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.

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.

An evaluation of the knowledge and attitudes of school staff related to diabetes care at school: The 10th year of the "diabetes program at school" in Turkey.

The aim of this study was to measure the knowledge and attitudes of school staff regarding care in school for children with type 1 diabetes and to evaluate the contribution of the "Diabetes Program at School"(DPS). The data were collected through an online survey consisting of 55 questions, which included 39 knowledge and 16 attitude questions. The survey was delivered to the participating school staff via a link. A total of 55,677 people who completed 100% of the survey were included. Of the participants, 76% were teachers, 23% were school administrators and 0.1% were school nurses. 73% (40732) of the participants stated that they had heard about the "DPS". Of the participants who were aware of the DPS 75%, 50%, and 41% stated an increase in their knowledge level, self-confidence, and awareness respectively. Both scores were positively associated with being female and school nurse, having students with diabetes in the school, having been trained in childhood diabetes, being familiar with the program and being from the Western region of Turkey. The DPS is well known among school staff including teachers, school administrators, and school nurses. However, there are clear regional differences in the knowledge and attitude of school staff regarding diabetes care at school. Therefore, regional differences should be taken into account when planning the necessary interventions to prevent any further increase in the current inequalities. In addition, increasing the number of school nurses, together with strengthening the knowledge and attitude of school staff, can improve the level of diabetes care at school.

A comparison of glycemic parameters and their relationship with C-peptide and Proinsulin levels during partial remission and non-remission periods in children with type 1 diabetes mellitus - a cross-sectional study.

BACKGROUND: Currently, there is a lack of data relating to glycemic parameters and their relationship with C-peptide (CP) and proinsulin (PI) during the partial remission period (PRP) in type 1 diabetes mellitus (T1D). The aim of this study was to evaluate glycemic parameters in children with T1D who are in the PRP using intermittently scanned continuous glucose monitoring systems (isCGMS) and to investigate any relationships between CP and PI levels. METHODS: The study included 21 children who were in the PRP and 31 children who were not. A cross-sectional, non-randomized study was performed. Demographic, clinical data were collected and 2 week- isCGMS data were retrieved. RESULTS: The Serum CP showed a positive correlation with time-in-range in the PRP (p:0.03), however PI showed no correlations with glycemic parameters in both periods. The Serum CP and PI levels and the PI:CP ratio were significantly higher in the PRP group than in the non-PRP group. In the non-PRP group, the PI level was below 0.1 pmol/L (which is the detectable limit) in only 2 of the 17 cases as compared with none in the PRP group. Similarly, only 2 of the 17 children in the non-PRP group had CP levels of less than 0.2 nmol / L, although both had detectable PI levels. Overall time-in-range (3. 9-1.0 mmol/L) was significantly high in the PRP group. In contrast, the mean sensor glucose levels, time spent in hyperglycemia, and coefficient of variation levels (32.2vs 40.5%) were significantly lower in the PRP group. CONCLUSIONS: Although the mean glucose and time in range during the PRP was better than that in the non-PRP group, the glycemic variability during this period was not as low as expected. While the CP levels showed an association with TIR during the PRP, there was no correlation between PI levels and glycemic parameters. Further studies are needed to determine if PI might prove to be a useful parameter in clinical follow-up.

Investigating the nutritional value of foods targeting children.

PURPOSE: This study aimed to investigate the nutritional values of some low-nutrition packaged foods widely sold in supermarkets and encouraged for consumption. METHODS: The study used 435 packaged foods from six hypermarkets with high sale capacities in Ankara to analyze their contents of energy/total fat/saturated fat/carbohydrate/sugar/salt based on label information. RESULTS: Among the products in the scope of the study, the highest values were found in chocolates for fat (33.0 ± 4.28/100 g) and sugar (45.6 ± 5.95/100 g), wafers for saturated fat (19.2 ± 3.89/100 g), and crackers for sodium (0.9 ± 0.23/100 g). Among the 435 packaged foods investigated in the study, the products exceeded the limits designated in the health codes declared by the Turkish Food Codex Labeling Directive in 83.4% of the instances in terms of sugar, 93.7% of the instances in terms of total fat, 92.4% of the instances in terms of saturated fat, and 70.3% of the instances in terms of sodium. CONCLUSION: Energy/fat/sugar/salt contents were high in the packaged products that are especially targeted for children for higher consumption. Children's frequent and excessive consumption of these products contribute to the prevalence of childhood obesity and increase in related health risks. LEVEL OF EVIDENCE: Level V, descriptive study.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

Subclinical Left Ventricular Longitudinal and Radial Systolic Dysfunction in Children and Adolescents with Type 1 Diabetes Mellitus.

INTRODUCTION: There are few studies of subclinical systolic dysfunctions in children and adolescents with type 1 diabetes mellitus (DM), and so the available data are limited. The aim of this study was to determine early echocardiographic signs of LV systolic dysfunction in children and adolescents with type 1 DM using two-dimensional speckle tracking echocardiography (2DSTE). MATERIAL AND METHODS: The study included 84 children and adolescents with type 1 DM and 32 sex-, age-, and body mass index-matched healthy subjects. The LV functions were assessed using conventional echocardiography, tissue Doppler imaging, and 2DSTE. RESULTS: The results showed LV diastolic dysfunction as reflected by significantly increased A-wave velocity, decreased E/A ratio, and increased early filling deceleration time in the patients with diabetes (P = 0.02, P = 0.029, and P = 0.04; respectively). Compared with the control group, patients with diabetes showed significantly lower values for longitudinal systolic strain and strain rate in most segments of the LV; for radial strain values of the LV; for lateral circumferential strain and posterior and anterolateral circumferential strain rate of the LV; and for global longitudinal and radial strain of the LV. Global longitudinal and radial strain values of the LV were significantly lower among patients with poor glycemic control than in the control group. CONCLUSION: In addition to diastolic dysfunction, LV longitudinal and radial function was found to be impaired in asymptomatic children and adolescents with type 1 DM who have normal LV ejection fraction by 2DSTE. Glycemic control may be the main risk factor for alteration of myocardial function.

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.

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.

Ovotesticular disorder of sexual development and a rare 46,XX/47,XXY karyotype.

Ovotesticular disorder of sexual development (DSD) is characterized by the presence of both ovarian and testicular tissues in the same individual. The most common karyotype is 46,XX. Here, we report the case of a boy with a 46,XX/47,XXY karyotype diagnosed as ovotesticular DSD by gonadal biopsy. A 5-month-old boy presented with hypospadias, unilateral cryptorchidism, and a micropenis. Pelvic magnetic resonance imaging revealed a suspicious gonad tissue that is solid in structure in the right scrotum and a suspicious gonad that is cystic in structure in the left inguinal canal. He underwent a diagnostic laparoscopy. Cytogenetic analysis of peripheral blood revealed a 46,XX/47,XXY karyotype. Histopathologic examination of the left gonad showed ovarian tissue containing primordial follicles with ipsilateral undifferentiated tuba uterina. The right gonad showed immature testis tissue. He underwent left gonadectomy and hypospadias repair, and was raised as a male. Through this rare case, we highlight the importance of histological and cytogenetic investigation in DSD.

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 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.

Vitamin D intoxication.

Vitamin D intoxication (VDI) may result from supplementation rarely, but it has been reported more frequently in recent years. This may be attributable to an increase in vitamin D supplement intake due to an understanding of the role of vitamin D (25OHD) in the pathogenesis of several diseases. The symptoms and findings associated with VDI are closely related to serum calcium concentration and duration of hypercalcemia. In patients with VDI, hypercalcemia, normal or high serum phosphorus levels, normal or low levels of alkaline phosphatase (ALP), high levels of serum 25OHD, low serum parathyroid hormone (PTH), and high urine calcium/creatinine are usually present. Serum 25OHD levels above 150 ng/ml are considered as VDI. The main goal of treatment for VDI is correction of the hypercalcemia. When the calcium concentration exceeds 14 mg/dl, emergency intervention is necessary because of the adverse effects of hypercalcemia on cardiac, central nervous system, renal, and gastrointestinal functions. However, since vitamin D is stored in fat tissues, effects of toxicity may last for months despite the removal of the exogenous source of vitamin D. Treatment for VDI includes: discontinuation of intake, a diet with low calcium and phosphorus content, intravenous hydration with saline, loop diuretics, glucocorticoids, calcitonin, and bisphosphonates. In conclusion, the diagnosis of vitamin D deficiency rickets (VDDR) without checking serum 25OHD level may cause redundant treatment that leads to VDI. All patients who are clinically suspected of VDDR should be checked for serum vitamin D status and questioned for previous vitamin D administration before starting vitamin D therapy. On the other hand, parents of all infants should be asked whether they are using dietary or oral supplements, and serial questioning may be required during supplementation to avoid excessive intake.