BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown. METHODS: In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events. RESULTS: Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome. CONCLUSIONS: Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Funded by Provention Bio and Sanofi; PROTECT ClinicalTrials.gov number, NCT03875729.).
- MeSH
- antigeny CD3 antagonisté a inhibitory imunologie MeSH
- beta-buňky účinky léků imunologie MeSH
- C-peptid analýza MeSH
- diabetes mellitus 1. typu * diagnóza imunologie terapie MeSH
- dítě MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * škodlivé účinky farmakologie terapeutické užití MeSH
- hypoglykemika aplikace a dávkování terapeutické užití MeSH
- inzulin aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- mladiství MeSH
- progrese nemoci MeSH
- T-lymfocyty účinky léků imunologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
The relationship between glycaemia and lipoprotein metabolism has not been completely clarified, and slight differences may be found between local authors, trials and evaluated parameters. Therefore this cross-sectional study investigated fasting cholesterol and glucose levels along with the determination of atherogenic index in a cohort of healthy individuals from the Czech Republic in relation to their fasting C-peptide levels. Data were collected between 2009 and 2018 and a total of 3189 individuals were stratified by C-peptide reference range (260-1730 pmol/l) into three groups - below (n = 111), within (n = 2952) and above (n = 126). Total, HDL, LDL cholesterol and atherogenic index were used to compare lipoprotein levels by relevant C-peptide concentrations. Participants using the supplements to affect lipid or glycaemia metabolism were excluded from this study. The evaluation of blood parameters in a fasting state included correlations between C-peptide and cholesterols, differences of variances (F-test) and the comparison of lipoprotein mean values (t-test) between the groups created by the C-peptide reference range. Mean values of total (4.9, 5.1, 5.3 mmol/l), LDL (2.6, 3.1, 3.4 mmol/l) cholesterol and atherogenic index (2.1, 2.8, 3.7) were higher with increasing C-peptide levels, whereas HDL was inversely associated with fasting C-peptide concentration. A positive and negative correlation between atherogenic index (rxy = 0.36) and HDL level (rxy = -0.36) with C-peptide values was found. Differences of HDL, LDL and atherogenic index were, in particular, recorded between the groups below and above the reference range of C-peptide (p ≤ 0.001). Considerable differences (p ≤ 0.001) were also observed for the same lipoprotein characteristics between the groups above and within the C-peptide reference. Generally, the type of cholesterol is crucial for the evaluation of specific changes concerning the C-peptide range. Lipoprotein concentrations differ in relation to C-peptide - not only below and above the physiological range, but also inside and outside of it.
- MeSH
- ateroskleróza epidemiologie metabolismus MeSH
- C-peptid * analýza metabolismus MeSH
- dospělí MeSH
- krevní glukóza analýza metabolismus MeSH
- LDL-cholesterol analýza metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- omezení příjmu potravy krev metabolismus MeSH
- průřezové studie statistika a číselné údaje MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
The study focused on changes or cut-offs of glycaemia, insulin resistance and body mass index within the C-peptide reference range (260-1730 pmol/l). The metabolic profile of individuals in the Czech Republic without diabetes (n = 3186) was classified by whiskers and quartiles of C-peptide into four groups with the following ranges: 290-510 (n = 694), 511-710 (n = 780), 711-950 (n = 720) and 951-1560 pmol/l (n = 673). Fasting levels of glucose, insulin, HOMA IR (Homeostasis Model Assessment for Insulin Resistance) and BMI (body mass index) were compared by a relevant C-peptide range. Participants taking medication to control glycaemia were excluded. The evaluation involved correlations between C-peptides and the above parameters, F-test and t-test. Changes in glucose levels (from 5.3 to 5.6 mmol/l) between the groups were lower in comparison to insulin, which reached relatively greater changes (from 4.0 to 14.2 mIU/l). HOMA IR increased considerably with growing C-peptide concentrations (0.9, 1.5, 2.2 and 3.5) and BMI values showed a similar trend (28.3, 31.0, 33.6 and 37.4). Considerable changes were observed for insulin (5.2 mIU/l, 57.8%) and HOMA IR (1.3, 61.3%) between groups with C-peptide ranges of 711-950 and 951-1560 pmol/l. Although correlations involving C-peptide, insulin, glucose and BMI seemed to be non-significant (up to rxy = 0.25), the mean values of insulin, HOMA IR and BMI showed statistically significant changes between all groups with various C-peptide concentrations (p ≤ 0.001). Generally, most important differences appeared in glucose metabolism and body mass index between C-peptide ranges of 711-950 and 951-1560 pmol/l. Absolute and relative changes of C-peptide concentrations are possible to use for the assessment of glucose regulatory mechanism. The spectrum of investigated parameters could be a useful tool to prevent the risks linked with the alterations of glycaemia.
- MeSH
- bazální metabolismus MeSH
- C-peptid * analýza MeSH
- dospělí MeSH
- glukózový toleranční test MeSH
- index tělesné hmotnosti MeSH
- inzulin lidský analýza MeSH
- inzulinová rezistence MeSH
- krevní glukóza analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
Genome-wide association studies have revealed several gene variants associated with obesity; however, only a few studies have further investigated their association with metabolic syndrome. We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. Genotyping was performed in 1,443 adolescents aged 13.0-17.9 years. Anthropometric parameters, biochemical parameters and blood pressure were assessed. Metabolic syndrome was defined according to the International Diabetes Federation. The FTO rs9939609 variant was associated with overweight/obesity (OR 1.40, 95% CI 1.21-1.63, P < 0.001). The minor allele of TMEM18 rs7561317 was related to underweight (OR 1.78, 95% CI 1.14-2.79, P = 0.015). BDNF rs925946 and MC4R rs17782313 were associated with metabolic syndrome (OR 1.53, 95% CI 1.14-2.04, P = 0.005; 1.51, 95% CI 1.12-2.04, P = 0.009). The PCSK1 rs6235 variant was negatively related to increased blood glucose (OR 0.69, 95% CI 0.49-0.97, P = 0.040). In conclusion, the FTO variant was associated with overweight/obesity in Czech adolescents. Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. The PCSK1 variant may have a protective role in the development of type 2 diabetes.
- MeSH
- adipozita genetika MeSH
- antropometrie MeSH
- C-peptid analýza MeSH
- celogenomová asociační studie MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- hubenost epidemiologie genetika MeSH
- inzulin krev MeSH
- kohortové studie MeSH
- krevní glukóza analýza MeSH
- lidé MeSH
- lipidy krev MeSH
- metabolický syndrom krev epidemiologie genetika MeSH
- mladiství MeSH
- nadváha epidemiologie genetika MeSH
- obezita krev epidemiologie genetika MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- C-peptid analýza diagnostické užití metabolismus MeSH
- diabetes mellitus 1. typu diagnóza farmakoterapie terapie MeSH
- diabetes mellitus 2. typu diagnóza farmakoterapie terapie MeSH
- diabetes mellitus diagnóza farmakoterapie terapie MeSH
- farmakoterapie metody využití MeSH
- inzulin farmakologie škodlivé účinky terapeutické užití MeSH
- kongresy jako téma MeSH
- krevní glukóza analýza účinky léků MeSH
- lidé MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- novinové články MeSH
Adult pancreatic stem and progenitor cells could represent an alternative source of insulin-producing tissue for diabetes treatment. In order to identify these cells, we have focused on the human pancreatic cells expressing cell surface molecule CD133, a marker of adult stem cells. We found that population of human CD133-positive pancreatic cells contains endocrine progenitors expressing neurogenin-3 and cells expressing human telomerase, ABCG2, Oct-3/4, Nanog, and Rex-1, markers of pluripotent stem cells. These cells were able to differentiate into insulin-producing cells in vitro and secreted C-peptide in a glucose-dependent manner. Based on our results, we suppose that the CD133 molecule represents another cell surface marker suitable for identification and isolation of pancreatic endocrine progenitors.
- MeSH
- buněčná diferenciace MeSH
- buněčné kultury MeSH
- C-peptid analýza MeSH
- CD antigeny analýza MeSH
- financování organizované MeSH
- glykoproteiny analýza MeSH
- Langerhansovy ostrůvky cytologie fyziologie MeSH
- lidé MeSH
- magnetismus MeSH
- pankreas cytologie MeSH
- peptidy analýza MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- RNA genetika izolace a purifikace MeSH
- separace buněk metody MeSH
- Check Tag
- lidé MeSH
Atypický idiopatický diabetes 1b představuje zřejmě samostatnou nosologickou jednotku, zatím neznámé etiologie. Vzniká v dospělosti, má některé znaky diabetu 1. typu, chybí však přítomnost protilátek proti beta buňkám pankreatu a typické predisponující HLA haplotypy. V této práci uvádíme dvě kazuistiky tohoto onemocnění, které pokládáme po klinické stránce za velmi poučné.
Atypical adult-onset type 1 diabetes (1b) represents new nosological entity. It is a rare disease, representing only about 10 % of type 1 diabetes. It is characterized by clinical signs of type 1 diabetes, however the islet cell antibodies are lacking as well as the predisposing HLA haplotypes. We report on two cases of this atypical form of type 1 diabetes.
- MeSH
- C-peptid analýza krev MeSH
- cyklosporin aplikace a dávkování terapeutické užití MeSH
- diabetes mellitus 1. typu diagnóza farmakoterapie MeSH
- dítě MeSH
- lidé MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- klinické zkoušky kontrolované MeSH
