Heterozygous variants in the NPR2 gene, which encodes the B-type natriuretic peptide receptor (NPR-B), a regulator of skeletal growth, were reported in 2–6% cases of idiopathic short stature (ISS). ...Using next-generation sequencing (NGS), we aimed to assess the frequency of NPR2 variants in our study cohort consisting of 150 children and adolescents with ISS, describe the NPR2 phenotypic spectrum with a growth pattern including birth data, and study the response to growth hormone (GH) treatment. A total of ten heterozygous pathogenic/likely pathogenic NPR2 variants and two heterozygous NPR2 variants of uncertain significance were detected in twelve participants (frequency of causal variants: 10/150, 6.7%). During follow-up, the NPR2 individuals presented with a growth pattern varying from low–normal to significant short stature. A clinically relevant increase in BMI (a mean gain in the BMI SDS of +1.41), a characteristic previously not reported in NPR2 individuals, was observed. In total, 8.8% participants born small for their gestational age (SGA) carried the NPR2 causal variant. The response to GH treatment was variable (SDS height gain ranging from −0.01 to +0.74). According to the results, NPR2 variants present a frequent cause of ISS and familial short stature. Phenotyping variability in growth patterns and variable responses to GH treatment should be considered.
Aims/hypothesis
Hypoglycaemia during and after exercise remains a challenge. The present study evaluated the safety and efficacy of closed-loop insulin delivery during unannounced (to the closed-loop ...algorithm) afternoon physical activity and during the following night in young people with type 1 diabetes.
Methods
A randomised, two-arm, open-label, in-hospital, crossover clinical trial was performed at a single site in Slovenia. The order was randomly determined using an automated web-based programme with randomly permuted blocks of four. Allocation assignment was not masked. Children and adolescents with type 1 diabetes who were experienced insulin pump users were eligible for the trial. During four separate in-hospital visits, the participants performed two unannounced exercise protocols: moderate intensity (55% of
V
⋅
O
2
max
) and moderate intensity with integrated high-intensity sprints (55/80% of
V
⋅
O
2
max
), using the same study device either for closed-loop or open-loop insulin delivery. We investigated glycaemic control during the exercise period and the following night. The closed-loop insulin delivery was applied from 15:00 h on the day of the exercise to 13:00 h on the following day.
Results
Between 20 January and 16 June 2016, 20 eligible participants (9 female, mean age 14.2 ± 2.0 years, HbA
1c
7.7 ± 0.6% 60.0 ± 6.6 mmol/mol) were included in the trial and performed all trial-mandated activities. The median proportion of time spent in hypoglycaemia below 3.3 mmol/l was 0.00% for both treatment modalities (
p
= 0.7910). Use of the closed-loop insulin delivery system increased the proportion of time spent within the target glucose range of 3.9–10 mmol/l when compared with open-loop delivery: 84.1% (interquartile range 70.0–85.5) vs 68.7% (59.0–77.7), respectively (
p
= 0.0057), over the entire study period. This was achieved with significantly less insulin delivered via the closed-loop (
p
= 0.0123).
Conclusions/interpretation
Closed-loop insulin delivery was safe both during and after unannounced exercise protocols in the in-hospital environment, maintaining glucose values mostly within the target range without an increased risk of hypoglycaemia.
Trial registration
Clinicaltrials.gov
NCT02657083
Funding
University Medical Centre Ljubljana, Slovenian National Research Agency, and ISPAD Research Fellowship
Abstract
The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels ...has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.
Graphical Abstract
Background Our aim was to determine whether child attachment to parents, parent attachment style, and morning cortisol levels were related to diabetes outcomes measured by average glycated hemoglobin ...(HbA1c), HbA1c variability over 4 years and time in range (TIR) in children with type 1 diabetes (T1D). Research design and methods 101 children with T1D and one of their parents were assessed at baseline for child attachment (Child Attachment Interview; CAI) and parent attachment (Relationship Structures Questionnaire; ECR-RS). Serum samples were collected for cortisol measurements before the interviews. HbA1c levels were measured during a 4-year follow-up period at regular 3-monthly visits, and data for TIR were exported from blood glucose measuring devices. Multivariate linear regression models were constructed to identify independent predictors of glycemic outcomes. Results More girls than boys exhibited secure attachment to their mothers. The results of the regression models showed that securely attached girls (CAI) had higher average HbA1c than did insecurely attached girls (B = -0.64, p = 0.03). In boys, the more insecure the parent's attachment style, the worse the child's glycemic outcome: the higher the average Hb1Ac (B = 0.51, p = 0.005), the higher the HbA1c variability (B = 0.017, p = 0.011), and the lower the TIR (B = -8.543, p = 0.002). Conclusions Attachment in close relationships is associated with glycemic outcomes in children with T1D, and we observed significant differences between sexes. A sex- and attachment-specific approach is recommended when treating children with less favorable glycemic outcomes. Special attention and tailored support should be offered to securely attached girls in transferring responsibility for diabetes care and at least to male children of insecurely attached parents to prevent suboptimal glycemic control. Further studies in larger samples and more daily cortisol measurements may help us better understand the links between stress response, attachment and T1D. Keywords: Attachment, Childhood and adolescence, Diabetes control, Time in range, Cortisol
Background/Objective:
Type 1 diabetes (T1D) is among the most common chronic diseases in children/adolescents, and the incidence continues to rise worldwide. Different environmental factors have been ...evaluated in the etiology. In the present study, we investigated the role of attachment examining whether insecure attachment to carers or carers' own attachment insecurity was related to a higher risk of T1D in children.
Methods:
We included 101 children with T1D (mean age 11.8 years), 106 healthy controls (11.6 years), and one of their carers. We assessed children's attachment using the Child Attachment Interview and carers' attachment using the Relationship Structures Questionnaire. We constructed binary multinomial logistic regression models using attachment to mothers, carers' attachment representations, and stressful life-events as T1D predictors.
Results:
Higher carer attachment anxiety was associated with the child's T1D diagnosis (
p
< 0.05;
R
2
= 0.0613) while security of attachment to mothers showed no significant association. When mothers' education was included in the model, both attachment anxiety in higher educated mothers and stressful life events showed a significant association with the child's T1D (
p
< 0.001;
R
2
= 0.293).
Conclusions:
Our findings suggest that higher attachment-related anxiety in carers with high education and stressful life events are associated with T1D in children.
The objective of this nationwide population-based cohort study was to evaluate the correlation between continuous glucose monitoring (CGM) use and glucose variability in pre-schoolers with type 1 ...diabetes.
We analysed data from the Slovenian National Registry. The primary endpoint was the difference in glucose variability between periods, during which participants were using CGM and periods, during which CGM was not used, over 5 years.
A total of 40 children <8 years old were followed for an estimated observational period of 116 patient/years. Mean age at CGM initiation was 3.5 (±1.7) years. Both standard deviation of mean glucose 3.6 mmol/L (3.2–3.9) with CGM and 4.3 mmol/L (3.8–4.7) without CGM, p < 0.001 and coefficient of variation 44.0% (40.4–47.0) with CGM and 46.1% (42.3–49.4) without CGM, p = 0.021 were lower during the periods, when CGM was used. Frequent CGM use (>5 days/week) was associated with a 0.4% 4.4 mmol/mol reduction in glycated haemoglobin level (7.6% compared to 7.2%, p = 0.047).
Our results indicate that the use of CGM was associated with reduced glucose variability during a 5 year follow-up period among pre-schoolers with type 1 diabetes.
Clinicaltrials.gov: NCT-03293082.
Sindrom relativnega energijskega primanjkljaja se razvije pri otrocih in mladostnikih športnikih ob negativni energijski bilanci, ki je posledica nezadostnega vnosa energije glede na velike potrebe ...ob intenzivni telesni vadbi. Energijsko neravnovesje privede do motenj v delovanju več organskih sistemov. Pri otrocih in mladostnikih so posledice lahko dolgoročne in se kažejo kot neugoden vpliv na rast, pubertetni razvoj in zdravje kosti. Zgodnji prepoznava in obravnava sta tako v tej starostni skupini ključni. Zaradi pomanjkljive ozaveščenosti med mladimi športniki, njihovimi starši, trenerji in zdravstvenim osebjem ter nespecifične klinične slike bolezen pogosto spregledamo.
This narrative review assesses the use of automated insulin delivery (AID) systems in managing persons with type 1 diabetes (PWD) in the pediatric population. It outlines current research, the ...differences between various AID systems currently on the market and the challenges faced, and discusses potential opportunities for further advancements within this field. Furthermore, the narrative review includes various expert opinions on how different AID systems can be used in the event of challenges with rapidly changing insulin requirements. These include examples, such as during illness with increased or decreased insulin requirements and during physical activity of different intensities or durations. Case descriptions give examples of scenarios with added user-initiated actions depending on the type of AID system used. The authors also discuss how another AID system could have been used in these situations.
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