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Aims: To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements.Methods: Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination.Results: CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%.Conclusion: This study suggests that CAN predominantly co-exists with concomitant DPN. Aims: To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements. Methods: Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination. Results: CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%. Conclusion: This study suggests that CAN predominantly co-exists with concomitant DPN.

Yiying Liu,1,&ast; Xin Wang,2,&ast; Linying Wang,1 Wenwen Chen,3 Wenyue Liu,1 Tingting Ye,1 Jing Hong,1 Hong Zhu,1 Feixia Shen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China; 3Department of Senile Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feixia ShenDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaEmail shenfeixia@wmu.edu.cnPurpose: Diabetic neurogenic bladder (DNB) has been widely recognized in recent years. It is common in patients with long-term diabetes and may also lead to many severe complications. Although there has been widespread evidence that inflammation is involved in the development of some diabetic complications, there is little evidence that this can also occur in the bladder. In recent years, platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been viewed as potential novel markers of inflammatory responses. This study was designed to evaluate the relationship between the presence of DNB and the PLR and NLR.Patients and Methods: A total of 371 cases of T2DM patients were included in this retrospective study. Patients were divided into two groups, with 115 diabetic subjects diagnosed with diabetic neurogenic bladder and 256 control subjects without DNB. The independent predictors of DNB were analyzed using logistic regression.Results: Compared with patients without DNB, the mean PLR and NLR were significantly higher in those with DNB (p < 0.001). Based on the logistic regression, PLR was found to be an independent risk factor for DNB (odds ratio [OR]: 1.408, 95% confidence interval [CI]: 1.248– 1.617). From the receiver operating characteristic (ROC) curve, using PLR as indicative of DNB was expected to be 101.1949, and it generated a sensitivity and specificity value of 89.6% and 23.4%, respectively. The area under the curve (AUC) was also found to be 0.899 (95% CI: 0.865– 0.932).Conclusion: In our study, PLR and NLR were significantly higher for patients with DNB. The PLR was found to be a risk factor in the presence of DNB after correcting for possible confounding factors. Considering the severe complications associated with DNB, patients with elevated PLR should be seriously cared for in clinics.Keywords: diabetic autonomic neuropathy, neurogenic bladder, oxidative stress, inflammatory response

Introduction. Early diagnosis of cardiac autonomic neuropathy is the basis for the risk of heart disease and premature death in patients with type 2 diabetes mellitus (type 2 diabetes). All patients with type 2 diabetes and prediabetes should undergo annual screening, including history taking and neurophysiologic evaluation, for early diabetic autonomic neuropathy. This article describes a modern diagnostic technique based on changes in heart rate variability, which allows early detection of damage to the parasympathetic nervous system and timely prescribing disease-modifying treatment in patients with type 2 diabetes.Materials and methods. The study included 50 patients with type 2 diabetes (cf. Age 56.5 ± 13.5 years) and 30 healthy subjects (cf. Age 58 ± 10 years), matched by sex and age. according to the NSC questionnaire, the severity of neurological deficit - according to the NIS-LL scale, neuropathic pain syndrome - according to the TSS scale.Results. In the study group of patients with type 2 diabetes, severe CAN was detected in 13.3%, moderate CAN in 40% of patients, in 46.6% of patients, CAN was not detected. In the group of healthy volunteers, disorders of the autonomic nervous system of moderate were detected in 3.3%, in the remaining 96.7% of autonomic disorders were not accepted.Conclusion. The results of pulse oximetric tests with deep breathing are comparable to the results of the QAT device Case-4 (p < 0.001). The method of pulse oximetric diagnostics is more practical to use in comparison with the hardware QAT.

Aim: There is a lack of methods for investigating the autonomic nerves of the gastrointestinal tract. Our aim was to explore a novel test measuring visceral sensory evoked potentials (EPs) in response to rapid balloon distention in the rectum and compare it to established tests for diabetic neuropathy.Method: Participants with longstanding type 2 diabetes, newly onset, untreated diabetes Results: The pressure at earliest sensation was higher in people with diabetes, 0.038 (0.012) bar vs. controls 0.030 (0.009) bar, p = 0.002, and in people with signs of peripheral neuropathy, 0.045 (0.014) bar, p < 0.01. Clinical correlations between EP amplitude and latency, and other tests were found.Conclusions: Rectal hyposensitivity was associated with both longstanding and early diabetes, indicating enteric sensory dysfunction already in early stages of diabetes. Correlation analyses may indicate that central afferent processing is affected in parallel with peripheral neuronal function. Aim: There is a lack of methods for investigating the autonomic nerves of the gastrointestinal tract. Our aim was to explore a novel test measuring visceral sensory evoked potentials (EPs) in response to rapid balloon distention in the rectum and compare it to established tests for diabetic neuropathy. Method: Participants with longstanding type 2 diabetes, newly onset, untreated diabetes

WOS:000632380600003 PMID: 33763793 Purpose We aimed to reveal whether static and dynamic pupillary responses can be used for the detection of autonomic nervous system (ANS) dysfunction in patients with obstructive sleep apnea syndrome (OSAS). Methods We included in this study patients with OSAS, who were divided into three groups according to the apnea-hypopnea index (AHI) (group 1, mild [n = 20]; group 2, moderate [n = 20]; and group 3, severe [n = 20]), and healthy controls (group 4, n = 20). Pupillary responses were measured using a pupillometry system. Results Static (mesopic PD, P = 0.0019; low photopic PD, P = 0.001) and dynamic pupil responses (resting diameter, P = 0.004; amplitude of pupil contraction, P < 0.001; duration of pupil contraction, P = 0.022; velocity of pupil contraction, P = 0.001; and velocity of pupil dilation, P = 0.012) were affected in patients with different OSAS severities. Also, AHI was negatively correlated with mesopic PD (P = 0.008), low photopic PD (P = 0.003), resting diameter (P = 0.001), amplitude of pupil contraction (P < 0.001), duration of pupil contraction (P = 0.011), velocity of pupil contraction (P < 0.001), and velocity of pupil dilation (P = 0.001). Conclusion We detected pupil responses innervated by the ANS were affected in the OSAS patients. This effect was more significant in the severe OSAS patients. Therefore, the pupillometry system can be an easily applicable, noninvasive method to detect ANS dysfunction in the OSA patients.

Background Sudden cardiac deaths are twice more frequent in diabetic patients with cardiac autonomic neuropathy. Sudden cardiac death etiologies remain unclear and no recommendations are made to identify factors associated with cardiorespiratory arrest in diabetic patients. We hypothesized, from two clinical cases, that impaired hypoxic ventilatory drive, induced by diabetic autonomic neuropathy, is a cause of misdiagnosed severe cardiac events. Case presentation We describe the cases of two patients with isolated low blood saturation on pulse oximeter during the systematic nurse check-up (77% and 85% respectively) contrasting with the absence of any complaint such as dyspnea, polypnea or other respiratory insufficiency signs observed during the clinical examination. Arterial blood gas measurements subsequently confirmed that blood oxygen saturation was low and both patients were indeed hypoxemic. Patient 1 suffered from vascular overload complicated by cardiac arrest caused by hypoxemia in light of the quick recovery observed after ventilation. Pulmonary edema was diagnosed in patient 2. The common denominator of these 2 cases described in this brief report is the absence of respiratory failure clinical signs contrasting with the presence of confirmed hypoxemia. Also, in both cases, such absence of precursory signs seems to be induced by an impaired ventilatory drive to hypoxemia. This appears to be related to the autonomic diabetic neuropathy encountered in those 2 patients. Conclusions Therefore, we describe, in this brief report, cardiac autonomic neuropathy as a cause of impaired hypoxic ventilatory drive involved in severe acute cardiorespiratory events in two type 1 diabetic patients. We assume that altered response to hypoxemia due to cardiac autonomic neuropathy and non-functional central neurological breathing command could play a key role in sudden deaths among diabetic patients. An important point is that hypoxemia can be easily missed since no clinical signs of respiratory failure are reported in these two clinical cases. Systematic screening of cardiac autonomic neuropathy in diabetic patients and proactive detection of impaired hypoxic ventilatory drive for early management (e.g. treatment of hypoxemia) should be systematically undertaken in diabetic patients to prevent its dramatic consequences such as cardiorespiratory arrest and death.

Objective The aim: Is to determine the peculiarities of changes in the gastric acid secretion against the background of diabetic autonomic neuropathy and autonomic dysfunction in patients with chronic pancreatitis (CP) and type 2 diabetes (T2DM). Patients and methods Materials and methods: We investigated 64 patients with CP and T2DM, who were included in the first group of the patients examined; Group II consisted of 40 patients with T2DM; and Group III of the patients examined consisted of 34 patients with CP. Results Results: Differences were found in assessing the degree of autonomic nervous system (ANS) dysfunction in the examined patients, namely - the most pronounced ANS dysfunction according to the Wayne questionnaire was diagnosed in patients Group I, while patients of Group III. Analysis of gastric acid secretion indicates that no patients of Group III had normal acidity. Normal acidity is more often found in the second group of subjects. Both in patients with CP and T2DM, and in isolation with CP, moderate hyperacidity was more often determined. Conclusion Conclusions: The predominance of the parasympathetic division of the ANS, as well as manifestations of severe ANS dysfunction, are observed in patients with CP and T2DM. The prevalence of gastric hyperacidity on the background of DAN was established in patients with CP and T2DM. In this case, the absence of clinical symptoms or their minimal severity is determined, which indicates the lesion of the digestive tract in these patients.

Background The exocrine function of the pancreas is controlled by the autonomic nervous system (ANS), and autonomic neuropathy is a common and serious complication of diabetes. There are many factors contributing to the development of autonomic neuropathy in diabetic patients. Cardiovascular tests have been developed to evaluate the function of the ANS. This study investigated the relationship between cardiovascular autonomic neuropathy (CAN) and pancreas exocrine insufficiency (PEI) in diabetic patients. Methods This study evaluated 110 individuals with type 2 diabetes mellitus (T2DM) and 40 healthy volunteers. Autonomous neuropathy tests were utilized to diagnose patients, and Ewing and Clarke's criteria were employed to assess the severity of autonomous dysfunction. Stool samples were also collected from patients to measure fecal elastase-1 (FE-1). Results A 65.5% incidence of PEI was observed in DM patients. There was no significant correlation among the duration of disease, C-peptide, HbA1c, and PEI, respectively (P = .782, P = .521, P = .580). However, a significant difference between DM patients and controls in terms of cardiac dysautonomia (P = .001) was seen. Moreover, a statistically significant correlation between the degree of cardiac dysautonomia and FE-1 level was observed within the patient group (P =.001). Conclusion It is possible that the disruption of exocrine hormone secretion in the pancreas due to the impairment of enteropancreatic reflexes is secondary to diabetic autonomic neuropathy and resulting in PEI. This study also showed that autonomic neuropathy might develop and cause PEI in diabetic patients without known added confounding factors.

Diabetic neuropathies are a group of heterogeneous peripheral neuropathies and are roughly classified into polyneuropathy and focal neuropathy. Diabetes-specific neuropathy is polyneuropathy, which is pathophysiologically associated with metabolic disorders due to hyperglycemia and microangiopathy. Recently, classification1,2) of the spectrum of diabetic polyneuropathy based on the different type of nerve fiber involved is growing (e.g. myelinated, unmyelinated, autonomic, somatic). Diabetic polyneuropathy (DPN) is divided into diabetic distal sensory neuropathy (DSN), diabetic small fiber neuropathy (DSFN) and diabetic autonomic neuropathy (DAN)2) .

Purpose Diabetic autonomic neuropathy (DAN) is a common and disabling complication of diabetes, with cardiac autonomic neuropathy (CAN) being a major cause of mortality and morbidity. Standard autonomic function tests (AFT) are cumbersome and time consuming to conduct in OPD setting. Objective To evaluate the diagnostic accuracy of composite autonomic symptom scale 31 (COMPASS-31) as a screening test for DAN. Patients and methods A cross-sectional study which enrolled 60 type 2 diabetes individuals was conducted at a tertiary care center. Autonomic functions were evaluated by COMPASS-31 questionnaire as well as by standard Ewing's battery of tests; short-term heart rate variability; sympathetic skin response along with nerve conduction studies. Results Thirty males and 24 females completed the study. Forty-nine (89%) participants had CAN, of which, 9 (17%) had definite CAN. Peripheral neuropathy was present in 20 (37%). COMPASS-31 scores showed no difference between "No CAN" and "Early CAN". "Definite CAN" individuals differed significantly from "No and Early CAN" on COMPASS-31 scores and its gastrointestinal sub-domain. Receiver operating characteristic between "Definite CAN" and "No and Early CAN" showed fair accuracy with AUC of 0.731 (95% CI 0.561-0.901), sensitivity 77.8%, specificity 71.7% at a cut-off of 28.67 of COMPASS-31 score. Gastrointestinal sub-domain, at a cut-off score of 5.8, had 77.8% sensitivity, 60% specificity, and AUC was 0.748 (95% CI 0.603-0.894). Conclusion COMPASS-31, a self-administered tool, requiring less time, qualifies as an acceptable screening tool, especially for definite CAN. However, individuals scoring low on COMPASS-31 are still required to be evaluated by Ewing's battery to differentiate between "Early CAN" and "No CAN".

BACKGROUND: Diabetic peripheral neuropathy (DPN) means the presence of symptoms and/or signs of peripheral nerve damage that occur to people with diabetes, excluding all other causes of neuropathy. Chronic hyperglycaemia leads to increased secretion of tumour necrotic factor-alpha (TNF-α), with the development of micro and macroangiopathy, damage to nerve fibres and local demyelination. AIM: To determine the role of inflammation in the peripheral nerve damage process concerning people suffering from type II diabetes mellitus. MATERIAL AND METHODS: The study included a total of 80 subjects, men and women, divided into two groups: an examined group (n = 50) consisting of subjects with DPN at the age from 30 to 80 years and a control group (n = 30) of healthy subjects aged from 18 to 45. In the investigated group, a neurological examination was performed using the Diabetic Neuropathy Symptoms (DNS) Score and Electroneurography. All the subjects had the blood plasma concentration of TNF-α by ELISA technique. RESULTS: The average value of TNF-α in the test group was 8.24 ± 2.899 pg/ml, while the control group was 4.36 ± 2.622 pg/ml (p < 0.0001). The average value of TNF-α was correlated with the achieved DNS score in the investigated group (p = 0.005). Concerning the linear association of the concentration of TNF-α with the peripheral nerve velocity in the investigated group, no statistical significance was detected. CONCLUSION: Inflammation can play a role in the pathogenesis of diabetic autonomic neuropathy and cranial neuritis.

Introduction. Diabetic neuropathy is the most wide-spread complication of diabetes mellitus and neuropathy is steadily progressing even with compensation of the underlying disease. The search of the new methods of treatment and diagnosis of neuropathy is required. Diabetic autonomic neuropathy lies in the base of early morbidity and mortality of diabetic patients.We estimated the potential of High-frequency Ultrasonic Dopplerography for diagnosis of autonomic neuropathy. Material and methods. 26 diabetic patients with sensorimotor neuropathy were examined. Microvascular blood flow of finger skin was assessed at rest as well as in functional tests: with cold impact and occlusion (cuff). Cardiac autonomic neuropathy was assessed using several cardiovascular autonomic reflex tests as a gold standard of diagnosis. Diagnostic values of microvascular blood flow test in detecting of cardiac autonomic neuropathy staging were evaluated in comparing with traditional modalities.Results. Cardiac autonomic neuropathy was found for all patients and definite/confirmed staging in 61.5 % cases. Initial parameters of microvascular blood flow velocity were significantly decreased in all patients in comparing with control (Vam= = (1.9±0.22); (1.7±0.51) and (6.7±0.51) sm/s in patients with early cardiac autonomic neuropathy, definite/confirmed staging and control subjects respectively, pConclusions. High-frequency Ultrasonic Dopplerography allowed to separate of cardiac autonomic neuropathy stages. This study is necessary to continue for revealing of all method possibilities.

Two diabetic women (case 1, 75 years old; case 2, 49 years old) being treated with glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) showed no suppression of cortisol secretion on a dexamethasone suppression test (DST). However, its secretion was suppressed after switching from GLP-1 RAs to insulin. We also checked the cortisol secretion by a DST in five consecutive inpatients (case 3-7) being treated with GLP-1 RAs. The coefficients of R-R interval variation at rest and during deep breathing were lower in the two false-positive cases (case 1 and 2) than in the five true-negative cases (case 3-6). GLP-1 RAs can be switched to insulin in order to eliminate the slow absorption effect of dexamethasone by GLP-1 RAs if a DST is planned in diabetic patients receiving GLP-1 RAs.

Introduction: Cardiac autonomic neuropathy (CAN) is one of major complications of diabetes mellitus (DM) that increases the risk of cardiovascular disorders, abnormal ventricular depolarization with poor prognosis as well as increased mortality and morbidity. Indeed, CAN has close relation with blood glucose level in diabetic patients. We investigated the relation of CAN with diabetes control. Materials and methods: Totally, 115 diabetic patients (mean age 50.87±13.90 years old; 78 females) underwent study. All patients had DM and cardiac sinus rhythm. Nobody had sickness affecting cardiac rhythm and blood pressure. In addition, they did not take drugs that had effect on blood pressure, cardiac rhythm, and QT interval. Forty-six patients had tight and 69 patients had uncontrolled DM according to American Diabetes Association (ADA) criteria. The CAN was assessed based on heart rate variation during physical examination (at rest tachycardia and orthostatic hypotension) and standard Ewing's tests (deep-breathing and laying-to-standing tests) with bedside continuous ECG recording. The P-value

Diabetic polyneuropathy affects 30–50% of patients with diabetes mellitus. It encompasses several neuropathic syndromes, the commonest being distal symmetrical polyneuropathy or ‘diabetic peripheral neuropathy’ (DPN). Risk factors for DPN include poor glycaemic control and drivers of macrovascular disease including hypertension. Strong evidence in humans and animals implicates nerve ischaemia as the cause of DPN. Despite several well-designed recent trials, no novel approved treatment with unequivocal effects on the decline in nerve function in DPN has emerged. Painful DPN affects 15–26% of those with diabetes, produces considerable disability, and is challenging to assess and manage. First-line therapies are tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors (e.g. duloxetine) or anticonvulsants (e.g. pregabalin, gabapentin). Second-line drugs include opioids. Diabetic autonomic neuropathy also results in considerable morbidity, reduced quality of life and increased mortality. It may involve cardiovascular, gastrointestinal, urogenital, pupillomotor, thermoregulatory and sudomotor function. Although counselling and non-pharmacological interventions are of some use, more severely afflicted patients require pharmacological intervention.

Introduction/Objective. Cardiovascular diabetic autonomic neuropathy (CDAN) mainly affects heart rhythm through sympathovagal imbalance. The objective of the study is to determine CDAN risk potential regarding electrical complications of acute myocardial ischemia (AMI), including admission glucose profile levels (AGP). Methods. Seventy-six patients suffering from type 2 diabetes mellitus were divided into two age-matched groups related to the presence of CDAN, and the influence of AGP on electrical complications was estimated. Ewing?s tests were used for diagnosis of CDAN. Results. Patients without CDAN have 42.86% risk for developing electrical complication into early post-AMI period. If it is a pre-existing condition, the risk is 63.64%, which is obvious, but not statistically significant. Considering the AGP, levels above 12.25 mmol/L as predictive for post-AMI electrical complications, in CDAN-positive patients with AGP levels above that cut-off value, the risk for electrical complications is raising up to 73.68%. The patients with CDAN who have AGP levels above the cut-off value have statistically higher risk for development electrical complications than those with lower levels (Z = 2.58, p < 0.01). On the other side, those without CDAN and with level of AGP lower than 12.25 mmol/L, the risk for electrical complications developing is as low as 23.08%. Conclusion. CDAN may be an important independent risk factor for electrical complications in postmyocardial ischemia period.

Purpose: To investigate the relation between erectile dysfunction (ED) severity and pupillary functions in patients with diabetes mellitus (DM). Methods: This prospective and observational study included 90 patients with type 2 DM and ED. Patients divided into three subgroups according to severity of ED: (i) Mild ED, (ii) Moderate ED and (iii) Severe ED groups. Thirty age-matched healthy subjects formed the control group. Main outcome measures were pupil diameter and average speed of pupil dilation. Static and dynamic pupillometry analysis was performed using the Sirius Topographer (CSO, Firenze, Italy). Results: Mean pupil diameter during static and dynamic pupillometry analysis were significantly greater in the control group than in the all study groups (P < 0.05). Mean pupil diameter in static pupillometry analysis was significantly different in each study group and pupil was more miotic in the Severe ED group than in the both Moderate and Mild ED groups (P < 0.05 for each). Dynamic pupillometry analysis revealed that mean pupil diameter and mean average dilation speed were significantly different in each study group throughout measurement period and the highest speed was observed in the Mild ED group and the lowest speed was observed in the severe ED group (P < 0.005 for each). Conclusion: Our study results suggest that abnormal pupil functions due to diabetic autonomic neuropathy may indicate the associated ED in patients with DM.

This study proposed a pupillary light reflex (PLR) inherent model based on the system identification method to demonstrate the dynamic physiological mechanism of the PLR, in which pupillary constriction and dilation are controlled by the sympathetic and parasympathetic nervous system. This model was constructed and verified by comparing the simulated and predicted PLR response with that of healthy participants. The least root-mean-square error (RMSE) of simulated PLR response was less than 0.7% when stimulus duration was under 3 ms. The RMSE of predicted PLR response increased by approximately 6.76%/s from the stimulus duration of 1 ms to 3 s, when the model directly used the parameters extracted from the PLR at the stimulus duration of 10 ms. When model parameters were derived from the regression by the measured PLR response, the RMSE kept under 8.5%. The model was applied to explore the PLR abnormalities of the people with Diabetic Mellitus (DM) by extracting the model parameters from 42 people with DM and comparing these parameters with those of 42 healthy participants. The parameter in the first-order term of the elastic force of the participants with DM was significantly lower than that of the healthy participants (p &lt, 0.05). The sympathetic force and sympathetic action delay of the participants with DM were significantly larger (p &lt, 0.05) and longer (p &lt, 0.0001) than that of the healthy ones, respectively. The reason might be that the sympathetic nervous system, which controls the dilator muscle, degenerated in diabetic patients.

Diabetic autonomic neuropathy has been proved to be associated with onset of heart failure in patients with diabetes. However, relationship between sudomotor dysfunction, the early manifestation of autonomic neuropathy, and cardiac diastolic function has not yet been investigated. This study aimed to explore the association between sudomotor function and cardiac diastolic function in patients with type 2 diabetes mellitus (T2DM). A total of 63 patients (65% male, 50±13 years old) with T2DM were enrolled and divided into two groups according to mean feet electrochemical skin conductance (ESC) assessed by sudoscan device: sudomotor dysfunction group(SDF group: ESC≤60 μS) and normal sudomotor function group (NSF group: ESC>60 μS). Impaired cardiac diastolic function detected by tissue Doppler imaging echocardiography manifested as elevations of late atrial (A) transmitral peak flow velocity (LgA) and the early (E) transmitral peak flow velocity/early diastolic velocity (e’) (E/e’ratio). The prevalence of sudomotor dysfunction was 30.2%. In SDF group, LgA and E/e’ ratio were significantly higher than those in NSF group (-0.2±0.2 m/s vs. -0.4±0.3 m/s, P=0.011 and 11.0±3.8 vs. 8.8±2.7, P=0.013, respectively). Pearson correlation analysis revealed that LgA was negatively correlated with mean feet ESC(r=-0.3, P=0.017). In logistic regression analyse, LgA (OR=0.05, 95%CI 0.004-0.585, P=0.017) and E/e‘ ratio (OR=0.79, 95%CI 0.641-0.970, P=0.025) were found to be independently associated with presence of sudomotor dysfunction. Cardiac diastolic function significantly decreased in type 2 diabetic patients with sudomotor dysfunction. Disclosure X. Chen: None. X. Yang: None. W. Xu: None. H. Deng: None. J. Wu: None. J. Yan: None. B. Yao: None. Funding Natural Science Foundation of Guangdong Province (2018A030313915); Medical Scientific Research Foundation of Guangdong Province (A2018286)

Background: There are many methods to diagnose diabetic autonomic neuropathy (DAN); however, often, the various methods do not provide consistent results. Even the two methods recommended by the American Diabetes Association (ADA) guidelines, Ewing's test and heart rate variability (HRV), sometimes give conflicting results. The purpose of this study was to evaluate the degree of agreement of the results of the Composite Autonomic Symptom Score 31 (COMPASS-31), skin sympathetic reaction (SSR) test, Ewing's test, and HRV in diagnosing DAN.Methods: Patients with type 2 diabetes were recruited and each received the COMPASS-31, SSR, Ewing's test, and HRV for the diagnosis of DAN. Patients were categorized as DAN(+) and DAN(–) by each of the tests. Kappa consistency tests were used to evaluate the agreement of diagnosing DAN between any two methods. Spearman's correlation test was used to evaluate the correlations of the severity of DAN between any two methods. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic value and the cutoff value of each method.Results: A total of 126 type 2 diabetic patients were included in the study. The percentages of DAN(+) results by HRV, Ewing's test, COMPASS-31, and SSR were 61, 40, 35, and 33%, respectively. COMPASS-31 and Ewing's test had the best agreement for diagnosing DAN (κ = 0.512, p < 0.001). COMPASS-31 and Ewing's test also had the best correlation with respect to the severity of DAN (r = 0.587, p < 0.001). Ewing's test and COMPASS-31 had relatively good diagnostic values (AUC = 0.703 and 0.630, respectively) in the ROC analyses.Conclusions: COMPASS-31 and Ewing's test exhibit good diagnostic consistency and severity correlation for the diagnosis of DAN. Either test is suitable for the diagnosis of DAN and treatment follow-up.

Diabetic neuropathy is a neurodegenerative disorder that may alter both the somatic and autonomic peripheral nervous systems in the context of diabetes mellitus (DM). It is a prevalent and burdensome chronic complication of DM, that requires timely management. Optimized glycemic control (mainly for type 1 DM), multifactorial intervention (mainly for type 2 DM), with lifestyle intervention/physical exercise, and weight loss represent the basis of management for diabetic distal symmetrical polyneuropathy, and should be implemented early in the disease course. Despite better understanding of the pathogenetic mechanisms of diabetic peripheral neuropathy, there is still a stringent need for more pathogenetic-based agents that would significantly modify the natural history of the disease. The paper reviews the available drugs and current recommendations for the management of distal symmetrical polyneuropathy, including pain management, and for diabetic autonomic neuropathy. Evaluation of drug combinations that would perhaps be more efficient in slowing the progression of the disease or even reversing it, and that would provide a better pain management is still needed.

IntroductionA high proportion of people with diabetes experience gastrointestinal (GI) symptoms, which may be manifestations of diabetic autonomic neuropathy (DAN). The current treatment regime is ineffective and associated with major side effects. Transcutaneous vagal nerve stimulation (tVNS) is a new therapeutic option, which has been shown to increase GI motility and reduce inflammatory responses. As vagus is the main neuronal pathway for extrinsic coordination of GI secretion and motility, we hypothesise that tVNS will improve DAN-induced GI symptoms in subjects with diabetes.Methods and analysisThe DAN-VNS study is a randomised multicentre clinical trial investigating the effect of short-term, high intensity as well as long-term, medium-intensity tVNS on GI symptom alleviation in 120 subjects with diabetes. The primary outcome consists of changes from baseline in subjective ratings of symptom severity. Secondary outcomes include changes in gastric motility and GI transit time measured by MRI and wireless motility capsule. Moreover, cardiovascular and sudomotor function, glycaemic control, brain sensory processing and presence of low-grade inflammation will be investigated as secondary outcome measures. Lastly, 15 responders of tVNS treatment will be included in an explorative, randomised, cross-over study, in which the acute endocrine and metabolic response to short-term tVNS will be investigated.Ethics and disseminationThe study has been approved by the North Denmark Region Committee on Health Research Ethics (N-20190020). Results will be published in relevant international peer-reviewed journals.Trial registration numberNCT04143269.

Diabetic autonomic neuropathy (DAN) is a common microvascular complication of diabetes mellitus (DM). The main clinical manifestations of DAN result from involvement of cardiac, gastrointestinal, and urogenital systems; sudomotor and ocular dysfunction are also common. Cardiac autonomic neuropathy (CAN) manifests with resting tachycardia, exercise intolerance, abnormal blood pressure regulation, and orthostatic hypotension; the Ewing tests are the proposed method for the assessment of CAN. The presence of CAN is associated with increased cardiovascular mortality. Optimization of glycemic control and symptomatic treatment are essential for the management of CAN. DAN can affect the gastrointestinal tract causing esophageal dysfunction, gastroparesis, and enteropathy. Exclusion of gastric obstruction is needed before testing for gastroparesis, while radiolabeled scintigraphy is the gold standard method for the diagnosis of gastroparesis. Dietary management and glycemic control are essential for the management of gastroparesis, while metoclopramide is the only FDA-approved medical drug for this disorder. Involvement of the urogenital tract manifests with bladder and sexual dysfunction in both genders. Phosphodiesterase type 5 inhibitors are the first-line treatment option for males with erectile dysfunction. Sudomotor dysfunction leads to dry skin, itching, anhidrosis, and gustatory sweating and is associated with the development of diabetic foot ulcers. Ocular dysfunction results in pupillomotor function impairment, reduced corneal sensation, and dry eyes.

Gastroparesis and other gastrointestinal motility diseases can be associated with various autonomic neuropathies. The gastrointestinal tract has its own enteric nervous system, a branch of the autonomic nervous system (ANS), and exchanges modulatory signals with the extrinsic autonomic systems. Autonomic neuropathies impairing functions of the extrinsic autonomic pathways can contribute to gastroparesis. Neurological evaluation is needed in patients with gastroparesis to assess systemic or extra-intestinal autonomic involvements as well as to identify an underlying neurological etiology. Self-assessed autonomic questionnaires such as composite autonomic symptom score (COMPASS) are feasible tools for such purposes. Autonomic reflex tests can localize impaired branches of the ANS and to support a diagnosis of autonomic neuropathy. Because autonomic reflex tests clinically available at most autonomic laboratories are relevant to cardiovascular and sudomotor (sweating) autonomic systems, findings of tests do not always have a strong association with the presence and severity of gastroparesis or other localized autonomic/neurological conditions. Skin biopsy to estimate sensory small-fibers in the epidermal layers and autonomic fibers innervating sweat glands is a pathological diagnostic method for small-fiber neuropathy. Autonomic neuropathies associated with gastroparesis include diabetic autonomic neuropathy, Guillain-Barre syndrome, autoimmune autonomic ganglionopathy, paraneoplastic autonomic neuropathy, hereditary amyloid neuropathy. Other autonomic disorders with or without evidence of peripheral autonomic nerve involvements such as postural orthostatic tachycardia syndrome are discussed. Ehlers-Danlos Syndrome is a hereditary connective tissue disorder with multiple subtypes but it is worth mentioning due to its high association with postural orthostatic tachycardia syndrome.

Diabetic autonomic neuropathy is an under-recognised complication of diabetes and the prediabetic state. A wide range of manifestations can be seen due to involvement of cardiovascular, gastrointestinal, genitourinary, sudomotor and neuroendocrine systems. Cardiac autonomic neuropathy is the most dreaded complication carrying significant mortality and morbidity. Early detection and control of diabetes and other cardiovascular risk factors is the key to treat and prevent progression of autonomic neuropathy. Recently, a new entity of treatment-induced neuropathy (TIND) of diabetes mellitus causing autonomic neuropathy is being increasingly recognised.

PURPOSE: Cardiovascular autonomic neuropathy (CAN) is one of the most common and serious complications associated with diabetes and is defined as the impairment of the autonomic control of the cardiovascular system, whose prevalence in Indian population has been reported to be > 50%. The risk factors associated with CAN include hyperglycemia, duration of diabetes, hypertension, dyslipidemia, and obesity. This study was conducted to examine the association of CAN with its determinants among diabetics. METHODS: Socio-demographic characteristics were noted alongwith performance of biochemical analyses of blood samples according to standard hospital pathology laboratory protocols. Clinical assessment of CAN comprised a of 5 indexes, including 3 heart rate variability parameters (resting tachycardia, Qtc interval > 440 msec, exercise intolerance) and 2 blood pressure parameters (orthostatic hypotension, abnormal hand gripping test). RESULTS: The odds of CAN increased with poor glycemic control (FBS ≥ 126 mg/dL (OR = 1.17 (1.02–10.68); 2 hr PPBS ≥ 200 mg/dL (OR 1.63 (1.26–8.82) and HbA1c ≥ 6.5% (OR = 10.68 (1.54–208.02). Significant difference was also found in relation to duration of diabetes, weight and body mass index of the participants with various grades of CAN. CONCLUSIONS: CAN is associated strongly with poor glycemic control. Obesity seems to be involved in the impairments of the cardiac autonomic function and this factor must therefore be taken into account in future studies when interpreting the results. Body mass control and glycemic control could provide an important approach to reducing CAN.

Orthostatic Intolerance (OI) refers to a heterogeneous group of disorders of hemodynamic regulation characterized by insufficient cerebral perfusion resulting in symptoms during upright posture relieved by recumbency. To our knowledge this would be the first case to describe a patient with type 1 diabetes mellitus (T1DM) who underwent bariatric surgery and developed debilitating OI. We describe the case of a 46 year old with class III obesity (BMI 42.9), T1DM, complicated by microalbuminuria, diabetic retinopathy, carpal tunnel syndrome, and HTN status post gastric sleeve surgery who presented to the emergency department 10 days after surgery for a syncopal episode, which resulted in head trauma. He endorsed multiple episodes of lightheadedness and falling after surgery. He lost 20 lbs in the first 10 days. His systolic blood pressure was 70 mmHg, however no other physical exam, laboratory, or imaging abnormalities were found. Thereafter he continued to have similar episodes and was only found to have a positive Tilt Test after extensive outpatient workup. He was started on midodrine 5 mg three times a day, fludrocortisone acetate 0.1 mg daily, and Pyridostigmine 60 mg three times a day with resolution of symptoms. There is a relationship between obesity and hypertension, possibly associated to its effect on the renin angiotensin aldosterone system, up regulation of sympathetic nervous system and simultaneous down regulation of parasympathetic nervous system. Bariatric surgery increases the risk of developing OI through the effects of weight loss itself, the type of procedure chosen and ultimately, vitamin deficiencies. Patients with diabetes are also at risk of developing OI following these procedures due to underlying Diabetic Autonomic Neuropathy (DAN) that had been masked by obesity related HTN. Physicians should be mindful of the risk of OI after bariatric surgery, especially in patients with possible underlying DAN. Close follow up is advised for these patients to avoid falls and trauma. Disclosure Z. Cardona: None. Y. Haider: None.

Background involvement of central and peripheral nervous systems are well-documented in SLE but literature on prevalence and pattern of autonomic neuropathy are few. Women with SLE have been found to have 5-8 fold increased risk of coronary heart disease. Autonomic dysfunction in the presence of structural cardiovascular disease is associated with adverse prognosis. Aim of the Work the purpose of this study is to evaluate the cardiovascular autonomic function in patients with Systemic lupus erythematosus, and to correlate it with SLE clinical features. Patients and Methods we conducted our study on one-hundred Egyptian SLE patients diagnosed according to SLICC classification criteria for SLE recruited from rheumatology outpatient clinic and inpatient department at Ain Shams University Hospitals. All the studied patients were subjected to history taking, clinical examination, and laboratory and radiological investigations related to SLE diagnosis and activity. SLE disease activity was assessed by SLE disease activity index-2000 (SLEDAI-2K).Tilt table test was used to assess for presence of cardiovascular autonomic neuropathy. Results we found that fifty (50%) of our SLE patients had symptoms suggestive for autonomic dysfunction, including orthostatic hypotension, palpitation and or Raynaud’s phenomenon. Regarding the result of tilt table test, sixty eight (68%) of the studied SLE patients were found to have positive tilt table responses. By doing the uni-variate analysis for predictors of SLE patients with positive tilt table test, we found that vasculitis, proteinuria, DNA, low TLC and complement levels, high SLEDAI, ESR and urinary P/C all were predictors for positivity of tilt table testing. Conclusion The prevalence of autonomic dysfunction was high among SLE patients.

Gastrointestinal autonomic neuropathy represents an important and diverse, but poorly appreciated, manifestation of diabetic autonomic neuropathy that impacts negatively on quality of life. There is no test to assess gastrointestinal autonomic nerve damage directly in humans; cardiovascular autonomic reflex tests are often used as a surrogate, but are suboptimal. Gastrointestinal symptoms are common in diabetes, but usually correlate only weakly with disordered motility. Diabetic gastroparesis, or abnormally delayed gastric emptying, occurs frequently and is the best characterized manifestation of gastrointestinal autonomic neuropathy. There is a bi-directional relationship between postprandial glycaemia and the rate of gastric emptying. However, autonomic neuropathy can affect the function of any gut segment from the esophagus to the anus. Current management options for gastrointestinal autonomic neuropathy are, for the main part, empirical and sub-optimal.

Diabetic autonomic neuropathy (DAN) is one of the least understood and attended complications which affects the quality of life. Increased oxidative stress, advanced glycation end products (AGEs), overactivation of protein kinase C (PKC) and reduced myoinositol content in autonomic nerves are major pathological conditions responsible for DAN. Limited treatment options appeal researchers to search for alternative treatments for DAN. Natural polyphenols are potent antioxidants and have been reported to have beneficial effects in above mentioned pathological conditions. Diabetes was induced in male Sprague Dawley rats weighing between 190-220 g with streptozotocin (55 mg/kg, i.p.). After 6 weeks of diabetes induction, animals were treated with catechin at dose 25 and 50 mg/kg for the next 28 days. Catechin treatment at dose 25 and 50 mg/kg showed significant improvement in body weight. The treatment with catechin at dose 50 mg/kg; significantly reduced heart hypertrophy (p 0.001) and plasma glucose levels (p 0.01). At dose 50 mg/kg catechin significantly improved hemodynamic parameters like heart rate, mean atrial pressure and left ventricular systolic pressure. Catechin also improved oxidative stress parameters in the nerves. Circulatory MMP-9 levels were significantly decreased (p 0.001) in catechin treated animals at a dose of 50 mg/kg. The histopathology results showed a significant reduction in neuronal damage due to catechin treatment for 28 days. The results of the study showed that catechin has a beneficial effect in the management of diabetic autonomic neuropathy in rats.

Aim This study evaluated the association of Heart rate variability (HRV) measurements with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. Methods This study included 102 Korean subjects with type 2 diabetes. The Michigan neuropathy screening instrument (MNSI) questionnaire score, the MNSI examination score (MNSIES) and the total symptom score were examined for DPN evaluation. Noninvasive HRV measurements were performed using photoelectric plethysmography. Patients with a MNSIES > 2 were considered to have DPN. Results The MNSIES showed significant negative associations with the high frequency (HF) (r = −0.212, p = 0.033) and low frequency (LF) (r = −0.286, p = 0.004) powers. Multiple linear regression analysis revealed that only HF power maintained a significant negative association with the MNSIES (β = −0.184; 95% CI −0.365 to −0.003; p = 0.047), after controlling for significant related confounders, with HRV parameters in male patients with type 2 diabetes. The HF (p = 0.010) and LF (p = 0.025) powers differed significantly between male patients without and those with DPN according to the MNSIES. Conclusions This study revealed a negative association of DPN, as assessed by the MNSIES, with HF power in male patients with type 2 diabetes. DPN defined by foot examination was predictive of cardiac autonomic neuropathy.

Diabetes has been one of the crucial diseases worldwide, which has to be controlled adequately for long years. It has three diabetic complications of micro-angiopathy such as neuropathy, retinopathy and nephropathy. Among them, Diabetic Peripheral Neuropathies (DPNs) are most prevalent to manage in primary care setting. In this article, recent topics concerning DPNs are introduced [1]. DPNs have a variety of symptoms and signs, then DPNs are often described in plural forms [2]. DPNs are classified into two categories, which are local and general. The former includes mononeuropathy and multifocal neuropathy. The latter includes diabetic polyneuropathy (DPN) and others. DPN has Distal Symmetric Polyneuropathy (DSPN) and Diabetic Autonomic Neuropathy (DAN) [2]. For examples, DSPN shows bilateral numbness of extremities and DAN shows Orthostatic Hypotension (OH).

Highlights • Cardiovascular autonomic nerve function (i.e. E/I ratio) deteriorates over time in type 1 diabetes. • HSP27, MIF and PAI-1 concentrations do not correlate with cardiovascular autonomic nerve function. • The change in HbA1c correlates negatively with the change in E/I over time. • Higher HbA1c is associated with worse cardiovascular autonomic nerve function., Aim Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.

Der Diabetes mellitus ist ein globales Problem zunehmenden Ausmases. Als Folge der Erkrankung treten Langzeitkomplikationen wie die autonome diabetische Neuropathie auf, die auch mit Funktionsstorungen im Urogenitaltrakt assoziiert ist. Dazu zahlen insbesondere Miktionsstorungen bzw. Blasenfunktionsstorungen. Obwohl Miktionsstorungen bei Menschen mit Diabetes haufig vorkommen, werden diese erst spat erkannt. Jedoch konnte bereits der Hausarzt oder der Diabetologe anhand einfacher Fragen durch ein jahrliches Screening diabetisch bedingte Miktionsstorungen fruhzeitig diagnostizieren und behandeln. Im Anfangsstadium der diabetischen Blasendysfunktion uberwiegen die irritativen Symptome. Nach einer gewissen zeitlichen Latenz, in der sogenannten Spatphase, treten uberwiegend obstruktive Symptome auf. Therapeutische Optionen sind nicht medikamentose und medikamentose Masnahmen.

Diabetic autonomic neuropathy (DAN) may contribute to significant morbidity, including orthostatic hypotension, arrhythmia, hypoglycemia unawareness, gastroparesis, enteropathy, urinary incontinence and sexual dysfunction in T1D. Contemporary data on DAN impact are scarce. We evaluated the frequency of DAN in adult T1D patients enrolled in the T1D Exchange Clinic Network using the validated Survey of Autonomic Symptoms (SAS). Surveys were emailed to registry participants who consented to be emailed about future studies. DAN was defined as a score >3 on the Symptom Score (SS). Severity of symptoms was graded with the Total Impact Score (TIS) defined as mild (≤25th percentile), moderate (≤50th percentile) and severe (≤75th percentile). Multivariable linear regression and stepwise logistic regression were used to analyze SAS-defined DAN and the correlations between DAN and glycemic control, medical comorbidities and socioeconomic factors. Among 965 T1D participants, DAN frequency was 17%, of which 76% presented with moderate and 24% with severe symptoms. Participants with DAN were older (44±16 vs. 39±17 years), were more often female (73% vs. 62%), had longer T1D duration (28±14 years vs. 23±14 years), and had higher hemoglobin A1c (8.1±1.7% vs. 7.7±1.5%) than those without DAN (all p-values Disclosure K.R. Mizokami-Stout: None. R. Bailey: None. N.C. Foster: None. L. Ang: None. G. Aleppo: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; Dexcom, Inc., Medtronic MiniMed, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Lilly Diabetes, Novo Nordisk Inc. C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan. M.R. Rickels: None. V.N. Shah: Advisory Panel; Self; Sanofi US. Consultant; Self; Dexcom, Inc. S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US. M. Katz: None. B.A. Nelson: None. A. Carlson: Consultant; Self; Sanofi US. Research Support; Self; Abbott, Dexcom, Inc., JDRF, Medtronic, National Institutes of Health, Novo Nordisk A/S. F. Vendrame: None. R. Pop-Busui: Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Diabetes is a metabolic disease leading to the development of numerous health complications. In developed countries, it is the main cause of blindness, end-stage renal disease, and non-traumatic amputation of the lower limbs. Neuropathy is the most common chronic complication of diabetes. A long-term course of a metabolically unbalanced disease causing damage to the autonomic nervous system of the digestive tract results in the development of many complications, such as intensification of gastro-oesophageal reflux disease, gastroparesis, chronic diarrhoea or faecal incontinence.

Urological complications in diabetes mellitus are very common; in fact, genitourinary complications are more common than diabetic neuropathy or nephropathy. These complications consist of sexual and urinary dysfunction, greatly impact quality of life, and result in increased morbidity. Diabetic autonomic neuropathy affects the entire autonomic nervous system and can lead to dysfunction of the cardiovascular, gastrointestinal, and genitourinary organ systems. Genitourinary dysfunction associated with diabetic autonomic neuropathy includes diabetic bladder dysfunction, sexual dysfunction, and recurrent urinary tract infections. While several studies have reported on genitourinary dysfunction in individuals with diabetes, UroEDIC, an ancillary study to the Diabetes Control and Complications Trial (DCCT) and its observational follow up, the Epidemiology of Diabetes Interventions and Complications study (EDIC), comprehensively characterized urologic complications in the cohort and examined the association between cardiovascular autonomic neuropathy and sexual and urinary dysfunction. UroEDIC demonstrated significant associations between autonomic neuropathy and urologic complications in type 1 diabetes, specifically erectile dysfunction, female sexual dysfunction, and lower urinary tract symptoms. In this narrative review, we review the current literature on urological complications in diabetes.

Background Few reports have evaluated the relationship between changes in postprandial blood pressure and the severity of autonomic dysfunction in patients with type 2 diabetes. This was a cross-sectional study designed to investigate postprandial blood pressure changes in individuals without type 2 diabetes and patients with type 2 diabetes and mild or severe cardiac autonomic dysfunction. Methods Forty patients with type 2 diabetes mellitus and 20 individuals without type 2 diabetes participated in this study. Fifty-two participants underwent a meal tolerance test. Blood pressure (brachial systolic blood pressure (bSBP) and central systolic blood pressure (cSBP)), electrocardiogram recordings, and blood samples were assessed before and after meal ingestion. Patients with diabetes were divided into two groups based on their coefficient of variation of R&ndash, R intervals (CVRR): a normal or mildly dysfunctional group (mild group, CVRR &ge, 2%, n = 20) and a severely dysfunctional group (severe group, CVRR &lt, n = 15). Results In the control group, bSBP and cSBP did not significantly change after meal ingestion, whereas both decreased significantly at 60 min after meal ingestion in the mild and severe groups. While blood pressure recovered at 120 min after meal ingestion in the mild group, a significant decrease in blood pressure persisted at 120 min after meal ingestion in the severe group. Conclusions Based on these results, adequate clinical attention should be paid to the risk of serious events related to postprandial decreases in blood pressure, particularly in patients with diabetes and severe cardiac autonomic dysfunction.

The brain-gut axis is a bidirectional nexus of the sensory input from the gastrointestinal (GI) tract and efferent pathways, which is involved in secretion of digestive hormones, homeostatic regulation and gut motility. This axis comprises among others the autonomic nervous system (ANS), comprising the enteric nervous system (ENS) and parasympathetic and sympathetic branches, which have a delicate regulatory interaction. Therefore, the ANS has an essential role, and any dysfunction leads to impaired mediation of visceral regulation. Consequently, damage to the ANS such as development of diabetic autonomic neuropathy (DAN) is one of the most burdensome complications to diabetes, yet frequently under-diagnosed. These complications cause symptoms in the GI tract such as nausea, vomiting, diarrhoea and constipation; see Fig. 54.1. It is difficult to diagnose DAN, but it may be defined as impaired functions of the involved nerves controlling the involuntary body functions such as the cardiovascular, urinary, pulmonary and digestive systems [1]. Cardiac autonomic neuropathy is a measureable impaired regulation of the heart function, leading to dysrhythmias such as atrial fibrillation, tachycardia and even cardiac arrest [2]. Patients with cardiac autonomic neuropathy develop an impaired adaptability of the heart rate, assessed as reduced heart rate variability [3]; see Chap. 59 for further elaboration. In this chapter we focus upon autonomic gastrointestinal neuropathy in patients with diabetes, explaining the underlying pathophysiology and the symptomatology in the GI tract.

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Gastroparesis is known as delayed gastric emptying in the absence of mechanical obstruction, typical symptoms being nausea, vomiting, bloating, early satiety, and upper abdominal pain. Gastroparesis is much prevalent in type 2 diabetes mellitus patients. Currently, methods used for the assessment of gastrointestinal (GI) motility involve radiation and invasiveness and are mostly limited to regional assessment, with a lengthy hospital stay, and most of the tests are even not standardized. Gastric emptying scintigraphy (GES) using a radiolabeled meal is the gold standard diagnostic test used to detect and quantify gastroparesis. The advantages of this test are physiological, economical, and non-invasive characteristics. However, lack of standardization poses radiation exposure. As diabetic patients already suffer from diabetic complications and comorbidities, availability of diagnostic tests by offering a non-radioactive, standardized, and ambulatory investigation may be a better alternative to GES to prevent unnecessary radiation exposure. This review summarizes the role of wireless motility capsule (WMC) in diagnosing gut diabetic autonomic neuropathy. The WMC is a novel technology that allows the physician to measure GI motility in a convenient, ambulatory, relatively non-invasive way, without exposing the patient to radiation. The WMC also established its diagnostic utility to assess diabetic gastroparesis in many multicentric studies; although it has some contraindications and limitations, it is the best available novel technology for diagnosing gut diabetic autonomic neuropathy.

Diabetic autonomic neuropathy includes damage of various organ systems. The manifestations of autonomic neuropathy usually occur in setting of distal sensory motor polyneuropathy but autonomic disorders may be presented disproportionately compared to sensory and motor disorders. Diabetic autonomic neuropathy increases the risk of cardiac arrhythmias and sudden death, significantly reduces the patients’ quality of life, and exacerbates other vascular complications of diabetes mellitus. There are cardiovascular, gastrointestinal and urogenital forms of diabetic autonomic neuropathy and damaged function of autonomic nerve fibers involving respiratory system, pupils, sudoriferous glands, thermoregulatory and endocrine system. Cardiovascular autonomic neuropathy is the most studied, clinically meaningful and prognostically pejorative form of autonomic neuropathy. Autonomous diabetic neuropathy can cause frequent emergency admissions of patients with this pathology, increased mortality in patients with diabetes, which requires informing of general practitioners, endocrinologists, and intensivists about the features of the clinical manifestations and course of this disease.

The article describes a variety of severe clinical manifestations of diabetic autonomic neuropathy in patients with type 2 diabetes mellitus and coronary heart disease. The peculiarity of this case is the simultaneous onset of autonomic neuropathy and lesions of the cardiovascular system, complications of untreated diabetes, without acute decompensation in carbohydrate metabolism.