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.

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.

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.

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.

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.

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.

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.

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.

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.

Association of diabetes mellitus with depression, anxiety and quality of life / A diabetes mellitus kapcsolata a depresszióval, a szorongással és az életminoséggel

"Introduction: Many studies demonstrated that psychological factors play an important role in the development and course of diabetes mellitus. Objective: The focus of our research, among the first in a Hungarian sample, was to examine depression and anxiety levels and diabetes-specific quality of life in people with type 2 diabetes, to explore gender differences, and to analyze the relationship of depression and anxiety with diabetes-specific quality of life. Method: 157 people diagnosed with type 2 diabetes (women: 58.6%, men: 40.1%) were assessed for levels of depression Center for Epidemiologic Studies Depression Scale ­ Hungarian version), anxiety (Spielberger's Trait Anxiety Questionnaire) and diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life ­ Hungarian version). Results: 65% of subjects did not show depressive symptoms, but 56.1% showed moderate trait anxiety. More severe depressive symptoms (U = 1625, p<0.001) and higher trait anxiety (U = 1556, p<0.001) were significantly more frequent in women compared to men. Depressive symptom severity and trait anxiety were inversely and weakly correlated with diabetes-specific quality of life. Discussion: In summary, the results suggest that the psychological state (depressive symptoms and anxiety) in patients with type 2 diabetes is associated with their diabetes-specific quality of life. Women with diabetes also have higher levels of depression and anxiety compared to men with diabetes. Conclusion: Psychological assessment of patients' depressive and anxiety symptoms and quality of life is recommended in the care of diabetic patients, and appropriate treatment is recommended as needed. This may improve patients' quality of life, therapeutic cooperation and disease prognosis."

Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies.

Type 2 diabetes mellitus (T2DM) is one of the world's leading causes of death and life-threatening conditions. Therefore, we review the complex vicious circle of causes responsible for T2DM and risk factors such as the western diet, obesity, genetic predisposition, environmental factors, and SARS-CoV-2 infection. The prevalence and economic burden of T2DM on societal and healthcare systems are dissected. Recent progress on the diagnosis and clinical management of T2DM, including both non-pharmacological and latest pharmacological treatment regimens, are summarized. The treatment of T2DM is becoming more complex as new medications are approved. This review is focused on the non-insulin treatments of T2DM to reach optimal therapy beyond glycemic management. We review experimental and clinical findings of SARS-CoV-2 risks that are attributable to T2DM patients. Finally, we shed light on the recent single-cell-based technologies and multi-omics approaches that have reached breakthroughs in the understanding of the pathomechanism of T2DM.

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.

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.

Screening, diagnosis and management of diabetic sensorimotor polyneuropathy in clinical practice: International expert consensus recommendations.

Diabetic sensorimotor polyneuropathy (DSPN) affects around one third of people with diabetes and accounts for considerable morbidity, increased risk of mortality, reduced quality of life, and increased health care costs resulting particularly from neuropathic pain and foot ulcers. Painful DSPN is encountered in 13-26% of diabetes patients, while up to 50% of patients with DSPN may be asymptomatic. Unfortunately, DSPN still remains inadequately diagnosed and treated. Herein we provide international expert consensus recommendations and algorithms for screening, diagnosis, and treatment of DSPN in clinical practice derived from a Delphi process. Typical neuropathic symptoms include pain, paresthesias, and numbness particularly in the feet and calves. Clinical diagnosis of DSPN is based on neuropathic symptoms and signs (deficits). Management of DSPN includes three cornerstones: (1) lifestyle modification, optimal diabetes treatment aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, (2) pathogenetically oriented pharmacotherapy (e.g. α-lipoic acid and benfotiamine), and (3) symptomatic treatment of neuropathic pain including analgesic pharmacotherapy (antidepressants, anticonvulsants, opioids, capsaicin 8% patch and combinations, if required) and non-pharmacological options. Considering the individual risk profile, pain management should not only aim at pain relief, but also allow for improvement in quality of sleep, functionality, and general quality of life.

Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care.

Introduction: The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care. Patients and Methods: Twenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Results: T1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01). Conclusion: In this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Peripheral sensory nerve hyperaesthesia in women with polycystic ovary syndrome.

Dysfunction of the nervous system is well-known in diabetes and also among patients with prediabetes, obesity and hypertension. However, there is only a limited amount of data available on the changes in neuronal function in polycystic ovary syndrome (PCOs), despite the fact that this condition is also accompanied by metabolic and vascular abnormalities. The aim of our study was to assess the cardiovascular autonomic and peripheral sensory function in patients with PCOs. The study involved 27 women with PCOs, and 24 healthy women as control subjects. Autonomic neuropathy (AN) was assessed using the four standard cardiovascular reflex tests. Peripheral sensory function was determined using the Neurometer. Electric stimulation was applied transcutaneously and the current perception threshold (CPT) values were determined on the median and peroneal nerves. No significant differences were found between the PCOs patients and the control group regarding the cardiovascular autonomic reflex tests and the AN scores. The CPT values of PCOs patients in the median and peroneal nerves were lower at all frequencies in comparison to controls. Conclusions: The cardiovascular autonomic nerve function was normal in the patients with PCOs. The current perception thresholds were consequently lower in the PCOs patients both in the upper and lower extremities at all frequencies, which serves as an early sign of neuropathy. As a novel observation, our results suggest that early neuronal damage manifests in the form of sensory hyperaesthesia in patients with PCOs.

Diabetic Retinopathy Screening in Patients with Diabetes Using a Handheld Fundus Camera: The Experience from the South-Eastern Region in Hungary.

PURPOSE: Diabetic retinopathy (DR) is the leading cause of vision loss among active adults in industrialized countries. We aimed to investigate the prevalence of diabetes mellitus (DM), DR and its different grades, in patients with DM in the Csongrád County, South-Eastern region, Hungary. Furthermore, we aimed to detect the risk factors for developing DR and the diabetology/ophthalmology screening patterns and frequencies, as well as the effect of socioeconomic status- (SES-) related factors on the health and behavior of DM patients. METHODS: A cross-sectional study was conducted on adults (>18 years) involving handheld fundus camera screening (Smartscope Pro Optomed, Finland) and image assessment using the Spectra DR software (Health Intelligence, England). Self-completed questionnaires on self-perceived health status (SPHS) and health behavior, as well as visual acuity, HbA1c level, type of DM, and attendance at healthcare services were also recorded. RESULTS: 787 participants with fundus camera images and full self-administered questionnaires were included in the study; 46.2% of the images were unassessable. T1D and T2D were present in 13.5% and 86.5% of the participants, respectively. Among the T1D and T2D patients, 25.0% and 33.5% had DR, respectively. The SES showed significant proportion differences in the T1D group. Lower education was associated with a lower DR rate compared to non-DR (7.7% vs. 40.5%), while bad/very bad perceived financial status was associated with significantly higher DR proportion compared to non-DR (63.6% vs. 22.2%). Neither the SPHS nor the health behavior showed a significant relationship with the disease for both DM groups. Mild nonproliferative retinopathy without maculopathy (R1M0) was detected in 6% and 23% of the T1D and T2D patients having DR, respectively; R1 with maculopathy (R1M1) was present in 82% and 66% of the T1D and T2D groups, respectively. Both moderate nonproliferative retinopathy with maculopathy (R2M1) and active proliferative retinopathy with maculopathy (R3M1) were detected in 6% and 7% of the T1D and T2D patients having DR, respectively. The level of HbA1c affected the attendance at the diabetology screening (HbA1c > 7% associated with >50% of all quarter-yearly attendance in DM patients, and with 10% of the diabetology screening nonattendance). CONCLUSION: The prevalence of DM and DR in the studied population in Hungary followed the country trend, with a slightly higher sight-threatening DR than the previously reported national average. SES appears to affect the DR rate, in particular, for T1D. Although DR screening using handheld cameras seems to be simple and dynamic, much training and experience, as well as overcoming the issue of decreased optic clarity is needed to achieve a proper level of image assessability, and in particular, for use in future telemedicine or artificial intelligence screening programs.

Periodontal Disease in Diabetes Mellitus: A Case-Control Study in Smokers and Non-Smokers.

INTRODUCTION: It is well established that periodontal disease (PD) and diabetes mellitus (DM) can have a detrimental effect on each other's disease course, and that cigarette smoking exacerbates both conditions. However, literature on the periodontal status of smokers with DM is scarce, and the studies conducted to date did not use healthy controls or non-smokers with DM as controls. Consequently, the individual effects of smoking and DM on PD are difficult to untangle and estimate. METHODS: A total of 128 participants were recruited to this study and their data analyzed. They were assigned to four groups: smoking patients with DM (SDM); non-smoking patients with DM (NSDM); smokers without DM (control group, SC) and (4) non-smokers without DM (control group, NSC). Each group consisted of 32 age-matched participants. The periodontal status of the participants was assessed by full oral examination. To express periodontal status, we used the four-stage classification introduced by Fernandes and colleagues (J Periodontol. 80(7):1062-1068, 2009). The control of DM was estimated by measuring hemoglobin A1c (HbA1c) levels in the peripheral blood. RESULTS: A significant difference in the severity of PD was found between the SC and NSC groups (p = 0.027) and between the NSC and SDM groups (p = 0.000), while the difference between the NSDM and SDM groups approached significance (p = 0.052). No person in the smoker groups could be classified as having a healthy periodontal status. The four-stage classification followed a normal distribution in the healthy, non-smoking controls (NSC). Smoking caused a shift toward medium-severe PD, while a marked shift toward the most severe stage was observed when both smoking and DM were present (SDM). There was no significant association between the type of DM and periodontal status, nor between diabetes control and the severity of PD. Persons in the SDM group had significantly fewer teeth than those in the NSC group (mean ± standard deviation: 16.0 ± 7.9 vs. 20.7 ± 5.6; p = 0.02). CONCLUSION: Smoking damages the periodontium of even healthy individuals, but the damage is multiplied in a smoker who has DM, even though the effect of DM alone on periodontium health is relatively mild. Our results suggest a synergy between DM and smoking in terms of damage to the periodontal tissues, but the limited sample size of this study does not allow any hard conclusion to be drawn.

Simplifying Complex Insulin Regimens While Preserving Good Glycemic Control in Type 2 Diabetes.

INTRODUCTION: Type 2 diabetic patients suffering from severe hyperglycemia are often assigned a regimen involving multiple daily injections (MDI) of insulin. If the glucose toxicity resolves, the regimen can potentially be simplified, but there are no guidelines for this, and many patients are left on the MDI regimen. We aimed to prospectively examine the safety and efficacy of switching from MDI to once-daily IDegLira, a fixed-ratio combination of insulin degludec and liraglutide, in relatively well controlled (HbA1c ≤ 7.5%) subjects with type 2 diabetes on a low total daily insulin dose (TDD). METHODS: 62 adults with type 2 diabetes (baseline age 64.06 ± 10.24 years, HbA1c 6.42 ± 0.68%, BMI 33.53 ± 6.90 kg/m2, body weight 93.81 ± 19.26 kg, TDD 43.31 ± 10.99 IU/day, insulin requirement 0.47 ± 0.13 IU/kg, duration of diabetes 10.84 ± 7.50 years, mean ± SD) treated with MDI ± metformin were enrolled in our study. Previous insulins were stopped and once-daily IDegLira was started. IDegLira was titrated by the patients to achieve a self-measured pre-breakfast blood glucose concentration of < 6 mmol/L. RESULTS: After a mean follow-up period of 99.2 days, mean HbA1c had decreased by 0.30% to 6.12 ± 0.65% (p < 0.0001), body weight had decreased by 3.11 kg to 90.70 ± 19.12 kg (p < 0.0001), and BMI had reduced to 32.39 ± 6.71 kg/m2 (p < 0.0001). After 3 months of treatment, the mean dose of IDegLira was 20.76 ± 6.60 units and the mean insulin requirement had decreased to 0.23 ± 0.08 IU/kg. IDegLira ± metformin combination therapy was found to be safe and generally well tolerated. During the month before the baseline visit, 28 patients (45%) had at least one episode of documented or symptomatic hypoglycemia, while only 6 (9.67%) patients reported a total of 13 documented episodes during the follow-up. CONCLUSION: In everyday clinical practice, switching from low-dose MDI to IDegLira in patients with well-controlled type 2 diabetes is safe, may result in weight loss and similar or better glycemic control, and substantially reduces the insulin requirement. Simplifying complex treatment regimens decreases treatment burden and may improve adherence to therapy. CLINICAL TRIAL NUMBER: NCT04020445.

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.