Diabetes mellitus je závažným zdravotnickým a ekonomickým problémem současnosti. Terapie je vnímána primárně jako prevence pozdních komplikací diabetu. Většina farmakoekonomických analýz uvádí, že náklady spojené s terapií diabetes mellitus jsou z větší části spotřebovány na terapii komplikací. Projekt Národního diabetologického informačního systému vychází ze základního principu automatizovaného sběru dat, která jsou k dispozici v České republice v elektronické podobě a která současně popisují kvalitu a kvantitu péče poskytovaného pacientů s diabetes mellitus i s jejími výsledky. Výhodou postulovaného Národního diabetologického informačního systému je minimalizace selektivní ztráty dat, komplexní pohled na epidemiologii, terapii a její výsledky, možnost sledování trendů, zahrnutí nákladů spojených s hospitalizací a sociálními dávkami. Rizikem zůstává správná interpretace a možnost systémové chyby. Jestliže by se podařilo v České republice podobný systém uskutečnit, bude to první takto komplexní plně automatizovaný informační systém na světě. Závěr: Data popisující incidenci a prevalenci diabetes mellitus, strukturu terapie, náklady přímé na zdravotní péči i indukované na sociálních platbách jsou v naprosté většině k dispozici v elektronické podobě. Vzniká tak možnost založení Národního diabetologického informačního systému, který umožní kontinuální vyhodnocování kvality péče o pacienty s diabetes mellitus včetně farmakoekonomických a sociálních důsledků. Klíčová slova: datové zdroje – diabetes mellitus – farmakoekonomika – informační systém – komplikace diabetes mellitus – registr, Diabetes mellitus is a serious health and economic problem of our time. Therapy is primarily perceived as prevention of the late complications of diabetes. Most pharmacoeconomic analyses state that the cost associated with the therapy of diabetes mellitus is largely spent on the therapy of its complications. The project of the National Diabetes Information System is based on the essential principle of automated collection of data which is available in digital form in the Czech Republic and which describes the quality and quantity of the care provided for patients with diabetes mellitus and its results. Benefits of the posited National Diabetes Information System embrace minimizing of selective loss of data, a comprehensive view of epidemiology, therapy and its results, possibility of following trends, inclusion of costs related to hospitalization and social benefits. Risks involve correct interpretation and a possible system error. If we succeeded in implementing such system in the Czech Republic, it would be the first fully automatic information system on such a comprehensive scale worldwide. Conclusion: The data describing the incidence and prevalence of diabetes mellitus, therapy structure, direct healthcare costs and induced costs of social payments is in the largest part available in digital form. This creates a basis for the foundation of the National Diabetes Information System which will allow for continuous quality assessment of care for patients with diabetes mellitus, including the related pharmacoeconomic and social impacts. Key words: data sources – diabetes mellitus – pharmacoeconomics – information system – complications of diabetes mellitus – register, and Milan Kvapil
Receptor pro konečné produkty pokročilé glykace hraje významnou roli v rozvoji chronických diabetických komplikací. Ukazuje se, že zasahuje více či méně do všech typů diabetické angiopatie. Hlavním jeho ligandem jsou samotné konečné produkty pokročilé glykace (AGEs), které se ve vyšší míře u diabetiků akumulují, ale v posledním desetiletí jsou známy i silnější aktivátory tohoto receptoru, tzv. alarminy. Ty se jinak uplatňují v rozvoji zánětlivé reakce organizmu. Aktivovaný RAGE spouští kaskádu dějů vedoucích k dalšímu hromadění AGEs a kyslíkových radikálů, a navíc je cestou NF-κB iniciována chronická zánětlivá odpověď organizmu. Centrální úloha RAGE v patogenezi cévních změn dělá z tohoto receptoru slibné místo možného budoucího terapeutického či preventivního zásahu. Klíčová slova: diabetes mellitus – hyperglykemie – konečné produkty pokročilé glykace – makroangiopatie – mikroangiopatie – metylglyoxal – receptor konečných produktů pokročilé glykace, Receptor for advanced glycation end-products plays a crucial role in chronic diabetes complications. It is supposed to be involved in the development of all kinds of diabetic angiopathy. Advanced glycation end-products (AGEs) excessively accumulated in diabetes belong to the most important ligands of RAGE, however there are more potent activators of this receptor – especially alarmins, often involved in inflammatory reactions. Activated RAGE triggers pathways leading to excessive accumulation of AGEs, reactive oxygen species and sustained inflammatory reactions via NF-κB. Central role of RAGE in the pathogenesis of vascular changes in diabetes represents suitable target for new therapeutic or preventive approach. Key words: advanced glycation end-products – diabetes mellitus – hyperglycaemia – macroangiopathy – methylglyoxal – microangiopathy – receptor for advanced glycation end-products, and Jan Škrha Jr, Marta Kalousová, Tomáš Zima
Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats., N. N. Hamouda, M. A. Qureshi, J. M. Alkaabi, M. Oz, F. C. Howarth., and Obsahuje bibliografii
Diabetes mellitus je onemocněním, jehož některé projevy mohou zvýšit riziko dopravní nehody, ovlivňuje tedy způsobilost k držení řidičského průkazu. Za nejrizikovější situaci je v tomto ohledu považována hypoglykemie během řízení, diabetes však uvedené riziko zvyšuje např. i díky možnému zhoršení zrakových schopností při případné retinopatii. Za nejrizikovější skupinu řidičů diabetiků stran nehod lze považovat ty, kteří mají v anamnéze těžkou hypoglykemii, hypoglykemii proběhlou při řízení, či silniční nehodu. Zásadním preventivním prvkem v rámci bezpečného silničního provozu je u diabetika léčeného inzulinem především měření glykemie před jízdou a znalost, jak hypoglykemii předcházet a léčit., Diabetes mellitus is a disease which may affect the eligibility to hold a driving license and increase the risk of a road accident. Hypoglycemia while driving is considered to be the most risky situation, with diabetes increasing the mentioned risk for instance due to impaired vision in the case of possible retinopathy. The group of drivers with diabetes being at the greatest risk as to accidents are those with a case history of severe hypoglycemia or hypoglycemia occurred while driving, or possibly of a road accident. Measuring glycaemia before driving and their knowledge how to prevent and treat hypoglycemia – those are the two crucial preventive elements indispensable for insulin treated diabetes patients in order to secure safe road traffic., and Jan Brož, Lenka Syčová Kriváňová, Zuzana Fedáková, Lilit Petrosyan, Milan Kvapil, Jan Polák
Diabetes mellitus is associated with increased inflammatory response, which may contribute to atherosclerosis progression. Experimental results demonstrated anti-inflammatory activity of glitazones; their effect on leukocyte adhesion molecules has not been studied to date. We therefore studied the effect of rosiglitazone treatment on leukocyte surface expression of adhesion molecules in patients with type 2 diabetes mellitus and compared our results with findings in healthy subjects. 33 subjects with type 2 diabetes and 32 healthy controls were included; patients were examined at baseline and after 5 months of rosiglitazone treatment (4 mg /d). Leukocyte expression of adhesion molecules LFA-1, CD 18 and ICAM-1 was quantified using flow cytometry; in addition, CD14 (lipopolysaccharide receptor) expression was analyzed as a marker of nonspecific immunity. The expression of examined molecules at baseline was higher in patients compared to controls. Despite only mild decrease in blood glucose, ro siglitazone treatment induced substantial decrease of CD18 and CD14 expression and borderline decrease of LFA-1 and ICAM-1 expression (on monocytes only). We thus observed improvement in the expression of leukocyte inflammatory markers after rosiglitazone treatment. This effect is supposed to be mediated by direct effect of rosiglitazone on PPAR- γ receptors on leukocytes., T. Štulc, H. Svobodová, Z. Krupičková, R. Doležalová, I. Marinov, R. Češka., and Obsahuje bibliografii
Glucokinase (GCK) plays a key role in glucose metabolism. GCK mutations are known as a pathogenic cause of maturity-onset diabetes of the young type 2 (MODY2). These mutations are also found in gestational diabetics. The aim of our study was to assess the variability of the GCK gene in the Czech diabetic and control populations. We screened all 10 exons specific for the pancreatic isoform of glucokin ase (1a and 2-10) including the intron flanking regions in 722 subjects (in 12 patients with an unrecognised type of MODY and their 10 family members, 313 patients with diabetes mellitus type 2 (DM2), 141 gestational diabetics (GDM), 130 healthy offspring of diabetic parents, and 116 healthy controls without family history of DM2). In two MODY families we identified two mutations in exon 2 of the GCK gene: a novel mutation Val33Ala and the previously described mutation Glu40Lys. In other subgroups (excluding MODY families) we detected only intronic variants and previously described polymorphisms in exons 6 (Tyr215Tyr) and 7 (Ser263Ser), we did not find any known GCK pathogenic mutation. We observed no difference in the frequencies of GCK polymorphisms between Czech diabetic (DM2, GDM) and non- diabetic populations., P. Lukášová, J. Včelák, M. Vaňková, D. Vejražková, K. Andělová, B. Bendlová., and Obsahuje bibliografii a bibliografické odkazy
Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis – cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage – intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes., I. Hoffmanová, D. Sánchez, V. Hábová, M. Anděl, L. Tučková, H. Tlaskalová-Hogenová., and Obsahuje bibliografii
Growing evidence suggests that diabetes mellitus is associated with impairment of the intestinal barrier. However, it is not clear so far if the impairment of the intestinal barrier is a consequence of prolonged hyperglycemia or the consequence of external factors influencing the gut microbiota and intestinal mucosa integrity. Aim of the study was to perform an estimation of relationship between serological markers of impairment of the intestinal barrier: intestinal fatty acid-binding protein (I-FABP), cytokeratin 18 caspase-cleaved fragment (cCK-18), and soluble CD14 (sCD14) and markers of prolonged hyperglycemia, such as the duration of diabetes mellitus and glycated hemoglobin (HbA1c) via a correlation analysis in patients with diabetes mellitus. In 40 adult patients with type 1 diabetes mellitus and 30 adult patients with type 2 diabetes mellitus the estimation has been performed. Statistically significant positive correlation was found between cCK-18 and HbA1c (r=0.5047, p=0.0275) in patients with type 1 diabetes mellitus with fading insulitis (T1D). In patients with type 1 diabetes mellitus with ongoing insulitis (T1D/INS) and in patients with type 2 diabetes mellitus (T2D), no statistically significant positive correlations were found between serological markers of intestinal barrier impairment (I-FABP, cCK-18, sCD14) and duration of diabetes or levels of HbA1c. Similarly, in cumulative cohort of patients with T1D/INS and patients with T1D we revealed statistically positive correlation only between HbA1c and cCK-18 (r=0.3414, p=0.0311). Surprisingly, we found statistically significant negative correlation between the duration of diabetes mellitus and cCK-18 (r=-0.3050, p=0.0313) only in cumulative group of diabetic patients (T1D, T1D/INS, and T2D). Based on our results, we hypothesize that the actual condition of the intestinal barrier in diabetic patients is much more dependent on variable interactions between host genetic factors, gut microbiota, and environmental factors rather than effects of long-standing hyperglycemia (assessed by duration of diabetes mellitus or HbA1c).
Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-α agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-α agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6±2.1 μg/l, T2DM before F: 55.6±5.7 μg/l, T2DM after F: 54.2±5.4 μg/l, p<0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCRglc/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus., M. M. Haluzík ... [et al.]., and Obsahuje seznam literatury
The aim of our study was to measure serum concentrations of fibroblast growth factor 19 (FGF-19) in patients with obesity (OB), obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C) at baseline and after selected interventions. We measured serum FGF-19 levels and other biochemical and hormonal parameters in 29 OB and 19 T2DM females and 30 sex- and age-matched control subjects. The interventions were acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp (n=11 for T2DM and 10 for C), very-low calorie diet (VLCD, n=12 for OB) and 3 months treatment with PPAR- α agonist fenofibrate (n=11 for T2DM). Baseline serum FGF-19 levels were significantly lower in OB relative to C group (132.1±12.7 vs. 202.2±16.7 pg/ml, p<0.05), while no significant difference was observed between T2DM and OB or control group. Acute hyperinsulinemia tended to decrease FGF-19 levels in both healthy and T2DM subjects. Three weeks of VLCD in OB group had no significant effect on FGF-19, whereas three months of fenofibrate treatment markedly reduced FGF-19 levels in T2DM patients (194.58±26.2 vs. 107.47±25.0 pg/ml, p<0.05). We conclude that FGF-19 levels in our study were at least partially dependent upon nutritional status, but were not related to parameters of glucose metabolism or insulin sensitivity., M. Mráz ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy