Background and Objectives: To determine whether continuous glucose monitoring (CGM)-derived metrics can differentiate between normoglycemia, increased diabetes risk (FINDRISC+) and prediabetes and to assess whether CGM-derived metrics provide additional discriminatory information beyond conventional laboratory markers. Materials and Methods: In this cross-sectional study, 41 adults without diabetes were classified as normoglycemic controls (HbA1c < 5.7%, FINDRISC < 12), individuals at increased diabetes risk (HbA1c < 5.7%, FINDRISC ≥ 12), or individuals with prediabetes (HbA1c 5.7-6.49%). All participants underwent 14-day CGM. Mean interstitial glucose, glycemic variability (SD, CV) and time in, above and below range (TIR, TAR, TBR) were analyzed. Group differences were assessed using ANOVA or non-parametric tests; correlations were evaluated using Pearson analysis. Results: HbA1c differed significantly across groups (F = 17.62; p < 0.001). Among CGM metrics, only mean interstitial glucose differed (F = 3.54; p = 0.039), driven by higher values in the prediabetes group. Glycemic variability and time-based metrics did not differ significantly. Substantial overlap was observed between the increased risk and prediabetes groups. No significant correlation was found between HbA1c and mean CGM glucose (r = 0.164; p = 0.30). Conclusions: In this exploratory cohort, short-term CGM-derived metrics provided limited additional discriminatory information beyond conventional laboratory markers and clinical risk assessment. Larger prospective studies are needed to determine the discriminatory and predictive value of CGM in early metabolic risk states.

IntroductionInsulinoma is a rare neuroendocrine tumor characterized by episodes of hypoglycemia. Peripheral neuropathy associated with hypoglycemia is an uncommon complication of insulinoma, and its reversibility remains a subject of debate within the literature.Case reportWe describe the case of a 22-year-old female patient diagnosed with a solitary pancreatic insulinoma. The patient experienced recurrent episodes of headache, blurred vision as well as numbness, tingling and burning pain of the limbs over a period of 6 to 12 months prior to definitive diagnosis. Electrophysiological investigations revealed findings consistent with multiple radiculopathies and a motor-predominant axonal sensorimotor polyneuropathy primarily affecting the upper limbs. The biochemical diagnosis of endogenous hyperinsulinemic hypoglycemia was confirmed through a supervised standard 72-hour fasting test. Abdominal computed tomography imaging identified a contrast-enhancing tumor at the pancreatic body-tail transition. The patient underwent a laparoscopic distal pancreatectomy with splenectomy. Postoperative follow-up revealed prompt resolution of hypoglycemia, alongside improvement in dysesthesia and sensory deficit in the extremities as well as most neurophysiological parameters. However, tendon reflexes remained diminished, and subtle distal-predominant lower limb weakness and gait imbalance persisted for several months postoperatively.DiscussionThis case underscores the importance of recognizing a rare neural complication associated with insulinoma. The incomplete resolution of neurological symptoms and neurophysiological abnormalities highlights the potentially lasting impact of recurrent severe hypoglycemia on peripheral neural function.

IntroductionIn prediabetes and in individuals at increased risk of diabetes, data on the relationship between continuous glucose monitoring (CGM)-derived glycaemic burden and autonomic neural dysfunction remain limited. Therefore, the objective of the present study was to investigate whether early neuropathic changes in these populations are related to short-term glycaemic variability or broader metabolic risk.Materials and methodsIncreased risk of prediabetes was defined by the Finnish Diabetes Risk Score (HbA1c<5.7% and FINDRISC ≥12 points: n=14; controls <12 points, n=12; and prediabetes by HbA1c 5.70–6.49% (n=15); total number of participants n=41). Associations between metabolic status, CGM-derived metrics and autonomic function (RMSSD, pNN50, E/I ratio) were assessed using univariable and multivariable models. Cardiac autonomic neuropathy (CAN) was analysed by logistic regression, metabolic status by multinomial regression.ResultsCAN was present in 16 participants (39%). Age showed a borderline association with autonomic neuropathy (OR = 1.06 per year; p=0.059), which was attenuated after adjustment for metabolic status. Both increased risk of prediabetes and prediabetes groups were significantly associated with older age (RRR = 1.11 and 1.43 per year; p=0.03 and p=0.002, respectively). In regression models, increased prediabetes risk (OR ~8.4) and prediabetes (OR ~7.0) status emerged as potential determinants of CAN independent of age, although confidence intervals were wide. Among CGM-derived metrics, only mean interstitial glucose differed across metabolic groups, while no glycaemic marker was associated with CAN.ConclusionIn this exploratory pilot cohort, CAN appeared to be more closely associated with metabolic risk status than with short-term glycaemic variability. CGM-derived metrics did not predict autonomic or sensory neuropathy, suggesting that early neural impairment in prediabetes and increased diabetes risk may be more closely linked to broader metabolic risk factors beyond short-term glycaemic variability. Larger longitudinal studies are warranted.

[This corrects the article DOI: 10.3389/fcdhc.2026.1875311.].

Introduction:In patients with type 2 diabetes, factors beyond hyperglycemia may contribute to the development of sensory neuropathy. This study aimed to determine whether diabetes duration was the strongest predictor of prevalent sensory neuropathy and to compare the diagnostic performance of commonly used clinical screening methods. Materials and methods:A total of 711 patients with type 2 diabetes from the Budapest metropolitan area were assessed between 2016 and 2022 using routine sensory neuropathy screening tests (128-Hz tuning fork and 10-g monofilament). A brief standardized questionnaire was also administered to support neuropathy detection. Independent predictors of sensory neuropathy were identified using binary logistic regression models and interrater agreement between diagnostic methods was assessed with Cohen's kappa. Results:Agreement between diagnostic methods was only moderate (Cohen's kappa: 0.3-0.4). In the final adjusted models, age emerged as the only independent predictor of neuropathy detected by tuning fork testing (OR 1.04; 95% CI 1.02-1.06), whereas for the monofilament test, self-reported neuropathic symptoms remained independently associated. Consistent with this, positive responses to standardized symptom questions correlated with both diagnostic tests, supporting their clinical validity. Conclusion:The overlap between routinely applied clinical methods for detecting sensory neuropathy is limited. Our findings suggest that, in an aging population with type 2 diabetes, peripheral nerve damage identified by standard screening tools is more strongly associated with age than with diabetes duration when assessed by commonly used bedside screening tools. Prospective studies are warranted to better differentiate diabetic neuropathy from age-related nerve dysfunction.

The management of type 2 diabetes (T2D) has recently witnessed a paradigm shift extending beyond blood glucose regulation towards cardiovascular and renal health targeted by cardiovascular outcome trials (CVOTs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Preclinical studies suggest a potential role for GLP-1RAs and SGLT2i in the treatment of diabetic neuropathy and neuropathic pain. However, to date largely only small-size phase II shorter-term randomized controlled trials (RCTs) of heterogeneous designs and quality have been performed, without clear evidence of favorable effect of both GLP-1RAs and SGLT2i on clinical and neurophysiological neuropathic outcomes. Moreover, responses to GLP1-RA and SGLT2i treatments in real‑world clinical practice appear heterogeneous, with relatively high rates of non-responders and discontinuation. Several possible risks associated with GLP-1RAs and SGLT2i treatment in real-world practice have been identified requiring increased attention by physicians, their professional societies, and patients alike. Unfortunately, the opportunity has been missed to use simple tools for the detection and monitoring of diabetic sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in the multiple published large-scale pivotal CVOTs. Diabetic neuropathy is linked to considerable patient burden and mortality, and there remains an unmet need for the disease modifying effects of novel pharmacotherapies derived from the pathogenetic concepts of diabetic neuropathy. In the future, when designing and conducting RCTs more emphasis should be placed on considering neuropathy as a serious and potentially life-threatening complication.

Diabetic neuropathy is a frequent and disabling complication of diabetes, encompassing distal symmetric polyneuropathy and cardiovascular autonomic neuropathy, both associated with reduced quality of life and increased cardiovascular risk. Beyond its traditional interpretation as a direct consequence of chronic hyperglycaemia, oxidative stress has emerged as a central integrative mechanism linking metabolic overload, inflammation, mitochondrial dysfunction, and microvascular injury to progressive neural damage. These processes converge within the neurovascular unit, promoting a self-perpetuating cycle of axonal degeneration, impaired nerve perfusion and altered neuronal excitability. This narrative review synthesises experimental and clinical evidence on oxidative stress-related pathways implicated in diabetic neuropathy, including hyperglycaemia-activated metabolic routes, mitochondrial dysfunction, endoplasmic reticulum stress, and chronic inflammatory signalling. Classical antioxidant and mitochondrial-supportive interventions are evaluated alongside pleiotropic glucose-lowering agents, with particular emphasis on sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, integrating mechanistic insights with biomarker and clinical outcome data. Conventional antioxidant strategies, such as α-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and N-acetylcysteine, show reproducible benefits on neuropathic symptoms and oxidative stress markers, but evidence for sustained structural or disease-modifying effects remains limited. In contrast, incretin-based therapies and sodium-glucose cotransporter-2 inhibitors exert broader pleiotropic actions by attenuating oxidative and inflammatory signalling, improving mitochondrial homeostasis and endothelial function, with emerging evidence for modest but consistent neurophysiological and autonomic benefits. Overall, oxidative stress emerges as a key mechanistic hub in diabetic neuropathy. Future progress will depend on mechanism-aligned, neuropathy-specific clinical trials incorporating multidimensional endpoints and validated biomarkers.

Diabetic neuropathy may present with a wide spectrum of sensory manifestations in the oral cavity, ranging from increased sensitivity to pain to impaired nociception. Early detection is crucial, since the changes have significant effects on dental treatment, patient safety and quality of life. We describe two contrasting pictures of patients with diabetes mellitus with signs of oral sensory neuropathy. The first case was a 14-year-old female with poorly controlled type 1 diabetes mellitus (T1DM) presenting with chronic carious lesions, gingivitis, and angular cheilitis. She also had amplified pain reactions to dental procedures despite adequate local anaesthesia and quantitative sensory testing revealed hyperaesthesia related to early diabetic neuropathy. The second patient was a 55-year-old male with a long-term history of type 2 diabetes mellitus (T2DM) with chronic periodontitis and reduced oral sensitivity. He complained of hypoesthesia and reduced pain perception during dental procedures with evidence of established neuropathic involvement. These cases illustrate the broad spectrum of clinical manifestations of diabetic sensory neuropathy in stomatology from early hyperaesthesia in a child with T1DM to late hypoesthesia in an adult with T2DM and illustrate the importance of metabolic control, interdisciplinary collaboration and individualised diagnostic and therapeutic strategies in dentistry.

Diabetic neuropathy is a common and multifactorial complication of type 2 diabetes, in which genetic susceptibility is increasingly recognized as a contributing factor. This study (cross-sectional case-control) aimed to investigate the associations between previously identified genetic variants and clinically relevant neurophysiological and symptomatic parameters. A total of 48 individuals with type 2 diabetes (24 with neuropathy and 24 without) were included. Neuropathy was assessed using standardized neurological, sensory, and cardiovascular autonomic function tests. Genetic variants were selected in a prior discovery analysis of this same cohort and re-tested here, precluding independent validation. Associations between genetic variants and clinical parameters were assessed through group-based comparisons using Mann-Whitney U tests and Fisher's exact test, correlation analysis using Spearman's rank correlation, permutation-based testing to improve robustness, and multivariable linear regression adjusted for age and sex to account for potential demographic confounding (q < 0.1). Mann-Whitney U test analysis identified several associations between genetic variants and neuropathy-related clinical parameters. In the Mann-Whitney U test analysis, only the rs6682221 variant remained significantly associated with heat detection threshold in the left hand after false discovery rate correction (p = 0.000150; q = 0.02736), although this association did not remain significant in the complementary permutation analysis based on median differences. Spearman's rank correlation analysis identified a significant positive association between rs6682221 allele burden and heat detection threshold in the left hand, which remained significant after permutation correction (r = 0.552, p = 0.000086, q = 0.016). Multivariable regression adjusted for age and sex revealed several independent associations between selected variants and sensory neuropathy-related parameters. These findings should be considered exploratory, as all analyses were performed within the original discovery cohort and no independent validation cohort was available. Independent replication and functional studies are required before any clinical relevance can be inferred.

Painful diabetic peripheral neuropathy (PDPN) remains a serious complication of diabetes mellitus (DM). Recent clinical trials have demonstrated promising outcomes for pilavapadin (LX9211), an orally administered selective, potent inhibitor of adapter protein-2-associated kinase 1 (AAK1) and vixotrigine, a broad spectrum voltage-gated sodium channels (Navs) inhibitor. Their beneficial role was reflected in improved average daily pain (ADP) score and Patient Global Impression of Change (PGIC). Gamma-aminobutyric acid (GABA) receptor agonism has yielded favourable outcomes in preliminary studies. Experimental studies have further expanded the spectrum of potential agents, therapeutic targets and mechanisms in PDPN. Some of potential therapeutic approaches include chemokine suppression (CCR2/CCR5 or CXCR1/2 inhibition) and transient receptor potential vanilloid 1 (TRPV1) pathway suppression. Impaired mitochondrial function in PDPN is now being discussed and the inhibition of poly (adenosine diphosphate [ADP]-ribose) polymerase 1(PARP1), a mitochondrial enzyme responsible for deoxyribonucleic acid (DNA) repair is emerging. Local treatments have also been examined in animal models, such as resiniferatoxin. Limited evidence exists regarding the therapeutic potential of antidiabetic agents, glucagon-like peptide-1 receptor agonists (GLP-1RAs), being most widely studied in experimental settings. Future large clinical trials are now required to confirm the efficacy of novel promising agents and to delineate further potential favourable effects of antidiabetic agents in clinical settings.

The present study was conducted in type 1 diabetic (T1DM) patients to evaluate the metabolic and glycemic control as well as the manifestations of neuropathy. The impact of continuous glucose monitoring (CGM) on the measured parameters was also analyzed. A total of 61 T1DM patients (age: 42.5 ± 1.8 years, DM duration: 22.8 ± 1.6 years, mean ± SE) participated in the study. In total, 24 patients had CGM sensors and 37 did not. Cardiovascular autonomic neuropathy was assessed using cardiovascular reflex tests. Peripheral sensory function was evaluated by a Neurometer and calibrated tuning fork on the upper and lower limbs. Metabolic status was characterized by the determination of triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and glycated haemoglobin (HbA1c). A positive correlation was found between HbA1c and triglyceride levels (r = 0.28, p < 0.05). CGM users and non-users differed in triglyceride (0.9 ± 0.1 vs. 1.24 ± 0.12 mmol/L, p < 0.05), HDL cholesterol (1.7 ± 0.1 vs. 1.4 ± 0.1 p < 0.05 mmol/L), and HbA1c (7.5 ± 0.2 vs. 8.3 ± 0.3%, p < 0.05) levels as well. Significant differences were found for the Valsalva ratio, Neurometer, and calibrated tuning fork results between CGM users and non-users. This study found a significant correlation between HbA1c and triglyceride levels in T1DM. CGM use resulted in improved metabolic parameters and less autonomic and sensory nerve damage. As a novel finding, CGM is presumed to prevent both micro-, and macrovascular complications and, by this way, potentially reducing mortality rates.

Introduction:The global rise in obesity is linked to metabolic disorders, such as neuropathy and infertility. Our study aimed to analyze the effects of preconceptional weight loss in infertile women with obesity on peripheral sensory and cardiovascular autonomic nerve function, metabolic parameters, and the success of in vitro fertilization (IVF). Methods:A retrospective cohort study included women with obesity and infertility undergoing weight optimization before IVF, alongside age-matched controls. Clinical and laboratory parameters, cardiovascular autonomic and peripheral sensory function, and body composition were evaluated before and following weight loss therapy. Results:Patients with obesity [n=58; mean ± SD; age: 33.1 ± 5.42 years; body mass index (BMI): 39.3 ± 6.90 kg/m2] had higher resting blood pressure, prevalence of metabolic disorders, and medication usage than controls (n=45; age: 32.1 ± 7.67 years; BMI: 21.1 ± 2.02 kg/m²). Laboratory findings indicated differences in blood cell counts, glucose metabolism markers, kidney and liver functions, and lipid profile between the groups. Cardiovascular autonomic function tests indicated impairment in Valsalva-ratio (1.4 ± 0.22 vs. 1.5 ± 0.23, p<0.001) and 30/15 ratio (1.07 ± 0.12 vs. 1.12 ± 0.13, p<0.05) in patients with obesity. Peripheral sensory function tests revealed significant deterioration in vibration sense and the current perception threshold of the median nerve at 2000 Hz in patients with obesity, as compared to controls. Before and following weight loss therapy no statistically significant difference was found on cardiovascular autonomic and peripheral sensory function. Following weight loss therapy with lifestyle/dietary intervention and liraglutide, 16 female patients with obesity attended the follow-up measurement. They achieved significant weight reduction (104.3 ± 16.64 vs. 89.1 ± 15.74 kg; p<0.05) and 8 became pregnant (5 via IVF, 3 spontaneously). Conclusion:Peripheral sensory neuronal impairments were detected in infertile women with obesity compared to the controls with normal BMI. Cardiovascular autonomic dysfunction was revealed by 30/15 and Valsalva-ratio in patients with obesity, suggesting the presence of parasympathetic dysfunction. Preconceptional weight loss improved metabolic parameters. Of the infertile female patients with obesity who reached their preconceptional target weight, 18.75% achieved spontaneous pregnancy without IVF, and 62.5% of those who underwent IVF successfully conceived.

Introduction:Diabetic neuropathy may develop on a background of hyperglycaemia and is associated with increased oxidative stress. Elevated asymmetric dimethylarginine (ADMA) levels are linked to oxidative stress reducing the synthesis of nitric oxide (NO) by uncoupling NO synthase. Oxidative stress induces considerable changes in nerve conduction velocity in diabetic patients. There is strong evidence that α-lipoic acid (ALA) as an antioxidant may improve nerve conduction and relieve neuropathic symptoms. We aimed to investigate the relationship between endothelial dysfunction and NO synthesis in type 2 diabetic patients with peripheral neuropathy after ALA treatment. Material and methods:Fifty-four type 2 diabetic patients with neuropathy were included in the study. Serum ADMA concentration, intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), oxidised low-density lipoprotein (oxLDL), and TNF-α levels were determined with Enzyme-Linked Immunosorbent Assay (ELISA). Nitric oxide concentration was measured by Griess reaction. Peripheral sensory nerve function was assessed by current perception threshold (CPT) testing. Autonomic function was assessed by Ewing's five standard cardiovascular reflex tests composite autonomic score (CAS). Results:Asymmetric dimethylarginine levels were significantly decreased (0.62 ±0.11 vs. 0.53 ±0.11 µmol/l, p < 0.001), as well as TNF-α concentrations (1.21 ±0.42 pg/ml vs. 1.05 ±0.5 pg/ml, p < 0.05), while NO levels were significantly increased (16.78 ±11.1 vs. 21.58 ±8.84 µmol/l, p < 0.05) after 6-months of 600 mg/day ALA treatment. VCAM-1, ICAM-1, and oxLDL levels did not change significantly. The CPT and CAS significantly improved after ALA treatment. The improvement of CPT values was correlated positively with the change of ADMA levels (r = 0.58, p < 0.001). The change in ADMA level was more pronounced in responder patients based on both CPT and CAS. Conclusions:Our results suggest that ALA supplementation improves endothelial function characterised by serum levels of ADMA and TNF-α in patients with diabetic neuropathy. Changes in serum ADMA levels may predict the clinical response to ALA treatment.

A közlemény folytatása az azonos címmel 2024-ben megjelent első közleménynek, amelyben bemutattuk, hogy a magyar közfinanszírozott egészségügy 2019-ben 1 060 500 beteget látott el cukorbetegség miatt, akik közül több mint négyszázezren nem váltottak ki támogatott antidiabetikumot a vizsgálat évében. A jelen közlemény a támogatott vénykiváltásból való kimaradás fő okait, a támogatással kezelt cukorbetegekre fordított tb-kiadás fő kiadási tételeit, valamint a támogatással kiváltott hatóanyagok belső arányait tárgyalja. 2019-ben a támogatott antidiabetikumot kiváltó betegekre az országos (közvetlen az ellátottakra fordított) kiadás közel 20%-át fordította a NEAK (285 milliárd forint). Egy cukorbetegre az országos átlaghoz képest 2,6-szeres tb-kiadás jutott. A gyógyszertámogatás és az aktív fekvőbeteg-ellátás tette ki a közfinanszírozott ellátás legnagyobb részét (37,8%-ot, illetve 28,6%-ot), míg a labor- és a járóbeteg-kiadás ezek mellett eltörpült (1,5%-ot, illetve 6,5%-ot tett ki). A magyar cukorbetegek 65 év alatti halálozása az uniós átlaghoz képest magas. A közkiadás arányában jelentős mértékű tb-támogatás, amely azonban nem rendelkezik megfelelő preventív hatással, arra utal, hogy a megelőzést szolgáló egészségügyi teljesítmény elmarad a szükségletektől. A jelenlegi vizsgálat szerint a támogatott hatóanyag-kiváltásból kimaradó cukorbetegek (több mint 400 000 fő) közel fele-fele arányban vagy nem támogatott antidiabetikumot váltottak ki, vagy egyáltalán nem váltottak ki készítményt. A támogatással kezelt felnőttkorú cukorbetegek 96%-a 40 évesnél idősebb volt. A kezelt betegek legnagyobb része a legolcsóbbak közé tartozó metformin-monoterápiát (53,14%), szulfonilureát (34,84%) illetve drága, de életmentő inzulinkészítményt (31,74%) váltott ki. (Egy beteg többféle hatóanyagot is kiválthatott.) A szulfonilureát kiváltók 70%-a elmúlt 65 éves. A vizsgálat évében az inzulin bevezetését időben kitolni képes terápiák (metforminkombinációk, a DPP-4-gátló monoterápia, az SGLT-2-gátló monoterápia, valamint a GLP-1-receptoragonista monoterápiák) együttes támogatása az antidiabetikum-támogatás 38,5%-át tette ki. A támogatásból kiesők magas száma és a támogatott antidiabetikum-kiváltási arány megoszlása a hatóanyagcsoportok között együttesen veti fel a háziorvosi kompetencia fejlesztése, a hatóanyag-felírási jogosultság és a támogatási rendszer felülvizsgálatának szükségességét.

Background/Objectives: Diabetic sensorimotor polyneuropathy (DSPN) is a frequent microvascular complication of diabetes mellitus, associated with increased morbidity and reduced quality of life. The existing literature offers a limited understanding of sex-specific cardiovascular risk profiles and their association with DSPN, particularly within Central and Eastern European populations. Methods: A retrospective analysis was conducted using data from 621 individuals with type 1 or type 2 diabetes mellitus who underwent comprehensive neuropathy screening at the University of Debrecen between 2017 and 2021. The diagnosis of DSPN was made in accordance with international criteria, incorporating symptom scores, and electrophysiological measurements. Multivariate logistic regression was applied in order to identify independent predictors. Results: The diagnosis of DSPN was made in 444 individuals (71.5%), of whom 58.2% were female. Despite similar glycemic control (HbA1c: 7.81% in men vs. 7.65% in women, p = 0.297), men had significantly more frequent occurrences of previous myocardial infarction (11.8% vs. 5.0%, p = 0.008), peripheral vascular disease (19.9% vs. 12.7%, p = 0.041) and atherosclerosis (31.7% vs. 22.0%, p = 0.021). Multivariate analysis showed that female gender was independently associated with a lower incidence of DSPN (odds ratio [OR] = 0.592, 95% confidence interval [CI]: 0.369-0.950, p = 0.030), while diabetic retinopathy was a significant predictor (OR = 2.728, 95% CI: 1.300-5.725, p = 0.008). Electrophysiological testing revealed lower nerve conduction amplitudes in females for selected nerves. Conclusions: Our findings highlight sex-specific differences in neuropathy risk and support the implementation of individualized screening strategies in diabetic populations with region-specific risk factors.

The pathogenesis of diabetic neuropathy involves complex interactions between metabolic and genetic factors. This study aimed to identify novel genetic variants associated with neuropathy risk in type 2 diabetes through reanalysis of whole-exome sequencing data. We identified seven new SNPs with significant associations, including intronic variants in TTN, PLCB1, CCNI, and CDC34 and a 5'-upstream variant in BTG2. These variants are implicated in muscle elasticity, neurotransmission, endothelial regeneration, and apoptosis resistance, suggesting multifaceted genetic contributions to neuropathy development. These findings enhance our understanding of diabetic neuropathy and may support future advances in risk stratification and therapy development.

IntroductionA 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 methodsIn 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.Results71 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).ConclusionPeripheral 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.

Chronic kidney disease (CKD) affects approximately 13% of people globally, including 20%-48% with type 2 diabetes (T2D), resulting in significant morbidity, mortality, and healthcare costs. There is an urgent need to increase early screening and intervention for CKD. We are experts in diabetology and nephrology in Central Europe and Israel. Herein, we review evidence supporting the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for kidney protection and discuss barriers to early CKD diagnosis and treatment, including in our respective countries. SGLT2 inhibitors exert cardiorenal protective effects, demonstrated in the renal outcomes trials (EMPA-KIDNEY, DAPA-CKD, CREDENCE) of empagliflozin, dapagliflozin, and canagliflozin in patients with CKD. EMPA-KIDNEY demonstrated cardiorenal efficacy across the broadest renal range, regardless of T2D status. Renoprotective evidence also comes from large real-world studies. International guidelines recommend first-line SGLT2 inhibitors for patients with T2D and estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2, and that glucagon-like peptide-1 receptor agonists may also be administered if required for additional glucose control. Although these guidelines recommend at least annual eGFR and urine albumin-to-creatinine ratio screening for patients with T2D, observational studies suggest that only half are screened. Diagnosis is hampered by asymptomatic early CKD and under-recognition among patients with T2D and clinicians, including limited knowledge/use of guidelines and resources. Based on our experience and on the literature, we recommend robust screening programmes, potentially with albuminuria self-testing, and SGLT2 inhibitor reimbursement at general practitioner (GP) and specialist levels. High-tech tools (artificial intelligence, smartphone apps, etc.) are providing exciting opportunities to identify high-risk individuals, self-screen, detect abnormalities in images, and assist with prescribing and treatment adherence. Better education is also needed, alongside provision of concise guidelines, enabling GPs to identify who would benefit from early initiation of renoprotective therapy; although, regardless of current renal function, cardiorenal protection is provided by SGLT2 inhibitor therapy.