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.

• 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

• MeSH
• diabetes mellitus 2. typu * imunologie   komplikace   MeSH
• infekce * etiologie   farmakoterapie   imunologie   komplikace   krev   MeSH
• krevní proteiny klasifikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocyty klasifikace   MeSH
• rizikové faktory MeSH
• senioři MeSH
• sérologické testy MeSH
• statistika jako téma MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

Immune cells are an inseparable component of adipose tissue intimately involved in most of its functions. Physiologically, they regulate adipose tissue homeostasis, while in case of adipose tissue stress, immune cells are able to change their phenotype, enhance their count and subsequently contribute to the development and maintenance of local adipose tissue inflammation. Immune cells are an important source of inflammatory cytokines and other pro-inflammatory products that further influence not only surrounding tissues but via systemic circulation also the whole organism being thus one of the main factors responsible for the transition from simple obesity to associated metabolic and cardiovascular complications. The purpose of this review is to summarize current knowledge on different adipose tissue immune cell subsets and their role in the development of obesity, type 2 diabetes mellitus and cardiovascular diseases.

• MeSH
• cytokiny metabolismus   MeSH
• diabetes mellitus 2. typu imunologie   metabolismus   MeSH
• imunitní systém metabolismus   fyziologie   MeSH
• kardiovaskulární nemoci etiologie   imunologie   metabolismus   MeSH
• lidé MeSH
• makrofágy patologie   fyziologie   MeSH
• obezita imunologie   metabolismus   MeSH
• rizikové faktory MeSH
• tuková tkáň imunologie   metabolismus   MeSH
• zánět imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Inflammation has received considerable attention in the pathogenesis of type 2 diabetes mellitus (T2DM). Supporting this concept, enhanced expression of interleukin (IL)-1β and increased infiltration of macrophages are observed in pancreatic islets of patients with T2DM. Although IL-1 receptor antagonist (IL-1Ra) plays a major role in controlling of IL-1β-mediated inflammation, its counteraction effects and epigenetic alterations in T2DM are less studied. Thus, we aimed to analyze the DNA methylation status in IL1RN, RELA (p65) and NFKB1 (p50) genes in peripheral blood mononuclear cells (PBMCs) from treated T2DM patients (n = 35) and age-/sex- matched healthy controls (n = 31). Production of IL-1β and IL-1Ra was analyzed in plasma and supernatants from LPS-induced PBMCs. Immunomodulatory effects of IL-1β and IL-1Ra were studied on THP-1 cells. Average DNA methylation level of IL1RN and NFKB1 gene promoters was significantly decreased in T2DM patients in comparison with healthy controls (P< 0.05), which was associated with the increased IL-1Ra (P< 0.001) and IL-1β (P = 0.039) plasma levels in T2DM patients. Negative association between average methylation of IL1RN gene and IL-1Ra plasma levels were observed in female T2DM patients. Methylation of NFKB1 gene was negatively correlated with IL-1Ra levels in the patients and positively with IL-1β levels in female patients. LPS-stimulated PBMCs from female patients failed to raise IL-1β production, while the cells from healthy females increased IL-1β production in comparison with unstimulated cells (P< 0.001). Taken together, the findings suggest that hypomethylation of IL1RN and NFKB1 gene promoters may promote the increased IL-1β/IL-1Ra production and regulate chronic inflammation in T2DM. Further studies are necessary to elucidate the causal direction of these associations and potential role of IL-1Ra in anti-inflammatory processes in treated patients with T2DM.

• MeSH
• antagonista receptoru pro interleukin 1 krev   metabolismus   MeSH
• chronická pankreatitida etiologie   imunologie   MeSH
• diabetes mellitus 2. typu imunologie   patologie   MeSH
• dospělí MeSH
• interleukin-1beta metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• NF-kappa B - podjednotka p50 krev   metabolismus   MeSH
• senioři MeSH
• THP-1 buňky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND AND AIMS: Macrophages are linked to the initiation of the chronic inflammation believed to underlie the changes taking place in the white fatty tissue of obese people. Both the number of macrophages, but their functional status, play an important role in the development of inflammation. Classically, macrophages are divided into two types: pro-inflammatory (M1) and anti-inflammatory (M2) types, and based on current immunological studies, further views on the functional distribution of macrophages are suggested. In this study, we evaluated the M1 and M2 macrophages ratio in obese subjects with, or without diabetes. To identify all macrophages, we used CD68 expression, while CD204 expression is typically used for the M2 macrophage. MATERIALS AND METHODS: During bariatric surgery, carried out in obese people with and without type 2 diabetes (T2D), we obtained subcutaneous adipose tissue from the navel and omental adipose tissue. We also obtained the same tissue from people with a physiological range of BMI from a judicial autopsy. Applying immunohistochemical staining anti-CD68 and anti-CD204, we carried out a quantitative evaluation of the number of macrophages. RESULTS: We found CD68+ and CD204+ positive macrophages in perivascular spaces and between fat cells, both isolated and in larger infiltrates. They were also present in so-called "crown-like structures" (CLS) around dying adipocytes. Quantitative analysis showed an increased number of macrophages in all obese patients compared to the control group of non-obese, individuals without T2D. The most striking observation was the macrophage increase in the visceral fatty tissue of diabetics. The number of CD68 and CD204 positive macrophages was statistically significantly smaller in patients without T2D. CONCLUSION: We demonstrated a significantly greater number of macrophages in visceral adipose tissue, especially in patients with T2D. Our results also show a positive correlation between the presence of T2D and the total number of macrophages; a significantly greater number of macrophages were found in visceral adipose tissue, especially in patients with T2D.

• MeSH
• antigeny diferenciační myelomonocytární MeSH
• bariatrická chirurgie MeSH
• bílá tuková tkáň imunologie   patologie   MeSH
• CD antigeny MeSH
• diabetes mellitus 2. typu imunologie   MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   patologie   MeSH
• mladý dospělý MeSH
• nitrobřišní tuk imunologie   patologie   MeSH
• obezita imunologie   patologie   chirurgie   MeSH
• omentum MeSH
• podkožní tuk imunologie   patologie   MeSH
• scavengerové receptory - třída A MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Testing for autoantibodies against the zinc transporter ZnT8 (ZnTA) is becoming routine in pediatric diabetes. However, available data are inconclusive when focusing on adult-onset diabetes, including autoimmune diabetes, which does not require insulin at diagnosis (LADA). BASIC PROCEDURES: We examined the ZnTA prevalence and titers and matched them with the clinical phenotype and PTPN22 genotypes of Czech LADA patients who were positive for GADA and/or IA2A and had a fasting C-peptide level >200 pmol/L at diagnosis as well as HNF4A-, GCK- or HNF1A-MODY patients and healthy controls. MAIN FINDINGS: Most LADA patients were negative for ZnTA, and the sensitivity of the assay was only 18-20% for patients with LADA-like progression to insulinotherapy compared to healthy controls. In LADA patients, there was no association between the ZnTA and PTPN22 risk genotypes. LADA patients positive for ZnTA had a lower BMI than those positive for other autoantibodies alone. Importantly, MODY patients were completely negative for ZnTA, and the levels of ZnTA in MODY patients were similar to those in healthy controls. CONCLUSIONS: ZnTA quantification did not improve LADA diagnosis. However, positivity for ZnTA can be used as a negative MODY pre-diagnostic criterion even in the region of Central and East Europe, where other islet cell autoantibodies are common in MODY patients.

• MeSH
• autoprotilátky krev   imunologie   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 1. typu krev   farmakoterapie   genetika   imunologie   MeSH
• diabetes mellitus 2. typu krev   farmakoterapie   genetika   imunologie   MeSH
• fenotyp MeSH
• genotyp MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci MeSH
• tyrosinfosfatasa nereceptorového typu 22 genetika   MeSH
• zinkový transportér 8 krev   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND AND AIMS: CD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM. METHODS AND RESULTS: Samples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm2; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm2; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm2; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024). CONCLUSIONS: Regional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.

• MeSH
• antigeny CD11c analýza   MeSH
• antigeny diferenciační myelomonocytární analýza   MeSH
• biologické markery analýza   MeSH
• CD antigeny analýza   MeSH
• diabetes mellitus 2. typu imunologie   patologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   patologie   MeSH
• myokard imunologie   patologie   MeSH
• nemoci koronárních tepen imunologie   patologie   MeSH
• obezita imunologie   patologie   MeSH
• počet buněk MeSH
• podkožní tuk imunologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zánět imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n = 12) and without (non-T2DM, n = 17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6 ± 0.7 vs. 5.8 ± 0.2 mmol/l, p < 0.001) and glycated hemoglobin (52.0 ± 3.4 vs. 36.9 ± 1.0 mmol/mol, p < 0.001) and tended to have more pronounced inflammation (hsCRP: 9.8 ± 3.1 vs. 5.1 ± 1.9 mg/ml, p = 0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57 ± 0.65 vs. 4.45 ± 1.56% for T2DM vs. non-T2DM, p = 0.041) with a similar, albeit insignificant, trend in EAT (0.996 ± 0.33 vs. 2.46 ± 0.78% for T2DM vs. non-T2DM, p = 0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5 ± 2.0 vs. 4.6 ± 1.9% of DC cells, p = 0.005) and EAT (29.1 ± 8.7 vs. 8.4 ± 2.4% of DC, p = 0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1 ± 8.7 vs. 13.5 ± 2.0% of DC, p = 0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.

• MeSH
• dendritické buňky metabolismus   MeSH
• diabetes mellitus 2. typu imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen imunologie   metabolismus   MeSH
• obezita imunologie   metabolismus   MeSH
• perikard imunologie   metabolismus   MeSH
• podkožní tuk imunologie   metabolismus   MeSH
• senioři MeSH
• tuková tkáň imunologie   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Diabetes mellitus patří mezi nejčastější chronická onemocnění dětského věku v naší populaci, postihuje přibližně každé pětisté dítě. V posledních 30 letech pozorujeme významný nárůst incidence, která stoupla více než trojnásobně na aktuálních 25 případů na 100 000 dětí mladších 15 let. Nejčastějším typem diabetu je v této věkové kategorii diabetes mellitus 1. typu, který tvoří přibližně 95 % případů dětského diabetu. Monogenní formy diabetu tvoří necelá 4 % diabetu u dětí, výskyt diabetu 2. typu je u dětí na rozdíl od dospělých marginální (1 %). Etiologická diagnostika představuje nezbytný předpoklad efektivní terapie dětského diabetu. Data z národního registru ČENDA ukazují, že kompenzace diabetu 1. typu se v posledních letech rychle zlepšuje, nejspíše v důsledku zavádění moderních technologií do každodenní praxe a zlepšení edukace. Článek shrnuje současné poznatky o etiologii a léčbě diabetu manifestovaného do 18 let věku.

Diabetes belongs to the most frequent chronic diseases in the Czech children affecting about 1 : 500 children. Incidence of childhood diabetes increased more than three times in the last 30 years actually reaching 25 new cases per 100 000 children. Type 1 diabetes is the most common diabetes type in this age category (95 % cases) followed by monogenic diabetes (4 %) and type 2 (1 %). Proper diagnostics based on molecular genetic analysis and detailed immunological investigations pose basic prerequisite for successful treatment. Data from the Czech registry of childhood diabetes (ČENDA) show that type 1 diabetes control has improved significantly over the last five years, very probably by implementation of modern technologies into clinical practice and tailored education. This article summarizes current knowledge on etiology and treatment of diabetes in subjects younger 18 years.

• MeSH
• diabetes mellitus 1. typu * diagnóza   farmakoterapie   genetika   MeSH
• diabetes mellitus 2. typu farmakoterapie   genetika   imunologie   klasifikace   MeSH
• dítě MeSH
• glykovaný hemoglobin normy   účinky léků   MeSH
• inzulinové infuzní systémy MeSH
• lidé MeSH
• mladiství MeSH
• registrace statistika a číselné údaje   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH

Klinická studie EXSCEL porovnávající podání exenatidu oproti placebu neprokázala statisticky významný rozdíl ve výskytu kardiovaskulárních příhod ani ve výskytu nežádoucích účinků u pacientů s diabetes mellitus 2. typu s kardiovaskulárním postižením nebo bez něj.

Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo.

• MeSH
• aplikace orální MeSH
• diabetes mellitus 2. typu * farmakoterapie   imunologie   komplikace   MeSH
• glukagonu podobný peptid 1 analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• hodnocení léčiv MeSH
• hypoglykemika * klasifikace   škodlivé účinky   terapeutické užití   MeSH
• inkretiny terapeutické užití   MeSH
• kardiovaskulární nemoci * farmakoterapie   komplikace   mortalita   MeSH
• lidé MeSH
• nežádoucí účinky léčiv komplikace   prevence a kontrola   MeSH
• peptidy farmakokinetika   farmakologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH