Correlations between vegetative autonomic function and specific left atrial functions in healthy adults: Insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

INTRODUCTION: The functioning of the left atrium (LA) is partly controlled by the neural system. It was purposed to evaluate correlations between the result of Ewing's 5 standard cardiovascular reflex tests (SCRTs) characterizing autonomic function and LA volumetric and functional features as assessed by three-dimensional speckle-tracking echocardiography (3DSTE) in healthy individuals. MATERIALS AND METHODS: The current study comprised 18 healthy volunteers being in sinus rhythm (mean age: 35 ± 12 years, 10 men). Measurement of blood pressure, ECG, 5 SCRTs, two-dimensional Doppler echocardiography and 3DSTE were performed. These parameters were in normal ranges in all cases. RESULTS: From LA volumetric parameters, only systolic total atrial emptying fraction (r = 0.559, p = 0.037) and early diastolic passive atrial emptying fraction (r = 0.539, p = 0.047) correlated with systolic blood pressure response to standing representing sympathetic autonomic function. From LA strains, peak mean segmental LA radial strain (RS) (r = -0.532, p = 0.050), global and mean segmental LA circumferential strain (CS) (r = 0.662, p = 0.010 and r = 0.635, p = 0.015, respectively) representing systolic LA function correlated with Valsalva ratio representing parasympathetic autonomic function. Global LA-RS (r = -0.713, p = 0.040) and LA-CS (r = 0.657, p = 0.011) and mean segmental LA-CS (r = 0.723, p = 0.003) at atrial contraction representing end-diastolic atrial contraction showed correlations with Valsalva ratio, as well. Peak global and mean segmental LA-CS (r = 0.532, p = 0.050 and r = 0.530, p = 0.050) and the same strains at atrial contraction (r = 0.704, p = 0.005 and r = 0.690, p = 0.006) representing systolic function and end-diastolic atrial contraction correlated with systolic blood pressure response to standing representing both parasympathetic and sympathetic autonomic functions. CONCLUSIONS: Significant correlations between features of vegetative autonomic function represented by Ewing's 5 SCRTs and specific LA functions represented by 3DSTE-derived LA volume-based functional properties and strains could be demonstrated in healthy adults.

Autonomic function and specific right atrial functions - Is there a relationship? Correlations from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

INTRODUCTION: Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard cardiovascular reflex tests (SCRTs) and three-dimensional speckle-tracking echocardiography (3DSTE)-derived right atrial (RA) volumes and strains in healthy subjects. MATERIALS AND METHODS: The study comprised 45 healthy adults, but 5 subjects were excluded due to inferior image quality for 3DSTE-derived RA assessments. The remaining 40 individuals being in sinus rhythm had a mean age of 35.1 ± 3.5 years (20 men). Two-dimensional, Doppler, 3DSTE and SCRTs were performed in all cases. RESULTS: RA maximum volume and total and passive RA stroke volumes correlated with the Valsalva ratio. Active RA stroke volume and emptying fraction showed correlations with 30/15 ratio. Peak global and mean segmental RA circumferential (CS) and longitudinal strains (LS) showed correlation with the Valsalva ratio. At atrial contraction, global RA-LS and mean segmental RA-CS showed correlations with the Valsalva ratio. Moreover, mean segmental RA-CS correlated with 30/15 ratio and mean segmental RA radial strain showed correlations with systolic blood pressure in response to standing. Autonomic neuropathy score correlated with peak global RA-LS. CONCLUSIONS: Autonomic function parameters have significant associations with specific RA functions in healthy adults, making the latter possible indicators of autonomic dysregulation.

Bone Loss in Diabetes Mellitus: Diaporosis.

The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles.

Temporal Speech Parameters Indicate Early Cognitive Decline in Elderly Patients With Type 2 Diabetes Mellitus.

INTRODUCTION: The earliest signs of cognitive decline include deficits in temporal (time-based) speech characteristics. Type 2 diabetes mellitus (T2DM) patients are more prone to mild cognitive impairment (MCI). The aim of this study was to compare the temporal speech characteristics of elderly (above 50 y) T2DM patients with age-matched nondiabetic subjects. MATERIALS AND METHODS: A total of 160 individuals were screened, 100 of whom were eligible (T2DM: n=51; nondiabetic: n=49). Participants were classified either as having healthy cognition (HC) or showing signs of MCI. Speech recordings were collected through a phone call. Based on automatic speech recognition, 15 temporal parameters were calculated. RESULTS: The HC with T2DM group showed significantly shorter utterance length, higher duration rate of silent pause and total pause, and higher average duration of silent pause and total pause compared with the HC without T2DM group. Regarding the MCI participants, parameters were similar between the T2DM and the nondiabetic subgroups. CONCLUSIONS: Temporal speech characteristics of T2DM patients showed early signs of altered cognitive functioning, whereas neuropsychological tests did not detect deterioration. This method is useful for identifying the T2DM patients most at risk for manifest MCI, and could serve as a remote cognitive screening tool.

SGLT2 inhibitors in T2D and associated comorbidities - differentiating within the class.

BACKGROUND: For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME. EXPERT OPINION: To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence. CONCLUSION: CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.

[Treatment of osteomyelitis in diabetes mellitus. Case report]. / Diabetes mellitus talaján kialakult osteomyelitis kezelése.

The authors summarize the medical history of a patient with impaired healing of a wound in the sole of foot. The 63-year-old male patient had a second-degree burn in the sole of the left foot as he stepped on the hot concrete after taking off his slipper. On admission to our department, local wound management had already been started, his wound showed no healing tendency. Bilateral X-ray was performed of his left leg, osteomyelitis was not confirmed, soft tissue drainage was applied, and bacterial culture from the wound confirmed methicillin-resistant Staphylococcus aureus infection. After soaking the leg in water, phlegmon developed on the dorsal part of the foot and the patient had septic fever. X-ray was repeated, and osteomyelitis was confirmed. Enucleation of the hallux of the left foot and metatarsal resection were performed. Wound dressing was exchanged and wound toilette was applied daily, insulin therapy was modified after consultation with a diabetologist. 7 months after the surgery, the wound was completely healed, carbohydrate metabolism of the patient was controlled. Our case draws attention to the importance of informing the patients of potential complications - in this case of the diabetic foot and its proper care. Treatment of ulcer of the lower leg requires multidisciplinary care, which means that the diabetologist and the surgeon has to cooperate in the care of these patients, carbohydrate metabolism should be balanced and regular wound care is necessary. Orv Hetil. 2018; 159(42): 1727-1730.

Further Evidence for the Utility of Electrophysiological Methods for the Detection of Subclinical Stage Retinal and Optic Nerve Involvement in Diabetes.

OBJECTIVE: To assess the utility of visual electrophysiological methods, visual evoked potentials (VEPs) and pattern electroretinograms (PERGs) were recorded for the detection of subclinical optic nerve and retinal involvement in patients with diabetes mellitus. SUBJECTS AND METHODS: The data of 63 patients (126 eyes) with no vascular retinopathy or optic neuropathy were retrospectively analyzed. The patients were divided into polyneuropathic/nonpolyneuropathic groups to differentiate between early and late subclinical stages. The recorded parameters were compared with local reference values. RESULTS: 116 eyes (92%) had VEP and 76 (60%) had PERG abnormalities. The most frequent alteration was latency delay, but waveform and amplitude irregularities were also observed. The simultaneous use of the two methods allowed us to differentiate abnormal VEPs of purely optic nerve origin from those reflecting retinal involvement. CONCLUSIONS: We suggest that regular electrophysiological screening should receive more attention in the ophthalmological care of diabetic patients.

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.

[Frequency of T-cell mediated rejection in new-onset diabetes after kidney transplantation]. / T-sejt-mediált rejectio gyakorisága vesetranszplantáció után, újonnan kialakult diabetes mellitusban.

INTRODUCTION: New-onset diabetes is one of the most common complications after kidney transplantation. AIM: The aims of the authors were to examine the frequency of new-onset diabetes mellitus in kidney transplanted patients receiving cyclosporine A (n = 95) and tacrolimus (n = 102) and to analyze the occurrence of T-cell mediated rejection in these two groups of patients. METHOD: Age, laboratory results, renal function and histological findings were evaluated one year after kidney transplantation. Histological evaluation was performed according to the 2007 modification of the Banff 1997 classification. RESULTS: New-onset diabetes developed in 12% of patients receiving cyclosporine A-based immunosuppression and in 24% of patients taking tacrolimus (p = 0.002). Uric acid level (p = 0.002) and the age of the recipient (p = 0.003) were significantly different in the new-onset diabetic and non-diabetic groups, while renal function showed no significant difference. Evaluation of tissue samples revealed a significant difference in T-cell mediated rejection between the new-onset diabetic and non-diabetic groups (13 vs. 8 patients; 37% vs. 6%; p = 0.001). CONCLUSIONS: The results indicate an early development of the pathological effect of new-onset diabetes after kidney transplantation on the morphology of the renal allograft.

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.

Prevalence of exocrine pancreatic insufficiency in type 2 diabetes mellitus with poor glycemic control.

OBJECTIVES: To evaluate the relationship between exocrine pancreatic insufficiency and the level of glycemic control in diabetes (DM). METHODS: Patients with type 2 DM treated in our clinic were prospectively recruited into the study. Pancreatic diabetes was excluded. Cases with HbA1c ≥7% formed Group A (n = 59), and with HbA1c <7% Group B (n = 42). The fecal level of pancreatic elastase (PE-1) was measured and morphological examinations of the pancreas were performed. RESULTS: The PE-1 level was significantly lower in Group A than in Group B (385.9 ± 171.1 µg/g, vs. 454.6 ± 147.3 µg/g, p = 0.038). The PE-1 level was not correlated with HbA1c (r = -0.132, p = 0.187), the duration of DM (r = -0.046, p = 0.65), age (r = 0.010, p = 0.921), BMI (r = 0.203, p = 0.059), or pancreatic steatosis (r = 0.117, p = 0.244). The size of the pancreas did not differ significantly between Groups A and B. CONCLUSIONS: An exocrine pancreatic insufficiency demonstrated by fecal PE-1 determination is more frequent in type 2 DM patients with poor glycemic control. The impaired exocrine pancreatic function cannot be explained by an alteration in the size of the pancreas or by pancreatic steatosis.

Cardiovascular autonomic and peripheral sensory neuropathy in women with obesity.

Introduction: A higher incidence of neural dysfunction in people with obesity has been described. We determined the prevalence of neuropathic lesions in obese women and evaluated their potential association with anthropometric and laboratory parameters. Patients and methods: In our cross-sectional study, we enrolled female patients with obesity and without diabetes before obesity treatment. Voluntary female subjects were controls with a normal body mass index (BMI). Autonomic function was assessed by Ewing's cardiovascular reflex tests, while comprehensive peripheral neuropathic assessments were conducted utilizing the Neurometer®, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Sudomotor function was assessed by the Neuropad®-test. Body composition was examined using the InBody 770. Results: 71 patients (mean ± SD; age: 36.1 ± 8.3 years; BMI: 40.2 ± 8.5 kg/m2) and 36 controls (age: 36.4 ± 13.3 years; BMI: 21.6 ± 2.1 kg/m2) were enrolled. Patients had significantly higher systolic (patients vs. controls; 137.5 ± 16.9 vs. 114.6 ± 14.8 mmHg, p<0.001) and diastolic (83.0 ± 11.7 vs.69.8 ± 11.2 mmHg, p<0.001) blood pressure compared to controls. Among autonomic tests, only the heart rate response to Valsalva maneuver (Valsalva-ratio) revealed significant impairment in patients (1.4 ± 0.2 vs. 1.7 ± 0.4, p<0.001). Neurometer® at the median nerve revealed increased current perception threshold (CPT) values at all stimulating frequencies in patients (CPT at 2000 Hz: 204.6 ± 70.9 vs. 168.1 ± 66.9, p=0.013; 250 Hz: 84.4 ± 38.9 vs. 56.5 ± 34.8, p<0.001; CPT at 5 Hz: 58.5 ± 31.2 vs 36.9 ± 29.1, p<0.001). The Rydel-Seiffer tuning fork test has revealed a significant impairment of vibrational sensing on the lower limb in patients (right hallux: 6.8 ± 0.9 vs. 7.4 ± 0.8, p=0.030; left hallux: 6.9 ± 0.8 vs. 7.3 ± 0.9, p=0.029). The Neuropad® testing showed a significant impairment of sudomotor function in women with obesity. A negative correlation was found in patients between BMI and the 25-hydroxy-D3/D2-vitamin levels (r=-0.41, p=0.00126) and a positive correlation between the BMI and resting systolic blood pressure (r=0.26, p=0.0325). Conclusion: Peripheral sensory neuronal and sudomotor function impairments were detected in female patients with obesity compared to the controls with normal BMI. Cardiovascular autonomic dysfunction was also revealed by the Valsalva-ratio in these patients, suggesting the presence of parasympathetic dysfunction. The negative correlation between BMI and the 25-hydroxy-D3/D2-vitamin highlights the potential deficiency of vitamin D in the population affected by obesity.

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Investigation of cardiac autonomic and peripheral sensory neuropathy in diabetic and nondiabetic patients with hypertension.

Peripheral sensory function and cardiac autonomic neuropathy were studied in 18 nondiabetic and 10 type-2 diabetic hypertensives compared with 11 healthy controls. All the patients were treated with antihypertensive drugs. Cardiac autonomic neuropathy using Ewing method was detected in all patient groups. The current perception threshold values on peroneal nerve at 250 Hz in nondiabetic group and at 250 Hz and at 5 Hz in diabetic group were found increased compared with the controls. In conclusion, so-called typical complications of diabetes can be observed in nondiabetic hypertensives also. Our data might support the essential role of vascular factors in the development of neuropathy.

Perspectives on weight control in diabetes - Tirzepatide.

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (GIP/GLP-1 RA) improves glycemic control. Besides improvement of glycemic control, tirzepatide treatment is associated with significantly more weight loss as compared to potent selective GLP-1 receptor agonists as well as other beneficial changes in cardio-metabolic parameters, such as reduced fat mass, blood pressure, improved insulin sensitivity, lipoprotein concentrations, and circulating metabolic profile in individuals with type 2 diabetes (T2D). Some of these changes are partially associated with weight reduction. We review here the putative mechanisms of GIP receptor agonism contributing to GLP-1 receptor agonism-induced weight loss and respective findings with GIP/GLP-1 RAs, including tirzepatide in T2D preclinical models and clinical studies. Subsequently, we summarize the clinical data on weight loss and related non-glycemic metabolic changes of tirzepatide in T2D. These findings suggest that the robust weight loss and associated changes are important contributors to the clinical profile of tirzepatide for the treatment of T2D diabetes and serve as the basis for further investigations including clinical outcomes.

One-year safety and efficacy results of insulin treatment simplification with IDegLira in type 2 diabetes.

INTRODUCTION: This study aimed to investigate the sustained safety and efficacy of insulin treatment simplification with IDegLira in patients with type 2 diabetes and an HbA1c ≤ 7.5% (58 mmol/mol) during a 12-month follow-up. METHODS: Seventy-two adults with type 2 diabetes and an HbA1c ≤ 7.5% (58 mmol/mol) treated with multiple daily insulin injections (MDI) participated in the trial (age 63.8 ± 9.5 years, HbA1c 6.4 ± 0.7%, [46 ± 8 mmol/mol] body weight 92.95 ± 18.83 kg, total daily insulin dose: 43.21 ± 10.80 units; mean ± SD). Previous insulins were stopped, and once daily IDegLira was started. IDegLira was titrated by the patients to achieve a self-measured prebreakfast plasma glucose concentration of ≥5 mmol/L to ≤6 mmol/L. RESULTS: After 12 months, good glycaemic control was maintained, while body weight decreased significantly. Mean HbA1c changed to 6.2 ± 0.8% (44 ± 9 mmol/mol) (p = .109) and body weight changed by -3.89 kg to 89.06 ± 18.61 kg (p < .0001). The simplified treatment was safe and well-tolerated. Percentage of patients experiencing at least one episode of hypoglycaemia was 49% during the month before simplification and 17% during the last 3 months of the follow-up. CONCLUSIONS: Insulin treatment simplification with IDegLira in selected patients with type 2 diabetes is safe, maintains adequate glycaemic control and is associated with weight loss over 12 months.

A three-month physical training program improves cardiovascular autonomic function in patients with metabolic syndrome with and without diabetes - a pilot study.

Introduction: Vascular complications and neuropathy may develop in the presence of metabolic syndrome. The aim of our study was to measure the cardiovascular autonomic function following physical training in patients with metabolic syndrome with and without diabetes. Subjects and methods: 56 patients with metabolic syndrome (32 men/24 women, 40 non-diabetic patients (NDMetS)/16 diabetic patients (DMetS) [mean ± SD]: age: 50.35 ± 8.03 vs. 56.8 ± 9.30 years, p=0.023; baseline BMI: 32.2 ± 7.03 vs. 32.8 ± 5.94 kg/m2, p=0.739) were involved in our study. All tests and measurements were carried out before and following a 3-month physical training period. Autonomic function was assessed by means of five standard cardiovascular reflex tests. ECG repolarization parameters, including short-term QT variability and stress-ECG were also measured. Results: In the whole population, Valsalva-ratio (VR) and the autonomic score (AS) improved following training (VR: 1.49 ± 0.24 vs. 1.64 ± 0.34, p=0.001; AS: 2.05 ± 1.73 vs. 1.41 ± 1.36, p=0.015) accompanied by the significant decrease of the systolic (150.3 ± 16.12 vs. 134.1 ± 16.67 mmHg, p<0.001) and diastolic (90.64 ± 12.8 vs. 82.79 ± 11.1 mmHg, p<0.001) blood pressure. An improvement in VR was detected in NDMetS patients following training (1.51 ± 0.24 vs. 1.67 ± 0.31, p= 0.002). No significant changes could be detected in autonomic tests' results in the DMetS patient group following training. The applied exercise training program did not lead to significant changes in ECG repolarization. The stress-ECG test in the whole study population yielded a significant increase in the test duration (12.9 ± 3.76 vs. 15.1 ± 2.96 min, p<0.001) and in the test load (10.5 ± 2.78 vs. 11.6 ± 2.39 MET, p<0.001). The load capability improved significantly in both subgroups: 11.1 ± 2.04 vs. 12.1 ± 1.82, (p<0.001) and 9.0 ± 3.64 vs. 10.4 ± 3.05, (p=0.033) in subpopulations of NDMetS and DMetS, respectively. The DMetS patients achieved a significantly lower MET score at baseline (p=0.039) and following training (p=0.044) in comparison to the NDMetS patients. Conclusion: The three-month exercise program improved the Valsalva-ratio and the AN score in the MetS patients, that is potentially protective against cardiovascular events. The training had some beneficial effect on blood pressure and the results of the stress-ECG tests in both groups. The absence of significant change in the reflex tests in DMetS group reflects an impaired adaptation compared to the NDMestS group.

Paclitaxel Protects against Isoproterenol-Induced Damage in Rat Myocardium: Its Heme-Oxygenase Mediated Role in Cardiovascular Research.

(1) Background: In cardiovascular applications, paclitaxel inhibits smooth muscle cell proliferation and migration and significantly reduces the occurrence of restenosis and target lesion revascularization. However, the cellular effects of paclitaxel in the myocardium are not well understood; (2) Methods: Wistar rats were divided into four groups: control (CTRL), isoproterenol (ISO) treated (1 mg/kg) and two groups treated with paclitaxel (PAC), which was administrated (10 mg/kg/day) for 5 days by gavage/per os alone or in combination (ISO + PAC) 3 weeks after ISO treatment. Ventricular tissue was harvested 24 h later for measurements of heme oxygenase (HO-1), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), NF-κB, TNF-α and myeloperoxidase (MPO); (3) Results: HO-1 protein concentration, HO-1 activity, SOD protein concentration and total glutathione significantly decreased in response to ISO treatment. When PAC was administered in conjunction with ISO, HO-1, SOD concentration and total glutathione were not different from control levels. MPO activity, NF-κB concentration and TNF-α protein concentration were significantly increased in the ISO-only group, while the levels of these molecules were restored when PAC was co-administered; (4) Conclusions: Oral administration of PAC can maintain the expression of important antioxidants, anti-inflammatory molecules, HO-1, SOD and GSH, and suppress the production of TNF-α, MPO and NF-κB, which are involved in myocardial damage. The principal component of this cellular defense seems to be the expression of HO-1.

Improved glycemic control in pancreatic diabetes through intensive conservative insulin therapy.

OBJECTIVE: The aim of this study was to evaluate the effectivity and safety of insulin therapy in patients with DM secondary to underlying chronic pancreatitis with initially inappropriate glycemic control. METHODS: Pancreatic DM patients treated with oral antidiabetics (OAD) or pre-mixed insulin (PMI) with HbA1c ≥7.0% were recruited. Intensive conservative insulin treatment (ICT) (Group A, n = 16) or PMI (Group B, n = 8) was introduced instead of OAD, or the initial PMI therapy was switched to ICT (Group C, n = 10). The changes in HbA1c, fasting plasma glucose, body weight and hypoglycemic events from baseline to 2 years were followed. RESULTS: The patients in Group A and B had been treated with oral antidiabetics for 55 ± 68 months before switching to insulin therapy. The level of HbA1c had worsened from 8.3 ± 1.5% to 9.8 ± 1.7% during this period. The ICT had reduced HbA1c significantly from 9.7 ± 1.8% to 7.6 ± 1.4% after 12 weeks, in Group A, and five patients had HbA1c<7.0%. The introduction of PMI in Group B reduced HbA1c from 10.0 ± 1.4% to 9.0 ± 0.6% by 12 weeks. None of the patients had HbA1c<7.0%. By 12 weeks, the introduction of ICT in Group C had reduced the level of HbA1c from 8.8 ± 1.7% to 7.7 ± 1.2%. Two patients reached HbA1c<7.0%. There were two severe hypoglycemic episodes during the 2 years, one-one case in Group A and B. CONCLUSIONS: Oral medication becomes insufficient early in pancreatic DM. Long-term improvement of glycemic control can be achieved through intensified insulin therapy and in selected cases through PMI with a low risk of hypoglycemia.

The right atrium in young patients with type 1 diabetes mellitus: Insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

Introduction: Early onset of cardiomyopathy represented by myocardial volumetric and deformation properties is a major concern for patients with type 1 diabetes mellitus (T1DM). Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is a novel methodology with capability of 3D assessment of the right atrium (RA) via virtual models. The present study was designed for detailed comparative analysis of T1DM-associated RA volumetric and functional abnormalities to those of matched healthy controls to be examined by 3DSTE. Methods: The present study comprised of 17 patients with typical features of T1DM (mean age: 36.4 ±â€¯13.0 years, 59% males). Their results were compared to those of 31 age- and gender-matched healthy controls (mean age: 35.0 ±â€¯2.9 years, 61% males). Results: 3DSTE-derived RA volumes respecting the cardiac cycle and RA stroke volumes and emptying fractions did not show differences between young T1DM patients and matched controls. From peak RA strains representing RA reservoir function, mean segmental RA 3D strain proved to be significantly increased. Some regional basal/midatrial end-systolic peak RA strains were found to be significantly increased as well in T1DM patients as compared to controls. T1DM duration and HbA1c correlated with certain RA strains and RA volume-based functional properties. Conclusions: In young patients with T1DM, preserved RA volumes respecting the cardiac cycle are accompanied with increase in certain regional end-systolic peak RA strains, which seems to be associated with T1DM duration and HbA1c.