The connection between QT dispersion and autonomic neuropathy in patients with type 2 diabetes.

It is controversial whether an increase in the QT dispersion (QTd) on the electrocardiogram (ECG) reflects cardiac autonomic neuropathy in diabetic patients. In the current study, the QTd was compared in 60 type 2 diabetic patients and in 30 healthy subjects, and its association with autonomic neuropathy in diabetic patients was investigated. An increased QTd was found in diabetic patients, compared to healthy subjects. The QTd had significant negative associations with the log of the low and high frequency power (log LF and HF, respectively) of the power spectral analyses (PSA) of heart rate variations and the systolic blood response during standing (Delta BP). There was no significant difference in the QTd between patients with and without sympathetic skin response (SSR), reflecting peripheral sympathetic function. A significant positive correlation was also found between QTd and the systolic blood pressure (SBP). On the other hand, there was no correlation between QTd and serum total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), hemoglobin (Hb) A (1C) concentrations or body mass index (BMI). By multiple regression analysis, the log HF, which reflects cardiac parasympathetic function, and the SBP alone were significantly associated with QTd as the dependent variable. The Delta BP and log LF, which partially reflect sympathetic nerve function, had no significant associations with QTd. These findings suggest that QTd reflects cardiac autonomic neuropathy (relative parasympathetic neuropathy) and that the QTd is also influenced by SBP, independent of autonomic neuro-function.     

2型糖尿病伴高血压患者QT离散度的影响因素

目的 探讨2型糖尿病伴高血压患者QT离散度（QTcd)的影响因素。方法 对60例2型糖尿病伴高血压患者,包括左心室肥厚（LVH）21例,非左心室肥厚（NLVH）39例,分别测量QTcd等,并与38例单纯2型糖尿病及60例正常组进行对照。应用相关分析及多因素逐步回归方法进行分析。结果 2型糖尿病各组的QTcd、QTd均较对照组明显延长,其中LVH组较NLVH组和单纯2型糖尿病组的QTcd、QTd的延长更为显著（P＜0.001)。相关分析表明,QTcd与左心室重量指数（LVMI）、糖尿病病程及空腹胰岛素水平显著正相关。逐步回归分析表明,QTcd主要决定于LVMI、糖尿病病程和空腹胰岛素水平。结论 影响2型糖尿病伴高血压患者QTcd的主要因素为左心室肥厚、糖尿病病程及空腹胰岛素水平。     

2型糖尿病外周感觉神经病变和心自主神经病变关系的研究

目的探讨T2DM外周感觉神经病变和心自主神经病变之间的关系。方法选取T2DM患者148例,采集临床资料,测定FPG、HbA1c及LDL-C等生化指标;进行定量感觉神经检查(以色列TSA-II定量感觉神经测定仪),结合临床症状评价糖尿病外周感觉神经病变;进行心血管反射试验检查,结合临床症状评价糖尿病心自主神经病变。结果外周感觉神经病变的患病率为28%,心自主神经病变的患病率为10%;无外周感觉神经病变的患者中心自主神经病变的患病率为6%,存在外周感觉神经病变的患者中心自主神经病变的患病率为21%;与对照组相比,外周感觉神经病变组和心自主神经病变组的病程较长,FPG、HbA1c及LDL-C水平较高,差异有统计学意义(P<0.05)。结论糖尿病心自主神经病变可发生于无外周感觉神经病变的患者;病程、FPG、HbA1c及LDL-C可能为糖尿病外周感觉神经病变和心自主神经病变的危险因素。     

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR >?3.4 mg/mmol) or an estimated (eGFR) <?60 ml min^?1 1.73 m^?2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (?9.0?±?17.8% vs ?3.3?±?10.3%, p?=?0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β?=??3.5, p?=?0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.     

Cardiac sympathetic dysinnervation in Type 2 diabetes mellitus with and without ECG-based cardiac autonomic neuropathy

To evaluate the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in Type 2 diabetes mellitus I-123-metaiodobenzylguanidine (I-123-MIBG) scintigraphy was applied to 15 Type 2 (noninsulin-dependent) diabetic patients with ECG-based cardiac autonomic neuropathy (> or = two of five age-related cardiac reflex tests abnormal) and 15 clinically comparable Type 2 diabetic patients without ECG-based cardiac autonomic neuropathy. Myocardial perfusion abnormalities were excluded by 99 m-Tc-methoxyisobutylisonitrile (99 m-MIBI) scintigraphy. Both in Type 2 diabetic patients with and without, ECG-based autonomic neuropathy, only one patient (7%) was found to have a normal homogeneous uptake of I-123-MIBG compared to 14 patients (93%) with a reduced I-123-MIBG uptake. The uptake of I-123-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral, and septal myocardium (P< .001, P< .001, P< .001, respectively). Diabetic patients with ECG-based cardiac autonomic neuropathy demonstrated a more pronounced reduction of the posterior I-123-MIBG myocardial uptake than diabetic patients without (P< .01). The mean global and the anterior, lateral, septal, and apical myocardial I-123-MIBG uptake was comparable between the two groups. The uptake of the posterior myocardial region correlated with all indices of heart rate variation at rest and during deep breathing. A correlation between global or regional myocardial I-123-MIBG uptake and QT interval was not observed. The study demonstrates that cardiac sympathetic dysinnervation is common in Type 2 diabetes mellitus both with and without ECG-based cardiac autonomic neuropathy. In Type 2 diabetes mellitus, the posterior myocardium is predominantly affected and the extent of dysinnervation is more pronounced in the presence of ECG-based cardiac autonomic neuropathy.     

2型糖尿病患者胃动力学与植物神经病变关系的探讨

目的研究胃动力障碍及植物神经病变与2型糖尿病(DM2)的关系。方法采用半流质核素胃排空试验对129例DM2患者的胃动力进行了研究,同时还用Ewing法对心血管植物神经功能、用B超对膀胱残余尿量、用神经病星对外周神经进行定量测定。结果糖尿病胃排空延迟发生率为62.02％。植物神经病变呈弥漫性分布,随病程延长而加重。胃动力异常者,其植物神经病变发生率较胃动力正常者显著增高。结论DM2胃动力异常及植物神经病变发生率均明显增高,二者显著相关。故早期进行胃排空试验,并同时对其它植物神经功能进行测定,对糖尿病胃及神经并发症的早期防治有重要意义。     

QTc and autonomic neuropathy in diabetes: effects of acute hyperglycaemia and n-3 PUFA

Background and aimsAutonomic function is also regulated by glycaemia and exerts a crucial role in the control of blood pressure and cardiac function. The disruption of this physiological mechanism impacts deeply on cardiovascular mortality in diabetes. We investigated the influence of autonomic dysfunction on QTc interval and on sympatho-vagal balance (LF/HF), in response to acute hyperglycaemia and to membrane electrical stabilization (n-3 PUFA).Methods and resultsTwenty-four type 2 diabetic patients, without (N−: n = 13) or with (N+: n = 11) autonomic neuropathy and 13 healthy subjects (C) underwent BP and ECG monitoring during a 24-h period and during a 2-h hyperglycaemic clamp. ΔQTc during the night was blunted in diabetics (0.5 ± 2.5 vs. C: 2.9 ± 2.5%, p = 0.001), and ΔLF/HF was decreased in N+ (−2.8 ± 38.2 vs. C = 34.8 ± 28.1%, p = 0.02). During hyperglycaemia, QTc increased in C; LF/HF significantly increased in C and N−. A 6-month treatment with n-3 PUFA partially restored ΔLF/HF and ΔQTc (2.1 ± 1.40, p = 0.04 vs. basal) only in N−.ConclusionHyperglycaemia increases QTc interval and sympathetic activity; electrical membrane stabilization improves autonomic function only in the absence of overt autonomic neuropathy. Strategies to prevent the disruption of autonomic function with newer approaches, other than just glucose control, should be implemented.     

Oesophageal function in diabetes mellitus and its association with autonomic neuropathy

We have evaluated oesophageal function in 34 diabetics and in 16 non-diabetic controls by a timed bolus transit method derived from dynamic oesophageal scintiscans (water transit time: WTT) and barium swallow. The diabetics were screened for autonomic neuropathy using standard cardiovascular responses and 10 patients were classified as abnormal. WTT was significantly prolonged in autonomic neuropaths compared with other diabetics (p less than 0.01) and controls (p less than 0.001). Abnormal peristalsis on barium swallow was seen more frequently in autonomic neuropaths (9/10) than in other diabetics (11/24, p less than 0.002). WTTs from all diabetic patients correlated with abnormal heart rate responses at rest (Rs = - 0.49, p less than 0.005), on deep inspiration (Rs = -0.48, p less than 0.005), and on standing (Rs = -0.39, p less than 0.025) but not with the Valsalva manoeuvre. A weaker correlation was found between the postural fall in blood pressure (Rs = 0.3, p less than 0.05). Diabetics with autonomic neuropathy frequently have asymptomatic oesophageal dysfunction which may result from a vagal neuropathy in view of its association with abnormalities of vagally mediated cardiovascular responses.     

Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus

AimsThis study investigated autonomic nervous system function in subjects with diabetes during exercise and recovery.MethodsEighteen type 2 diabetics (age 55 ± 2 years) and twenty healthy controls (age 51 ± 1 years) underwent two 16-min bicycle submaximal ECG stress tests followed by 45 min of recovery. During session #2, atropine (0.04 mg/kg) was administered at peak exercise, and the final two minutes of exercise and entire recovery occurred under parasympathetic blockade. Plasma catecholamines were measured throughout. Parasympathetic effect was defined as the difference between a measured parameter at baseline and after parasympathetic blockade.ResultsThe parasympathetic effect on the RR interval was blunted (P = .004) in diabetic subjects during recovery. Parasympathetic effect on QT–RR slope during early recovery was diminished in the diabetes group (diabetes 0.13 ± 0.02, control 0.21 ± 0.02, P = .03). Subjects with diabetes had a lower heart rate recovery at 1 min (diabetes 18.5 ± 1.9 bpm, control 27.6 ± 1.5 bpm, P < .001).ConclusionsIn subjects with well-controlled type 2 diabetes, even with minimal evidence of CAN using current methodology, altered cardiac autonomic balance is present and can be detected through an exercise-based assessment for CAN. The early post-exercise recovery period in diabetes was characterized by enhanced sympathoexcitation, diminished parasympathetic reactivation and delay in heart rate recovery.     

Insulin resistant state in type 2 diabetes is related to advanced autonomic neuropathy

To elucidate the relationships between obesity, glycemic control, dyslipidemia, hypertension, microvascular complications, and insulin resistance assessed using an euglycemic hyperinsulinemic clamp technique, we studied 54 hospitalized type 2 diabetic subjects (DM) and 10 age- and sex-matched normotensive, nonobese control subjects (C). Glucose infusion rate (GIR) derived from the clamp study was used as an index of insulin resistance. Body mass index (BMI), the prevalence of hypertension, HbA1c and serum nonesterified fatty acids (NEFA) were significantly higher, and serum high-density-lipoprotein (HDL)-cholesterol was significantly lower in DM than in C (p < 0.05 or less). The median GIR level was significantly lower inDM than in C (p = 0.038). The difference in GIR between the two groups wasstill statistically significant even after adjustment for BMI, mean BP, HbA1c, NEFA, and HDL-cholesterol. However, after simultaneous adjustment for these factors, there was no difference in GIR between the two groups. Body mass index, mean BP, HbA1c, and NEFA showed negative correlations, and serum HDL-cholesterol showed a positive correlation with GIR, but neither age nor duration of diabetes correlated with GIR. When GIR values in DM were divided according to the degree of neuropathy, retinopathy, and nephropathy, and compared to those in C, GIR levels tended to be decreased with increasing severity of each microvascular complication, but there was no difference in median GIR levels among the diabetic subgroups. Relationships between the GIR levels and confounding factors such as age, sex, BMI, mean BP, HbA1c, serum NEFA, and serum HDL-cholesterol, were examined simultaneously with a multiple regression analysis. This analysis revealed that HbA1c and serum NEFA may affect the GIR level. Furthermore, together with these two factors, the relationships between the GIR levels and the severity of each microvascular complication were explored with the same analysis. This model clearly demonstrated that both the decreased CVR-R and pronounced orthostatic fall in systolic BP were independent factors for the decreased GIR. These findings suggest that marked autonomic dysfunction, rather than other confounding factors, is related to increased insulin resistance in DM.     

Gastric myoelectrical activity in patients with type I diabetes mellitus and autonomic neuropathy

In patients with diabetes mellitus and gastroparesis, dysrhythmias of gastric myoelectrical activity, especially tachygastrias, are thought to be involved in the pathogenesis of dyspeptic symptoms. Using surface electrogastrography we studied the prevalence of these abnormalities, and their relationships to dyspeptic symptoms and the extent of cardiac autonomic neuropathy in 30 euglycemic patients with type I diabetes mellitus and 12 controls. Neither in the fasting nor in the postprandial state were differences in mean frequency of gastric electrical control activity and its variability found between patients and controls. In the fasting state, the power content of the 3 cpm component in the power spectrum of the electrogastrogram was even higher in patients than in controls (P=0.049). In the fasting state, second harmonics of the 3 cpm fundamental gastric signal were seen more often in patients than in controls (P=0.03). In patients with symptoms during the study, no second harmonics were found after the meal. The postprandial/fasting power ratio was decreased in patients with symptoms during the study as compared to patients without symptoms and controls (P<0.05). The incidence of dysrhythmias, such as tachygastrias and bradygastrias, was not higher in patients than in controls (17% and 8%, respectively). No correlation was found between electrogastrographic parameters and the severity of autonomic neuropathy or dyspeptic symptoms scored before the study. In conclusion, this study has shown that patients with type I diabetes mellitus and autonomic neuropathy studied under euglycemic conditions do not have grossly disturbed myoelectrical activity, except when symptomatic during the study.Supported by the Dutch Diabetic Foundation.     

Cardiac autonomic balance and QT dispersion during head-up tilt testing in diabetics with and without sensory neuropathy

BACKGROUND: Cardiovascular autonomic dysfunction is associated with higher mortality in diabetics. However, detection methods of early cardiac diabetic dysautonomia, and its correlation with severity of sensory neuropathy, have not been described. METHODS: We analyzed the heart rate variability (HRV) by spectral analysis and QT dispersion in 23 diabetics with and without sensory neuropathy, and in 5 age-matched controls, in the supine position and during head-up tilt testing (HUT). Diabetics were divided into 3 groups according to the degree of sensory neuropathy. RESULTS: In the spectral analysis of HRV, the high frequency components in the supine position decreased as a function of severity of the neuropathy. High frequency in diabetics was significantly decreased in the supine position, even in absence of sensory neuropathy. The low/high frequency ratio (L/H) in the supine position was similar among controls and the 3 patient groups. L/H in diabetics with moderate or severe neuropathy did not increase from the supine to the upright position. Baseline QT dispersion increased proportionally to the severity of sensory neuropathy and, in patients without apparent sensory neuropathy, QT dispersion increased significantly during HUT. CONCLUSIONS: The spectral analysis of HRV and measurements of QT dispersion, before and during HUT, were reliable detection methods of early abnormalities in autonomic balance and may predict a risk of sudden cardiac death in diabetics.     

Clinical usefulness of corrected QT intervals in diabetic autonomic neuropathy in patients with type 2 diabetes

BACKGROUND: It is recognized that QTc intervals reflect autonomic nerve function. To investigate the clinical usefulness of corrected QT intervals (QTc) in assessing autonomic nerve function in type 2 diabetes, we measured QTc intervals using Bazett's formula in 58 type 2 diabetic patients and 20 age-matched healthy subjects. METHODS: We examined relationships between QTc intervals and the coefficient of variation of RR intervals (CV(RR)), systolic blood pressure response to standing, and sympathetic skin response (SSR) whose tests reflect autonomic nerve function. We also studied the correlation between QTc and blood pressure or serum lipid concentrations. RESULTS: QTc intervals in diabetic patients were significantly longer than those in healthy subjects and showed a significant but weak negative correlation with CV(RR), as well as systolic blood pressure response to standing. No significant difference in QTc intervals was observed between patients with and without a detectable SSR. QTc intervals showed a significant positive correlation with systolic and diastolic blood pressure although it did not correlate with serum lipid concentrations. QTc also tended to be long in obese diabetic subjects (body mass index > 25). CONCLUSION: QTc intervals might also be affected by other factors such as arteriosclerotic macroangiopathy and obesity, and not only autonomic nerve function. Therefore it might be considered as an overall index for complications, and not for pure autonomic impairment.     

2型糖尿病患者糖化血红蛋白指数与糖尿病心脏自主神经病变的相关性研究

目的:探讨2型糖尿病患者糖化血红蛋白指数（HGI）与糖尿病心脏自主神经病变（DCAN）的相关性及HGI在DCAN发病风险预测中的作用。方法:本研究为回顾性研究。选取2017年10月至2020 年5月在重庆医科大学附属第一医院内分泌科住院的993例2型糖尿病患者作为研究对象。收集所有患者的性别、年龄、糖尿病家族史、糖尿病...