Assessing the feasibility of time in tight range (TITR) targets with advanced hybrid closed loop (AHCL) use in children and adolescents: A single-centre real-world study.

AIMS: Time in Tight Range (TITR) is a novel glycaemic metric in monitoring type 1 diabetes (T1D) management. The aim of this study was to assess the attainability of the TITR target in children and adolescents using the advanced hybrid closed loop (AHCL). METHODS: The 2128-day CGM data from 56 children and adolescents with T1D using AHCL (Minimed-780G) were analysed. Time in Range (TIR) (3.9-10 mmol/L), TITR (3.9-7.7 mmol/L), and other glycaemic parameters were separately analysed in terms of whole day, daytime (06.00-23:59), and nighttime (00.00-05.59) results. The participants were divided into two groups by autocorrection rate where Group 1 had a rate of <30% and Group 2 had a rate of ≥30. RESULTS: All glycaemic parameters indicated a better glycaemic outcome in the nighttime with higher TIR and TITR values compared with daytime (for TIR 87.5 ± 9.5% vs. 78.8 ± 8%, p < 0.001, and TITR 68.2 ± 13.5% vs. 57.5 ± 8.8%, p < 0.001). The rates of TITR >50% and >60% were 87% and 52%, respectively. When those with TITR >60% (n: 29) and those without (n: 27) were evaluated in terms of hypoglycaemia, no statistically significant difference was found in time below range (TBR) 3-3.9 mmol/L (0.3% vs. 2.1%, p: 0.084) and TBR < 3 mmol/L (0.47% vs. 0.3%, p: 0.298). Group 1 had a significantly higher TIR and TITR compared to Group 2 (82.6 ± 6.1% vs. 75.6 ± 8.6%, p: 0.008 and 62.1 ± 7.5% vs. 53.8 ± 7.5%, p: 0.002, respectively). CONCLUSIONS: Most children and adolescents on AHCL achieved the 50% target for TITR whereas more than half achieved the >60% target. A target of >50% for TITR seems realistic in children with T1D using AHCL.

The association of milk and multiple food avoidance with growth parameters in infants and children.

BACKGROUND: Recent studies reported that strict avoidance of milk products in cow's milk allergy (CMA) affects growth and bone turnover, causing negative calcium balance and changes in bone metabolism. OBJECTIVE: To investigate biochemical parameters to predict bone turnover and its relations with height and weight measurements and nutritional intake. METHODS: Height, weight, and body mass index z scores were plotted for age according to the World Health Organization. A 3-consecutive day food record was analyzed for nutritional values of foods. The blood levels of calcium, phosphorus, alkaline phosphatase, vitamin D, and parathyroid hormone (PTH) were determined. RESULTS: The study included 69 controls, 66 children with isolated CMA, and 59 children with multiple food allergy (FA). The z scores for weight, height, and body mass index were lower in isolated CMA and multiple FA groups than controls (P < .001, P = .004, and P = .002, respectively). The nutritional intakes of protein, fat, carbohydrates, vitamins B2 and B12, niacin, calcium, and phosphorus were significantly lower in isolated CMA and multiple FA than controls. In infants (≤2 years of age), although blood calcium level was in normal range, it was significantly lower in isolated CMA and multiple FA than in controls (P < .001). In children older than 2 years, PTH level was significantly higher in isolated CMA and multiple FA groups than in controls (P = .003). CONCLUSION: Our study revealed that children with isolated CMA and multiple FA had a high nutrition gap, growth deceleration, and unbalanced bone metabolism, as illustrated by low blood calcium and elevated PTH levels.

Current Management of Type 1 Diabetes in Children: Guideline-based Expert Opinions and Recommendations.

Successful management of type 1 diabetes (T1D) requires not only optimal glycemic outcomes, but also a holistic approach that encompasses all aspects of life and recommendations to address needs. Current goals include optimal glycaemic values, quality of life and life expectancy similar to peers, prevention of long-term complications, prevention of severe hypoglycaemia as much as possible, facilitation of glucose management, etc. International Society for Pediatric and Adolescent Diabetes (ISPAD) has been updating its guidelines for diabetes care every 4 years since 1995, covering more and more topics. For optimal metabolic outcomes, diabetes teams need to follow these current recommendations, adapt them to their clinical practice and provide guidance to people with type 1 diabetes/families. In this review, in the light of ISPAD 2018-2022 guidelines and clinical experiences, "10 Key Recommendations", emphasizing the importance of teamwork and the use of technology, current type 1 diabetes treatment is described for practical applications.

An Overlooked Manifestation of Hypercortisolism: Cerebral Cortical Atrophy and Challenges in Identifying the Etiology of Hypercortisolism - A Report of 2 Pediatric Cases.

INTRODUCTION: Endogenous Cushing's syndrome (CS) is a rare, severe disease that can cause multiple systemic involvements and behavioral problems due to excessive cortisol production. Structural changes can be noted in the brain magnetic resonance imaging (MRI) scans of these cases. CASES: A 9-year-old girl and a 13-year-old boy were admitted with hypercortisolism. In the female patient, altered consciousness was prominent along with cerebral and cerebellar brain atrophy, and findings indicating posterior reversible encephalopathy syndrome were detected in the brain MRI. Although the male patient's neurological examination was normal, significant cerebral atrophy was seen in the brain MRI. Case 1 was diagnosed as having ectopic ACTH syndrome (EAS) due to a thymic carcinoid tumor. Case 2 underwent a pulmonary lobectomy upon detection of a bronchial lesion in the Ga-68 DOTATATE PET/CT scan while being examined for EAS due to a lack of suppression in the high-dose dexamethasone suppression test. However, hypercortisolism persisted despite the removal of the bronchial lesion, and subsequently, a diagnosis of Cushing's disease was established following bilateral inferior petrosal sinus sampling. DISCUSSION: Endogenous hypercortisolism may cause brain atrophy of varying severity. The central nervous system findings can be overlooked in children with CS. More comprehensive studies are needed to better understand the behavioral changes caused by the effects on the brain and to evaluate whether these changes are reversible. In addition, identifying the source of hypercortisolism can be difficult due to a lack of experience related to the rarity of the disease in children.

The effect of problem-solving skills on blood glucose regulation and disease management in children with type 1 diabetes mellitus.

OBJECTIVES: This cross-sectional study examined the relationship between problem-solving skills, glucose regulation, and disease management in children with type 1 diabetes mellitus (T1DM) as well as the role of depression in this association. METHODS: The participants (n=54) were recruited from a diabetes camp. Problem-solving inventory (PSI), Beck depression inventory (BDI), and diabetes self-management profile (DSMP) were administered as tests. Forty-six participants who have been diagnosed with T1DM for at least a year and completed the survey were included in the analyses. Participants were categorized into high and low depression groups based on the median split. Student's t-test was used to detect demographic differences in groups. Linear regression models were used to examine the association between PSI, HbA1c, and DSMP. Regressions for PSI and DSMP were repeated in low and high-depression groups. RESULTS: Of the 46 participants with T1DM, 52 % were female, with a mean age of 13.96 ± 1.94 (range 10-17). Avoidant and monitoring style of problem solving as well as the total score of PSI significantly predicted HbA1c levels. Impulsive and avoidant style of problem solving, problem-solving confidence, and total scores of PSI significantly predicted DSMP (p<0.05). The high depression group had a significantly higher DSMP score than the low depression group (p=0.001), with no difference in HbA1c levels (p=0.968). When the DSMP regressions were repeated, no significant associations were seen in the low depression group. Avoidant style of problem solving, problem-solving confidence, and the total score of PSI significantly predicted DSMP in the high depression group (p<0.005). CONCLUSIONS: Problem solving-skills are essential in children with T1DM for a successful disease management. Depression modulates the association between the problem-solving and self-management profile.

Associations between sleep characteristics and glycemic variability in youth with type 1 diabetes.

OBJECTIVE: This study aimed to determine sleep characteristics and their associations with glycemic variability in youth with type 1 diabetes (T1D). MATERIAL AND METHODS: This cross-sectional study conducted at two pediatric diabetes centers in Istanbul, Turkey, included 84 children with T1D (mean age 10.5 years). Sleep characteristics and glycemic variability were determined by actigraphy, DSM-5 Level 2-Sleep Disturbance Scale Short Form and continuous glucose monitoring. Circadian preference was evaluated by the Children's Chronotype Questionnaire. Sleep disturbances were assessed by the. The sleep quality was determined by actigraphy-derived sleep measures. RESULTS: Eighty-eight percent of participants had insufficient age-appropriate total sleep time (TST) (<9 h for 6-13-year-olds and <8 h for 14-17-year-olds). Chronotype was classified as intermediate in 50%, evening in 45.2%, and morning in 4.8%. A higher chronotype score indicating a stronger eveningness preference was associated with more time spent in hypoglycemia (ß = 0.433, p = 0.002). On nights when participants had lower sleep efficiency and longer sleep onset latency, they had significantly higher overnight glycemic variability (ß = -0.343, p = 0.016, ß = 0.129, p = 0.017, respectively). Prolonged nocturnal wake duration was significantly associated with more time spent in daytime hypoglycemia (ß = 0.037, p = 0.046) and higher overnight glycemic variability (J index, ß = 0.300, p = 0.015). The associations between TST and glycemic variability indices were not significant. CONCLUSIONS: Sleep quality rather than TST was significantly associated with glycemic variability in children with T1D. Eveningness preference might contribute to an increased risk of hypoglycemia. Addressing sleep patterns and chronotypes can be crucial in management plans for youth with T1D.

The Advanced Hybrid Closed Loop Improves Glycemia Risk Index, Continuous Glucose Monitoring Index, and Time in Range in Children with Type 1 Diabetes: Real-World Data from a Single Center Study.

Introduction: The Glycemia Risk Index (GRI) and Continuous Glucose Monitoring Index (COGI) are newly defined composite metric parameters derived from continuous glucose monitoring (CGM) data. GRI is divided into five separate risk zones (from lowest to highest: A-E). In this study, the effect of the advanced hybrid closed loop (AHCL) system on GRI and COGI in children with type 1 diabetes was evaluated. Materials and Methods: Forty-five children who had started using the AHCL and whose baseline and sixth-month CGM data were available were analyzed in terms of achievement of CGM consensus goals and changes in GRI scores and zones. The paired t-test was used for the analyses. Results: The mean age and duration of diabetes of the participants were 10.95 ± 3.41 and 3.85 ± 2.67 years, respectively. The mean GRI score significantly decreased from 35.66 ± 17.46 at baseline to 22.83 ± 9.08 at 6 months (P < 0.001). Although the proportion of those in the A zone was 20% at baseline, it increased to 42% at 6 months. AHCL also improved COGI from 72.59 ± 12.44 to 82.90 ± 7.72 (P < 0.001). Time in range (TIR) increased significantly from 70.54% to 80.51% (P < 0.001) at 6 months. Conclusion: AHCL provides not only an improvement in TIR but also a significant improvement in both GRI and COGI at 6 months. The incorporation of GRI and COGI alongside TIR may enhance the assessment of the glycemic profile by providing a more comprehensive and in-depth analysis.

The effects of the covid-19 pandemic on puberty: a cross-sectional, multicenter study from Turkey.

BACKGROUNDS: During the Coronavirus-19 disease (Covid-19) pandemic it was observed that the number of girls presenting with early puberty had increased. The aim of this study was to carry out a retrospective evaluation of the characteristics of girls who had been referred for evaluation of precocious puberty in five different pediatric endocrinology units, before and during the pandemic. METHODS: The study participants comprised 359 girls who were assigned into 2 groups a pre-pandemic group (n:214) and a pandemic group (n:145). Those participants (n:99) who had medical records in the follow-up period were classified into 3 subgroups according to the time of presentation and follow-up visits (group-1: first admission and follow-up visit before the pandemic, group-2: first admission before the pandemic, the follow-up visit during the pandemic, group-3: first admission and follow-up visit during the pandemic). RESULTS: The age at presentation and age at pubertal onset were both significantly lower in the pandemic group than those in the pre-pandemic group(8.1 vs 8.6, p: < 0.001,7.7 vs 7.9,p:0.013, respectively). There was no significant difference between the body mass index standard deviation scores (BMI-SDS) values of the groups (0.57 vs 0.51, p:0.430). The initiation rate of pubertal suppression therapy at the time of presentation was significantly higher in the pandemic group compared to that of the pre-pandemic group (7.7%vs 27.5%), and in groups-2 & 3 compared to group-1, during follow-up (20%&44%vs 8%). CONCLUSION: Our research showed that the onset of puberty occurred earlier in the pandemic period compared to the previous year, and the need for pubertal suppression therapy increased during the pandemic.

Insulin Requirements for Basal and Auto-Correction Insulin Delivery in Advanced Hybrid Closed-Loop System: 4193 Days' Real-World Data of Children in Two Different Age Groups.

BACKGROUND: The insulin requirements of people with type 1 diabetes (T1D) can vary throughout the day due to factors such as biorhythm, exercise, and food intake. The MiniMed 780G system delivers micro boluses to adjust basal insulin and delivers auto-correction boluses to meet insulin needs when micro bolus increases are insufficient. Through analysis of MiniMed 780G data, this study investigates the variations in insulin requirements throughout the day. METHODS: 4193 days' pump and continuous glucose monitoring (CGM) data of 34 children using MiniMed 780G were collected from Medtronic CareLink. Micro and auto-correction boluses were analyzed on an hourly basis for two age groups: below nine years old and above nine years old. Glycemic metrics were analyzed based on International CGM consensus. RESULTS: The mean age was 12.3 years and mean duration of diabetes was 6.1 years. The mean time in range (TIR) and glucose management indicator (GMI) were 80.5% and 6.6%, respectively. The micro bolus (basal) ratio between 05.00 and 07.00 was significantly higher than the ratio between 10.00 and 03.00 (P < .01), whereas micro bolus was significantly lower between 19.00 and 21.00 than those between 00.00 and 10.00 (P < .001). The auto-correction ratio between 21.00 and 00.00 was significantly higher than those between 03.00-17.00 (P < .001) and 19.00-21.00 (P = .008), whereas auto-correction was significantly lower between 07.00 and 10.00 than those between 10.00 and 03.00 (P < .001). The micro bolus ratio was significantly higher in children below nine years old than in children above nine years old between 21.00-00.00 (P = .026) and 00.00-03.00 (P = .003). CONCLUSION: The basal insulin need follows a diurnal pattern with two significantly different periods-high between 00.00 and 10.00 and low between 10.00 and 00.00. The auto-correction rates are low between 05.00 and 10.00 and show an increasing pattern peaking between 21.00 and 00.00. These findings are compatible with the dawn and reverse dawn phenomena.

The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience.

BACKGROUND: Unlike in Western countries, the use of diabetes technologies has been limited in Turkey, or at least until the last few years. This low adoption frequency may be attributed to the lack of experience of pediatric diabetes teams in working with new technologies. The aim of this study is to evaluate the attitudes, experiences and self-efficacies of pediatric endocrinology fellows and attending physicians in terms of use of continuous subcutaneous insulin infusion (CSII) therapy and continuous glucose monitoring (CGM) systems. METHODS: The questionnaire used in this study consisted of 63 questions including 10 questions evaluating the demographic characteristics and experience of the participants, 33 Likert-type questions related to self-competency, 17 yes/no questions and 3 open-ended questions which evaluated attitudes towards our study area. This questionnaire was e-mailed to pediatric endocrinology fellows and attending physicians working in Turkey. RESULTS: A total of 24 fellows and 28 attending physicians working in the field of pediatric endocrinology participated in the survey. Of the respondents, 61% reported that there was no formal training curriculum regarding diabetes technology at their institutions. The mean scores obtained from the Likert scale questions measuring self-competency in using CSII and CGM were 3.8 and 3.3 out of 5, respectively. Of the respondents, 55% judged themselves to be under-skilled in interpreting pump reports while 39% of the respondents reported themselves as being under-skilled in interpreting CGM reports. CONCLUSIONS: While it is true that training programs for using diabetes technology have been established by the National Pediatric Endocrinology Association in Turkey, the development of a specific curriculum for institutions that provide pediatric endocrinology fellowship training in this framework will increase the self-confidence of pediatric endocrinologists in this matter and this will ultimately contribute to the improvement of the metabolic control of children with diabetes.

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features.

Biallelic loss of function mutations in the CLDN16 gene cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and chronic kidney disease. Here we report two cases of FHHNC with diverse clinical presentations and hypercalcemia in one as a novel finding. Pt#1 initially presented with urinary tract infection and failure to thrive at 5.5 months of age to another center. Bilateral nephrocalcinosis, hypercalcemia (Ca: 12.2 mg/dl), elevated parathyroid hormone (PTH) level, and hypercalciuria were detected. Persistently elevated PTH with high/normal Ca levels led to subtotal-parathyroidectomy at the age of 2.5. However, PTH levels remained elevated with progressive deterioration in renal function. At 9-year-old, she was referred to us for evaluation of hyperparathyroidism and, hypomagnesemia together with hypercalciuria, elevated PTH with normal Ca levels, and medullary nephrocalcinosis were detected. Compound heterozygosity of CLDN16 variants (c.715G>A, p.G239R; and novel c.360C>A, p.C120*) confirmed the diagnosis. Pt#2 was a 10-month-old boy, admitted with irritability and urinary crystals. Hypocalcemia, hypophosphatemia, elevated PTH and ALP, low 25(OH)D levels, and radiographic findings of rickets were detected. However, additional findings of hypercalciuria and bilateral nephrocalcinosis were inconsistent with the nutritional rickets. Low/normal serum Mg levels suggested the diagnosis of FHHNC which was confirmed genetically as a homozygous missense (c.602G > A; p.G201E) variant in CLDN16. Yet, hypocalcemia and hypomagnesemia persisted in spite of treatment. In conclusion, FHHNC may present with diverse clinical features with mild hypomagnesemia leading to secondary hyperparathyroidism with changing Ca levels from low to high. Early and accurate clinical and molecular genetic diagnosis is important for proper management.

Benefits and Drawbacks of Continuous Glucose Monitoring (CGM) Use in Young Children With Type 1 Diabetes: A Qualitative Study From a Country Where the CGM Is Not Reimbursed.

Investigating the daily life experiences of patients using Continuous Glucose Monitoring (CGM) can highlight the benefits and barriers in using this system for people with type 1 diabetes (T1D). Semi-structured qualitative interviews were conducted with the caregivers of 10 children aged <9 years, all of whom had been treated for T1D and had used CGM >6 months. These interviews were analyzed using the content analysis approach and from these interviews, four meta themes emerged: metabolic control, barriers to CGM use, CGM use in daily life, and comparison with fingersticks. Families reported the following as benefits of CGM: pain relief, better hypoglycemia and hyperglycemia management, increased control over diet and social life, reduced worries at school and during the night, and convenience in entrusting the child to the care of others. Cost, concerns related to accuracy and reliability of measurements, insertion, adhesion and removal issues all emerged as barriers to CGM use. The most prominent issue was the economic burden of CGM. Families accept this burden, even though it is challenging, as their experiences in using CGM are positive and they feel that CGM is necessary for T1D management.

Vitamin D Deficiency Prevalence in Late Neonatal Hypocalcemia: A Multicenter Study

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns. Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels. Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (<12 ng/mL) was high in both the neonates (86.5%) and mothers (93%). Serum 25(OH)D levels of the infants and mothers showed a strong correlation (p<0.001). While the majority (93.7%) of the neonates had normal/high phosphorus levels, iPTH levels were low or inappropriately normal in 54.2% of the patients. Conclusion: Vitamin D deficiency prevalence was found to be high in LNH. Efforts to provide vitamin D supplementation during pregnancy should be encouraged. Evaluation of vitamin D status should be included in the workup of LNH.

Care and Support of Children with Type 1 Diabetes at School: The Turkish Experience

Diabetes care at school has recently appeared on the agenda of international diabetes organizations, the basic principles of which have been newly determined. The aim of this review was to summarize the activities and output of the Diabetes at School Program - a program that has been delivered in Turkey for the last 10 years - and to focus on different aspects of Diabetes Care at School through a national model. Recently, a detailed set of national regulations, including the basic principles proposed by the International Society for Pediatric and Adolescent Diabetes and the experience in Turkey, was prepared and has come into force. The future agenda includes giving priority to socio-economically disadvantaged regions, provision of an Individual Treatment Plan at School for each child with diabetes and ensuring that each school has an action plan for the care of children with diabetes. We believe that if all countries have programs and structured national regulations similar to the Diabetes at School Program, this will enable significant progress in the level of care delivered to children with diabetes.