Tamás Várkonyi

Diabetic neuropathy: new strategies for treatment

Current therapeutic possibilities can be divided into two groups: the pathogenetically oriented and the symptomatic therapy. One of the most important component of etiology‐based treatment is the stabilization of glycemic control. Based on efficacy and safety data benfotiamine and alpha‐lipoic acid should be considered as first choices among pathogenetically oriented treatments of diabetic neuropathy. Promising data were published about the aldose reductase inhibitor ranirestat. The symptomatic effect of antiepileptic drugs in diabetic painful neuropathy (DPN) is originated from several possible pharmacological properties. Pregabalin and gabapentin have the highest efficacy and the lowest frequency of adverse events among these drugs. Antidepressants also extensively used for symptomatic treatment in DPN. In the last years several studies were published about the benefial effect of duloxetine. Most likely combination therapy will be frequently applied in the future for the treatment of DPN, the optimal choice could be to combine pathogenetically oriented and symptomatic treatment.

Impaired Accommodation of Proximal Stomach in Patients with Alcoholic Liver Cirrhosis

Background: Impaired gastric emptying has previously been detected by ultrasonography in cirrhotic patients, and the role of the type of meal has also been discussed. While these earlier studies dealt with the distal part of the stomach, the aim of our study was to examine the effects of three different types of meal on the proximal stomach in cirrhotic patients. Methods: The proximal stomach was examined by ultrasonography in 15 healthy volunteers and in 21 alcoholic cirrhotic patients. The subjects received a liquid meal with a low calorie content and two different semisolid test meals with a low calorie content or high calorie and fat contents. The proximal gastric size was assessed by ultrasonography in a sagittal area and a frontal diameter. On the basis of assessment of the autonomic nervous function, the cirrhotic patients were divided into two groups: autonomic neuropathy positive and autonomic neuropathy negative. Results: The postcibal gastric size immediately after ingestion of the liquid test meal was significantly lower in the cirrhotic patients than in the healthy controls. In the healthy volunteers, the measures of the proximal gastric size were significantly higher than in either group of cirrhotic patients at t 0 , and at 10, 20 or 30 min after ingestion of a semisolid test meal with low calorie and fat contents. The proximal gastric sizes in the three groups of investigated subjects did not differ when the meal with high fat and calorie contents was tested. When the liquid meal was administered, the proximal gastric size was significantly lower in the cirrhotic patients with autonomic neuropathy. A significant intragroup difference was not observed when the semisolid meals were tested. Conclusions: This study reveals an impairment of the proximal stomach in alcoholic cirrhotic patients. The low calorie liquid meal distinguishes between the two groups of cirrhotic patients and healthy controls.

Somatosensory hypersensitivity in the referred pain area in patients with chronic biliary pain and a sphincter of oddi dysfunction: New aspects of an almost forgotten pathogenetic mechanism

BACKGROUND AND AIMS: Somatosensory hyperalgesia in the referred pain area (RPA) in patients with acute or chronic abdominal pain syndromes may result from the convergence of nerve fibers from visceral and somatic tissues at the spinal and supraspinal levels. Chronic biliary pain in patients with the postcholecystectomy syndrome (i.e., biliary hypersensitivity) may be explained by persistent hyperexcitability of neurons in the central nervous system (CNS). The aim of this study was to evaluate the cutaneous neural sensory perception in the RPA in patients with chronic postcholecystectomy biliary pain and a sphincter of Oddi (SO) dysfunction (SOD).METHODS: Forty-two patients with persistent biliary pain and suspected SOD, 27 age-matched healthy volunteers, and 18 age-matched asymptomatic cholecystectomized controls were prospectively investigated by quantitative sensory testing (Neurometer CPT). The biliary symptoms and the severity of pain were classified on a visual analog pain severity scale system via a previously validated and standardized questionnaire. The patients helped the doctors locate the RPA in the right upper quadrant. The sensory detection threshold was determined noninvasively (Neurometer CPT) with transcutaneous electrical stimulation at 5, 250, and 2,000 Hz, and different current intensities (range from 0.01 to 9.99 mA) applied in a single (patient) blinded method. These three frequencies selectively excite small unmyelinated (C fibers), small myelinated (A-delta), and large myelinated (A-beta) fibers, which transmit dull pain, sharp pain, and touch, respectively. The contralateral region of the abdomen left upper quadrant served as the control area. The sensory current perception threshold ratio (SCPTR) of the data measured in the contralateral area and the RPA was calculated.RESULTS: The SCPTRs in the definite SOD patients with biliary pain, healthy volunteers, the asymptomatic cholecystectomized controls, and the symptomatic cholecystectomized patients but without SOD were 2.32 ± 1.4 versus 1.06 ± 0.24 versus 0.97 ± 0.16 versus 0.83 ± 0.35 at 2,000 Hz; 2.19 ± 1.0 versus 1.01 ± 0.26 versus 1.02 ± 0.25 versus 0.88 ± 0.35 at 250 Hz; and 2.19 ± 1.1 versus 1.12 ± 0.26 versus 0.99 ± 0.37 versus 0.84 ± 0.32 at 5 Hz, respectively. Significant hypersensitivity was detected in the RPA at different stimulation frequencies in the SOD patients with biliary pain versus the cholecystectomized controls: at 5 Hz: P= 0.00001; at 250 Hz: P= 0.00001; and at 2,000 Hz: P= 0.0001, respectively.CONCLUSION: Continuous visceral pain (biliary pain) caused by local inflammatory/sensitizing processes or a CNS malfunction could lead to significant hypersensitivity of the peripheral nociceptive nerve fibers in SOD patients. Postcholecystectomy pain may be explained by persistent hyperexcitability of the nociceptive neurons in the CNS with or without objective motility disorders of the SO.

Correlations between aortic stiffness and parasympathetic autonomic function in healthy volunteers

Cardiovascular autonomic dysfunction and alterations in vascular elasticity are known complications of several disorders, including diabetes mellitus, hypertension, hypercholesterolemia, aging, and chronic kidney disease. The current study was designed to test whether a relationship existed between pulse wave velocity (PWV), augmentation index (AIx), aortic elastic properties, and cardiovascular autonomic function in healthy volunteers. The study comprised 25 healthy volunteers, whose aortic strain, distensibility, and stiffness index were measured by echocardiography, whereas PWV and AIx were evaluated by Arteriograph (TensioMed, Budapest, Hungary) in all cases. Autonomic function was assessed by means of 5 standard cardiovascular reflex tests. We found that heart rate response to deep breathing, as the most reproducible cardiovascular reflex test to characterize parasympathetic function, showed low to moderate correlations with PWV (r = -0.431, p = 0.032), aortic strain (r = 0.594, p = 0.002), distensibility (r = 0.407, p = 0.043), and stiffness index (r = -0.453, p = 0.023). Valsalva ratio and autonomic neuropathy score (ANS) correlated with PWV (r = -0.557, p = 0.004 and r = -0.421, p = 0.036, respectively) and AIx (r = -0.461, p = 0.020 and r = -0.385, p = 0.057, respectively), while ANS correlated with even aortic stiffness index (r = -0.457, p = 0.022). Cardiovascular reflex tests mainly characterizing sympathetic function had no correlation with aortic stiffness parameters (p = NS for all correlations). Correlations exist between parameters characterizing aortic elasticity and parasympathetic autonomic function, as shown by standard cardiovascular reflex tests in healthy volunteers.

Self-Monitoring of Blood Glucose in Diabetes: From Evidence to Clinical Reality in Central and Eastern Europe—Recommendations from the International Central-Eastern European Expert Group

Self-monitoring of blood glucose (SMBG) is universally considered to be an integral part of type 1 diabetes management and crucial for optimizing the safety and efficacy of complex insulin regimens. This extends to type 2 diabetes patients on intensive insulin therapy, and there is also a growing body of evidence suggesting that structured SMBG is beneficial for all type 2 diabetes patients, regardless of therapy. However, access to SMBG can be limited in many countries in Central and Eastern Europe. A consensus group of diabetes experts from 10 countries in this region (with overlapping historical, political, and social environments)--Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia, and Ukraine--was formed to discuss the role of SMBG across the spectrum of patients with diabetes. The group considered SMBG to be an essential tool that should be accessible to all patients with diabetes, including those with non-insulin-treated type 2 diabetes. The current article summarizes the evidence put forward by the consensus group and provides their recommendations for the appropriate use of SMBG as part of individualized patient management. The ultimate goal of these evidence-based recommendations is to help patients and providers in Central and Eastern Europe to make optimal use of SMBG in order to maximize the efficacy and safety of glucose-lowering therapies, to prevent complications, and to empower the patient to play a more active role in the management of their diabetes.

Diabetic Gastroparesis: Functional/Morphologic Background, Diagnosis, and Treatment Options

The regulation of gastrointestinal motility mainly involves the smooth muscle, neural (extrinsic and intrinsic), and hormonal elements, the glial cells, and the interstitial cells of Cajal. An orchestrated function of all these components is required for the appropriate propulsive movement of the food in the gastrointestinal tract. Gastroparesis, a pathological slowing-down of gastric emptying, is a result of the damage to the tissue elements involved in the regulation of motility. Gastroparesis is one of the well-known complications of long-standing diabetes mellitus. Although it is rarely a life-threatening complication, it has a deteriorating effect on the quality of life, leads to unpredictable oscillation of the blood glucose level, and increases the time required for the absorption of food and medicines. This review describes the clinical characteristics of diabetic gastroparesis and summarizes the organic and functional motility abnormalities caused by this complication. Finally, the currently available and potential future therapeutic approaches are summarized.

Diabetes-Related Dysfunction of the Small Intestine and the Colon: Focus on Motility

In contrast to gastric dysfunction, diabetes-related functional impairments of the small and large intestine have been studied less intensively. The gastrointestinal tract accomplishes several functions, such as mixing and propulsion of luminal content, absorption and secretion of ions, water, and nutrients, defense against pathogens, and elimination of waste products. Diverse functions of the gut are regulated by complex interactions among its functional elements, including gut microbiota. The network-forming tissues, the enteric nervous system) and the interstitial cells of Cajal, are definitely impaired in diabetic patients, and their loss of function is closely related to the symptoms in diabetes, but changes of other elements could also play a role in the development of diabetes mellitus-related motility disorders. The development of our understanding over the recent years of the diabetes-induced dysfunctions in the small and large intestine are reviewed in this article.

Severity of Autonomic and Sensory Neuropathy and the Impairment of Visual- and Auditory-Evoked Potentials in Type 1 Diabetes: Is there a relationship?

It became clear in the last decades that neuropathy is not a separate clinical entity, but a component of several related complications (1). Although the functional consequences of neuropathy are well defined in various organ systems, the relationship of the alterations in the networks of the neuronal system is still poorly documented. Assessment of the potential common alterations of the different neuronal functions in patients with diabetic neuropathy may provide new pathogenetic and diagnostic considerations. Previously, we observed correlations between the delay of certain auditory-evoked potentials and the severity of autonomic and peripheral sensory neuropathy in patients with type 1 diabetes (2). In addition, we found a relationship between the latency of visual-evoked potentials and the peripheral neuronal function (3). The aims of this study were to analyze the possible correlations between the central auditory and visual afferentations and the severity of autonomic and sensory neuropathy in patients with long-standing type 1 diabetes. A total of 10 middle-aged type 1 diabetic patients …

Correlations between Arteriograph‐derived pulse wave velocity and aortic elastic properties by echocardiography

Introduction:  There is an increased scientific interest on the evaluation of parameters characterizing aortic elasticity. The current study was designed to compare two characteristics of aortic distensibility: Arteriograph‐derived pulse wave velocity (PWV) and augmentation index standardized to 80 per minutes heart rate (AIx80) and aortic elastic properties by echocardiography.

Brainstem auditory-evoked potential examinations in diabetic patients

Brainstem auditory-evoked potential (BAEP) examinations were performed in 15 patients with long-standing type-1 diabetes mellitus (DM). Cardiovascular reflex tests were applied for assessment of autonomic neuropathy. The aim of our investigation was to compare the BAEP results of this patient group with controls and to look for a possible correlation between the alteration of the auditory brainstem function and the cardiovascular autonomic neuropathy. Analysis of the latencies (waves I, II, III and V) and the inter-peak latencies (waves I-III and I-V) of BAEPs revealed a significant difference between diabetics and healthy controls. The amplitudes of waves I, III and V were definitely lower in comparison with those of healthy controls. A positive correlation was observed between the overall autonomic score and the latencies (waves III and V) and inter-peak latencies (waves I-III and I-V). These data support the hypothesis that long-standing DM and diabetic neuropathy might be related as a cause of certain dysfunctions of the central auditory pathways.