Survey of Australian general paediatricians regarding insulin initiation practices in children with new onset of type 1 diabetes.

AIM: Australian and New Zealand (NZ) paediatric endocrinologists' and NZ general paediatricians' insulin initiation strategies for children with type 1 diabetes (T1D) was recently described. The aim of this study was to document the insulin initiation practices of Australian general paediatricians in newly diagnosed children with T1D. METHODS: An online survey was sent to Australian general paediatricians identified through the Australian Paediatric Society diabetes database. RESULTS: Twenty four general paediatricians participated on behalf of their Australian regional and metropolitan diabetes units managing 2059 patients. The diabetes units averaged 86 patients and all practices were multidisciplinary models of care. Intensive insulin therapy regimens were initiated at diagnosis for children age 2-10 years by 93% respondents compared with 73% Australian endocrinologists, 17% NZ endocrinologists and 36% NZ general paediatricians. Carbohydrate counting as part of flexible bolus dosing was usual practice for 83% of respondents, which was substantially more than Australian endocrinologists (63%), NZ endocrinologists (64%) and NZ general paediatricians (33%). CONCLUSION: Almost all Australian general paediatricians who completed the survey initiate intensive insulin therapy regimes with carbohydrate counting in newly diagnosed children with T1D, consistent with the 2018 evidence-based recommendations of the International Society of Pediatric and Adolescent Diabetes. A substantial proportion of children with T1D within Australia are managed by general paediatricians who tend to align with international peak body guidelines.

Dietary sodium intake relates to vascular health in children with type 1 diabetes.

BACKGROUND AND OBJECTIVE: Children with type 1 diabetes (T1D) have vascular dysfunction and frequently struggle to adhere to dietary recommendations. Limited data exist for the vascular consequences of poor diet quality in children. We aimed to evaluate the association between dietary components and vascular function in children with T1D. METHODS: Cross-sectional study including 90 children (13.6 [3.5] years, 41 boys) with T1D. They had evaluation of dietary micro and macronutrients (Australian Child and Adolescent Eating Survey), vascular endothelial and smooth muscle function (flow-mediated dilatation and glyceryl trinitrate mediated dilatation [GTN], respectively), clinical and biochemical variables. RESULTS: Children had a sodium intake of 3.013 (0.76) (mean [SD]) g/day. Vascular smooth muscle dysfunction, as measured by GTN, related to higher daily sodium intake (r = -0.31, P = .003), independent of the inverse relationships between GTN and total energy (r = -0.30, P = .005) and fat intake (r = -0.28, P = .007). Multiregression model showed that an increase in 1 g of daily sodium intake was independently associated with a deterioration of 3 percentage units in GTN (95% CI -4.3, -0.9; P = .003). There was an association between sodium intake and systolic blood pressure after adjustment for age and gender (regression coefficient 2.4; 95% CI 0.5, 4.3; P = .01). CONCLUSIONS: High dietary sodium intake in children with T1D is common and relates to vascular dysfunction, independently of other dietary intake, blood pressure, and glycemic control.

Does metformin improve vascular health in children with type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in Type 1 diabetes (T1D). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2D for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1D. METHODS/DESIGN: This study is a 12 month, double blind, randomised, placebo controlled trial to determine the effect of metformin on vascular health in children (age 8-18) with T1D. The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group. Vascular health and biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness, using standardised protocols. DISCUSSION: This study will be the first to investigate the effect of metformin on vascular health in children with T1D. It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000148976.

Effect of Metformin on Vascular Function in Children With Type 1 Diabetes: A 12-Month Randomized Controlled Trial.

Context: Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis. Early interventions are needed to reduce cardiovascular disease. Objective: To evaluate the effect of metformin on vascular function in children with type 1 diabetes. Design: Twelve-month double-blind, randomized, placebo-controlled trial. Setting: Tertiary pediatric diabetes clinic. Participants: Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI), with type 1 diabetes. Intervention: Metformin (up to 1 g twice a day) or placebo. Main Outcome Measure: Vascular function measured by brachial artery ultrasound [flow-mediated dilatation/glyceryl trinitrate-mediated dilatation (GTN)]. Results: Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45 per group], 10 discontinued intervention, and 1 was lost to follow-up. On metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3 percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or other cardiovascular risk factors. Median (95% CI) adherence, evaluated by electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis. Conclusions: Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children. These benefits and good safety profile warrant further consideration of its use.

Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A.

Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance.