Aim: To describe the demographic and clinical characteristics of patients with Charcot neuro-osteoarthropathy (CNO) and to examine for differences between participants with Type 1 diabetes mellitus (DM) (T1DM) and Type 2 diabetes mellitus (T2DM). Materials and Methods: Multicenter observational study in eight diabetic foot clinics in six countries between January 1, 1996, and December 31, 2022. Demographic, clinical, and laboratory parameters were obtained from the medical records. Analyses were performed using parametric or nonparametric statistical tests for variables with normally or nonnormally distributed values, respectively. Comparisons of the qualitative data were performed using the chi-square test. Results: Seven hundred seventy-four patients with DM and CNO were included. The mean age at diagnosis of CNO was 54.5 ± 11.7 years, and the median (interquartile range (IQR)) diabetes duration at diagnosis of CNO was 15 (10-22) years. Among participants, 71.8% (n = 546) were male and 83.2% (n = 634) had T2DM. Neuropathy was present in 91.7% (n = 688), retinopathy in 60.2% (n = 452), and nephropathy in 45.2% (n = 337). Subjects with T1DM, compared to T2DM, were diagnosed with CNO at a younger age (46.9 ± 11.0 vs. 57.9 ± 10.2 years, p < 0.001), had longer diabetes duration (median value (IQR): 29.0 (21.0-38.0) vs. 14.0 (8.0-20.0) years, p < 0.001), and had more often microvascular complications (neuropathy, 95.2% in T1DM vs. 87.4% in T2DM, p = 0.006; retinopathy, 83.3% vs. 55.4%, p < 0.001; and nephropathy 67.5% vs. 40.5%, p < 0.001). Conclusions: CNO is predominant in males, occurs in long-standing DM, and is often accompanied by microvascular complications. People with T1DM, compared to those with T2DM, are affected at a younger age, have longer diabetes duration, and have more often microvascular complications.

• Klíčová slova
• Charcot joint, arthropathy neurogenic, diabetes mellitus Type 1, diabetes mellitus Type 2,
• MeSH
• diabetes mellitus 1. typu * epidemiologie   komplikace   MeSH
• diabetes mellitus 2. typu * epidemiologie   komplikace   MeSH
• diabetická noha epidemiologie   diagnóza   MeSH
• diabetická retinopatie epidemiologie   MeSH
• diabetické neuropatie epidemiologie   diagnóza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuropatická artropatie * epidemiologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

OBJECTIVE: patients with type 2 diabetes (T2DM) and obesity are generally known to have increased risk of various types of cancer, though studies addressing associations between T2DM/obesity and thyroid cancer are inconclusive. The aim of our study was to evaluate the risk of thyroid cancer focusing on diabetic patients under conditions of euthyroid status. A retrospective study in 184 patients was performed. Three cohorts were established according to tumor histology: malignant (M), benign (B) and low-risk carcinoma (MB). Fisher's exact test and Kruskal-Wallis one-way ANOVA of ranks were used for statistical analysis. The M (39.1 %), B (57.6 %) and MB (3.3 %) cohorts had comparable age (p=0.4), BMI (p=0.452), glycaemia (p=0.834), Hb1AC (p=0.157) and HOMA-IR (p=0.235). T2DM patients had larger thyroid gland volumes (28.8 vs 17.6 mL;p=0.001) compared to the cohort with normal glucose tolerance. Compared to women, men had more frequently present distal metastases (p=0.017), minimally invasive disease (p=0.027), more advanced staging (p=0.01) and positive pathogenic mutations in the TERT gene (p=0.009);these results were also significant for the diabetic male cohort (p=0.026). Type 2 diabetes and obesity are not risk factors for thyroid cancer, but a subgroup of males seems to have thyroid cancers of poorer prognosis. In general, diabetic patients with insulin resistance and hyperinsulinemia are also prone to have a goiter. KEY WORDS: Thyroid cancer, Type 2 diabetes, Obesity, Thyroid nodule, Insulin resistance.

• MeSH
• diabetes mellitus 2. typu * epidemiologie   komplikace   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy * epidemiologie   patologie   MeSH
• obezita * komplikace   epidemiologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

• Klíčová slova
• Diabetes mellitus, Diabetic kidney disease, Genetic predisposition, Genetic risk score, Single nucleotide polymorphism,
• MeSH
• celogenomová asociační studie MeSH
• chronická renální insuficience * genetika   patologie   MeSH
• diabetes mellitus 2. typu * genetika   komplikace   MeSH
• diabetické nefropatie * genetika   MeSH
• genetická predispozice k nemoci * MeSH
• genetické rizikové skóre MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci * MeSH
• rizikové faktory MeSH
• senioři MeSH
• sfingosin-N-acyltransferasa genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• sfingosin-N-acyltransferasa MeSH

UNLABELLED: This study aims to explore the correlation between renal blood perfusion (RBP) and diabetic nephropathy (DN). METHODS: A total of 72 mice included db/db and db/m mice at the ages of 6, 14, and 22 weeks, forming six groups. RBP was assessed using Laser Speckle Contrast Imaging (LSCI). Kidney function markers and the extent of pathological damage were evaluated. Pearson correlation analysis was employed to predict the relationship between RBP and various indicators of kidney damage. RESULTS: Compared to db/m mice of all ages, 6-week-old db/db mice showed no significant difference in kidney function markers and had no apparent pathological damage. However, db/db mice at other ages showed deteriorating kidney functions and evident pathological damage, which worsened with age. The RBP in db/m mice of all ages and 6-week-old db/db mice showed no significant difference; however, RBP in db/db mice demonstrated a significant declining trend with age. The correlation between RBP and kidney damage indicators was as follows: 24 h urinary microalbumin (r=-0.728), urinary transferrin (r=-0.834), urinary beta2-microglobulin (r=-0.755), urinary monocyte chemoattractant protein-1 (r=-0.786), Masson's trichrome staining (r=-0.872), and Periodic Acid-Schiff staining (r=-0.908). CONCLUSION: RBP is strongly correlated with the extent of diabetic kidney damage.

• MeSH
• diabetes mellitus 2. typu * komplikace   patofyziologie   MeSH
• diabetické nefropatie * patofyziologie   patologie   etiologie   MeSH
• experimentální diabetes mellitus komplikace   patofyziologie   MeSH
• ledviny patologie   krevní zásobení   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• renální oběh * MeSH
• stárnutí patologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• SGLT2 inhibitor, chronic kidney disease, dapagliflozin, empagliflozin, renal protection, type 2 diabetes,
• MeSH
• benzhydrylové sloučeniny terapeutické užití   MeSH
• časná diagnóza * MeSH
• chronická renální insuficience * farmakoterapie   diagnóza   MeSH
• diabetes mellitus 2. typu * farmakoterapie   komplikace   MeSH
• diabetické nefropatie * diagnóza   prevence a kontrola   farmakoterapie   MeSH
• glifloziny * terapeutické užití   MeSH
• glukosidy terapeutické užití   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• lidé MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny * MeSH
• glukosidy MeSH

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) has been firmly established; however, the entity of diabetic myocardial disorder (previously called diabetic cardiomyopathy) remains a matter of debate. Diabetic myocardial disorder was originally described as the occurrence of myocardial structural/functional abnormalities associated with T2DM in the absence of coronary heart disease, hypertension and/or obesity. However, supporting evidence has been derived from experimental and small clinical studies. Only a minority of T2DM patients are recognized as having this condition in the absence of contributing factors, thereby limiting its clinical utility. Therefore, this concept is increasingly being viewed along the evolving HF trajectory, where patients with T2DM and asymptomatic structural/functional cardiac abnormalities could be considered as having pre-HF. The importance of recognizing this stage has gained interest due to the potential for current treatments to halt or delay the progression to overt HF in some patients. This document is an expert consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases. It summarizes contemporary understanding of the association between T2DM and HF and discuses current knowledge and uncertainties about diabetic myocardial disorder that deserve future research. It also proposes a new definition, whereby diabetic myocardial disorder is defined as systolic and/or diastolic myocardial dysfunction in the presence of diabetes. Diabetes is rarely exclusively responsible for myocardial dysfunction, but usually acts in association with obesity, arterial hypertension, chronic kidney disease and/or coronary artery disease, causing additive myocardial impairment.

• Klíčová slova
• Cardiac abnormalities, Diabetic myocardial disorder, Heart failure, Prevention, Risk assessment, Treatment, Type 2 diabetes mellitus,
• MeSH
• diabetes mellitus 2. typu * komplikace   MeSH
• diabetická kardiomyopatie * diagnóza   patofyziologie   MeSH
• lidé MeSH
• společnosti lékařské MeSH
• srdeční selhání * diagnóza   etiologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH

Autophagy is an evolutionarily conserved process that plays a pivotal role in the maintenance of cellular homeostasis and its impairment has been implicated in the pathogenesis of various metabolic diseases including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review synthesizes the current evidence from human studies on autophagy alterations under these metabolic conditions. In obesity, most data point to autophagy upregulation during the initiation phase of autophagosome formation, potentially in response to proinflammatory conditions in the adipose tissue. Autophagosome formation appears to be enhanced under hyperglycemic or insulin-resistant conditions in patients with T2D, possibly acting as a compensatory mechanism to eliminate damaged organelles and proteins. Other studies have proposed that prolonged hyperglycemia and disrupted insulin signaling hinder autophagic flux, resulting in the accumulation of dysfunctional cellular components that can contribute to β-cell dysfunction. Evidence from patients with MASLD supports autophagy inhibition in disease progression. Nevertheless, given the available data, it is difficult to ascertain whether autophagy is enhanced or suppressed in these conditions because the levels of autophagy markers depend on the overall metabolism of specific organs, tissues, experimental conditions, or disease duration. Owing to these constraints, determining whether the observed shifts in autophagic activity precede or result from metabolic diseases remains challenging. Additionally, autophagy-modulating strategies are shortly discussed. To conclude, more studies investigating autophagy impairment are required to gain a more comprehensive understanding of its role in the pathogenesis of obesity, T2D, and MASLD and to unveil novel therapeutic strategies for these conditions.

• Klíčová slova
• Autophagy modulators, Cellular quality control, Metabolic diseases, Patients, Therapies, Tissue biopsy,
• MeSH
• autofagie * fyziologie   MeSH
• diabetes mellitus 2. typu * komplikace   patofyziologie   metabolismus   MeSH
• lidé MeSH
• obezita * komplikace   patofyziologie   metabolismus   MeSH
• ztučnělá játra patofyziologie   komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Diabetic cardiomyopathy may result from the overproduction of ROS, TRPM2 and TRPV2. Moreover, the therapeutic role of ginger, omega-3 fatty acids, and their combinations on the expression of TRPM2 and TRPV2 and their relationship with apoptosis, inflammation, and oxidative damage in heart tissue of rats with type 2 diabetes have not yet been determined. Therefore, this study aimed to investigate the therapeutic effects of ginger and omega-3 fatty acids on diabetic cardiomyopathy by evaluating the cardiac gene expression of TRPM2 and TRPV2, oxidative damage, inflammation, and apoptosis in male rats. Ninety adult male Wistar rats were equally divided into nine control, diabetes, and treated diabetes groups. Ginger extract (100 mg/kg) and omega-3 fatty acids (50, 100, and 150 mg/kg) were orally administrated in diabetic rats for 6 weeks. Type 2 diabetes was induced by feeding a high-fat diet and a single dose of STZ (40 mg/kg). Glucose, cardiac troponin I (cTnI), lipid profile, insulin in serum, and TNF-alpha IL-6, SOD, MDA, and CAT in the left ventricle of the heart were measured. The cardiac expression of TRPM2, TRPV2, NF-kappaB, Bcl2, Bax, Cas-3, and Nrf-2 genes was also measured in the left ventricle of the heart. An electrocardiogram (ECG) was continuously recorded to monitor arrhythmia at the end of the course. The serum levels of cTnI, glucose, insulin, and lipid profile, and the cardiac levels of MDA, IL-6, and TNF-alpha increased in the diabetic group compared to the control group (p<0.05). Moreover, the cardiac levels of SOD and CAT decreased in the diabetic group compared to the control group (p<0.05). The cardiac expression of TRPM2, TRPV2, NF-kappaB, Bax, and Cas-3 increased and Bcl2 and Nrf-2 expression decreased in the diabetic group compared to the control group (p<0.05). However, simultaneous and separate treatment with ginger extract and omega-3 fatty acids (50, 100, and 150 mg/kg) could significantly moderate these changes (p<0.05). The results also showed that the simultaneous treatment of ginger extract and different doses of omega-3 fatty acids have improved therapeutic effects than their individual treatments (p<0.05). It can be concluded that ginger and omega-3 fatty acids showed protective effects against diabetic cardiomyopathy by inhibiting inflammation, apoptosis and oxidative damage of the heart and reducing blood glucose and cardiac expression of TRPM2 and TRPV2. Combining ginger and omega-3 in the diet may provide a natural approach to reducing the risk or progression of diabetic cardiomyopathy while preserving heart structure and function.

• MeSH
• diabetes mellitus 2. typu farmakoterapie   metabolismus   komplikace   MeSH
• diabetická kardiomyopatie * metabolismus   farmakoterapie   prevence a kontrola   MeSH
• experimentální diabetes mellitus * farmakoterapie   metabolismus   MeSH
• kationtové kanály TRPM metabolismus   genetika   MeSH
• kationtové kanály TRPV metabolismus   genetika   MeSH
• krysa rodu Rattus MeSH
• kyseliny mastné omega-3 * farmakologie   aplikace a dávkování   terapeutické užití   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar * MeSH
• potravní doplňky MeSH
• rostlinné extrakty * farmakologie   terapeutické užití   aplikace a dávkování   MeSH
• zázvor lékařský * chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kationtové kanály TRPM MeSH
• kationtové kanály TRPV MeSH
• kyseliny mastné omega-3 * MeSH
• rostlinné extrakty * MeSH

BACKGROUND: The increased diuresis after sodium-glucose cotransporter 2 inhibitor (SGLT2i) was associated with a reduction of the estimated plasma volume (ePV) in type 2 diabetic patients. HYPOTHESIS: We hypothesized that the early effect of SGLT2i on ePV may be monitored by the change of biomarkers of hemoconcentration. PATIENTS AND METHODS: We analyzed the early- and long-term effect of SGLT2i empagliflozin on the ePV as assessed by biomarkers of hemoconcentration in a nondiabetic patient with heart failure and reduced ejection fraction (HFrEF) and a nondiabetic patient with heart failure and preserved ejection fraction (HFpEF). The ePV was calculated from hemoglobin and hematocrit levels by Duarte formula and ePV change was calculated by Strauss formula. RESULTS: The ePV change was -22.56% between baseline and 1 month, and -37.60% between baseline and 12 months follow-up in a patient with HFrEF, and -6.18% and -16.40% in a patient with HFpEF, respectively. CONCLUSION: The early effect of SGLT2i on ePV in patients with heart failure may be monitored by biomarkers of hemoconcentration.

• Klíčová slova
• biomarker, heart failure, hemoconcentration, plasma volume, sodium−glucose co‐transporter‐2 inhibitor,
• MeSH
• benzhydrylové sloučeniny terapeutické užití   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• diabetes mellitus 2. typu farmakoterapie   komplikace   krev   patofyziologie   MeSH
• funkce levé komory srdeční účinky léků   fyziologie   MeSH
• glifloziny * terapeutické užití   MeSH
• glukosidy terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• objem plazmy * MeSH
• senioři MeSH
• srdeční selhání * patofyziologie   farmakoterapie   krev   MeSH
• tepový objem * fyziologie   účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• biologické markery MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny * MeSH
• glukosidy MeSH

AIMS: Autoantibodies against hexokinase 1 (HK1) were recently proposed to be associated with diabetic macular edema (DME). We hypothesized that anti-HK1 autoantibodies can be used as DME markers and to predict DME onset. MATERIALS AND METHODS: Serum from patients with 1) DME, 2) diabetes mellitus (DM), 3) allergies or autoimmunities, and 4) control subjects was tested for anti-HK1 and anti-hexokinase 2 (HK2) autoantibodies by immunoblotting. Patients with DM were prospectively followed for up to nine years, and the association of anti-HK1 antibodies with new-onset DME was evaluated. The vitreous humor was also tested for autoantibodies. RESULTS: Among patients with DME, 32 % were positive for anti-HK1 autoantibodies (42 % of those with underlying type 1 DM and 31 % of those with underlying type 2 DM), and 12 % were positive for anti-HK2 autoantibodies, with only partial overlap of these two groups of patients. Anti-HK1 positive were also 7 % of patients with DM, 6 % of patients with allergies and autoimmunities, and 3 % of control subjects. The latter three groups were anti-HK2 negative. Only one of seven patients with DM who were initially anti-HK1 positive developed DME. CONCLUSIONS: Anti-HK1 autoantibodies can be used as DME markers but fail to predict DME onset.

• Klíčová slova
• Autoimmunity, Disease marker, Disease prediction, Glycolysis, Tissue damage, Vitreous fluid,
• MeSH
• autoprotilátky * krev   imunologie   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 1. typu imunologie   komplikace   krev   MeSH
• diabetes mellitus 2. typu imunologie   komplikace   krev   MeSH
• diabetická retinopatie * imunologie   krev   MeSH
• dospělí MeSH
• hexokinasa * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární edém * imunologie   krev   MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky * MeSH
• biologické markery MeSH
• hexokinasa * MeSH
• HK1 protein, human MeSH Prohlížeč