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.

The effect of coexisting autoimmune thyroiditis in children with Type 1 diabetes on optical coherence tomography results.

OBJECTIVE: To assess the influence of thyroid hormones status and coexistence of autoimmune thyroiditis on optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) results in children with Type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In the prospective, observational study (n = 175) we analyzed the impact of thyroid hormones on OCT results and the differences between the matched groups of children with T1D (n = 84; age = 13.14 ± 3.6; diabetes duration = 5.99 ± 3.3 years) and the children with T1D and autoimmune thyroiditis (AT) (n = 20; age = 13.94 ± 3.6; diabetes duration = 6.7 ± 4 years). We analyzed the following parameters: fovea avascular zone (FAZ), foveal thickness (FT), parafoveal thickness (PFT), ganglion cell complex (GCC), loss volume (global-GLV, focal-FLV), capillary vessel density: superficial (whole-wsVD, foveal-fsVD, parafoveal-psVD), and deep (whole-wdVD, foveal-fdVD, parafoveal-pdVD. The differences between the groups were tested by the unpaired t-Student test, Mann-Whitney U test as appropriate, whereas p level .05 was recognized as significant. RESULTS: We detected the significant correlations between thyroid-stimulating hormone (TSH) level and PFT (r = -0.14; p < .05), psVD (r = -0.18; p < .005). The level of free triiodothyronine (FT3) was correlated with psVD (r = -0.14; p < .05). We found significant correlation between free thyroxine (FT4) and fsVD (r = -0.17; p < .01). In the studied T1D and AT groups there were statistical differences in FT (p < .005), PFT (p < .03), GCC (p < .01), and GLV (p < .003). We did not observe any significant differences in the FAZ area between the groups. CONCLUSIONS: In our patients the co-occurrence of T1D and AT worsens the status of retinal parameters. Further studies are necessary to observe these relations and their potential influence on the occurrence of diabetic retinopathy (DR).

Epidemiology of type 1 diabetes in Polish children: A multicentre cohort study.

BACKGROUND: The incidence of childhood type 1 diabetes (T1D) varies greatly between populations, and the estimates and/or predictions of the rates would aid in adequate planning of health care resources. The study's aim was to assess the incidence of T1D in the paediatric population of eastern and central Poland. METHODS: In this cohort study covering the period from January 2010 to December 2014, data were collected for children and adolescents below 18 years of age with newly diagnosed T1D living in eastern and central Poland. A total of 2174 children were included in the analysis. The population estimates were from the Central Statistical Office of Poland. RESULTS: Overall, the annual incidence of T1D increased from 12.84/100,000 in 2010 to 18.46/100,000 in 2014 with the incidence rate (IR) ratio of 1.5 (an increase in the IR by 12.7% per year over 5 years). The lowest increase in the IR by 7.1% per year was seen in 15 to 17-year-olds. In the urban population (age 0-17 years), the overall incidence rate was significantly higher than in subjects from rural communities (P < .02). The incidence of T1D in rural areas was significantly higher (p = .004) in voivodeships of higher population density. Such dependence was not observed in urban areas. CONCLUSIONS: The incidence of T1D in children living in eastern and central Poland increased 1.5-fold over the 5-year observation period with the highest rise in 10 to 14-year-olds and significantly higher rates in urban children compared with their peers living in rural areas.

High incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes among Polish children aged 10-12 and under 5 years of age: A multicenter study.

AIM: Despite its characteristic symptoms, type 1 diabetes (T1D) is still diagnosed late causing the development of diabetic ketoacidosis (DKA). The aim of this study was to estimate the incidence of DKA and factors associated with the development of acidosis at T1D recognition in Polish children aged 0-17. METHODS: The study population consisted of 2100 children with newly diagnosed T1D in the years 2010-2014 in 7 hospitals in eastern and central Poland. The population living in these areas accounts for 35% of the Polish population. DKA was defined as a capillary pH < 7.3, blood glucose > 11 mmol/L. The analyzed data included age, sex, diabetes recognition, pH, glycated hemoglobin (HbA1c), fasting C-peptide, and body mass index standard deviation score (BMI-SDS). RESULTS: We observed DKA in 28.6% of children. There were 2 peaks in DKA occurrence: in children <5 years of age (33.9%) and aged 10-12 (34%). The highest incidence of DKA was noted in children aged 0-2 (48.4%). In the group with DKA, moderate and severe DKA occurred in 46.7% of children. Girls and children <2 years of age were more prone to severe DKA. The multiple logistic regression analysis showed the following factors associated with DKA: age (P = .002), fasting C-peptide (P = .0001), HbA1c (P = .0001), no family history of T1D (P = .0001), and BMI-SDS (P = .0001). CONCLUSIONS: The incidence of DKA is high and remained unchanged over the last 5 years. Increasing the awareness of symptoms of DKA is recommended among children <5 years of age (especially <2 years of age) and aged 10-12. Children <2 years of age and girls were at the highest risk of severe DKA.

Selected Serum Markers Associated with Pathogenesis and Clinical Course of Type 1 Diabetes in Pediatric Patients-The Effect of Disease Duration.

Biochemical abnormalities in the course of type 1 diabetes (T1D) may cause the production/activation of various proteins and peptides influencing treatment and causing a risk of complications. The aim of this study was to assess concentrations of selected serum substances involved in the pathogenesis and course of T1D and to correlate their concentrations with the duration of T1D. The study included patients with T1D (n = 156) at the age of 3-17, who were divided according to the duration of the disease into those newly diagnosed (n = 30), diagnosed after 3-5 (n = 77), 6-7 (n = 25), and over 7 (n = 24) years from the onset of T1D, and age-matched healthy controls (n = 30). Concentrations of amylin (IAPP), proamylin (proIAPP), catestatin (CST), chromogranin A (ChgA), nerve growth factor (NFG), platelet-activating factor (PAF), uromodulin (UMOD), and intestinal fatty acid binding protein (I-FABP) were measured in sera using immunoenzymatic tests. There were significant differences in concentrations of all the substances except UMOD and NGF between T1D patients and healthy children. The duration of the disease affected concentrations of CST, ChgA, PAF, and NGF, i.e., proteins/peptides which could have an impact on the course of T1D and the development of complications. In long-term patients, a decrease in concentrations of CST and ChgA, and an increase in PAF concentrations were found. In the case of NGF, a decrease was observed after the initial high values, followed by an increase over 7 years after T1D diagnosis. Concluding, the results show that concentrations of selected serum indicators may change in the course of T1D. Further studies are needed to establish whether these indicators could be used in the context of predicting long-term complications.

Foot Plantar Pressure Abnormalities in Near Adulthood Patients with Type 1 Diabetes.

Increased ulcer risk diminishes the quality of life in diabetes. This study assessed abnormalities in foot plantar pressure distribution in adolescents with T1D to detect early signs of ulcer risk. A total of 102 T1D patients, without diabetic neuropathy, were included (mean age 17.8 years, mean diabetes duration 7.4 year). Pedography was captured using Novel emed. Data from the study group were compared with reference data. The study revealed a statistically significant reduced foot contact area in both feet in the entire foot and under the head of the fifth metatarsal bone and the second toe. In both feet, the peak pressure was increased under the entire foot, hindfoot, midfoot, first metatarsal head, big toe, and second toe. There was no statistically significant difference in peak pressure. The mean plantar pressure rating was statistically significantly increased in both feet across the entire sole, in the hindfoot, midfoot, and first metatarsal head. T1D patients of age near adulthood without neuropathy have increased values in mean pressure and reduced contact area, pointing to the need of monitoring and preventive measures. These results point to the need of further research and analysis which should include various risk factor such as foot anatomy, body posture, or certain metabolic factors.

Influence of emotional intelligence on glycemic control in adolescents with diabetes type 1.

INTRODUCTION: Psychological factors can have a significant impact on diabetes control. We aimed to evaluate the correlation between emotional intelligence and glycemic control in type one diabetes (T1D) adolescents. MATERIAL AND METHODS: This prospective study enrolled 97 consecutive children admitted to our department and aged 15 to 17 with T1D. The Emotional Intelligence Questionnaire INTE was used to measure emotional intelligence. The results were correlated with a glycemic control status, measured by current and mean (since the diagnosis of T1D, minimum four tests per year) and hemoglobin A1c (HbA1c). An additional questionnaire collected the demographic and social data. RESULTS: Our study found a significant, negative correlation between HbA1c level and the ability to utilize emotions to support thinking and actions (Factor I of the INTE questionnaire). There was no significant correlation between emotional intelligence General Score or Factor II (the ability to recognize emotions) and glycemic control. CONCLUSIONS: A higher ability to utilize emotions to support thinking and actions positively correlates with metabolic control in the adolescent population with T1D. The appropriate emotional intelligence training and better psychological care may improve the metabolic outcomes of children with T1D. This merits further study.

Could I-FABP Be an Early Marker of Celiac Disease in Children with Type 1 Diabetes? Retrospective Study from the Tertiary Reference Centre.

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Assessment of insulin resistance in preterm children appropriate for gestational age versus term and preterm children with intrauterine growth restriction.

INTRODUCTION: Estimation of carbohydrate metabolism parameters in the groups: AGA preterm, SGA term, SGA preterm and AGA term. MATERIAL AND METHODS: 89 children were qualified: group A - AGA preterm 22, group B - SGA preterm 26, SGA term group C - 30 children, AGA - term group D - 11 children; at the age of 6-7 years. Insulin and fasting glucose levels were measure. HOMA IR and QUICKI, lipid profile were calculated. RESULTS: Higher insulin concentration were found in groups C vs. A (6.93 vs. 3.68 uIU/ml, p = 0.00005); B vs A (5.49 vs. 3.68 uIU/ml, p = 0.02). HOMA IR was significantly higher in the C vs A group (1.38 vs. 0.73, p = 0.00014); and B vs A (1.11 vs. 0.73, p = 0.03). Quicki were lower in C vs. A (0.7 vs. 0.96, p = 0.00068). CONCLUSIONS: The risk of insulin resistance appears to be more associated with lower birth weight than time of birth. No greater risk of insulin resistance has been established in preterm births with AGA.

Diabetic Retinopathy in Children with Type 1 Diabetes-Occurrence and Screening Using Optical Coherence Tomography.

PURPOSE: To describe the occurrence of diabetic retinopathy, the principles for pediatric care of patients with diabetes, and the utility of optical coherence tomography. Pediatric patients with type 1 diabetes should be screened for diabetic retinopathy upon the lapse of 5 years following the diagnosis. The patients in the time of puberty, who should be screened promptly after the diabetes diagnosis, and patients with type 2 diabetes are the exceptions. Special attention must be paid not only to retinopathy, but also to other possible concomitant conditions, such as cataract, refractive errors, or neuropathy. New techniques, such as optical coherence tomography angiography (OCTA), may contribute greatly to the early detection of retinopathy, facilitating the decision to modify the treatment. The application of modern insulin pumps with continuous glucose monitoring systems has greatly diminished the incidence rate of early symptoms of diabetic retinopathy in the pediatric population.

Gender-Specific Risk Factors for the Development of Retinal Changes in Children with Type 1 Diabetes.

The aim of the study was to determine gender-specific risk factor sets which could influence optical coherence tomography (OCT) results in children with type 1 diabetes (T1D). MATERIAL AND METHODS: 175 children with T1D without symptoms of diabetic retinopathy were enrolled, but 330 eyes were used for the final analysis (168 children, mean age 12.81 ± 3.63 years, diabetes duration 4.59 ± 3.71 years). The multivariate regression models for retinal thickness (foveal FT, and parafoveal PFT) and vascular densities (superficial and deep) were carried out separately for both genders using all metabolic and demographic parameters. RESULTS: In the statistically significant multiple regression models for all analyzed OCT parameters for both genders, pH at the onset of diabetes were in existence, as well as for retinal thickness current HbA1c. Duration of continuous insulin infusion (CSII) was an important factor in all parameters, except PFT. For the girls, the most significant factors were daily insulin dose, uric acid, and triglycerides, but for the boys, it was serum creatinine, systolic pressure, and free thyroxine level. CONCLUSIONS: We detected significant risk factors set for development of OCT parameters changes, and they were not identical for both genders. Current metabolic control, diabetic ketoacidosis at the disease onset, serum creatinine and longer use of CSII are the most important factors for retinal thickness and vessel densities in both genders in children with type 1 diabetes. For the girls, elements of metabolic syndrome (uric acid and triglycerides) and parameters of insulin amount were more pronounced.

Influence of puberty on retinal microcirculation in children with type 1 diabetes without retinopathy using optical coherence tomography angiography.

BACKGROUND: This study aimed to assess the influence of pubertal status on the results of optical coherence tomography angiography (OCTA) in children with type 1 diabetes (T1D). METHODS: We enrolled 167 consecutive children with T1D. Retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density data underwent analysis. We divided the study population into three subgroups depending on the pubertal status. RESULTS: Analysis of the prepubertal and pubertal subgroups revealed statistically significant differences in foveal thickness (FT) (p < 0.05) and foveal SCP (p < 0.02). Analyzing subgroups of the prepubertal and postpubertal children, we observed statistically significant differences in FT (p < 0.03), whole SCP (p < 0.02), and foveal SCP (p < 0.02). Comparison of the pubertal and postpubertal subjects revealed differences in parafoveal DCP (p < 0.003). In the groups matched depending on diabetes duration, we observed differences between prepubertal, pubertal, and postpubertal children in FT, PFT, and parafoveal SCP and DCP. CONCLUSION: Our data suggest that in a cohort of pubertal children with a short duration of diabetes, alterations in retinal vessel density occur early and progress during puberty.

Thyroid Hormones, Peripheral White Blood Count, and Dose of Basal Insulin Are Associated with Changes in Nerve Conduction Studies in Adolescents with Type 1 Diabetes.

Type 1 diabetes (T1D) in the child population is the third most common chronic disease. Diabetic peripheral neuropathy (DPN) is a very disabling and silently developing complication. This prospective, observational study enrolled 182 (93 girls) patients with T1D, aged 16.5-18 years. The aim of the study was to assess the correlation between factors of diabetes metabolic control, blood count, thyroid hormones, thyroid-stimulating hormone (TSH), level of cortisol, vitamin D3, metabolic factors, demographic data, and nerve conduction study (NCS) parameters. We revealed that in multivariate regression models for almost all NCS parameters, beside height and diabetes duration, significant factors were basal insulin dose per kilogram of weight (BID/kg), body mass index (BMI), and thyroid hormones. For conduction velocities of the motor nerves, mean HbA1c exists in models. In all models for all NCS parameters there exists at least one parameter of peripheral white blood cell counts (predominantly monocytes). There is a significant influence of thyroid hormones, peripheral blood white cells count, and BID per weight on parameters of NCS. It is essential to take care of the proper insulin dose per weight of patients and the adequate proportion of basal to prandial insulin.

Comparison of Frequency and Severity of Sleep-Related Breathing Disorders in Children with Simple Obesity and Paediatric Patients with Prader-Willi Syndrome.

Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader-Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients-with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea-hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients' care.

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome - a case report and literature review.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.

Associations of nerve conduction parameters and OCT angiography results in adolescents with type 1 diabetes.

AIM: To evaluate dependence of abnormalities in peripheral nerves and retina in children with type 1 diabetes (T1D) using optical coherence tomography angiography (OCTA) and nerve conduction studies (NCS). MATERIAL AND METHODS: 50 adolescents with T1D without any signs and symptoms of diabetic retinopathy and neuropathy (mean age 16.92±1.6 years, diabetes duration 6.88 ±4.34years) were included. In OCTA capillary plexuses superficial (SCP) and deep (DCP) vessel density: whole, foveal and parafoveal, ganglion cell complex (GCC), loss volume focal (FLV) and global loss volume (GLV) were analyzed in relation to NCS parameters (motor nerves median and tibial potential amplitude (CMAP), velocity (CV), distal latency (DML) and F wave and sensory nerves median and sural potential amplitude (SNAP), CV and distal latency (DSL). RESULTS: We detected the correlations between median sensory SNAP and GCC (r = -0.3, p <0.04), motor nerves tibial DML and CV and FLV (respectively r = -0.53, p<0.001, and r = -0.34, p<0.05), and median DML and GLV (r = 0.47, p<0.001). Vessel densities were related to changes in motor nerves tibial velocity (whole SCP r = 0.43, p <0.01, parafoveal SCP r = 0.41, p <0.01), CMAP (parafoveal SCP r = -0.35, p<0.03), median DML (whole DC r = 0.36, p<0.03, foveal DCP r = 0.37, p<0.02) and in sensory median SNAP (whole SCP r = -0.31, p<0.05). CONCLUSIONS: In adolescents with T1D without diabetic neuropathy and retinopathy we detected associations between NCS and OCT and OCTA parameters, regarding decreased GCC and density of superficial and deep vessel plexuses in relation to DML and CV and amplitudes of sensory and motor potential.

Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial.

INTRODUCTION: The gut microbiota may be relevant in the development of type 1 diabetes (T1D). We examined the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed T1D. RESEARCH DESIGN AND METHODS: Children aged 8-17 years with newly (within 60 days) diagnosed T1D were enrolled in a double-blind, randomised controlled trial in which they received L. rhamnosus GG and B. lactis Bb12 at a dose of 109 colony-forming units or placebo, orally, once daily, for 6 months. The follow-up was for 12 months. The primary outcome measure was the area under the curve (AUC) of the C-peptide level during 2-hour responses to a mixed meal. RESULTS: Ninety-six children were randomised (probiotics, n=48; placebo n=48; median age 12.3 years). Eighty-eight (92%) completed the 6-month intervention, and 87 (91%) completed the follow-up at 12 months. There was no significant difference between the study groups for the AUC of the C-peptide level. For the secondary outcomes at 6 months, there were no differences between the study groups. At 12 months, with one exception, there also were no significant differences between the groups. Compared with the placebo group, there was a significantly increased number of subjects with thyroid autoimmunity in the probiotic group. However, at baseline, there was also a higher frequency of thyroid autoimmunity in the probiotic group. There were no cases of severe hypoglycemia or ketoacidosis in any of the groups. No adverse events related to the study products were reported. CONCLUSIONS: L. rhamnosus GG and B. lactis Bb12, as administered in this study, had no significant effect in maintaining the residual pancreatic beta-cell function in children with newly diagnosed T1D. It remains unclear which probiotics, if any, alone or in combination, are potentially the most useful for management of T1D. TRIAL REGISTRATION NUMBER: NCT03032354.

Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader-Willi Syndrome: A Polish Multicentre Study.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.