Efficacy and safety of faster aspart in insulin pumps in children and adolescents with type 1 diabetes mellitus: A single-center study with real-world data.

AIMS: To assess the efficacy and safety of faster aspart (FIAsp) in paediatric population with type 1 diabetes mellitus (T1DM) and insulin pumps in real-world settings. METHODS: Of 44 patients, 20 used FIAsp, 16 of which switched from aspart to FIAsp and 24 used aspart/lispro. We performed within-groups and between-groups analyses in three time points for anthropometric data, % of 24-h time in range of 70-180 mg/dl (TIR), time < 70 mg/dl and <54 mg/dl and time > 180 mg/dl and >250 mg/dl, bolus and basal insulins doses (units/kg/day and %), total daily dose (TDD, units/kg/day), glycaemic variability, frequency of set changes, sensor wear per week and meals per day. RESULTS: Use of FIAsp over time increased TIR (P = 0.002) and TDD (P = 0.008 and P = 0.004, respectively for three months after the switch and recent use) and decreased time in hyperglycaemia (>180 P = 0.003 and > 250 mg/dl, P = 0.004). Frequency of set changes differ in the first 3 months (P = 0.042). Patients with FIAsp consumed more meals per day compared to those with aspart/lispro (P = 0.032). CONCLUSION: Real-world data confirm that use of FIAsp in insulin pumps in paediatric populations improves glycaemic control long-term.

Puberty in boys with type 1 diabetes mellitus: What has changed?

AIMS: To study the age of pubertal onset and secular trend in boys with Type 1 diabetes mellitus (T1DM) followed in two centers in North Greece. METHODS: Boys with T1DM visited the Outpatient Clinics of the 1st and 2nd Department of Paediatrics of Aristotle University of Thessaloniki from March until June 2022 were enrolled. Recent anthropometric data were recorded during the follow-up visit whereas previous anthropometric data and demographic data were collected from medical files. A volume of testis > 3 ml was indicative for the onset of puberty. RESULTS: A total of 46 boys with T1DM with documented pubertal onset after the diagnosis of T1DM were included in the study. Precocious puberty (<9 years old) was recorded in 5 boys (10.2 %), early puberty (<10 years but >9 years) in 10 (20.4 %) and 34 (69.4 %) entered puberty normally. The duration of T1DM was inversely correlated to the likelihood of earlier puberty (P < 0.001). However, no notable year predominance was observed suggesting no COVID-19 effect. CONCLUSION: A considerable number of Greek boys with T1DM appear to develop precocious and early puberty, raising thoughts regarding diabetes management and other possible cofactors.

The impact of COVID-19 vaccination on glycaemic control in children and adolescents with type 1 diabetes mellitus on continuous glucose monitoring.

AIMS: To investigate the impact of SARS-COV-2 vaccination on the glycaemic control in children and adolescents with T1DM wearing continuous glucose monitoring (CGM). METHODS: Caregivers of children and adolescents with T1DM were questioned regarding SARS-CoV-2 vaccination during their regular visits at the Pediatric Diabetes Outpatient Clinic. Data regarding Time in Range (TIR) (glucose levels: 70-180 mg/dl) 7 days prior and 7 days after a vaccination dose were collected in patients wearing CGM and data regarding insulin daily doses were also obtained for the insulin pump users. RESULTS: From a total of 135 patients eligible for SARS-CoV-2 vaccination, 70 (51.9%) children (37 boys, 52.9%) were vaccinated with at least one dose. Seven patients received only one dose, whereas two children received a third booster shot. No statistically significant difference was observed in either TIR (64.19% post vs. 65.53% pre, p = 0.158) or total daily insulin dose (40.08 U/day post vs. 39.32 U/day pre, p = 0,282). Additionally, in ten patients on Hybrid Closed-Loop System the percentage of the automated insulin boluses given post-vaccination was not statistically significant different compared to the boluses given pre-vaccination (15.80% vs. 16.90%, p = 0,491). CONCLUSIONS: Vaccination against SARS-CoV-2 in children and adolescents with T1DM is safe and is not associated with immediate glucose imbalance.

Arterial stiffness indices in children and adolescents with type 1 diabetes mellitus: A meta-analysis.

AIMS: Cardiovascular disease (CVD) represents the most frequent cause of morbidity and mortality among patients with type 1 diabetes mellitus (T1DM). Our aim was to review the evidence and conduct a meta-analysis assessing measures of arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx) in children and adolescents with T1DM compared to healthy controls. METHODS: PubMed and the Cochrane Library were searched for relevant studies published up to 10 May 2021. RESULTS: Twenty-one studies were finally included in the meta-analysis. The T1DM group had significantly higher carotid to femoral PWV levels than that of the control group (mean difference [d]: 0.53 CI: 0.35-0.71, P < 0.00001) but with a fair heterogeneity (I 2:73%). By omitting one study with marked heterogeneity, mean difference in cfPWV remained significantly increased in the T1DM group compared to the control group (mean difference [d]: 0.37 CI: 0.27-0.48, P < 0.00001) but with improved heterogeneity (I2 = 26%). Regarding Aix, the T1DM group had a significantly higher AI@75 index than that of the control group (mean difference [d]: 0.28 CI: 0.17-0.39, P < 0.00001) and with no heterogeneity (I 2 = 8%). CONCLUSIONS: Youths with T1DM show increased arterial stiffness, either as increased carotid-femoral pulse wave velocity or increased augmentation index, early in their course of life compared to healthy controls. PROSPERO REGISTRATION NUMBER: CRD42021253236.

The Effect of Various, Everyday Practices on Glucose Levels in Critically Ill Children.

BACKGROUND: To evaluate the effect of various, everyday intensive care unit (ICU) practices on glucose levels in critically ill pediatric patients with the use of a continuous glucose monitoring system. METHODS: Seventeen sensors were placed in 16 pediatric patients (8 male). All therapeutic and diagnostic interventions were recorded and 15 minutes later, a flash glucose measurement was obtained by swiping the sensor with a reader. Glucose difference was calculated as the glucose value 15 minutes after the intervention minus the mean daily glucose value for each individual patient. Additionally, the consciousness status of the patient (awake or sedated) was recorded. RESULTS: Two hundred and five painful skin interventions were recorded. The mean difference of glucose values was higher by 1.84 ± 14.76 mg/dL (95% CI: -0.19 to 3.87 mg/dL, P = .076). However, when patients were categorized regarding their consciousness level, mean glucose difference was significantly higher in awake state than in sedated patients (4.76 ± 28.07 vs -2.21 ± 15.77 mg/dL, P < .001). Six hundred forty-nine interventions involving the respiratory system were recorded. Glucose difference during washings proved to be significantly higher than the ones during simple suctions (4.74 ± 14.18 mg/dL vs 0.32 ± 18.22 mg/dL, P = .016). Finally, glucose difference in awake patients was higher by 3.66 ± 13.91 mg/dL compared to glucose difference of -2.25 ± 21.07 mg/dL obtained during respiratory intervention in sedated patients. CONCLUSIONS: Diagnostic and therapeutic procedures in the ICU, especially when performed in an awake state, exacerbate the stress and lead to a significant rise in glucose levels.

Coronavirus lockdown effect on type 1 diabetes management οn children wearing insulin pump equipped with continuous glucose monitoring system.

AIMS: On the 10th of March, Greece imposed the closure of schools and universities and a full lockdown a few days later in order to counter the spread of the coronavirus outbreak. Our aim was to monitor the effect of the coronavirus lockdown in diabetes management in children with Type 1 Diabetes Mellitus (T1DM) wearing insulin pump equipped with continuous glucose monitoring system. METHODS: In 34 children with T1DM on Medtronic 640G insulin pump equipped with the Enlite Sensor uploaded CareLink data were categorized in 2 three-week periods before and after the 10th of March. RESULTS: Mean time in range (TIR) did not significantly differ between the two periods. However, a significantly higher Coefficient of Variation (CV) indicating an increased glucose variability in the pre-lockdown period was observed (39.52% versus 37.40%, p = 0.011). Blood glucose readings were significantly fewer during the lockdown period (7.91 versus 7.41, p = 0.001). No significant difference was recorded regarding the total daily dose of insulin and the reported carbohydrates consumed. However, the meal schedule has changed dramatically as the percentage of breakfast consumed before 10.00 a.m. has fallen from 80.67% to 41.46% (p < 0.001) during the lockdown. Correspondingly, the percentage of dinner consumption before 10.00 p.m. significantly fell during the lockdown period (60.22% versus 53.78%, p = 0.019). CONCLUSIONS: Glycemic control during the coronavirus lockdown can be adequately achieved and be comparable to the pre-lockdown period in children with type 1 diabetes mellitus wearing insulin pump equipped with sensor.

Evaluation of continuous flash glucose monitoring in a pediatric ICU setting.

Glucose monitoring is of great importance among patients in intensive care units (ICU). The purpose of this study is to assess the performance of a new flash glucose monitoring (FGM) system in a pediatric ICU setting. Sixteen consecutive patients admitted in pediatric ICU aged > 4 years, expected length stay > 2 days and with no medication or existing diagnosis affecting glucose metabolism were enrolled. FreeStyle Libre sensor was applied to the upper arm of the patients (8 boys). FGM measurements were compared to 3 "references": arterial blood gas analysis, capillary blood analysis and biochemical serum analysis. Mean age of patients was 8.03 ± 2.91 years. Sensors remained in situ for a median of 9.71 ± 5.35 days. Removal of the sensor was mainly attributed to the completion of the predefine life-span of the sensor or discharge of the patient from the ICU. We compared 711 pairs of measurements between the sensor and other glucose measurement methods. Glucose values from the sensor were consistently lower with mean absolute relative difference (MARD) being 28.34%, 25.11% and 18.99% compared to the blood gas analyzer, capillary blood glucose meter, and biochemical serum analysis, respectively, but a wide interindividual variability. Significant linear correlations between age and MARD values were observed. Surveillance error grid (SEG) analysis showed 92.04%, 94.67% and 95.52% of the readings in the none or slight risk zone respectively. FreeStyle Libre is well tolerated although not adequately accurate with a tendency to underestimate glucose levels in critically ill pediatric patients.

Level of knowledge and evaluation of perceptions regarding pediatric diabetes among Greek teachers.

AIM: To assess the knowledge and attitudes of nursery school, preschool and primary school Greek teachers regarding pediatric diabetes. METHODS: Our anonymous questionnaire was comprised of three parts: the first part was regarding sociodemographic characteristics; the second part was assessing basic knowledge about diabetes and the third part was about personal perceptions regarding diabetes management in the school setting. A total of 375 fully completed questionnaires were collected (22.67% from males). RESULTS: Males had a higher percentage of correct answers than females (80.71 ± 10.58% versus 80.17 ± 11.77%), but without reaching statistical significance (p = 0.763). Teachers aged over 45 years, tertiary education graduates and teachers in the public sector proved to be more knowledgeable about the disease. Question scoring the lowest percentage of correct answers were those dealing with the management of diabetic emergencies, such as the course of action in case a diabetic pupil is found unconscious. One out of four participants incorrectly declared that a delay in the diagnosis of diabetes mellitus cannot possibly be life-threatening whereas, an embarrassing 7.47% of the participants stated that diabetes is a contagious disease and another 6.67% declared that diabetic children should stop school. CONCLUSIONS: It is evident that there is an urgent need for providing further information, as well as practical training to schoolteachers with emphasis being placed on the initial symptoms of diabetes and also in the detection and management of diabetic emergencies.

Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations.

To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 µg/dl vs. 24.04±7.20 µg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=-0.234, p<0.001 and r=-0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=-0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=-0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.

TIMING OF GH PEAK IN BOTH GLUCAGON AND CLONIDINE TESTS IS OF MAJOR CLINICAL IMPORTANCE.

Objective: To detect a possible correlation between timing of the peak value of growth hormone (GH) during stimulatory tests (STs) and the effectiveness of treatment with recombinant human growth hormone (rhGH) in children with idiopathic GH deficiency (iGHD). Methods: We retrospectively studied 92 patients with iGHD (57 boys; mean age at diagnosis: 9.93 years). Diagnosis was confirmed by 2 different STs, glucagon stimulation test (GST), and clonidine stimulation test (CST). Auxologic parameters were recorded, while observed and predicted (according to KIGS Prediction Model) height velocity during the first year of treatment and the index of responsiveness (IoR) were calculated for the prepubertal children (n = 65). Results: Atypical GST was defined as that with peak GH value at time 0 minutes, 30 minutes, 60 minutes, or 180 minutes, whereas atypical CST was defined as that with peak timing at 0 minutes, 30 minutes, or 120 minutes. Atypical GST was detected in 18 patients (19.57%). IoR was lower in the prepubertal children with atypical GST (-1.81 ± 0.67 versus -1.34 ± 0.85; P = .051). In the CST, the 18 children who had atypical timing, had significantly lower IoR (-1.86 ± 0.66 versus -1.35 ± 0.84; P = .047). When the patients were categorized according to the number of atypical tests, significant differences in the IoR were detected (-2.09 ± 0.68 with 2 atypical STs [n = 6], -1.64 ± 0.61 with 1 atypical ST [n = 16], and -1.29 ± 0.87 with no atypical ST [n = 43], P = .045). Conclusion: The presence of atypical peak GH timing during ST may be a factor that predicts lower growth hormone velocity during the first year of rhGH treatment in prepubertal children with iGHD. Abbreviations: CST = clonidine stimulation test; GH = growth hormone; GHD = growth hormone deficiency; GST = glucagon stimulation test; iGHD = idiopathic growth hormone deficiency; IoR = index of responsiveness; rhGH = recombinant human growth hormone; SDS = standard deviation scores; ST = stimulatory test.

Level of Internet use among Greek adolescents with type 1 diabetes.

Background Compulsive Internet use has emerged as a contemporary addictive behavior. Our aim was to investigate the reasons for Greek adolescents with type 1 diabetes mellitus (T1DM) and their families to use the Internet and additionally to investigate the level of Internet use and its associations to demographic, socio-economic parameters and glycemic control. Methods Patients with T1DM, aged >12 years and their parents were recruited during their regular visits to the Pediatric Diabetes Clinic. A similar group of healthy children, age- and sex-matched served as a control group. All participants were asked to fill out the Greek translated version of the Internet Addiction Test (IAT). Caregivers of patients with T1DM were asked to complete a second questionnaire consisting of questions regarding demographic and socio-economic data of the family and data concerning disease management. Results Thirty-five patients with T1DM (mean decimal age of 14.95 ± 1.90 years) and 35 controls participated in the study. Nine patients were on an insulin pump whereas the rest were on multiple daily injections. The mean total score of the patients' IAT questionnaires was significantly lower compared to the controls (26.26 ± 12.67 vs. 39.91 ± 18.55, p = 0.003). Controls were characterized as exhibiting moderate addictive behavior at a significantly higher percentage than patients (31.43% vs. 2.86%, p = 0.002). All patients on insulin pumps demonstrated normal Internet use. Mild addictive behavior was associated with a lower parental educational level. Finally, level of Internet use (IAT score) was positively associated to glycemic control (HbA1c value) with a correlation that was approaching significance (r = 0.315, p = 0.065). Conclusions Adolescents with T1DM and especially those on an insulin pump exhibit normal Internet use compared to their healthy peers. Time consumed on Internet correlates reversibly with glycemic control.

Glucose Levels Before the Onset of Asparaginase Predicts Transient Hyperglycemia in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Transient hyperglycemia (TH) represents an acknowledged adverse event that occurs during treatment in children with acute lymphoblastic leukemia (ALL) and has recently been associated with an increased risk for developing metabolic disturbances in future life. Our aim was to estimate the incidence of TH and to identify risk factors, thus serving as markers for identifying candidates for prevention interventions. PROCEDURE: All patients treated with induction treatment for ALL in our department from January 2004 to April 2015 had their data retrieved from medical files and retrospectively analyzed. RESULTS: One hundred and two children with ALL treated at our department were identified (49 females and 53 males) with a mean age of 6.03 ± 3.78 years at the time of diagnosis. Sixteen patients developed TH (15.68%). Age at diagnosis >10 years is associated with an 11-fold increase in the risk of developing TH. Additionally, fasting glucose on the eighth day of treatment is an important prognostic factor as fasting glucose >100 mg/dl at that time point is associated with a threefold increase in developing TH during residual treatment period. CONCLUSIONS: Fasting glucose levels >110 mg/dl on the eighth day of treatment could serve as a trigger for intervention strategies that will prevent the development of TH in pediatric patients treated for ALL. Additional studies are needed to confirm and further extend this preliminary observation.

Sizeable acquired subglottic cyst in a baby with Williams-Beuren syndrome: association or coincidence?

We describe a case of an acquired subglottic cyst presented with persistent stridor and voice hoarsening in a baby diagnosed with Williams-Beuren syndrome that was born premature and required intubation during neonatal period. We also comment on whether this is a coincidence or there can be an association between impaired elastogenesis, a feature of patients with the syndrome and the formation of a subglottic cyst.

Impressive shrinkage of a giant prolactinoma treated with cabergoline in a prepubescent girl. What now?

Giant prolactinomas are extremely rare in the pediatric population. We describe the case of a giant prolactinoma in a girl aged 14 years and 9 months old presented with delayed puberty. Medical treatment with dopamine agonist cabergoline resulted in a rapid normalization of prolactine levels and an impressive shrinkage and liquefaction of the mass as illustrated in serial MRIs. The therapeutic dilemma regarding the type of treatment (medical versus surgical) has now been replaced by the dilemma regarding the optimal treatment strategy and duration. Initial, rather optimistic, estimations regarding the probability of treatment discontinuation without increased relapsing risk have now been replaced by guidelines with more strict criteria for selecting candidates for treatment discontinuation.

Restrictive pulmonary dysfunction and its predictors in young patients with ß-thalassaemia major.

BACKGROUND: Pulmonary dysfunction represents one of the most undervalued and less recognized complications in patients with ß-thalassaemia. OBJECTIVES: The aim of this study was to assess the pattern of pulmonary dysfunction and consequently to investigate possible associated factors that might contribute to lung impairment in young patients with ß-thalassaemia major. METHODS: Fifty-two children and young adults (mean age: 21.33 ± 6.24 years) with ß-thalassaemia major on conventional treatment (transfusions and iron chelation therapy) were included in the study. A complete computerized pulmonary function testing (PFT) system for recording pulmonary diffusion capacity and simultaneous determination of alveolar volume and pulmonary volumes was equipped. RESULTS: Results showed that 20 patients (38.46%) had restrictive pulmonary pattern that was preferentially observed in older and shorter patients. Serum ferritin levels were higher in the restrictive group (2,096 ± 1,831 ng/dl) compared to patients with normal pulmonary function (1,354 ± 942 ng/dl) (P = 0.066). Diffusional impairment characterized by significantly lower DLCO*% values, was observed in the restrictive group (P = 0.004), implicating the 62.5% of the population studied. Paired linear correlations showed that age was negatively correlated to DLCO*% (r = -0.548, P < 0.001) and SaO(2) % (r = -0.789, P < 0.001) and with most of the pulmonary functional parameters that determine a restrictive. Multivariate regression analysis identified age as the major predictor for restrictive pulmonopathy followed by serum ferritin levels. CONCLUSIONS: Our study shows that pulmonary impairment is shown in a great proportion even among asymptomatic young thalassaemic patients, thus, regular screening of pulmonary function should be adopted in the routine clinical follow up of these patients.

Fok-I polymorphism of vitamin D receptor gene and the presence of renal dysfunction in patients with ß-thalassemia major.

Recent evidence supports the presence of renal dysfunction even among young patients with ß-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with ß-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5-22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary ß(2)-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.