Excessive BMI is associated with higher C-peptide level at recognition but also with its greater loss in two years clinical observation in children with new onset type 1 diabetes.

Introduction: The prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual ß-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation. Methods: We assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and ß-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients' levels of selected inflammatory cytokines at baseline. Results: Subjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group. Discussion: Higher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual ß-cell function. The process seems to be mediated by inflammatory cytokines.

The Relationship between Selected Inflammation and Oxidative Stress Biomarkers and Carotid Intima-Media Thickness (IMT) Value in Youth with Type 1 Diabetes Co-Existing with Early Microvascular Complications.

Recent years have confirmed the importance of oxidative stress and biomarkers of inflammation in estimating the risk of cardiovascular disease (CVD) and explaining not fully understood pathogenesis of diabetic macroangiopathy. We aimed to analyze the relation between the intima-media thickness (IMT) of common carotid arteries and the occurrence of classical cardiovascular risk factors, together with the newly proposed biomarkers of CVD risk (high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), adiponectin, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and vitamin D) in youth with type 1 diabetes (T1D) recognized in screening tests to present early stages of microvascular complications (VC). The study group consisted of 50 adolescents and young adults with T1D, mean age 17.1 years (10-26 age range), including 20 patients with VC (+) and 30 VC (-). The control group (Control) consisted of 22 healthy volunteers, mean age 16.5 years (11-26 age range). In the VC (+) patients, we found a significantly higher concentration of HbA1c, lipid levels, hsCRP and NT-proBNP. BMI and blood pressure values were highest in the VC (+) group. Higher levels of MPO and lower levels of vitamin D were found in both diabetic groups vs. Control. IMT in VC (+) patients was significantly higher and correlated positively with HbA1c, hsCRP, NT-pro-BNP and negatively with vitamin D levels. In conclusion, youth with T1D and VC (+) present many abnormalities in the classical and new CVD biomarkers. hsCRP and MPO seem to be the most important markers for estimating the risk of macroangiopathy. NT-proBNP may present a possible marker of early myocardial injury in this population.

Prevalence of Metabolic Syndrome in Relation to Cardiovascular Biomarkers and Dietary Factors among Adolescents with Type 1 Diabetes Mellitus.

The occurrence of metabolic syndrome (MetS) significantly affects the course of diabetes mellitus (DM), resulting in deterioration of insulin sensitivity and metabolic control, as well as many cardiometabolic complications. The aim of the study was to investigate the relationships between cardiovascular biomarkers, nutritional status, dietary factors and the occurrence of MetS among 120 participants from northeast Poland (adolescents with type 1 DM and healthy peers). MetS was assessed using several criteria: nutritional status by anthropometric measurements, body composition analysis by bioelectrical impedance, and diet using a food diary and questionnaire. MetS was diagnosed in every third diabetic. Compared to healthy peers, MetS patients had higher total body fat (26% vs. 14%, p < 0.001) and visceral fat (77 cm2 vs. 35 cm2, p < 0.001), and lower total antioxidant status (1.249 mmol/L vs. 1.579 mmol/L, p < 0.001). Additionally, their diet was rich in saturated fatty acids, but low in dietary fiber as well as mono- and polyunsaturated fatty acids. The group of diabetics reported many inappropriate eating behaviors. The combination of those with the presence of an excessive content of visceral fat tissue and abnormal values of MetS components may negatively affect metabolic control, thus accelerating the development of cardiometabolic complications.

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.

Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes.

INTRODUCTION: The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). AIM OF THE STUDY: Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. MATERIALS AND METHODS: The study consisted of 138 patients aged 5-18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p < 0.05. RESULTS: The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. CONCLUSIONS: Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.

Assessment of Serum Concentrations of Ghrelin, Obestatin, Omentin-1, and Apelin in Children with Type 1 Diabetes.

The increasing knowledge on the functions of gastric peptides and adipokines in the body allows the assumption of their major role linking the process of food intake, nutritional status, and body growth, largely through the regulation of glucose metabolism and insulin resistance. The aim of the study was the assessment of serum levels of selected gastric peptides and adipocytokines in children with type 1 diabetes, with respect to the disease duration. The study involved 80 children aged 4-18 years (M/F -37/43). Children with type 1 diabetes (n = 46) were compared to the control group (n = 34). The study group was divided into 4 subgroups: (I) patients with newly diagnosed type 1 diabetes, after an episode of ketoacidosis (n = 10), (II) patients with type 1 diabetes of duration no longer than 5 years (n = 9), (III) patients with 5 to 10 years of DT1 (n = 20), and (IV) patients with type 1 diabetes of duration longer than 10 years (n = 7). The concentrations of gastric peptide and adipocytokines across all subgroups were lower than in the control group. The differences were statistically significant (p < 0.0001), which may be of importance in the development of the disease complications.

[Epidemiology of diabetes type 1 in children aged 0-14 in Podlasie Province in years 2005-2012]. / Epidemiologia cukrzycy typu 1 wsród dzieci w wieku 0­14 lat w makroregionie podlaskim w latach 2005­2012.

INTRODUCTION: Epidemiological studies performed during last decades in many European countries and in the world proved increasing incidence rate of diabetes, especially diabetes type 1 in children (DMT1). In Europe there is one of the highest diabetes incidence rate. The aim of the study was to estimate the incidence rate of diabetes type 1 in children aged 0-14 years in North-East Poland during 2005-2012 years and to analyse this rates in relation to age, gender and season of the diabetes onset. PATIENTS AND METHODS: The study was performed among patients staying under care of outpatient diabetes clinic of the Department of Pediatric, Endocrinologym Diabetology with Cardilogy Division, medical University of Bialystok, Poland. The DMT1 incidence rate was calculated as the number of all newly diagnosed cases per 100 000 persons 0-14 aged matched. RESULTS: During the studied 8-years- period DMT1 was diagnosed in 306 children aged 0-14 years, 159 boys and 147 girls, in Podlasie Province. The highest number of new cases was found in 2011: 49, and 2012: 47, with the lowest number in 2005 and 2009: 32 each year. The average incidence rate in the studied period was 20,84/100 000 population, aged matched. The lowest incidence rate was found in 0-4 yrs old group: 14,59 /100 000, in 5-9 years old group was: 22,04/100 000, and was highest in 10-14 years old group: 24,94/100 000. The highest increase in incidence rate was noted in the youngest group: from 9,14/100 000 in 2005, to 23,45/100 000 in 2012. The greatest number of new recognisions was found in from November to March, and the lowest number from June to August. CONCLUSIONS: 1. The DMT1 incidence rate among children aged 0-14 years, in Podlasie Province, during 2005-2012 years was 20,84/100 000. 2. Increase in incidence rate was observed in the studied period from 15,23/100 000 in 2005 to 26,71/100 000 in 2012. The highest increase in incidence rate, 2,5 times, was fund in the youngest group, aged 0-4 years. 3. The seasonal incidence of New onset was observed with the greater number in autumn-winter months.

[Risk factors for cardiovascular disease in children with type 1 diabetes in 2000-2010 in Podlasie Province]. / Wystepowanie czynników ryzyka chorób sercowo-naczyniowych u dzieci z cukrzyca typu 1 w latach 2000-2010 na terenie województwa podlaskiego.

INTRODUCTION: There has been an increase over the last decade in the number of young patients with type 1 diabetes treated with a continuous subcutaneous insulin infusion (CSII). The accelerated development of atherosclerosis is closely linked to metabolic control and traditional risk factors. AIM: Analysis of changes in the treatment and clinical picture of type 1 diabetes in children over the years 2000-2010, with emphasis on risk factors for cardiovascular disease. MATERIALS AND METHODS: The study included 567 children diagnosed with type 1 diabetes. 251 children who were treated in 2000 were compared with 316 children treated in 2010. The study analyzed anthropometric parameters, laboratory tests and data obtained using questionnaires. RESULTS: In 2010, there was an increase in the percentage of children treated with CSU (up to 60.1%) and a decrease in the percentage of children using traditional insulin In favour of insulin analogues. An increase in HbA1c was observed from 7.4% to 8% (p < 0.001) and an increase in the percentage of patients with HbA1c>7.5%. There was an increase in the percentage of children with obesity from 5.2% to 13.7% (p =0.004) and an increase in BMI SDS. The number of children with hypertension was comparable in both groups (17.9% vs 15.8%), as was the percentage of children with dyslipidemia (48.6% ys 513%). Antihypertensive drugs were used in 97.8% vs. 70% of children with hypertension, metformin in 15.4% vs. 14% of children with obesity, and lipid-lowering drugs only in 3.3% vs; 2.5% of patients with dyslipidemia. It has been shown that nowadays children live in families burdened with risk factors for atherosclerosis. CONCLUSIONS: Contemporary patients frequently have excessive body weight and live in families burdened with risk factors for atherosclerosis. Despite the use of modern technology, metabolic control is not satisfactory.

NS3 Peptide, a novel potent hepatitis C virus NS3 helicase inhibitor: its mechanism of action and antiviral activity in the replicon system.

Hepatitis C virus (HCV) chronic infections represent one of the major and still unresolved health problems because of low efficiency and high cost of current therapy. Therefore, our studies centered on a viral protein, the NS3 helicase, whose activity is indispensable for replication of the viral RNA, and on its peptide inhibitor that corresponds to a highly conserved arginine-rich sequence of domain 2 of the helicase. The NS3 peptide (p14) was expressed in bacteria. Its 50% inhibitory activity in a fluorometric helicase assay corresponded to 725 nM, while the ATPase activity of NS3 was not affected. Nuclear magnetic resonance (NMR) studies of peptide-protein interactions using the relaxation filtering technique revealed that p14 binds directly to the full-length helicase and its separately expressed domain 1 but not to domain 2. Changes in the NMR chemical shift of backbone amide nuclei ((1)H and (15)N) of domain 1 or p14, measured during complex formation, were used to identify the principal amino acids of both domain 1 and the peptide engaged in their interaction. In the proposed interplay model, p14 contacts the clefts between domains 1 and 2, as well as between domains 1 and 3, preventing substrate binding. This interaction is strongly supported by cross-linking experiments, as well as by kinetic studies performed using a fluorometric assay. The antiviral activity of p14 was tested in a subgenomic HCV replicon assay that showed that the peptide at micromolar concentrations can reduce HCV RNA replication.