Inflammation and Neurodegeneration in Glaucoma: Isolated Eye Disease or a Part of a Systemic Disorder? - Serum Proteomic Analysis.

Introduction: Glaucoma is the most common optic neuropathy and the leading cause of irreversible blindness worldwide, which affects 3.54% of the population aged 40-80 years. Despite numerous published studies, some aspects of glaucoma pathogenesis, serum biomarkers, and their potential link with other diseases remain unclear. Recent articles have proposed that autoimmune, oxidative stress and inflammation may be involved in the pathogenesis of glaucoma. Methods: We investigated the serum expression of 92 inflammatory and neurotrophic factors in glaucoma patients. The study group consisted of 26 glaucoma patients and 192 healthy subjects based on digital fundography. Results: Patients with glaucoma had significantly lower serum expression of IL-2Rß, TWEAK, CX3CL1, CD6, CD5, LAP TGF-beta1, LIF-R, TRAIL, NT-3, and CCL23 and significantly higher expression of IL-22Rα1. Conclusion: Our results indicate that patients with glaucoma tend to have lower levels of neuroprotective proteins and higher levels of neuroinflammatory proteins, similar to those observed in psychiatric, neurodegenerative and autoimmune diseases, indicating a potential link between these conditions and glaucoma pathogenesis.

Long-term effects of COVID-19 on the endocrine system - a pilot case-control study.

Background: Coronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection. Methods: We compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol. Results: We found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors. Conclusion: Our study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels.

Immune Response to Vaccination against COVID-19 at Different Second-Dose Intervals and Their Associations with Metabolic Parameters.

Obesity and diabetes are associated with severe outcomes of coronavirus disease (COVID-19). Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven protective against infection and severe COVID-19. However, the immune response of metabolically burdened individuals to the vaccines remains unclear. Thus, we aimed to assess whether the metabolic status of individuals affects their humoral immune responses to the vaccination. Moreover, we evaluated whether the interval between the first two doses influenced antibody concentration. Sixty-seven individuals (21 males, 46 females) were vaccinated with the BNT162b2 mRNA COVID-19 vaccine. Fifty-four individuals were vaccinated with the second dose after 3 weeks and 13 after 5 weeks. We measured the antibody titers in all participants during the 19-week follow-up period. Patients diagnosed with COVID-19 were excluded. In the 5-week interval group, a significantly higher level of maximal antibody titers was observed. However, there were no differences in antibody concentrations after 19 weeks and no significant correlation between cardiometabolic factors and humoral response. The elongation of second-dose timing to 5 weeks leads to a higher acute antibody response but does not change long-term levels of antibody titers. Moreover, dysregulation of metabolic parameters does not lead to a diminished immune response to vaccination.

Atypical diabetes mellitus in children - when to suspect drug-induced diabetes. A case-based review of the literature.

INTRODUCTION: Drug-induced diabetes mellitus (DIDM) could be defined as a heterogenic group of diabetes caused by pharmacotherapy. The DIDM is considered to be reversible after discontinuation of diabetogenic treatment, but there is a risk of persistence, which is related to the duration of treatment, prescribed medication, and body mass index. CASE PRESENTATION: A 13-year-old boy treated for nephrotic syndrome with the use of tacrolimus and prednisone was diagnosed with diabetes during a check-up visit. On admission, he showed a cushingoid appearance and complained of dry mouth, which was not accompanied by polyuria or polydipsia. Blood tests showed elevated levels of glucose, and glycated A1c fraction of haemoglobin (HbA1c = 10.2%). Pancreatic islet autoantibodies were negative. The fasting and postprandial C-peptide levels were within the normal range. Diabetic ketoacidosis was excluded. Intensive insulin therapy was initially introduced; the daily dose of insulin per kilogram was low (TDD/kg = 0.31 U/kg). Those findings prompted us to consider diabetes mellitus type 2 or DIDM. Moreover, the TDD/kg and HbA1c additionally decreased after the steroid withdrawal. Because he was constantly on diabetogenic therapy and experienced periodical hyperglycaemia, DIDM could not be excluded. Therefore, our patient remained on insulin treatment. CONCLUSIONS: DIDM in children is challenging for all specialists. Diabetologists need to remember about this rare subtype of diabetes, and other specialist should perform screening on their patients who are at risk of DIDM. There is a great need for guidelines that would provide a standardized approach for diagnosing and treating DIDM in the paediatric population.

Coincidence of juvenile idiopathic arthritis and type 1 diabetes: a case-based review.

The study was aimed to review a rare coexistence of type 1 diabetes (T1D) and juvenile idiopathic arthritis (JIA) regarding different clinical approaches to the management and treatment options. Medical complications of the two autoimmune disorders in children and adolescents have been evaluated, particularly in those treated with glucocorticosteroids (GCS) and insulin. A review of the literature regarding reports on concomitant T1D and JIA was conducted using resources available in Medline, Google Scholar, and Web of Science databases, with a specific focus on the combination of T1D and JIA in a pediatric population. The review was extended by our analysis of two patients treated in a single center for this comorbidity. Eligible reports of four cases were found, and including our two original records, a total of six pediatric patients (5 females) were analyzed, of which three had also other autoimmune diseases (thyroiditis, coeliac disease, autoimmune hepatitis), whereas four had been treated with a long-term GCS, and two were receiving biological therapy (etanercept or adalimumab). Only one of them had good metabolic control of diabetes. Diabetes in childhood may coexist with other autoimmune diseases, including rheumatologic conditions. Hyperglycemia can worsen JIA therapy by induction and maintaining inflammation. Using modern diabetes technologies (like personal insulin pumps and continuous glucose monitoring) helps to minimize the deteriorating effect of JIA exacerbations and the rheumatoid treatment on metabolic control of diabetes.

Increasing Co-occurrence of Additional Autoimmune Disorders at Diabetes Type 1 Onset Among Children and Adolescents Diagnosed in Years 2010-2018-Single-Center Study.

Objectives: The prevalence of type 1 diabetes mellitus (T1D) in children is growing, but its relation to other autoimmune disorders that coexist since the onset of diabetes is not recognized. The objective of this study was to assess the incidence of T1D and the prevalence of autoimmune illnesses additionally coexisting since the diabetes mellitus onset in children during a period of 9 years' observation. Methods: In this retrospective study, the incidence rate (IR) of the T1D was calculated as the total number of all cases that were newly diagnosed per 100,000 population people between 0 and 18 years of age. The selected age groups (0-4, 5-9, 10-14, and 15-18 years) were examined, respectively. The studied group included 493 children (264 [53.55%] boys) between 0 and 18 years old newly diagnosed with T1D in one of the Polish centers in the years 2010-2018. Other autoimmune illnesses diagnoses were obtained from medical records taken from the first hospital treatment, when T1D was recognized. Results: The annual standardized IR of T1D increased from 19.2/100,000 in year 2010 to 31.7/100,000 in 2018 (1.7-fold over 9 years' observation), with an increase in the incidence rate ratio (IRR) by 4% per year. The highest growth in IR was recorded in 5- to 9-year-olds (from 19.61 in 2010 to 43.45 in 2018). In 61 (12.4%) of the studied group, at least one additional autoimmune disease was diagnosed. The prevalence doubled from 10.4% in the year 2010 to 20.8% in the year 2018. Autoimmune thyroid illnesses were found in 37 children (7.5%); their incidence increased from 6.3% to almost 2-fold, 12.5%, in 2018. In 26 children (5.3%), celiac disease was recognized; the prevalence increased from 4.2 to 9.8% in the study period. The prevalence of additional autoimmune thyroid disease was higher in glutamic acid decarboxylase-positive antibodies (χ2 = 3.4, p = 0.04) patients, the oldest age group (15-18 years) (χ2 =7.1, p = 0.06), and in girls (χ2 =7.1, p = 0.007). Conclusions:The standardized IR of T1D in children increased 1.7-fold over the 9-year observation period, and IRR increased 4% per year. Additional autoimmunity represents a significant comorbidity in patients with new-onset T1D. The number of children diagnosed with additional autoimmune diseases that accompany T1D is rapidly growing in all age groups throughout recent years.