AimsTo assess the prevalence of ZnT8-ab and its correlation to other autoimmune markers and diabetic ketoacidosis occurrence in children and adults with T1DM onset. MethodsThe study included 367 patients (218 children; 149 adults) at the T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8-ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of HCO3 < 15 mmol/l, presence of ketone bodies in the blood and urine.ResultsThe autoantibodies pattern differs in both study groups. Children were mostly positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab (p < 0.0001) titers were significantly higher in children, but adults had higher titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p = 0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with ketoacidosis. A correlation between the number of positive antibodies and the severity of ketoacidosis was observed (Rs − 0.129 p = 0.014). ZnT8-ab were associated with a greater risk of ketoacidosis independent of gender, age group and the autoantibodies number [OR = 2.44 (95% CI 1.0–5.94), p = 0.04]. ConclusionsChildren are at greater risk of ketoacidosis at the diagnosis of diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute diabetes onset.Electronic supplementary materialThe online version of this article (10.1007/s00592-017-1091-x) contains supplementary material, which is available to authorized users.

Background. Diabetic ketoacidosis (DKA) is a life-threatening condition frequently present at type 1 diabetes diagnosis (T1D). Younger children are at greater risk of developing this acute complication. It is alarming due to worldwide rise in T1D incidence with the greatest increase in children aged < 5 years. The aim of this study was to identify the prevalence of DKA and factors related to its occurrence in children at T1D diagnosis from Wielkopolska province in Poland. Methods. The study cohort comprised 735 children (girls: 329; boys: 406) aged 0-18 years with new onset T1D admitted to one hospital between 2009 and 2014. The mean age at diagnosis was 9.3 years. DKA was defined as blood pH < 7.30. To confirm autoimmune diabetes origin typical autoantibodies were tested. Results. DKA was diagnosed in 36% of patients with newly diagnosed T1D. DKA occurred significantly more often in children aged < 4 years (p = 0.001). The highest prevalence of DKA was associated with symp-toms' duration (> 28 days) (p = 0.014) and diabetes misdiagnosis (p = 0.001). Autoantibody against zinc transporter 8 was detected significantly more often in children with DKA (p = 0.044). In the group with DKA, glycated hemoglobin level was significantly higher (p = 0.0004), while insulin and C-peptide levels were lower (p = 0.0001 and p = 0.0001, respectively). Conclusions. The prevalence of DKA is high and its severity is substantial in children with newly diagnosed T1D from Wielkopolska province. Diabetes misdiagnosis, symptoms' duration and age under 4 years are the most common risk factors of DKA development at T1D onset. Autoantibody against zinc transporter 8 is associated with acute T1D onset.

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.

Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing beta-cells in the pancreas, caused by the interplay of genetic and environmental factors. Despite the introduction of advanced technologies for diabetes management, most patients fail to achieve target glycemic control, and T1D still has a high burden of long-term end-organ complications. Over several decades, multiple clinical trials have attempted to find prevention for T1D in at-risk individuals or to stabilize, ultimately reverse, the disease in those with T1D. To date, T1D remains yet incurable condition; however, recently improved understanding of the natural history of the disease may lead to new strategies to preserve or improve beta-cell function in those at increased risk and T1D patients. This publication aims to provide an overview of past experiences and recent findings in the prevention of T1D.

There were 443 adolescents with type 1 diabetes recruited into the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and exposed to treatment with two oral drugsdan ACE inhibitor and a statindas well as combinations of both or placebo for 2-4 years. Adherence was assessed every 3 months with the Medication Event Monitoring System (MEMS) and pill count. RESULTSMedian adherence during the trial was 80.2% (interquartile range 63.6-91.8) based on MEMS and 85.7% (72.4-92.9) for pill count. Adherence based on MEMS and pill count dropped from 92.9% and 96.3%, respectively, at the first visit to 76.3% and 79.0% at the end of the trial. The percentage of study participants with adherence ≥75% declined from 84% to 53%. A good correlation was found between adherence based on MEMS and pill count (r 5 0.82, P < 0.001). Factors associated with adherence were age, glycemic control, and country. CONCLUSIONSWe report an overall good adherence to ACE inhibitors and statins during a clinical trial, although there was a clear decline in adherence over time. Older age and suboptimal glycemic control at baseline predicted lower adherence during the trial, and, predictably, reduced adherence was more prevalent in subjects who subsequently dropped out.Adherence to a medication regimen, defined as the extent to which a person's medication-taking behavior corresponds with the agreed recommendations from a health care provider, is a key determinant of response to therapy and patients' outcomes (1). Adherence is a complex and multifactorial paradigm that varies depending on the disease and treatment regimen and is also influenced by physicianand patient-related factors (1-3).

Introduction: type 1 diabetes (t1D) is caused by the autoimmune destruction of pancreatic β cells, resulting from coincident genetic predisposition and some environmental triggers. signal transducer and activator of transcription 4 (stat4) gene encodes a transcription factor, which promotes th1 cell differentiation, interferon γ production, and development of th17 cells. Polymorphisms of stat4 are associated with several autoimmune conditions, while studies in t1d provided inconsistent results. this analysis was designed to investigate the association of stat4 rs7574865 with t1d in Polish children and to assess stat4 expression in newly diagnosed subjects. Material and methods: rs7574865 was genotyped in 656 t1d children and 782 healthy individuals. stat4 mrna expression was analyzed in peripheral blood mononuclear cells (PBMcs) from 29 children with t1d and 27 age-matched controls. β-cell and thyroid-specific serum autoantibodies were assessed with radioimmunoassays. Results: the distribution of rs7574865 genotypes and alleles demonstrated significant difference (p = 0.002, p < 0.001, respectively) between patients vs. controls. carriers of the minor t allele presented earlier t1d onset (p = 0.017). no differences were found in β-cell autoantibody in genotype-stratified patients (p > 0.050), while anti-thyroid antibodies were more frequent in carriers of the minor allele (p = 0.039 for anti-thyroperoxidase, p = 0.007 for anti-thyroglobulin antibodies, respectively). stat4 was overexpressed in PBMcs from t1d patients (p = 0.008), especially subjects with two/three circulating β-cell antibodies (p < 0.001). Conclusions: the study confirms an association of stat4 rs7574865 with t1d in Polish patients, and provides an evidence for its relationship with an earlier disease onset and concomitant thyroid autoimmunity. stat4 expression appears elevated in t1d, especially with more severe reaction against β-cell antigens.

INTRODUCTION    Regulated on activation, normal T‑cell expressed and secreted chemokine (RANTES), the product of the CCL5 gene, is involved in trafficking immune cells into the inflammation site. It acts as coactivator of T cells and promotes polarization of the immune response towards the Th1 profile. In autoimmune Addison disease (AAD), the adrenal cortex is gradually destroyed by adrenal‑specific immune cell infiltration. RANTES might be implicated in autoimmune adrenal failure through recruitment and activation of the immune cells. Furthermore, the promoter CCL5 variant, rs2107538, seems to be associated with autoimmune endocrine conditions: diabetes and thyroid disease. OBJECTIVES    Our analysis was designed to evaluate the prevalence of rs2107538 and serum RANTES levels in AAD. PATIENTS AND METHODS    rs2107538 was genotyped using TaqMan technology in 239 individuals with AAD and 542 controls, while serum RANTES levels were evaluated by an enzyme‑linked immunosorbent assay in 114 patients with AAD and 111 healthy age- and sex‑matched individuals. RESULTS    No differences were found in rs2107538 genotype or allele frequencies between patients and controls (P = 0.53 and P = 0.39, respectively), and no association was detected with age at AAD onset (P = 0.14). Serum RANTES levels were elevated in patients with AAD compared with controls (mean [SD], 59.2 [30.3] ng/ml vs 45.5 [20.4] ng/ml, P = 0.001). Healthy carriers of various rs2107538 genotypes demonstrated differences in serum RANTES levels (P = 0.02), whereas AAD patients did not (P = 0.26). No correlation was found between circulating RANTES levels and age, AAD duration, serum autoantibodies, hydrocortisone dose, and body mass (P >0.05). CONCLUSIONS    This study demonstrates for the first time elevated serum RANTES levels in AAD and confirms that rs2107538 may affect serum chemokine levels.

Purpose of review Individuals with type 1 diabetes (T1D) have excess cardiovascular risk and reduced life expectancy. Adolescence is the time when the first signs of vascular complications appear and a critical window for interventions. This article reviews recent evidence on cardiometabolic risk factors and their management in youth with T1D. Recent findings Adolescents with T1D show early signs of vascular complications, as a result of several cardiometabolic risk factors. Poor glycemic control is one of the main risk factors and the main target of treatment. However, only a minority of adolescents with T1D reaches recommended targets for glycemic control. Hypertension, dyslipidemia, smoking, alcohol use, obesity and insulin resistance are other common cardiometabolic risk factors in this age group. Recent data confirm that screening for these risk factors is suboptimal and use of pharmacological interventions for hypertension and dyslipidemia remains low. Data on adjunctive noninsulin agents to improve glycemic control and other cardiometabolic risk factors are still lacking in this age group. Summary Vascular complications and the associated mortality remain a major issue for youth with T1D. Better screening strategies for cardiometabolic risk factors and interventions are required to improve the long-term prognosis of youth with T1D.