Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterised by a destruction of pancreatic β cells, which leads to absolute insulin deficiency. Persistently high glycaemia causes vascular damage throughout the body. Microvascular complications comprise the following: nephropathy, retinopathy, and neuropathy. Macrovascular complications include coronary heart disease (CHD), which may result in myocardial infarction, cerebrovascular disease (leading to strokes), and peripheral vascular disease. The pathogenesis of vascular complications is multifactorial and is probably the combination of direct glucose-mediated endothelial damage, oxidative stress, production of sorbitol, and advanced glycation end-products. Precise understanding of these mechanisms could help clinicians to identify diabetic complications earlier and subsequently implement indispensable therapy on time. It is vital to determine biomarkers of microvascular and macrovascular complications in children affected with T1DM. Advanced glycation end-products and their receptors, adhesive molecules, pro-and anti-inflammatory cytokines, enzymes such as N-acetyl-β-D-glucosaminidase, and growth factors are the subject of ongoing studies. Numerous biomarkers of diabetic microangiopathy are already known and may constitute therapeutic targets in the future. Unfortunately, despite substantial progress in the understanding of the processes by which microvascular and macrovascular complications develop, much effort still needs to be devoted to the matter, and further investigations are required.
Background There are several observations that the onset of coronavirus 19 (COVID‐19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country‐specific healthcare policies, more national‐level evidence is needed to provide generalizable conclusions. Objective To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID‐19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). Methods Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new‐onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily‐reported number of COVID‐19‐related deaths in each region. Results We recorded 3062 cases of new‐onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre‐ and post‐COVID‐19 period, we observed a significant increase in the rate of DKA (37.5%–49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly ( p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID‐19 death toll (March/April 2020) ( R = .6, p = .0287) and change in T1D incidence ( R = .7, p = .0080). Conclusions The clinical picture of new‐onset children T1D in Poland deteriorated over a 2‐year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID‐19 epidemic.
ObjectiveHere we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets.Research design and methodsWe compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs.ResultsPatients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vβ/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures.ConclusionsT1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs.Trial registration numberEudraCT 2014-004319-35.
Aims: Monotherapy with autologous expanded CD4 + CD25 high CD127 À T regulatory cells (Tregs) or rituximab has been documented to slow disease progression in patients with recent-onset type 1 diabetes mellitus (T1DM). Whether a combined therapy including both drugs would further benefit this patient population is unknown. Materials and Methods:We conducted a three-arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n = 13), Tregs + rituximab (n = 12) and control (n = 11). The key primary efficacy analyses were C-peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24 months.Results: At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C-peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24 months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21 months but not at 18 and 24 months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%. Maciej Zieli nski, Magdalena _ Zali nska contributed equally to this work.
In spite of continuous diabetes care, adolescents with T1D do not possess sufficient knowledge regarding the consequences of hyperglycemia during pregnancy. This study has emphasized the need for including reproductive health issues in diabetes education addressed to adolescent patients.
Introduction Transcutaneous oxygen pressure (tcPO 2 ) is a non-invasive method of measuring skin oxygenation that may reflect its superficial perfusion. Skin microvasculature may be impaired in patients with late onset of type 1 diabetes (DM1). However, its condition in children has not been fully determined. Aim To compare tcPO 2 in children with short-lasting non-complicated DM1 and age-matched healthy controls with regard to concomitant vascular risk factors. Material and methods The study group consisted of 51 paediatric patients aged 14.9 (8.4–18.0) years with short-lasting DM1 without clinical evidence of diabetic micro- or macroangiopathy and 28 control subjects aged 14.8 (11.3–17.7) years. TcPO 2 was tested prior, during and after applying post-occlusive reactive hyperaemia (PORH) test in standardized conditions. Biochemical parameters were assessed and then compared between the groups. Results TcPO 2 at maximal ischemia during PORH was higher in the DM1 patients than in healthy controls (2.4 (0.7–18.8) vs. 1.6 (0.4–12.0), p = 0.002). No differences were found regarding the tcPO 2 measurements recorded prior to ischemia or after recovery. In DM1, concentrations of total cholesterol, triglycerides, HbA 1c and TSH were significantly higher than in healthy controls. The fT4 levels were significantly lower in the DM1 group. After adjusting for lipid levels, no differences in tcPO 2 were found, and a multivariate analysis showed the cholesterol levels have a significant impact on tcPO 2 response to maximal ischemia. Conclusions Our results indicate that increased lipid levels are responsible for the impaired skin response to ischemic stimuli in short-lasting DM1. This supports the importance of aggressive lipid control in prevention of early onset microangiopathy in those patients.
Familial hypercholesterolemia (FH) is the most common monogenic autosomal dominant disorder. FH results in an increased cardiovascular mortality rate. However, cardiovascular risk control factors enable the avoidance of approximately 80% of strokes and cardiovascular diseases. Therefore, early detection and implementation of lipid-lowering treatment is essential. In the present study, 57 pediatric patients aged 9.57 ± 3.26 years with FH were enrolled in the study. Researchers checked the lipid profile and performed the ultrasound imaging including intima-media thickness (IMT) measurement and echo (e)-tracking in the study group. Patients were treated with a low-cholesterol diet solely or along with pharmacological treatment with statins. Subsequently, patients were monitored for 12 months. The positive results of dietary treatment were observed in 40 patients. The efficacy of 12 months of nutritional therapy along with pharmacological treatment was reported in 27 patients. We observed a significant decrease in the carotid beta index stiffness and an insignificant decrease in the IMT in the group of patients treated with statins. The obtained data show that statin therapy in children with FH allow for the reduction of the degree of atherosclerotic vessel changes.
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