Comparison Between Continuous Versus Flash Glucose Monitoring in Children, Adolescents, and Young Adults with Type 1 Diabetes: An 8-Week Prospective Randomized Trial.

INTRODUCTION: To assess the impact of real-time continuous glucose monitoring (RT-CGM) instead of first-generation flash glucose monitoring (FGM) on hypoglycaemia in children and adolescents with type 1 diabetes. METHODS: In this randomized controlled interventional study, young individuals with type 1 diabetes used RT-CGM or FGM for 8 weeks. We evaluated changes in time below range (TBR), severe hypoglycaemia (SH), HbA1c, glycaemic variability, and impaired awareness of hypoglycaemia with RT-CGM (intervention group) in comparison with FGM. RESULTS: We randomly assigned 37 participants to either the intervention group (n = 19) or the control group (n = 18). At 8 weeks, we did not find a decrease in TBR in either group, but there was a significant reduction in SH in the intervention group. For participants with TBR ≥ 5% at baseline, we observed significant reductions in 24-h TBR, wake TBR, sleep TBR, and glucose variability at 8 weeks in the intervention group. CONCLUSIONS: The use of RT-CGM versus FGM decreased SH in young individuals with type 1 diabetes, and TBR and glucose variability in patients with a higher TBR at baseline. The patient's history should be taken into account when advising on the method of blood glucose monitoring, as RT-CGM could be more effective in younger patients at high risk for SH. TRIAL REGISTRATION: ClinicalTrials.gov NCT04249102.

Anti-SARS-CoV-2 antibodies in new-onset type 1 diabetes in children during pandemic in Belgium.

OBJECTIVES: Questions are emerging concerning the long-term consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, as a possible increase in type 1 diabetes. This study aims to describe the prevalence of anti-SARS-CoV-2 antibodies in children developing type 1 diabetes during this pandemic in Belgium. METHODS: This observational study included children and adolescents (under 16 years) admitted with new-onset type 1 diabetes. SARS-CoV-2 serology was taken within the first month of diabetes. RESULTS: Of the 75 participants, anti-SARS-CoV-2 antibodies were positive in 20% of patients. They had an increased bicarbonate and base excess at diagnosis. Overall 29% of patients presented diabetic ketoacidosis at diagnosis and 9% of them were positive for anti-SARS-CoV-2 antibodies. Insulinoma-associated protein 2 antibodies positivity had significantly higher frequencies in children without anti-SARS-CoV-2 antibodies (49 (81%) vs. 5 (33%), p=0.038). Nine (15%) patients, initially seronegative, have developed anti-SARS-CoV-2 antibodies between the two samples (mean time 8 ± 4 weeks). CONCLUSIONS: The prevalence of anti-SARS-CoV-2 antibodies in children with newly diagnosed type 1 diabetes (20%) is similar to that found in children without diabetes in Belgium, a country severely affected by this pandemic.

Diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: Role of demographic, clinical, and biochemical features along with genetic and immunological markers as risk factors. A 20-year experience in a tertiary Belgian center.

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). Little is known about the association between genetic and immunological markers and the risk for DKA at onset of T1D. The aim of this study was to create a model foreseeing the onset of DKA in newly diagnosed patients. METHODS: This retrospective study included 532 T1D children (aged <18 years at diagnosis) recruited in our hospital, from 1995 to 2014. DKA and its severity were defined according to the criteria of ISPAD. Genetic risk categories for developing T1D were defined according to the Belgian Diabetes Registry. Multivariate statistical analyses were applied to investigate risk factors related to DKA at diagnosis. RESULTS: Overall 42% of patients presented DKA at diagnosis. This study outlined the major risk of DKA at diagnosis for younger children (<3 years) and for those belonging to ethnic minorities. Children carrying neutral genotypes had a 1.5-fold increased risk of DKA at diagnosis than those with susceptible or protective genotypes, a paradoxical observation not previously reported. Only solitary positive IA-2A increased the risk of DKA at diagnosis. The proposed model could help to predict the probability of DKA in 70% of newly diagnosed cases. CONCLUSIONS: This was the first reported implication of IA-2A positivity and neutral genotypes predisposing to DKA at diagnosis regardless of its severity. Earlier diagnosis through genetic and immunological screening of high-risk children could decrease DKA incidence at diabetes onset.

Flash Glucose Monitoring Accepted in Daily Life of Children and Adolescents with Type 1 Diabetes and Reduction of Severe Hypoglycemia in Real-Life Use.

Background: Flash glucose monitoring (FGM) is covered by the Belgian public health insurance for type 1 diabetes since 2016. The objective of this study was to describe the use of FGM and diabetes outcomes in type 1 diabetic children and adolescents 1 year after reimbursement. Methods: All patients had the choice to convert to FGM or to continue with self-monitoring of blood glucose (SMBG). Clinical data were collected at baseline, at the next visit, and after 12 months; glucose profiles at next visit and after 12 months. Regression analyses were performed to identify predictors of FGM acceptance and changes in metabolic control. Results: A total of 334 subjects were included, of whom 278 (83.2%) switched to FGM. They were younger (13.6 vs. 15.2 years; P = 0.012) and performed more SMBG testing at baseline than patients who did not switch (4.3 vs. 4.1 tests daily; P = 0.008). At the end of follow-up, the rate of severe hypoglycemia decreased by 53% in the group of FGM users (P = 0.012) while it remained stable in SMBG users. Median glycated hemoglobin did not change significantly in both groups. Among subjects who switched to FGM, 15.8% reverted to SMBG after a median use of 5.3 months. Adverse events, diabetes duration, and FGM utilization were independent predictors of the risk for reverting. FGM-related adverse events were associated with a fivefold increased risk to revert to SMBG (hazard ratio = 5.12; P < 0.0001). Conclusions: FGM is relatively well accepted and decreases the risk of severe hypoglycemic events in our pediatric population. FGM is more often discontinued in patients experiencing adverse events and with longer diabetes duration.

Twenty-Year Progression Rate to Clinical Onset According to Autoantibody Profile, Age, and HLA-DQ Genotype in a Registry-Based Group of Children and Adults With a First-Degree Relative With Type 1 Diabetes.

OBJECTIVE: We investigated whether islet autoantibody profile, HLA-DQ genotype, and age influenced a 20-year progression to diabetes from first autoantibody positivity (autoAb+) in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Persistently islet autoAb+ siblings and offspring (n = 462) under 40 years of age were followed by the Belgian Diabetes Registry. AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A) were determined by radiobinding assay. RESULTS: The 20-year progression rate of multiple-autoAb+ relatives (n = 194) was higher than that for single-autoAb+ participants (n = 268) (88% vs. 54%; P < 0.001). Relatives positive for IAA and GADA (n = 54) progressed more slowly than double-autoAb+ individuals carrying IA-2A and/or ZnT8A (n = 38; P = 0.001). In multiple-autoAb+ relatives, Cox regression analysis identified the presence of IA-2A or ZnT8A as the only independent predictors of more rapid progression to diabetes (P < 0.001); in single-autoAb+ relatives, it identified younger age (P < 0.001), HLA-DQ2/DQ8 genotype (P < 0.001), and IAA (P = 0.028) as independent predictors of seroconversion to multiple positivity for autoAbs. In time-dependent Cox regression, younger age (P = 0.042), HLA-DQ2/DQ8 genotype (P = 0.009), and the development of additional autoAbs (P = 0.012) were associated with more rapid progression to diabetes. CONCLUSIONS: In single-autoAb+ relatives, the time to multiple-autoAb positivity increases with age and the absence of IAA and HLA-DQ2/DQ8 genotype. The majority of multiple-autoAb+ individuals progress to diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or ZnT8A, regardless of age, HLA-DQ genotype, and number of autoAbs. These data may help to refine the risk stratification of presymptomatic type 1 diabetes.

[Growth in type 1 diabetic children]. / Croissance de l'enfant diabétique.

Despite the fact that height in diabetic children has extensively been studied, many controversies remain. The aim of this study is to review growth in type 1 diabetes. Height at diagnosis is probably not increased compared with appropriate reference data. Later loss of height is observed due to a reduced peak height velocity during puberty. The poor pubertal growth can be linked to abnormalities of the growth hormone--insulinlike growth factor-I axis. It has also been showed that good metabolic control is necessary to allow normal growth in diabetic children. Metabolic control and the age at onset of type 1 diabetes are reported to be significant factors influencing final height. Careful monitoring of height and weight in diabetic patients must be made and good glycemic control has to be maintained to allow normal growth and development in diabetic patients.

Bone age corresponds with chronological age at type 1 diabetes onset in youth.

OBJECTIVE: To our knowledge, only two controversial articles have reported the study of bone age at diagnosis in diabetic children. The aim of this study was to compare chronological age with bone age and to evaluate the impact of A1C on bone age in children at diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: In 496 diabetic children, height was measured at diagnosis and height SD score was calculated using the British 1990 growth reference. Bone age was determined according to the Greulich and Pyle method, and A1C levels were measured. RESULTS: Participants' height was normal for age and sex. No significant differences were found between chronological age and bone age, and there was no correlation between Delta (bone age - chronological age) and A1C. CONCLUSIONS: This study showed that height and bone maturation among diabetic children are normal for age and sex and independent of A1C at diagnosis of type 1 diabetes.

Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency.

Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative lysosomal disease characterized by accumulation of sulfatides, extensive white matter damage and loss of both cognitive and motor functions. In vivo, the catabolism of sulfatide requires both the enzyme arylsulfatase A and a specific sphingolipid activator protein, saposin-B, encoded by the PSAP gene. Arylsulfatase A activity is deficient in the classical forms of MLD, but exceedingly rare cases of MLD are due to saposin-B deficiency. We report here a detailed clinical, radiological and histological description of a new case in a 2-year-old Italian girl, who presented as a late infantile case of MLD with normal arylsulfatase A activity, urinary excretion of sulfatides and mutations in the PSAP gene.