BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure. METHODS: 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed. RESULTS: SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects. CONCLUSIONS: Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

• Klíčová slova
• Adipose tissue, Ether lipids, Heart failure, Inflammation, Sodium-glucose cotransporter 2 inhibitors,
• MeSH
• antiflogistika terapeutické užití   farmakologie   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu farmakoterapie   metabolismus   diagnóza   MeSH
• epikardiální adipózní tkáň MeSH
• funkce levé komory srdeční účinky léků   MeSH
• glifloziny * terapeutické užití   farmakologie   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu * metabolismus   MeSH
• metabolomika MeSH
• perikard * metabolismus   účinky léků   MeSH
• srdeční selhání * metabolismus   patofyziologie   farmakoterapie   MeSH
• stupeň závažnosti nemoci * MeSH
• tepový objem účinky léků   MeSH
• tuková tkáň * účinky léků   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika MeSH
• biologické markery MeSH
• glifloziny * MeSH
• mediátory zánětu * MeSH

AIMS/HYPOTHESIS: Monogenic diabetes is estimated to account for 1-6% of paediatric diabetes cases in primarily non-consanguineous populations, while the incidence and genetic spectrum in consanguineous regions are insufficiently defined. In this single-centre study we aimed to evaluate diabetes subtypes, obtain the consanguinity rate and study the genetic background of individuals with syndromic and neonatal diabetes in a population with a high rate of consanguinity. METHODS: Data collection was carried out cross-sectionally in November 2021 at the paediatric diabetic clinic, Dr Jamal Ahmad Rashed Hospital, in Sulaimani, Kurdistan, Iraq. At the time of data collection, 754 individuals with diabetes (381 boys) aged up to 16 years were registered. Relevant participant data was obtained from patient files. Consanguinity status was known in 735 (97.5%) participants. Furthermore, 12 families of children with neonatal diabetes and seven families of children with syndromic diabetes consented to genetic testing by next-generation sequencing. Prioritised variants were evaluated using the American College of Medical Genetics and Genomics guidelines and confirmed by Sanger sequencing. RESULTS: A total of 269 of 735 participants (36.5%) with known consanguinity status were offspring of consanguineous families. An overwhelming majority of participants (714/754, 94.7%) had clinically defined type 1 diabetes (35% of them were born to consanguineous parents), whereas only eight (1.1%) had type 2 diabetes (38% consanguineous). Fourteen (1.9%) had neonatal diabetes (50% consanguineous), seven (0.9%) had syndromic diabetes (100% consanguineous) and 11 (1.5%) had clinically defined MODY (18% consanguineous). We found that consanguinity was significantly associated with syndromic diabetes (p=0.0023) but not with any other diabetes subtype. The genetic cause was elucidated in ten of 12 participants with neonatal diabetes who consented to genetic testing (homozygous variants in GLIS3 [sibling pair], PTF1A and ZNF808 and heterozygous variants in ABCC8 and INS) and four of seven participants with syndromic diabetes (homozygous variants in INSR, SLC29A3 and WFS1 [sibling pair]). In addition, a participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes. CONCLUSIONS/INTERPRETATION: This unique single-centre study confirms that, even in a highly consanguineous population, clinically defined type 1 diabetes is the prevailing paediatric diabetes subtype. Furthermore, a pathogenic cause of monogenic diabetes was identified in 83% of tested participants with neonatal diabetes and 57% of participants with syndromic diabetes, with most variants being homozygous. Causative genes in our consanguineous participants were markedly different from genes reported from non-consanguineous populations and also from those reported in other consanguineous populations. To correctly diagnose syndromic diabetes in consanguineous populations, it may be necessary to re-evaluate diagnostic criteria and include additional phenotypic features such as short stature and hepatosplenomegaly.

• Klíčová slova
• Consanguineous population, Consanguinity, Diabetes genes, Genetics, Monogenic diabetes, Neonatal diabetes, Paediatric diabetes, Syndromic diabetes,
• MeSH
• diabetes mellitus 1. typu * epidemiologie   genetika   MeSH
• diabetes mellitus 2. typu * epidemiologie   genetika   diagnóza   MeSH
• dítě MeSH
• kohortové studie MeSH
• lidé MeSH
• mutace genetika   MeSH
• nemoci novorozenců * genetika   MeSH
• novorozenec MeSH
• pokrevní příbuzenství MeSH
• proteiny přenášející nukleosidy genetika   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Irák epidemiologie   MeSH
• Názvy látek
• proteiny přenášející nukleosidy MeSH
• SLC29A3 protein, human MeSH Prohlížeč

OBJECTIVES: The significant differences in the fingerprint pattern frequencies in type 2 diabetes mellitus (T2DM) patients and controls could be a possible way to identify patients with a risk of developing T2DM. The results could be used in the earlier diagnosis and treatment. The study was undertaken to find out the reliability of fingerprint patterns as a possible predictive tool for T2DM diagnosis. METHODS: A total of 1,260 fingerprints were acquired using the optical contact sensor DactyScan 26i. The results of the qualitative analysis of the fingerprint pattern frequencies have been compared between T2DM patients and controls and also between the fingers to each other. We have detected the frequency of patterns: plain arch (Ap) and tented arch (At), radial loop (Lr), ulnar loop (Lu), double loop (Ld), spiral whorl (W), and plain whorl (concentric) (Wp). Statistical analysis was performed using Pearson's chi-square by Statistica ver. 12. RESULTS: We found statistically significant differences (p < 0.05) in the frequency of individual dermatoglyphic patterns among patients with diabetes and healthy controls as follows: in the left thumb (L1) in a radial loop, double loop and spiral whorl pattern; in the left middle finger (L3) in a tented arch and radial loop; in the right ring finger (R4) in a tented arch, spiral and plain whorl; and in the right little finger (R5) in a tented arch and spiral whorl. CONCLUSION: Fingerprint pattern frequencies might be used as another screening tool and indicator in T2DM prevention. Qualitative analysis of fingerprint patterns could be useful regarding the additional prevention diagnostics of T2DM in the population.

• Klíčová slova
• dermatoglyphics, diabetes prevention, diabetes screening, fingerprints,
• MeSH
• dermatoglyfika MeSH
• diabetes mellitus 2. typu * diagnóza   MeSH
• lidé MeSH
• pilotní projekty MeSH
• reprodukovatelnost výsledků MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• Diabetes, Diabetes screening, HbA1c, Prediabetes,
• MeSH
• diabetes mellitus 2. typu * diagnóza   MeSH
• krevní glukóza MeSH
• lidé MeSH
• prediabetes * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH
• Názvy látek
• krevní glukóza MeSH

Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

• Klíčová slova
• Alzheimer’s disease, GC-MS, differential diagnostics, multivariate statistics, steroidome, type 2 diabetes mellitus,
• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• androstendion MeSH
• diabetes mellitus 2. typu * diagnóza   epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• steroidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androstendion MeSH
• steroidy MeSH

The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10-12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year's focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23-24, 2023 ( http://www.cvot.org ).

• Klíčová slova
• Cardiovascular disease, Chronic kidney disease, Diabetes, GIP/GLP-1 receptor agonist, Heart failure, Obesity, SGLT2 inhibitor,
• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• chronická renální insuficience * diagnóza   farmakoterapie   epidemiologie   MeSH
• diabetes mellitus 2. typu * diagnóza   farmakoterapie   epidemiologie   MeSH
• hypoglykemika terapeutické užití   MeSH
• kardiovaskulární nemoci * diagnóza   farmakoterapie   epidemiologie   MeSH
• krevní glukóza MeSH
• ledviny MeSH
• lidé MeSH
• selfmonitoring glykemie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• hypoglykemika MeSH
• krevní glukóza MeSH

Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous GLP-1 incretin hormone, improving glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. However, as cardiovascular (CV) morbidity and mortality is common in patients with T2DM, several trials with the use of GLP-1 receptor agonists (RAs) have been performed focusing on endpoints related to cardiovascular disease rather than metabolic control of T2DM. Following the positive cardiovascular effects of liraglutide, dulaglutide and semaglutide observed in these trials, major changes in T2DM management guidelines have occurred. This document from a Eastern and Southern European Diabetes Expert Group discusses the results of GLP-1 RA CV outcomes trials, their impact on recent clinical guidelines for the management of T2DM, and some selected combination regimens utilising GLP-1 RAs. We also propose an algorithm for guiding GLP-1 RA-based treatment according to patients' characteristics, which can be easily applied in every day clinical practice.

• Klíčová slova
• Algorithm, Cardiovascular outcomes trials, GLP-1 receptor agonists, Treatment, Type 2 diabetes mellitus,
• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• diabetes mellitus 2. typu * diagnóza   farmakoterapie   epidemiologie   MeSH
• glukagonu podobný peptid 1 metabolismus   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci * farmakoterapie   epidemiologie   MeSH
• lidé MeSH
• liraglutid farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• glukagonu podobný peptid 1 MeSH
• hypoglykemika MeSH
• liraglutid MeSH

BACKGROUND: Guidelines from 2016 onwards recommend early use of SGLT2i or GLP-1 RA for patients with type 2 diabetes (T2D) and cardiovascular disease (CVD), to reduce CV events and mortality. Many eligible patients are not treated accordingly, although data are lacking for Central and Eastern Europe (CEE). METHODS: The CORDIALLY non-interventional study evaluated the real-world characteristics, modern antidiabetic treatment patterns, and the prevalence of CVD and chronic kidney disease (CKD) in adults with T2D at nonhospital-based practices in CEE. Data were retrospectively collated by medical chart review for patients initiating empagliflozin, another SGLT2i, DPP4i, or GLP-1 RA in autumn 2018. All data were analysed cross-sectionally, except for discontinuations assessed 1 year ± 2 months after initiation. RESULTS: Patients (N = 4055) were enrolled by diabetologists (56.7%), endocrinologists (40.7%), or cardiologists (2.5%). Empagliflozin (48.5%) was the most prescribed medication among SGLT2i, DPP4i, and GLP-1 RA; > 3 times more patients were prescribed empagliflozin than other SGLT2i (10 times more by cardiologists). Overall, 36.6% of patients had diagnosed CVD. Despite guidelines recommending SGLT2i or GLP-1 RA, 26.8% of patients with CVD received DPP4i. Patients initiating DPP4i were older (mean 66.4 years) than with SGLT2i (62.4 years) or GLP-1 RA (58.3 years). CKD prevalence differed by physician assessment (14.5%) or based on eGFR and UACR (27.9%). Many patients with CKD (≥ 41%) received DPP4i, despite guidelines recommending SGLT2is owing to their renal benefits. 1 year ± 2-months after initiation, 10.0% (7.9-12.3%) of patients had discontinued study medication: 23.7-45.0% due to 'financial burden of co-payment', 0-1.9% due to adverse events (no patients discontinued DPP4i due to adverse events). Treatment guidelines were 'highly relevant' for a greater proportion of cardiologists (79.4%) and endocrinologists (72.9%) than diabetologists (56.9%), and ≤ 20% of physicians consulted other physicians when choosing and discontinuing treatments. CONCLUSIONS: In CORDIALLY, significant proportions of patients with T2D and CVD/CKD who initiated modern antidiabetic medication in CEE in autumn 2018 were not treated with cardioprotective T2D medications. Use of DPP4i instead of SGLT2i or GLP-1 RA may be related to lack of affordable access, the perceived safety of these medications, lack of adherence to the latest treatment guidelines, and lack of collaboration between physicians. Thus, many patients with T2D and comorbidities may develop preventable complications or die prematurely. Trial registration NCT03807440.

• Klíčová slova
• Cardiovascular disease (CVD), Cardiovascular outcomes trials (CVOTs), Cardiovascular safety, Chronic kidney disease (CKD), Dipeptidyl peptidase-4 inhibitors (DPP4i), Glucagon-like peptide-1 receptor agonists (GLP-1 RA), Glucose-lowering drug, Sodium-glucose cotransporter-2 inhibitors (SGLT2i), Type 2 diabetes,
• MeSH
• benzhydrylové sloučeniny MeSH
• chronická renální insuficience * diagnóza   farmakoterapie   epidemiologie   MeSH
• diabetes mellitus 2. typu * diagnóza   farmakoterapie   epidemiologie   MeSH
• dospělí MeSH
• glifloziny * škodlivé účinky   MeSH
• glukagonu podobný peptid 1 terapeutické užití   MeSH
• glukosidy MeSH
• hypoglykemika škodlivé účinky   MeSH
• kardiovaskulární nemoci * diagnóza   epidemiologie   prevence a kontrola   MeSH
• lidé MeSH
• průřezové studie MeSH
• receptor pro glukagonu podobný peptid 1 MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny * MeSH
• glukagonu podobný peptid 1 MeSH
• glukosidy MeSH
• hypoglykemika MeSH
• receptor pro glukagonu podobný peptid 1 MeSH

BACKGROUND: HNF1A-MODY is a monogenic form of diabetes caused by variants in the HNF1A gene. Different HNF1A variants are associated with differences in age of disease onset, but other factors are postulated to influence this trait. Here, we searched for genetic variants influencing age of HNF1A-MODY onset. METHODS: Blood samples from 843 HNF1A-MODY patients from Czech Republic, France, Poland, Slovakia, the UK and the US were collected. A validation set consisted of 121 patients from the US. We conducted a genome-wide association study in 843 HNF1A-MODY patients. Samples were genotyped using Illumina Human Core arrays. The core analysis was performed using the GENESIS package in R statistical software. Kinship coefficients were estimated with the KING and PC-Relate algorithms. In the linear mixed model, we accounted for year of birth, sex, and location of the HNF1A causative variant. RESULTS: A suggestive association with age of disease onset was observed for rs2305198 (p = 2.09E-07) and rs7079157 (p = 3.96E-06) in the HK1 gene, rs2637248 in the LRMDA gene (p = 2.44E-05), and intergenic variant rs2825115 (p = 2.04E-05). Variant rs2637248 reached nominal significance (p = 0.019), while rs7079157 (p = 0.058) and rs2825115 (p = 0.068) showed suggestive association with age at diabetes onset in the validation set. CONCLUSIONS: rs2637248 in the LRMDA gene is associated with age at diabetes onset in HNF1A-MODY patients.

• Klíčová slova
• Age at disease onset, Diabetes, GWAS, HNF1A-MODY,
• MeSH
• celogenomová asociační studie * MeSH
• diabetes mellitus 2. typu * diagnóza   genetika   MeSH
• fenotyp MeSH
• hepatocytární jaderný faktor 1-alfa genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-alfa MeSH
• HNF1A protein, human MeSH Prohlížeč

AIMS: Correct genetic diagnosis of maturity-onset diabetes of the young (MODY) is beneficial for person's diabetes management compared to no genetic testing. Aim of the present study was a search for optimal time- and cost-saving strategies by comparing two approaches of genetic testing of participants with clinical suspicion of MODY. METHODS: A total of 121 consecutive probands referred for suspicion of MODY (Group A) were screened using targeted NGS (tNGS), while the other 112 consecutive probands (Group B) underwent a single gene test based on phenotype, and in cases of negative findings, tNGS was conducted. The study was performed in two subsequent years. The genetic results, time until reporting of the final results and financial expenses were compared between the groups. RESULTS: MODY was confirmed in 30.6% and 40.2% probands from Groups A and B, respectively; GCK-MODY was predominant (72.2% in Group A and 77.8% in Group B). The median number of days until results reporting was 184 days (IQR 122-258) in Group A and 91 days (44-174) in Group B (p < 0.00001). Mean costs per person were higher for Group A (639 ± 30 USD) than for Group B (584 ± 296 USD; p = 0.044). CONCLUSIONS: The two-step approach represented a better strategy for genetic investigation of MODY concerning time and costs compared to direct tNGS. Although a single-gene investigation clarified the diabetes aetiology in the majority of cases, tNGS could reveal rare causes of MODY and expose possible limitations of both standard genetic techniques and clinical evaluation.

• Klíčová slova
• Dideoxy sequencing, MODY, Monogenic diabetes, Targeted next generation sequencing,
• MeSH
• diabetes mellitus 2. typu * diagnóza   genetika   MeSH
• fenotyp MeSH
• genetické testování * metody   MeSH
• lidé MeSH
• mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH