患者200例,根据尿蛋白排泄率分为正常蛋白尿组(80例)、微量蛋白尿组(66例)和大量蛋白尿组(54例);采集临床资料,测定收缩压、舒张压、空腹血糖、糖化血红蛋白及血脂等指标;行心血管反射试验检查,结合临床症状评价糖尿病患者心自主神经病变.结果 三组患者在糖尿病病程、收缩压、甘油三酯、空腹血糖、糖化血红蛋白和心自主神经病变之间的差异有统计学意义.心自主神经病变者分别占1.3％、9.1％、22.2％(两两比较,P均＜0.05).尿蛋白排泄率与糖尿病病程、空腹血糖、糖化血红蛋白、收缩压、甘油三酯、低密度脂蛋白-胆固醇、心自主神经病变呈正相关(P均＜0.05).多元回归分析显示收缩压(X1)、甘油三酯(X2)、心自主神经病变(X3)、糖尿病病程(X4)是UACR的影响因素,回归方程为Y=-398.454+2.789X1 +49.092X2+147.969X3 +5.659X4.结论 随着蛋白尿程度加重,合并心自主神经病变的患病率增加;收缩压、甘油三酯、心自主神经病变、糖尿病病程是尿蛋白排泄率的独立影响因素.     

Dynamic cerebral autoregulation assessment using chaotic analysis in diabetic autonomic neuropathy

Cerebral autoregulation (CA) was assessed by chaotic analysis based on mean arterial blood pressure (MABP) and mean cerebral blood flow velocity (MCBFV) in 19 diabetics with autonomic neuropathy (AN) and 11 age-matched normal subjects. MABP in diabetics dropped significantly in response to tilting (91.6 ± 14.9 vs. 74.1 ± 13.4 mmHg, P < 0.05). Valsalva ratio of heart rate was reduced in diabetics compared to normal (1.1 ± 0.1 vs. 1.5 ± 0.2, P < 0.05). It indicated AN affects the vasomotor tone of peripheral vessels and baroreflex. Nonlinear results showed higher correlation dimension values of MABP and MCBFV in diabetics compared to normal, especially MABP (3.7 ± 2.3 vs. 2.0 ± 0.8, P < 0.05). It indicated CA is more complicated in diabetics. The lower Lyapunov exponent and the higher Kolmogorov entropy values in diabetics indicated less predictable behavior and higher chaotic degree. This study suggests impaired autoregulation would be more chaotic and less predictable.     

Heart rate turbulence in patients with poorly controlled diabetes mellitus type 2

Introduction

Cardiac autonomic neuropathy (CAN) causes substantial morbidity and increased mortality in patients with diabetes mellitus (DM). Besides heart rate variability (HRV), heart rate turbulence (HRT) is an important method of assessment of cardiac autonomic regulation. The aim of the study was to assess the correlation between HRT and diabetic control.

Material and methods

Fifty-nine patients met the inclusion criteria – 38 males and 21 females, age 64.4 ±7.6. The patients included had inadequately controlled DM type 2 defined as glycated haemoglobin (HbA_1c) > 9% (mean 11.8 ±2.7%). In all patients, intensive insulin treatment had been applied for 6 months. After 6 months, HbA_1c was measured. ECG Holter monitoring was performed before and after insulin treatment to evaluate the time domain HRV and HRT parameters (turbulence onset (TO) and turbulence slope (TS)).

Results

After 6 months of intensive insulin treatment, HbA_1c concentrations ranged from 6.3% (45 mmol/mol) to 11.2% (99 mmol/mol) – mean 8.5 ±3.8% (69 ±18 mmol/mol). Significant improvement of TO, TS and SDNN was observed. The TO and TS significantly correlated with HbA_1c (r = 0.35, p = 0.006 and r = –0.31, p = 0.02 respectively). Among analyzed HRV time domain parameters such as SDNN, rMSSD and pNN50, only SDNN correlated with HbA_1c (r = –0.41, p = 0.001). It was further concluded that intensive insulin therapy led to better glycemic control, resulting in improvement of HRT.

Conclusions

Heart rate turbulence may be useful in monitoring changes of the autonomic nervous system functions in patients with DM, similarly to HRV parameters.     

Esophageal dysfunction in diabetes mellitus: is there a relation to clinical manifestation of neuropathy?

Summary In a prospective study, we evaluated 33 diabetic patients [type I (n = 8) and type II (n = 25)]. Esophageal motor functions were examined by registering clinical symptoms and by performing esophageal manometry. We also investigated peripheral and autonomic neuropathy. In diabetics, the lower and upper esophageal sphincter pressure and amplitudes of peristaltic waves were reduced. Compared with controls (n = 30), in diabetics the esophageal peristaltic velocity was reduced significantly, and the duration of contractions were decreased as well. Multipeaked waves were uncommon in diabetics, while non-propulsive contractions were seen more often. No correlation was found between esophageal dysfunction and peripheral or autonomic neuropathy. Some 60% of diabetics reported esophageal symptoms; however, no relationship between these symptoms and the extent of dysfunction in esophageal motility was found.Abbreviations PNP peripheral sensorimotor polyneuropathy - ACN autonomic cardiac neuropathy - LES lower esophageal sphincter - UES upper esophageal sphincter - EMG electromyography - ECG electrocardiography     

Sex differences in cardiac autonomic function of depressed young adults

Background

Cardiac autonomic dysfunction has been proposed as an important contributing factor to the increased cardiovascular risk observed in major depression (MDD). However, the evidence regarding alterations in heart rate variability (HRV) in otherwise healthy depressed subjects has been inconclusive.

Methods

A case–control study in 50 treatment-naïve young adults with a first MDD episode without comorbid psychiatric disorders and 50 healthy control subjects was conducted. Time- and frequency-domain indexes of HRV were determined at baseline supine and after 5-min of orthostatic stress at 60°.

Results

There were no significant differences in the time- or frequency-domain variables of HRV between depressed patients and controls. However, a random-effect ANOVA model showed that during orthostatic stress depressed men had a reduced HRV and decreased parasympathetic activity compared to control subjects, while no differences were found between depressed women and controls.

Conclusion

These results suggest a sex-dependent relationship between major depression and cardiac autonomic dysfunction and provide one potential explanation for sex differences in the association of depressive symptoms with cardiovascular morbidity.     

一种建立小鼠2型糖尿病心肌病模型的方法

目的:采用连续喂养高脂饮食(high-fat diet,HFD)结合单次腹腔注射链脲佐菌素(streptozotocin,STZ)的方法建立小鼠2型糖尿病心肌病模型。方法:将40只5~6周龄C57BL/6J雄性小鼠随机分成2组(每组各20只):对照(control)组,持续以普通饲料喂养;HFD+STZ组,持续以HFD喂养,并于造模第5周注射STZ(100mg/kg)。于造模实验开始(第0周)、第5周、第6周、第11周和第16周,测量体重和血糖,并于第11周和第16周分别对control组和HFD+STZ组小鼠进行心功能检测、胰岛素水平检测、组织学观察和心肌细胞凋亡分析。结果:造模过程中HFD+STZ组小鼠各时期的体重均大于control组(P0.05),注射完STZ后小鼠体重略有下降,但仍高于control组。注射STZ 1周后,HFD+STZ组小鼠空腹血糖值均持续高于13.89 mmol/L。在造模第11周和16周时,HFD+STZ组小鼠胰岛素水平与control组相比均有降低(P0.05)。心功能检测、组织学观察和心肌细胞凋亡分析显示,造模第11周时,HFD+STZ组小鼠的超声、心肌细胞面积和凋亡率等指标与control组相比变化不明显;造模第16周,HFD+STZ组小鼠出现心室功能障碍,心肌细胞肥大,心肌细胞的面积和心肌细胞凋亡率明显大于control组(P0.05)。结论:采用连续喂养HFD结合单次注射STZ可成功建立小鼠2型糖尿病心肌病模型。     

Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan

Hereditary sensory and autonomic neuropathy (HASN) refers to a group of rare congenital disorders characterized by loss of pain sensation and other sensory or autonomic abnormalities. Among them, a relatively large proportion of patients with HSAN type IV, which is accompanied by anhidrosis and intellectual disability, are reported from Israel and Japan. HSAN type V, with normal sweating and mental development, is rarely reported in Japan. In 2009, we founded a research group for congenital insensitivity to pain and performed the first epidemiological survey of HSAN types IV and V in Japan. Questionnaires were sent to a total of 3,488 certified training institutions of five nationwide medical societies comprising pediatricians, neurologists, orthopedic surgeons, and dentists. Answers were obtained from 1,610 institutions, and 192 HSAN patients (152 with type IV and 28 with type V) were reported from 105 institutions. After excluding duplicated patients, we identified a total of 62 current, 36 past, and five deceased patients for HSAN‐IV, and a total of 14 current, 13 past, and 0 deceased patients for HSAN‐V. Using these figures, we estimated that the number of Japanese patients with HSAN types IV and V as 130–210 and 30–60 patients, respectively. We identified no gender differences, and patients with a family history of the disorder were limited to affected siblings in both conditions. Most patients with HSAN‐IV were 5–40 years of age, whereas half of the patients with HSAN‐V were 40 years or older. © 2013 Wiley Periodicals, Inc.     

Regional cerebral blood flow correlates with heart period and high-frequency heart period variability during working-memory tasks: Implications for the cortical and subcortical regulation of cardiac autonomic activity

The aim of the present study was to characterize the functional relationships between behaviorally evoked regional brain activation and cardiac autonomic activity in humans. Concurrent estimates of regional cerebral blood flow (rCBF; obtained by positron emission tomography), heart period, and high-frequency heart period variability (HF-HPV; an indicator of cardiac parasympathetic activity) were examined in 93 adults (aged 50-70 years) who performed a series of increasingly difficult working-memory tasks. Increased task difficulty resulted in decreased heart period (indicating cardioacceleration) and decreased HF-HPV (indicating decreased cardiac parasympathetic activity). Task-induced decreases in heart period and HF-HPV were associated with concurrent increases and decreases in rCBF to cortical and subcortical brain regions that are speculated to regulate cardiac autonomic activity during behavioral processes: the medial-prefrontal, insular, and anterior cingulate cortices, the amygdala-hippocampal complex, and the cerebellum. These findings replicate and extend a small number of functional neuroimaging studies that suggest an important role for both cortical and subcortical brain systems in human cardiac autonomic regulation.     

Autonomic and sensory ganglionopathy occurring in a patient with fulminant type 1 diabetes mellitus

A 63‐year‐old male with a previous infection was admitted to our hospital because of acute pancreatitis. Although he had no history of diabetes mellitus, laboratory examinations revealed marked hyperglycemia on admission, and intensive insulin treatment was required. After 2 weeks, he developed severe pandysautonomia and sensory impairment, and eventually died from colonic perforation caused by paralytic ileus at 1 year after onset. Autopsy findings showed a complete loss of pancreatic islet beta cells with mild fibrosis of the exocrine pancreas. Neuropathological examination showed myelin loss of the dorsal fasciculus at all levels of the spinal cord and ganglionopathy of the dorsal root and sympathetic truncus, revealing degeneration of ganglion cells and a decrease in their number with the formation of Nageotte nodules. On the basis of this clinicopathological evidence, fulminant type 1 diabetes mellitus (T1DM) and idiopathic immune‐mediated autonomic neuropathy were suspected. Here, we suggest a close etiological relationship between both diseases.     

Analysis of cardiac autonomic modulation in obese and eutrophic children

INTRODUCTION:

Obesity causes alterations in cardiac autonomic function. However, there are scarce and conflicting data on this function with regard to heart rate variability in obese children.

OBJECTIVE:

To compare the autonomic function of obese and eutrophic children by analyzing heart rate variability.

METHODS:

One hundred twenty-one children (57 male and 64 female) aged 8 to 12 years were distributed into two groups based on nutritional status [obese (n  =  56) and eutrophic (ideal weight range; n  =  65) according to the body mass index reference for gender and age]. For the analysis of heart rate variability, heart rates were recorded beat by beat as the children rested in the dorsal (prone) position for 20 minutes. Heart rate variability analysis was carried out using linear approaches in the domains of frequency and time. Either Student''s t-test or the Mann-Whitney U-test was applied to compare variables between groups. Statistical significance was set at 5%.

RESULTS:

The SDNN, RMSSD, pNN50, SD1, SD2, LF and HF indices in milliseconds squared were lower among the obese children when compared to the eutrophic group. There were no alterations in the SD1/SD2 ratio, LF/HF ratio, LF index or HF index in normalized units. There was a significant difference between groups in the RR interval (R-to-R EKG interval).

CONCLUSION:

The obese children exhibited modifications in heart rate variability, characterized by a reduction in both sympathetic and parasympathetic activity. These findings stress the need for the early holistic care of obese children to avoid future complications.     

Spectral analysis of heart rate variability signal and respiration in diabetic subjects

The paper deals with methods of processing ECG and respiration signals which aim at detecting parameters whose values may be correlated to normal and diabetic subjects with or without cardiovascular autonomic neuropathy (CAN). Beatto-beat R-R duration values of the ECG and discrete series of respiration are obtained from original signals using a recognition algorithm. Power spectrum analysis (autospectra, cross-spectra and coherence via autoregressive modelling) is carried out on segments of about 200 consecutive cardiac cycles. Spectral parameters of the R-R variability signal are obtained as follows: total power, power of low-frequency (LF) and high-frequency (HF) components, power of the signal which is (or is not) coherent with respiration, in absolute or in percentage values. The experimental protocol considers 40 diabetic patients (21 of whom have diabetic neuropathy) and 14 normals in three different conditions: resting, standing and controlled respiration. The developed spectral parameters seem sensitive enough to differentiate between normal and pathological subjects. These parameters may constitute a quantitative means to be edded to the classical diabetic tests for the diagnosis of cardiovascular autonomic neuropathy.     

Classification of the severity of diabetic neuropathy: a new approach taking uncertainties into account using fuzzy logic

OBJECTIVE:

This study proposes a new approach that considers uncertainty in predicting and quantifying the presence and severity of diabetic peripheral neuropathy.

METHODS:

A rule-based fuzzy expert system was designed by four experts in diabetic neuropathy. The model variables were used to classify neuropathy in diabetic patients, defining it as mild, moderate, or severe. System performance was evaluated by means of the Kappa agreement measure, comparing the results of the model with those generated by the experts in an assessment of 50 patients. Accuracy was evaluated by an ROC curve analysis obtained based on 50 other cases; the results of those clinical assessments were considered to be the gold standard.

RESULTS:

According to the Kappa analysis, the model was in moderate agreement with expert opinions. The ROC analysis (evaluation of accuracy) determined an area under the curve equal to 0.91, demonstrating very good consistency in classifying patients with diabetic neuropathy.

CONCLUSION:

The model efficiently classified diabetic patients with different degrees of neuropathy severity. In addition, the model provides a way to quantify diabetic neuropathy severity and allows a more accurate patient condition assessment.     

2型糖尿病视网膜病变患者血清炎症因子和脂联素水平的变化

目的: 观察2型糖尿病合并视网膜病变(DR)患者血清炎症因子和脂联素的变化。方法: 110例糖尿病患者分为3组:糖尿病无视网膜病变组(DM)35例、糖尿病伴非增殖期视网膜病变组(NPDR)45例和糖尿病伴增殖期视网膜病变组(PDR)30例,并与40名正常人对照(NC组)。观察患者的体检指标,并检测空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、餐后2 h血糖(2hPG),总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、脂联素、血清细胞间黏附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)和高敏C-反应蛋白(hs-CRP)。计算稳态模型评估的胰岛素抵抗指数(HOMA-IR)。结果: DM组、NPDR组和PDR组患者的收缩压、体重指数、腰臀比、血清TG、LDL-C、FPG、2hPG、 HbA1c、ICAM-1、TNF-α、hs-CRP水平和HOMA-IR均高于NC组(P<0.05),而NPDR组和PDR组的收缩压、血清ICAM-1、TNF-α、hs-CRP水平和HOMA-IR均高于DM组(P<0.05)。DM组、NPDR组及PDR组的患者血清脂联素水平均低于NC组(P<0.05),而NPDR组及PDR组的患者血清脂联素水平低于DM组患者(P<0.05)。血清脂联素水平与ICAM-1、TNF-α、hs-CRP和HOMA-IR之间呈负相关(r值分别为-0.735、-0.781、-0.768、-0.752,均P<0.01),HOMA-IR与ICAM-1、TNF-α和hs-CRP之间呈正相关(r值分别为0.857、0.906、0.888,均P<0.01)。结论: 炎症因子和脂联素参与了DR的发生和发展,而脂联素可能通过拮抗炎症反应减轻胰岛素抵抗,对DR有一定的改善作用。     

8周游泳运动对2型糖尿病大鼠周围神经病变的影响

 目的： 探讨长期游泳运动对2型糖尿病大鼠周围神经病变的影响及可能机制。方法: 雄性Wistar大鼠高糖高脂饲料喂养联合链脲佐菌素注射制备成T2DM大鼠模型后,随机分为空白对照组（C组）、单纯运动组（CE组）、糖尿病对照组（DM组）和糖尿病运动组（DME组）。CE组和DME组进行8周游泳训练（6 d/week）,第1周前3 d练习时间分别为20、30和45 min,第4天起每天持续游泳60 min。运动8周后测定各组大鼠坐骨神经的传导速度（MNCV）,以及该组织中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、C反应蛋白（CRP）的含量,观察其形态结构。结果: 实验末,与DM组相比,DME组的MNCV明显提高（P<0.05）,坐骨神经组织中TNF-α、IL-6和CRP水平均有所降低,但差异无统计学意义（P>0.05）。DM组坐骨神经光镜下可见明显的损伤,经运动干预后病变程度减轻。结论: 8周游泳运动可提高MNCV,减轻DM造成的神经损伤,对周围神经起保护作用,其机制可能与减轻炎症反应有关。