Incidence of hyperglycaemic disorders in children and adolescents with obesity.

INTRODUCTION: The prevalence of obesity in the paediatric population has increased significantly in recent decades. To date, the rarest metabolic disturbance associated with obesity has been the hyperglycaemia, including diabetes. The aim of the study was to compare the prevalence of hyperglycaemic disorders diagnosed on the basis of (1) the oral glucose tolerance test (OGTT) and (2) the HbA1c value, and to estimate the prevalence of hyperglycaemia in continuous glucose monitoring (CGM) records in adolescents with obesity. MATERIAL AND METHODS: The study included patients aged 9-18 years with obesity (BMI ≥ 95th percentile). The height, body weight, and waist circumference were measured, and the BMI and BMI Z-score were calculated. Sexual maturity was assessed on the Tanner scale. OGTT was performed, and the HbA1c value was measured. Six-day retrospective blinded CGM was performed. RESULTS: In the group of 143 children (mean age 13.4 years), the severity of obesity positively increased with patients age (r = 0.36 and p < 0.0001). Abdominal obesity was found in 93.4% of children. Based on OGTT, 18.8% of the subjects had hyperglycaemic disorders; impaired glucose tolerance was the most common one (16.1%). Impaired fasting glucose was found in 4 patients (2.8%), and type 2 diabetes was found in 2. The mean HbA1c was 5.4%. HbA1c values ranged from 5.7 to 6.4% in 20.3% of the patients, and it did not exceed 6.4% in any patient. In 27.6% of patients with HbA1c 5.7-6.4%, abnormalities in OGTT were observed (IGT 17.25%, IFG 6.9%, DM2 3.45%). There was a significant discrepancy between OGTT results and HbA1c in the diagnosis of hyperglycaemic disorders (diagnosis agreement - 69.92%). In CGM 1.4% of results were above 140 mg/dl. CONCLUSIONS: Hyperglycaemic disorders are diagnosed in nearly 20% of children with obesity. However, there are significant discrepancies in the diagnosis of glucose disturbances using OGTT and HbA1c. Concordance in the diagnosis of hyperglycaemic disorders was achieved only in 70% of patients. CGM may be useful in the diagnosis of pre-diabetes in people with obesity.

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.

Clinical heterogeneity among pediatric patients with autoimmune type 1 diabetes stratified by immunoglobulin deficiency.

BACKGROUND: Type 1 diabetes (T1D) may coexist with primary immunodeficiencies, indicating a shared genetic background. OBJECTIVE: To evaluate the prevalence and clinical characteristics of immunoglobulin deficiency (IgD) among children with T1D. METHODS: Serum samples and medical history questionnaires were obtained during routine visits from T1D patients aged 4-18 years. IgG, IgA, IgM, and IgE were measured by nephelometry and enzyme-linked immunosorbent assay (ELISA). IgG and IgM deficiency (IgGD, IgMD) were defined as IgG/IgM >2 standard deviations (SD) below age-adjusted mean. IgE deficiency was defined as IgE <2 kIU/L. IgA deficiency (IgAD) was defined as IgA >2 SD below age-adjusted mean irrespective of other immunoglobulin classes (absolute if <0.07 g/L, partial otherwise) and as selective IgAD when IgA >2 SD below age-adjusted mean with normal IgG and IgM (absolute if <0.07 g/L, partial otherwise). RESULTS: Among 395 patients (53.4% boys) with the median age of 11.2 (8.4-13.7) and diabetes duration 3.6 (1.1-6.0) years, 90 (22.8%) were found to have hypogammaglobulinemia. The IgGD and IgAD were the most common each in 40/395 (10.1%). Complex IgD was found in seven patients. Increased odds of infection-related hospitalization (compared to children without any IgD) was related to having any kind of IgD and IgAD; OR (95%CI) = 2.1 (1.2-3.7) and 3.7 (1.8-7.5), respectively. Furthermore, IgAD was associated with having a first-degree relative with T1D OR (95%CI) = 3.3 (1.4-7.6) and suffering from non-autoimmune comorbidities 3.3 (1.4-7.6), especially neurological disorders 3.5 (1.2-10.5). CONCLUSIONS: IgDs frequently coexist with T1D and may be associated with several autoimmune and nonimmune related disorders suggesting their common genetic background.

Evaluation of skin autofluorescence as a surrogate of advanced glycation end products accumulation in children and adolescents with normal haemoglobin A1c values.

INTRODUCTION: Skin autofluorescence (sAF) represents tissue accumulation of advanced glycation end products (AGEs) and correlates with cardiovas-cular morbidity and diabetes risk. THE AIM: To assess sAF in Polish children without diabetes and to investigate whether sAF values in children with chronic diseases (but without glucose metabolism disorders) differ from sAF in healthy children. MATERIAL AND METHODS: Children without diseases known to influence sAF results (diabetes, renal failure) and with HbA1c < 5.7% (39 mmol/mol) were includ-ed, and the total study group was divided into two subgroups: with and without chronic conditions. Skin autofluorescence was meas-ured with an AGE Reader (Diagnoptics BV, Groningen, Netherlands). Data were presented as medians; Mann-Whitney U-test, Kruskall Wallis test, and Spearman's correlation coefficients were used in statistical analyses. RESULTS: The study group included 86 children (41 girls; mean age 10.1 ±4.2 years). Median sAF was 1.20 AU (25th-75th centile: 1.06-1.30). There was a positive correlation between sAF and age (R = 0.37, p = 0.0005). Skin autofluorescence values were higher in children with chronic diseases than in healthy children (1.23 AU [25th-75th centile: 1.10-1.40], n = 51 vs. 1.16 AU [1.06-1.26], n = 36, p = 0.0272). CONCLUSIONS: To our knowledge we present the first data on sAF values in Polish children without glucose metabolism disorders. We suggest that larger, homogenous populations of different ages should be studied to determine if and which diseases affect sAF measurements, and to develop pediatric reference values for sAF. This will allow a wider use of sAF measurement in the assessment of cardiovascular risk in the paediatric population.

Achieving target levels for vascular risk parameters in Polish school-age children with type 1 diabetes - a single center study.

Background Therapeutic goals have been established to decrease the risk of long-term complications of type 1 diabetes (T1DM). The effects of these guidelines should be constantly evaluated. Hence, the present study examines the frequency at which children with T1DM treated by one of the Polish reference centers complied with the therapeutic targets issued in 2014 by the International Society for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD). Methods A retrospective analysis (years 2011-2014) was performed in patients with T1DM aged 6.5-18 years, with diabetes duration >12 months and no change of insulin regimen within 6 months. Collected data included insulin therapy regimen, weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated hemoglobin (HbA1c) level from the last hospitalization. Results The records of 447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD targets. Optimal HbA1c was achieved by 224 (50.1%) according to ISPAD criteria (HbA1c<7.5%) and by 87 (19.6%) patients according to PTD (HbA1c≤6.5%). Obesity was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In logistic regression, patient age was the only independent predictor of failing to achieve complete T1DM control (p=0.001, OR=1.12 [1.05-1.23]) and optimal HbA1c (p=0.01, OR=1.1 [1.0-1.2]) according to ISPAD guidelines. Moreover, girls had a greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16; ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys. Conclusions Overall, control of vascular risk factors in Polish children with T1DM is unsatisfactory. While too few children are achieving the HbA1c target set by PTD, it is possible that such strict national target helps half of the Polish school-age patients achieve ISPAD-issued aim which is more liberal. High prevalence of overweight among children with T1DM warrants initiatives focused not only on glycemic control but also on motivation of patients to lead a healthy lifestyle.

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.

Markers influencing the presence of partial clinical remission in patients with newly diagnosed type 1 diabetes.

BACKGROUND: The aim of the study was to compare the selected markers in children with and without partial clinical remission (CR) of newly diagnosed type 1 diabetes (T1D). METHODS: The study group consisted of 186 patients (F/M; 87/99) at onset of T1D and 24 months of follow-up. Partial CR was defined as insulin requirement <0.5 IU/kg and glycated hemoglobin (HbA1c) <7%. RESULTS: Partial CR was observed in 115/186 (61.83%) of patients. At diagnosis body mass index standard deviation (BMI SDS) was higher among remitters than in non-remitters (p=0.0051) and remitters were younger (p=0.0029). In the follow-up a higher triglyceride concentration in non-remitters compared to remitters (p=0.0455) and a lower high density lipoprotein (HDL) cholesterol level (p=0.0119) were noticed. CONCLUSIONS: Younger age and higher BMI at diagnosis of T1D can predispose to partial CR in children. In patients with CR of T1D after 2 years of follow-up a lipid profile improvement is observed.

Fetal hemoglobin and hemoglobin A1c level among pediatric patients with type 1 diabetes.

INTRODUCTION: Glycated hemoglobin (HbA1c) is used as a cumulative estimate of mean blood glucose levels from the preceding 5-12 weeks. This is the gold standard in assessing glycemic control in patients with diabetes. The ADA criteria for the diagnosis of diabetes, including HbA1c level, contribute to the importance of recognizing any variation pertaining to the HbA1c measurement. HbA1c is often used as a primary endpoint in the interventional studies among patients with diabetes. Thus, knowledge about factors independently to glycemia, affecting HbA1c is clinically useful. AIM OF STUDY: Evaluation variability of fetal hemoglobin (HbF) level among Polish children with diabetes and how it may affect the HbA1c level measurement. MATERIAL AND METHODS: This was a prospective cohort study. A laboratory HbA1c testing was performed for more than 96% of pediatric diabetic patients in the region. In our study we included all consecutive patients aged 2 to 18 years with type 1 diabetes (T1D) and the disease duration longer than one year (555 patients). All patients had HbA1c and HbF measured at three time-points during minimum one-year period. In the same time, clinical data were recorded. The measurements of HbA1c and HbF were performed by means of cation-exchange high-pressure liquid chromatography (HPLC) on a D-10 Dual A2/F/A1c (Bio-Rad Laboratories, Hercules, CA, USA). Statistical analysis was performed using the Statistica 10.0 package (StatSoft, Tulsa, USA). RESULTS: An average age in the observed group was 12.9±3.8 years, diabetes duration 5.6±3.4 years, HbA1c was 7.59±1.33% (59±10.65 mmol/mol). In 78 (14%) patients elevated levels of HbF (>0.8%) were found at each time-point, mean value 1.2±0.45%. Elevated HbF was associated with younger age at examination (p=0.03) and younger age of diagnosis (p=0.01). It was not related to diabetes duration (p=0.21). No correlation between HbA1c and HbF was observed in the study (R=-0.09; p=0.43). CONCLUSIONS: Fetal hemoglobin does not affect HbA1c measurement among pediatric patients with type 1 diabetes older that 2 years.

Altered platelets' morphological parameters in children with type 1 diabetes ­ a case-control study.

BACKGROUND: Platelet hyperreactivity is a factor which contributes towards increased risk of cardiovascular events in adults with type 2 diabetes (T2DM). However, little is known about platelets' disturbances among children with type 1 diabetes (T1DM). The aim of the study was to investigate whether platelets' morphology or function are altered in children with type 1 diabetes, potentially predisposing them to cardiovascular events in the future. METHODS: The study group consisted of 389 children with T1DM during the 2008-2010 period. Patients with acute diabetes complications and ongoing infections were excluded from the study. An equinumerous (N = 389), age and sex-matched control group was assembled from children undergoing routine, minor surgical procedures in the same hospital. Platelet: count (PLT), mean volume (MPV), distribution width (PDW) and platelet large cell ratio (P-LCR) as well as HbA1c levels were measured. For statistical analysis we used Chi-square tests, the student's t-test, one-way analysis of variance (ANOVA), the Pearson's correlation coefficient and linear regression models in order to adjust for covariates. RESULTS: MPV, PDW and P-LCR were significantly higher among children with diabetes in comparison with the control group (MPV 10.47+/-0.85 fL vs 10.23+/-0.94 fL, p = 0.0007; PDW 12.09+/-1.80% vs 11.66+/-1.90%, p = 0.0032; P-LCR 28.21+/-6.15% vs 26.29+/-6.38%, p < 0.0001). PLT however, were shown to be similar (263.55+/-60.04 vs 268.77+/-65.78 10(3)/µl; p = 0.5637). In both cases and controls age was inversely correlated with platelet count (for study group: r = -0.30, p < 0.0001; for control group: r = -0.34, p < 0.0001), positively correlated with MPVs (r = 0.20, p < 0.0001; r = 0.26, p < 0.0001), PDW (r = 0.25, p < 0.0001 and r = 0.24, p < 0.0001) and P-LCR (r = 0.26, p < 0.0001; r = 0.26, p < 0.0001). After adjustment for confounding factors, higher platelet counts were associated with poorer metabolic control (beta = 0.20; 0.0001). CONCLUSIONS: Platelets of paediatric patients with T1DM show morphological evidence of hyperreactivity (higher MPV, PDW and P-LCR), while poorer metabolic control increases their number potentially predisposing the patients to future cardiovascular events.

Unequal contribution of familial factors to autoimmunity and clinical course of childhood diabetes.

INTRODUCTION: collection of family history of diabetes mellitus (DM) is commonly performed when this illness is diagnosed in children. However the significance of gleaned information may differ depending on the affected family members. AIM OF THE STUDY: this study was performed in order to describe detailed familial history of DM in patients and to evaluate the impact of it on the natural course of childhood DM. MATERIAL AND METHODS: After exclusion of patients with confirmed monogenic basis of the disease or type 2 diabetes, the study group numbered 989 diabetic children. The data on detailed family history of DM among the first- and second- degree relatives, age at the onset of DM, recent percentage of glycated hemoglobin (HbA1c), presence of diabetes-related antibodies and the highest observed fasting c-peptide level were collected. RESULTS: Having siblings with DM was linked to early onset of diabetes in the study group (mean difference -2.83 95% confidence interval [cI] -4.24 to -1.42). Dominant mode of inheritance, particularly from the maternal side was significantly associated with diabetes onset at an older age. Children of diabetic mothers developed diabetes at a mean age of 10.83 in comparison to those without family history of DM - 8.75 years (p=0.0228). However, children whose mothers had any type of DM, had a significantly higher level of glycated hemoglobin than the others (8.34 vs 7.56%, p=0.0315). Additionally, a rising number of units of the family tree affected by any type of diabetes was associated with later onset of diabetes in children (p for trend = 0.0452). CONCLUSION: Familial factors influence the natural course of childhood diabetes, but their contribution is not equal, showing more pronounced effects of maternal factors.