Pacient byl dlouhou veden a léčen pod diagnózou diabetes mellitus 2. typu. Laboratorní hodnoty potvrzovaly společně s přítomnou arteriální hypertenzí diagnostická kritéria syndromu inzulínové rezistence. Tato kombinace vyústila v mnohočetné závažné specifické i nespecifické komplikace diabetu. Jistá liknavost pacienta vedla ke zpomalení diagnostického procesu, nicméně průkaz významného poklesu sekrece inzulínu a přítomnost protilátek antiGAD vedly k překvalifikování diagnózy na LADA s možností využití moderní a bezpečné intervence inzulínovou pumpou MiniMed 780G, propojenou v okruhu se senzorem. Výsledek byl velmi pozitivní stran zlepšení kompenzace diabetu, během dvou měsíců se glykovaný hemoglobin snížil z 88 na 45 mmol/mol bez komplikací. Předkládaná kazuistika upozorňuje na potřebu neustále přehodnocovat „diagnózu“ typu diabetu s cílem optimalizovat terapii.
The patient was managed and treated for a long time under the diagnosis of type 2 diabetes mellitus. Laboratory values, together with the presence of arterial hypertension, confirmed the diagnostic criteria of insulin resistance syndrome. This combination has resulted in multiple severe specific and non-specific complications of diabetes. A certain idleness of the patient led to a slowdown of the diagnostic process. However, evidence of a significant decrease in insulin secretion and the presence of anti-GAD antibodies led to reclassification of the diagnosis to LADA with the possibility of using a modern and safe intervention with a MiniMed 780G insulin pump connected in a circuit with a sensor. The result was very positive in terms of improvement in diabetes control, glycohaemoglobin decreased from 88 to 45 mmol/mol within 2 months without complications. The presented case report draws attention to the need to constantly reassess the diagnosis of the type of diabetes in order to optimize the therapy.
- Keywords
- Sapirova-Whorfova hypotéza,
- MeSH
- C-Peptide analysis blood MeSH
- Diabetes Mellitus, Type 2 * diagnosis drug therapy MeSH
- Glycated Hemoglobin analysis MeSH
- Insulin Resistance MeSH
- Latent Autoimmune Diabetes in Adults diagnosis drug therapy MeSH
- Humans MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
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
- CD3 Complex antagonists & inhibitors immunology MeSH
- Insulin-Secreting Cells drug effects immunology MeSH
- C-Peptide analysis MeSH
- Diabetes Mellitus, Type 1 * diagnosis immunology therapy MeSH
- Child MeSH
- Double-Blind Method MeSH
- Antibodies, Monoclonal, Humanized * adverse effects pharmacology therapeutic use MeSH
- Hypoglycemic Agents administration & dosage therapeutic use MeSH
- Insulin administration & dosage therapeutic use MeSH
- Humans MeSH
- Adolescent MeSH
- Disease Progression MeSH
- T-Lymphocytes drug effects immunology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Randomized Controlled Trial 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
- Atherosclerosis epidemiology metabolism MeSH
- C-Peptide * analysis metabolism MeSH
- Adult MeSH
- Blood Glucose analysis metabolism MeSH
- Cholesterol, LDL analysis metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Fasting blood metabolism MeSH
- Cross-Sectional Studies statistics & numerical data MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged MeSH
- Publication type
- Research Support, Non-U.S. Gov't 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
- Basal Metabolism MeSH
- C-Peptide * analysis MeSH
- Adult MeSH
- Glucose Tolerance Test MeSH
- Body Mass Index MeSH
- Insulin, Regular, Human analysis MeSH
- Insulin Resistance MeSH
- Blood Glucose analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged MeSH
- Statistics as Topic MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged MeSH
- Publication type
- Clinical Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- C-Peptide * analysis urine secretion MeSH
- Diabetes Mellitus, Type 1 MeSH
- Insulin * analysis secretion MeSH
- Creatinine analysis urine MeSH
- Humans MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't 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
- Adiposity genetics MeSH
- Anthropometry MeSH
- C-Peptide analysis MeSH
- Genome-Wide Association Study MeSH
- Gene Frequency MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Thinness epidemiology genetics MeSH
- Insulin blood MeSH
- Cohort Studies MeSH
- Blood Glucose analysis MeSH
- Humans MeSH
- Lipids blood MeSH
- Metabolic Syndrome blood epidemiology genetics MeSH
- Adolescent MeSH
- Overweight epidemiology genetics MeSH
- Obesity blood epidemiology genetics MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- MeSH
- C-Peptide analysis diagnostic use metabolism MeSH
- Diabetes Mellitus, Type 1 diagnosis drug therapy therapy MeSH
- Diabetes Mellitus, Type 2 diagnosis drug therapy therapy MeSH
- Diabetes Mellitus diagnosis drug therapy therapy MeSH
- Drug Therapy methods utilization MeSH
- Insulin pharmacology adverse effects therapeutic use MeSH
- Congresses as Topic MeSH
- Blood Glucose analysis drug effects MeSH
- Humans MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Newspaper Article 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
- Cell Differentiation MeSH
- Cell Culture Techniques MeSH
- C-Peptide analysis MeSH
- Antigens, CD analysis MeSH
- Financing, Organized MeSH
- Glycoproteins analysis MeSH
- Islets of Langerhans cytology physiology MeSH
- Humans MeSH
- Magnetics MeSH
- Pancreas cytology MeSH
- Peptides analysis MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- RNA genetics isolation & purification MeSH
- Cell Separation methods MeSH
- Check Tag
- Humans MeSH
- MeSH
- C-Peptide analysis blood MeSH
- Cyclosporine administration & dosage therapeutic use MeSH
- Diabetes Mellitus, Type 1 diagnosis drug therapy MeSH
- Child MeSH
- Humans MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Controlled Clinical Trial MeSH
