Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

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.

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.

Above 40% of Polish children and young adults with type 1 diabetes achieve international HbA1c target - results of a nationwide cross-sectional evaluation of glycemic control: The PolPeDiab HbA1c study.

BACKGROUND: Youth with type 1 diabetes (T1D) (16-18 y.o.) present worst disease control of all age groups and need structured interventions. Those should be based on unbiased, national-scale outcomes, which have not yet been successfully assessed in Poland. OBJECTIVE: To evaluate the glycemic control in young patients with T1D in Poland. METHOD: All pediatric diabetes care centers and the nine largest centers for adults with T1D were invited to this cross-sectional study, conducted in March 2018. Eligibility was defined as age ≤ 30 years and diabetes duration ≥1 year. Blinded samples of capillary blood and clinical questionnaires were sent to coordinating center, where HbA1c was measured by high-pressure liquid chromatography. RESULTS: Nine adult and 25/28 pediatric centers participated, providing data for 1255 patients (50.8% males), mean age 12.3 years (95%CI:12.1-12.6) for children and 23.2 years (22.9-23.6) for adults; mean diabetes duration 7.1 years (6.8-7.3). This covered ~8% of pediatric population and 2% of 18-30-years-olds with T1D. Mean HbA1c was comparable between children and adults (57 mmol/mol [7.4%], 95%CI:56-57 mmol/mol [7.3-7.4%] vs. 57 mmol/mol [7.4%], 95%CI:56-60 mmol/mol [7.3-7.6%], p = 0.1870). Overall, 45.2% of patients achieved ISPAD target (<53 mmol/mol [<7.0%]). During the month preceding the study, 0.9% of patients experienced severe hypoglycemia and 0.4% suffered ketoacidosis. HbA1c was related to the method of insulin therapy, continuous glucose monitoring use and body weight (p < 0.0001). CONCLUSIONS: In Polish children and young adults with T1D glycemic control expressed as HbA1c is promising in the light of ISPAD guidelines. Our results confirm the known associations between better glycemic control and the use of new technologies and maintaining optimal body weight.

Regular physical activity as a physiological factor contributing to extend partial remission time in children with new onset diabetes mellitus-Two years observation.

BACKGROUND: Beneficial effects of physical activity (PA) are confirmed in patients with all types of long-lasting diabetes. The possibility of PA to be a factor prolonging remission phase in children with new-onset type 1 diabetes (T1D) has not yet been thoroughly studied. OBJECTIVE: The aim of the study was to elucidate the influence of regular PA on prevalence of partial remission (PR), metabolic control, daily insulin requirement (DIR), and C-peptide secretion in children newly diagnosed with T1D. METHODS: A total of 125 children diagnosed with T1D were studied prospectively for 2 years. Patients were controlled every 3 months and advised with PA according to ISPAD recommendations. Anthropometric parameters, HbA1c, C-peptide level and DIR were analyzed. Patients' PA level was assessed using a self-designed questionnaire. RESULTS: We classified 43% of participants as physically-active. In this group, lower HbA1c after 2 years, lower DIR after 3, 6 months, and after 2 years (all P < .05) were found. At discharge from hospital, the prevalence of DIR < 0.5 U/kg/24 h with near normoglycemia was similar in both groups. Then, we observed higher PR prevalence in active group lasting over time and resulting in 44% vs 13% after 2 years (P < .001). C-peptide after 2 years was comparable in both groups, with higher prevalence of clinically significant levels (>0.2 nmoL/L) in active group: 79.6% vs 61.4% (P = .029). CONCLUSIONS: These data support the view that regular PA may essentially contribute to extending PR time in pediatric diabetes, and may therefore lead to a better long-term metabolic control of the disease.

Monogenic diabetes prevalence among Polish children-Summary of 11 years-long nationwide genetic screening program.

BACKGROUND: Estimated monogenic diabetes (MD) prevalence increases as screening programs proceeds. OBJECTIVE: To estimate prevalence of MD among Polish children. SUBJECTS: Patients and their family members suspected of suffering from MD (defined as causative mutation in one of the Maturity Onset Diabetes of the Young or permanent neonatal diabetes mellitus genes) were recruited between January 2005 and December 2015. METHODS: Nationwide prevalence was estimated based on data from 6 administrative provinces (out of 16 in Poland) with high referral rates of patients (>10 per 100 000 children). RESULTS: During the analysis, probands from 322 of 788 screened families tested positive yielding a total of 409 children and 299 family members with MD. An average of 70 probands/year were referred. Screening success rate reached 40% over the study period. We estimated the prevalence of MD in 2015 to 7.52/100 000 children (1 in 13 000). The most frequent MODY in this group was GCK- MODY (6.88/100 000). The prevalence estimates increased nearly 2-fold since our report in 2011 (4.4/100 000). However, the figure reached a plateau because of screening saturation in 2014 what was also proven by lowering of the median age of diagnosis lowered in time (R = -0.73, P = .0172) along with shortening of the delay between clinical and genetic diagnosis (R = -0.65, P = .0417). CONCLUSIONS: The screening for childhood MD in Poland reached a plateau phase after 10 years showing a stable prevalence estimate. The true frequency of MD in the overall population may be higher given later onset of reportedly more frequent types of MD than GCK -MODY.

Five-year observation of the relationship between body mass index and glycated hemoglobin in children with Type 1 diabetes mellitus.

BACKGROUND: Poor metabolic control is a well-recognized risk factor for cardiovascular disease. However, the relationship between such factor as body weight and metabolic control in children with diabetes mellitus type 1 (DM1) is unclear. The aim of this study was to examine the relationships between body weight, age, metabolic control, sex, and form of insulin therapy in children with DM1. METHODS: This was a retrospective study of children with DM1 treated at one diabetes center for a minimum of 5 years since diagnosis. RESULTS: Median body mass index standard deviation score (BMI-SDS) increased annually (p = .0042) on average 0.08 ± 0.27 per year throughout the observation. As well HbA1c and daily dose insulin increased annually (p < .0001; p < .0001, respectively) on average by 0.43 ± 0.79 and by 0.13 ± 0.17 per year. Percentage of good metabolic control - HbA1c cut-off of 6.5% - gradually worsened in all patients over the 5 years, with a higher percentage of girls experiencing poor metabolic control (84.48% of girls vs. 77.87% of boys; p = .01895). No correlation between BMI-SDS and metabolic control (HbA1c) was found (R = 0.09, p = .60). CONCLUSIONS: Body weight appears to be more affected by non-diabetic factors (e.g. irregular eating and sedentary lifestyle) than by the clinical course of diabetes. Metabolic control and body weight must be maintained in all children with DM1 (males and females) to reduce their future risk of cardiovascular disease.

The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes.

The exact cause of the obesity epidemic remains unknown; however, both environmental and genetic factors are involved. People at risk of developing obesity include children with type 1 diabetes mellitus (T1DM), which in turn increases their cardiovascular disease risk. Here, we discuss the clinical and genetic factors influencing weight in patients with T1DM. In children with T1DM, the presence of obesity depends mainly on sex, metabolic control, and disease duration. However, genetic factors, including the fat mass and obesity-associated (FTO) gene, are also associated with body weight. Indeed, children with the FTO gene rs9939609 obesity-risk allele (homozygous = AA or heterozygous = AT) are predisposed to a higher body mass index and have a greater risk of being overweight or obese. However, in this review, we show that FTO gene polymorphisms only have a small effect on body weight in children, much weaker than the effect of clinical factors. The association between FTO gene polymorphisms and body weight is only statistically significant in children without severe obesity. Moreover, other genetic factors had no effect on weight in patients with T1DM, and further research involving larger populations is required to confirm the genetic basis of diabetes and obesity. Therefore, identifying the clinical features of children with T1DM, such as their initial body mass index, sex, metabolic control, and disease duration, will still have the strongest effect on reducing risk factors for cardiovascular diseases. Physicians should pay close attention to modifiable elements of these relationships, for example, metabolic control and energy and insulin intake, when caring for patients with T1DM. Copyright © 2016 John Wiley & Sons, Ltd.

Elevated levels of Th17 cells in children with central obesity.

BACKGROUND: It is believed that the recently discovered interleukin 17-producing Th17 cells play a role in the pathogenesis of chronic inflammation in the course of obesity and diabetes. OBJECTIVES: The purpose of our study was to complete data on this subject in children. METHODS: We assessed Th17 cell levels in the peripheral blood of children diagnosed with central obesity (n = 14) and compared the results with data obtained in patients with newly diagnosed (n = 11) and long-term type 1 diabetes mellitus (n = 18), and in a control group as well (n = 24). RESULTS: (i) Children with central obesity were characterized by higher percentages of Th17 cells as compared to children from the control group; (ii) in the peripheral blood of patients with long-term type 1 diabetes the Th17 cell counts were higher compared to the control group; (iii) total plasma cholesterol concentration correlated positively with Th17/Treg cells ratio; and (iv) among patients with long-term diabetes, disease duration correlated positively with Th17 cell count and Th17/Th1 cell ratio. CONCLUSION: The results of our study indicate that Th17 cells may be involved in chronic inflammation accompanying obesity and type 1 diabetes mellitus in children.

Disease associated clinical factors and FTO polymorphism: effect on body mass in children with type 1 diabetes mellitus.

BACKGROUND: One of the consequences of excessive weight gain during insulin therapy in type 1 diabetes mellitus (T1DM) is an increased predisposition to cardiovascular diseases (CVD). Not only clinical but also genetic factors may play a role in the pathogenesis of this phenomenon. The aim of this study was to evaluate the prevalence of cardiovascular disease risk factors as well as the fat mass and obesity associated (FTO) gene rs9939609 variant in a large group of children with T1DM of the same ethnic-Polish origin. A total of 1237 children with T1DM and 1015 controls were recruited. RESULTS: The proportions of patients with obesity, hypertension, and abnormal LDL-cholesterol levels among children with T1DM were significantly higher than those in the non-diabetic. There was a higher rate of overweight, central obesity, and abnormal LDL-cholesterol levels among girls in comparison to that in boys in the group of children with diabetes. Children with inadequate metabolic control were characterized by the presence of more CVD risk factors. Similar differences were observed in children treated with the use of pens versus those using insulin pumps. The FTO gene single nucleotide polymorphism (SNP) correlated with body mass index (BMI) in both control and diabetic children, but the effect was lesser in diabetics. In a regression model the current BMI-SDS value in diabetics was significantly affected by the baseline BMI, disease duration, metabolic control, and subject's sex, but not the FTO genotype. CONCLUSIONS: Clinical rather than genetic factors have a greater impact on the development of overweight and obesity in insulin-treated children

Not Only Metabolic Complications of Childhood Obesity.

The increasing incidence of obesity in the pediatric population requires attention to its serious complications. It turns out that in addition to typical, well-known metabolic complications, obesity as a systemic disease carries the risk of equally serious, although less obvious, non-metabolic complications, such as cardiovascular diseases, polycystic ovary syndrome, chronic kidney disease, asthma, thyroid dysfunction, immunologic and dermatologic conditions, and mental health problems. They can affect almost all systems of the young body and also leave their mark in adulthood. In addition, obesity also contributes to the exacerbation of existing childhood diseases. As a result, children suffering from obesity may have a reduced quality of life, both physically and mentally, and their life expectancy may be shortened. It also turns out that, in the case of obese pregnant girls, the complications of obesity may also affect their unborn children. Therefore, it is extremely important to take all necessary actions to prevent the growing epidemic of obesity in the pediatric population, as well as to treat existing complications of obesity and detect them at an early stage. In summary, physicians treating a child with a systemic disease such as obesity must adopt a holistic approach to treatment.

Decreased CD127 expression on CD4+ T-cells and elevated frequencies of CD4+CD25+CD127- T-cells in children with long-lasting type 1 diabetes.

Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127- phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127- T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127- T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25- T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127- T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype.

Insulin therapy with personal insulin pumps and early angiopathy in children with type 1 diabetes mellitus.

OBJECTIVE: Assessment of the effect of a treatment method change from multiple daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII) on the development of early angiopathy in children with T1DM with or without retinopathy. METHODS: The study pump group involved 32 diabetic children aged 14.8, with the initial HbA1c level of 8.3%, previously treated by MDI. The patients were examined before pump insertion and after 3 and 6 months of CSII. We assessed HbA1c level, carotid artery intima-media thickness (c-IMT), and flow-mediated dilatation (FMD) of the brachial artery. The pump group was compared to a group of eight teenagers with diagnosed nonproliferative retinopathy, treated with MDI. RESULTS: HbA1c in the entire group was found to improve in the second and in the third examination. During 6 months of CSII, FMD increased and IMT decreased. Retinopathic adolescents had significantly thicker IMT and lower FMD compared to baseline results of the pump group. Treatment intensification in the retinopathy-free children enhanced these differences. CONCLUSIONS: CSII is associated with lower IMT and higher FMD. Whether on the long-run CSII is superior to MDI to delay the occurrence of diabetes late complications remains to be explained.

Subclinical cardiovascular system changes in obese patients with juvenile idiopathic arthritis.

OBJECTIVE: We aimed to determine the prevalence of excess body mass in juvenile idiopathic arthritis (JIA) children and to investigate the influence of obesity into the early, subclinical changes in cardiovascular system in these patients. METHODS: Fifty-eight JIA patients, aged median 13 years, were compared to 36 healthy controls. Traditional cardiovascular risk factors and inflammatory markers (hsCRP, IL-6, TNF α, adiponectin) were studied together with IMT (intima-media thickness), FMD (flow mediated dilation), and LVMi (left ventricle mass index) as surrogate markers of subclinical atherosclerosis. RESULTS: Thirteen JIA children (22%) were obese and had increased systolic blood pressure, cholesterol, triglycerides, insulin, HOMA, hsCRP, and IL-6 compared to nonobese JIA and controls. FMD was decreased compared to nonobese JIA and controls, whereas IMT and LVMi were increased. In multivariate regression analysis, TNF α, SDS-BMI, and systolic blood pressure were independent predictors of early CV changes in JIA. CONCLUSIONS: Coincident obesity is common in JIA children and is associated with insulin resistance, dyslipidemia, and increased levels of inflammatory markers leading to early changes in cardiovascular system. Thus, medical care of children with JIA should include strategies preventing cardiovascular disease by maintenance of adequate body weight.

[The assessment of glucose and lipid parameters in children with a positive family history of hypertension]. / Ocena parametrów przemiany weglowodanowej i lipidowej u dzieci z dodatnim wywiadem rodzinnym w klerunku nadcisnienia tetniczego.

UNLABELLED: Arterial hypertension in adults is often associated with excess body weight, and lipid or carbohydrate disorders. The incidence of hypertension in children is growing, although its connection with metabolic disorders and family history of hypertension has not been previously understood. THE AIM OF THE STUDY: To evaluate the relationship between a family history of hypertension and metabolic parameters (carbohydrate and lipid metabolism) and anthropometric measurements in children and adolescents. MATERIAL AND METHODS: The study group consists of 40 children (mean age 13.6 years +/-2.7 years) with a positive family history of hypertension, and a comparative group of 44 children with a negative family history of hypertension. Anthropometric measurements, blood pressure, plasma insulin, glucose, homeostasis model assessment insulin resistants (HOMA IR), and lipid profiles were determined in all children. RESULTS: Body weight, BMI, WHR, and measurements of skinfolds did not differ significantly between the groups. Systolic blood pressure was significantly higher in the study group (108 vs. 100 Me mmgHg, p = 0.031) Significant differences were observed in the levels of glucose (80 vs. Me. 67 mg/dl, p < 0.001), and insulin (8.89 vs. Me. 5.34 microIU / ml, p = 0.024). The HOMA index showed values significantly higher in the study group (1.68 vs. 0.80 Me p = 0.007). Children with a positive family history of hypertension were characterized by insignificantly higher values of total cholesterol, TG, LDL-cholesterol, and lower HDL-cholesterol. CONCLUSIONS: A positive family history of hypertension correlates with higher systolic blood pressure and changes in carbohydrate metabolism parameters in the direction of the development of insulin resistance in children.

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.

Multi-Faceted Influence of Obesity on Type 1 Diabetes in Children - From Disease Pathogenesis to Complications.

The prevalence of overweight and obesity among youth patients with diabetes type 1 is increasing. It is estimated, that even up to 35% of young patients with this type of diabetes, considered so far to be characteristic for slim figure, are overweight or even obese. General increase of obesity in children's population complicates differential diagnosis of the type of diabetes in youths. Coexistence of obesity has clinical implications for all stages of diabetes course. It is confirmed that obesity is the risk factor for autoimmune diabetes, and is connected with the earlier onset of diabetes in predisposed patients. Many diabetic patients with obesity present additional risk factors for macroangiopathy, and are recognised to present metabolic syndrome, insulin resistance, and typical for diabetes type 2 - polycystic ovary syndrome, or non-alcoholic fatty liver disease. The prevalence of obesity rises dramatically in adolescence of diabetic child, more often in girls. It has negative impact on metabolic control, glycaemic variability and insulin demand. The risk for microangiopathic complications increases as well. The treatment is difficult and includes not only insulinotherapy and non-pharmacological trials. Recently treatment of insulin resistance with biguanids, and treatment with typical for type 2 new diabetes drugs like GLP-1 analogues, SGLT-2 receptor inhibitors, or even cases of bariatric surgery also has been reported.

Comparison of novel markers of metabolic complications and cardiovascular risk factors between obese non-diabetic and obese type 1 diabetic children and young adults.

Introduction: For the past years, the prevalence of obesity is growing in the general population of children, as well as among diabetic patients, resulting in increased risk of cardiovascular complications. Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children and young adults, leading to decreased life quality and lifespan, with obesity being recognized recently as a major contributing factor to these health problems. The objective of this study was to analyze and compare the selected novel markers for metabolic complications of obesity and vascular risk factors between obese non-diabetic and obese T1DM children and young adults. Methods: One hundred four subjects, aged between 10 and 24 years (31 with T1DM and excessive body weight, 41 with obesity without diabetes, and 32 with T1DM and normal weight), and 32 matched lean controls were included in the study. Clinical characteristics, blood pressure measurements, daily requirement for insulin, HbA1c%, plasma lipids, fetuin-A, E-selectin, and osteoprotegerin levels were compared with respect to body mass index (BMI), body mass index standard deviation score (BMI-SDS), and carotid intima-media thickness (cIMT) of common carotid arteries. Results: Patients with T1DM and excessive body weight compared to non-diabetic obese subjects had similar values of systolic blood pressure (125.6 ± 8.2 vs. 127.3 ± 12.9 mmHg, p = 0.515), diastolic blood pressure (78.19 ± 7.03 vs. 78.02 ± 8.01 mmHg, p = 0.918), cholesterol (175.26 ± 34.1 vs. 163.51 ± 26.08 mg/dl, p = 0.102), LDL (108.03 ± 32.55 vs. 112.22 ± 26.36 mg/dl, p = 0.548), and triglyceride levels (118.19 ± 71.20 vs. 117 ± 55.80 mg/dl, p = 0.937); all values were found to be higher compared to non-obese T1DM and healthy controls. HbA1c level and insulin resistance indices were significantly worse in T1DM obese vs. T1DM non-obese patients. Fetuin-A levels were higher among obese non-diabetic patients (p = 0.01), and E-selectin and osteoprotegerin levels were similar in both groups with obesity, but higher than in the reference group. There were no statistical differences in cIMT with T1DM with normal weight, excessive weight, and non-diabetic obese children; however, the cIMT value was higher compared to the reference group. Discussion: Novel markers of metabolic complications of obesity are similar between obese T1DM and non-diabetic subjects. Obesity in patients with T1DM results in worse metabolic control, insulin resistance, and increased risk for vascular complications.

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.

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.

Immunological balance between Treg and Th17 lymphocytes as a key element of type 1 diabetes progression in children.

Type 1 diabetes (T1D) is autoimmune destruction of the beta cells of pancreatic islets. Due to complexity of that disease, the mechanisms leading to the tolerance breakdown are still not fully understood. Previous hypothesis of imbalance in the Th1 and Th2 cells as the main contributing factor has been recently changed towards role of other lymphocytes - regulatory (Treg) and IL-17A-producing (Th17). Our study aims to assess changes within Treg and Th17 cells in newly diagnosed T1D pediatric patients and their association with disease remission. Flow cytometry implementation allowed for Treg and Th17 analysis in studied groups and further combination with clinical and laboratory data. In addition, expression of diabetes-related genes was tested and evaluated in context of their association with studied lymphocytes. Initial results revealed that Treg and ratio Treg/Th17 are significantly higher in T1D than in healthy controls. Moreover, patients with lower HbA1c and daily insulin requirements demonstrated higher levels of Tregs. Similar tendency for insulin intake was also observed in reference to Th17 cells, together with high levels of these cells in patients demonstrating higher values for c-peptide after 2 years. In low-level Treg patients, that subset correlates with the c-peptide in the admission stage. In addition, higher levels of IL-10 were associated with its correlation with HbA1c and insulin dosage. In the context of gene expression, moderate associations were demonstrated in T1D subjects inter alia between CTLA4 and Treg or ratio Treg/Th17. Cumulatively, our data indicate a possible novel role of Treg and Th17 in mechanism of type 1 diabetes. Moreover, potential prognostic value of these populations has been shown in reference to diabetes remission.