Increased prevalence of celiac disease and its clinical picture among patients with diabetes mellitus type 1 - observations from a single pediatric center in Central Europe.

INTRODUCTION: The aim of our study was to analyze the incidence and the clinical characteristic of celiac disease (CD) in pediatric population with type 1 diabetes mellitus (T1DM). MATERIAL AND METHODS: The data of 880 patients with T1DM, 429 girls, mean age 12.14 ±4.0 years was retrospectively retrieved from medical records. Patients with T1DM and CD were selected and a detailed analysis of CD prevalence and its clinical characteristic at the time of CD diagnosis was performed. The data were compared with the previous data from our center published a decade ago. RESULTS: CD was suspected in 85/880 patients (9.65%) on the base of results of serological tests, but finally CD was diagnosed in 73/880 patients with T1DM (8.3%), in 53/429 girls (12.3%) and in 20/451 boys (4.4%). Most patients (71%) had CD diagnosed after T1DM onset. The majority of CD patients (72%) was asymptomatic. The CD diagnosis was not associated with inappropriate metabolic control of diabetes. The onset age of diabetes in children with CD was significantly lower than in those without CD (5.8 ±3.6 years vs. 7.56 ±4.0 years, p = 0.04). The prevalence of CD is significantly higher than a decade ago in our center (8.3% vs. 5.7%, p = 0.001). CONCLUSIONS: In light of increasing prevalence of mainly asymptomatic CD in patients with T1DM, CD screening is necessary. However positive serological tests, which are currently used in screening, and are the first step of diagnostics, in some patients allow only to suspect the CD and further diagnostic steps should be performed.

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.

Phenotype Heterogeneity in Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) Patients.

OBJECTIVE: The aim of the study was to evaluate the clinical phenotypes of glucokinase-maturity-onset diabetes of the young (GCK-MODY) pediatric patients from Southwest Poland and to search for phenotype-genotype correlations. METHODS: We conducted a retrospective analysis of data on 37 CGK-MODY patients consisting of 21 girls and 16 boys of ages 1.9-20.1 (mean 12.5±5.2) years, treated in our centre in the time period between 2002 and 2013. RESULTS: GCK-MODY carriers were found in a frequency of 3% among 1043 diabetes mellitus (DM) patients and constituted the second most numerous group of DM patients, following type 1 DM, in our centre. The mean age of GCK-MODY diagnosis was 10.4±4.5 years. The findings leading to the diagnosis were impaired fasting glucose (IFG) (15/37), symptoms of hyperglycemia (4/37), and a GCK-MODY family history (18/37). Mean fasting blood glucose level was 6.67±1.64 mmol/L. In the sample, there were patients with normal values (4/37), those with DM (10/37), and IFG (23/37). In OGTT, 120 min glucose level was normal in 8, diabetic in 2, and characteristic for glucose intolerance in 27 of the 37 cases. Twelve of the 37 cases (32%) were identified as GCK-MODY carriers. In the total group, mean C-peptide level was 2.13±0.65 ng/mL and HbA1c was 6.26±0.45% (44.9±-18 mmol/mol). Thirty-two patients had a family history of DM. DM autoantibodies were detected in two patients. The most common mutations were p.Gly318Arg (11/37) and p.Val302Leu (8/37). There was no correlation between type of mutations and plasma glucose levels. CONCLUSION: The phenotype of GCK-MODY patients may vary from those characteristic for other DM types to an asymptomatic state with normal FG with no correlation with genotype.

Incidence of type 1 diabetes mellitus during 26 years of observation and prevalence of diabetic ketoacidosis in the later years.

UNLABELLED: The prevalence of type 1 diabetes (T1D) varies greatly between countries. However, over the past several decades, a global rise in the incidence of T1D in the pediatric population has been noted. The aim of our study was to investigate the incidence of T1D in children living in the Lesser Poland during the period of time from January 1, 1987, to December 31, 2012, and to analyze the demographic characteristics and occurrence of diabetic ketoacidosis (DKA) in patients with newly diagnosed T1D in the second part of the study (2006-2012). During 26 years, 636 children (331 boys, 305 girls) aged 0-14 years were newly diagnosed with T1D (0-4 years old, n = 131; 5-9 years old, n = 253, 10-14 years old, n = 252). The standardized incidence ratio (SIR) ranged significantly (p < 0.001) from 5.2/100,000/year in 1987 to 21.9/100,000/year in 2012. The highest SIR was observed in age group 5-9 years old (21.2) and the lowest in 0-4 years old (8.8). There was no association with sex or living in urban or rural area. On admission, DKA was diagnosed in 22.4 % of patients. There were no significant differences relating to the presence of DKA (p = 0.912) in subsequent years. CONCLUSIONS: The incidence of T1D among children is increasing rapidly with the highest SIR in the 5-9 years old age group. DKA is still an important problem in the pediatric population. WHAT IS KNOWN: • The incidence of pediatric type 1 diabetes mellitus in Europe is increasing. The initial manifestation of the type 1 diabetes mellitus is diabetic ketoacidosis. What is New: • This is the longest (26 years) continuous analysis of the incidence of type 1 diabetes in Poland and the first analysis focused on the incidence rate and also on presence of diabetic ketoacidosis.

Diabetes mellitus after allogeneic hematopoietic stem cell transplantation.

Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are known to be at risk of developing endocrine abnormalities, but occurrence of diabetes mellitus (DM) is a relatively recent observation. We present a 17.5-year-old girl with DM after high-dose radio- and chemotherapy followed by allogeneic HSCT for the treatment of acute lymphoblastic leukemia, diagnosed when she was 10 years old. In the posttransplantation period, multiple acute and chronic complications occurred. Among them, we observed graft versus host disease requiring corticosteroid therapy, pancreatitis and some endocrine complications like primary hypothyroidism, growth hormone deficiency and hypergonadotropic hypogonadism. DM with some components of metabolic syndrome-like insulin resistance, high arterial blood pressure and dyslipidemia developed during the first year after HSCT. Five years later, a trend towards increased requirement of insulin with deterioration in metabolic control of DM was observed, despite a normal level of C-peptide and negative diabetes autoantibodies. After the addition of metformin to continuous subcutaneous insulin infusion in the therapy of DM, an improvement in metabolic control was observed. Due to the possible mechanism of insulin resistance which is associated with impaired insulin receptors after HSCT procedure, metformin with insulin appears to be effective in the treatment of this type of diabetes.

[Disorders of lipid metabolism in adolescents with simple obesity]. / Zaburzenia metabolizmu lipidów u mlodziezy z otyloscia prosta.

BACKGROUND: Obesity affects approximately 45 millions of children worldwide. Some of them present with secondary dyslipidemia that leads to premature atherosclerosis. AIM OF THE STUDY: 1) Assessment of the frequency and type of dyslipidemia in obese adolescents. 2) An attempt at defining risk factors of atherogenic lipid profile in obese adolescents. MATERIAL AND METHODS: In 146 (84 girls/62 boys) obese (mean BMI SDS 4.95, 95% CI 4.62-5.29) adolescents (age 10-18, mean 14.7 years), the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglicerydes (TG) were measured. Atherogenic dyslipidemia was defined as a high TG level with a concomitant low HDLc level. Standard oral glucose tolerance test was performed with the assessment of fasting and after 120' post-load of 75 g of glucose and insulin levels; the insulin resistance index HOMA-IR was calculated. RESULTS: The mean values of the lipid fractions were in normal ranges: TC 4.64 mmol/L (95% CI 4.48-4.8), LDLc 2.86 mmol/L (95% CI 2.73-2.99), TG 1.4 mmol/L (95% CI 1.3-1.5), and HDLc 1.16 (95% CI 1.1-1.2). However, in 50.69% of the patients (45.24% girls and 58.06% boys), elevated levels of TC, LDLc, and TG were observed respectively in 23.29%, 17.81% and 37.67%, and low HDLc in 15.07% of patients. A total of 10.96% of the patients presented with coexistence of a low HDLc and a high TG. In 26.7%, dyslipidemia was followed by arterial hypertension. There was a reverse correlation between a low HDLc value and BMI SDS [R (-) 0.22, p < 0.05] and not with TC, LDLc, and TG. The relative risk of abnormal lipid profile occurrence was higher in obese patients with insulin resistance (OR 1.72; 95% CI 0.8-3.4; p = 0.12), being significant only for boys (OR 3.67; 95% CI 1.1-12.1; p = 0.03). There was a reverse correlation between fasting insulin level, HOMA-IR and HDLc [R (-) 0.2; p < 0.05; R (-) 0.2; p < 0.05) respectively], as well as TG (R 0.26 ; p < 0.05; R 0.26; p < 0.05, respectively), and between post-load insulin level and TG (R 0.24; p < 0.05). CONCLUSIONS: 1) Lipid disorders occur in about one-half of obese adolescents, of which 10% presents with atherogenic lipid profile. 2) One of the most important risk factors of atherogenic lipid profile occurrence is insulin resistance, especially in boys. The severity of the obesity (BMI-SDS) is of lesser importance.