OBJECTIVEMonogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing.
RESEARCH DESIGN AND METHODSWe studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ‡0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes.
RESULTSA total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients).
CONCLUSIONSThis large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.
ObjectiveTo determine accuracy, safety and acceptability of the FreeStyle Libre Flash Glucose Monitoring System in the paediatric population.Design, setting and patientsEighty-nine study participants, aged 4–17 years, with type 1 diabetes were enrolled across 9 diabetes centres in the UK. A factory calibrated sensor was inserted on the back of the upper arm and used for up to 14 days. Sensor glucose measurements were compared with capillary blood glucose (BG) measurements. Sensor results were masked to participants.ResultsClinical accuracy of sensor results versus BG results was demonstrated, with 83.8% of results in zone A and 99.4% of results in zones A and B of the consensus error grid. Overall mean absolute relative difference (MARD) was 13.9%. Sensor accuracy was unaffected by patient factors such as age, body weight, sex, method of insulin administration or time of use (day vs night). Participants were in the target glucose range (3.9–10.0 mmol/L) ∼50% of the time (mean 12.1 hours/day), with an average of 2.2 hours/day and 9.5 hours/day in hypoglycaemia and hyperglycaemia, respectively. Sensor application, wear/use of the device and comparison to self-monitoring of blood glucose were rated favourably by most participants/caregivers (84.3–100%). Five device related adverse events were reported across a range of participant ages.ConclusionsAccuracy, safety and user acceptability of the FreeStyle Libre System were demonstrated for the paediatric population. Accuracy of the system was unaffected by subject characteristics, making it suitable for a broad range of children and young people with diabetes.Trial registration numberNCT02388815.
In the UK, there have been reports of significant reductions in paediatric emergency attendances and visits to the general practitioners due to COVID-19. A national survey undertaken by the UK Association of Children’s Diabetes Clinicians found that the proportion of new-onset type 1 diabetes (T1D) presenting with diabetes ketoacidosis (DKA) during this COVID-19 pandemic was higher than previously reported, and there has been an increase in presentation of severe DKA at diagnosis in children and young people under the age of 18 years. Delayed presentations of T1D have been documented in up 20% of units with reasons for delayed presentation ranging from fear of contracting COVID-19 to an inability to contact or access a medical provider for timely evaluation. Public health awareness and diabetes education should be disseminated to healthcare providers on the timeliness of referrals of children with T1D.
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ObjectivesPrader-Willi Syndrome (PWS) is characterised by hyperphagia often leading to obesity; a known risk factor for insulin resistance and type 2 (T2) diabetes. We present a prepubertal girl with PWS who developed diabetes.Case presentationOur case was diagnosed with PWS in infancy following investigation for profound central hypotonia and feeding difficulties. She commenced growth hormone (GH) aged 8 years for short stature and treatment improved linear growth. At age 12 years, she presented with polydipsia, polyuria and vulvovaginitis. She was overweight (BMI SDS +1.43). Diabetes was diagnosed (Blood glucose = 24.2 mmol/L, HbA1c = 121 mmol/mol or 13.2%). She was not acidotic and had negative blood ketones. Autoantibodies typical of type 1 diabetes were negative. She was initially treated with basal bolus insulin regime. GH was discontinued 3 months later due to concerns regarding GH-induced insulin resistance. Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy. However off GH, she reported significant lethargy with static growth and increased weight. Combinations of Metformin with differing insulin regimes did not improve glucose levels. Liraglutide (GLP-1 agonist) and Metformin did not improve glucose levels nor her weight. Liraglutide and Empaglifozin (SGLT-2 inhibitor) therapy used in combination were well tolerated and demonstrated rapid normalisation of blood glucose and improvement in her HbA1c to within target (48 mmol/mol) which was sustained after 6 months of treatment.ConclusionsNewer treatments for type 2 diabetes (e. g. GLP-1 agonists or SGLT-2 inhibitors) offer potential treatment options for those with diabetes and PWS when conventional treatments are ineffective.
There was a wide variation in the practice of monitoring and advice given during illness. Both surveys highlight need for national guidance as well and to improve quality of sick-day rule education programmes for parents of children with type 1 diabetes.
Current physical activity guidelines for youth with type 1 diabetes (T1D) are poorly supported by empirical evidence and the optimal dose of physical activity to improve glycemic control is unknown. This case report documents the effect of acute high‐intensity interval exercise (HIIE) and moderate‐intensity exercise (MIE) on 24‐h glycemic control in three adolescents with T1D using continuous glucose monitoring. Results highlight varied individual response to exercise across the participants. In two participants both MIE and HIIE resulted in a drop in blood glucose during exercise (−38 to −42% for MIE and −21–46% in HIIE) and in one participant both MIE and HIIE resulted in increased blood glucose (+19% and + 36%, respectively). Over the 24‐h period average blood glucose was lower for all participants in the HIIE condition, and for two for the MIE condition, compared to no exercise. All three participants reported HIIE to be more enjoyable than MIE. These data show both HIIE and MIE have the potential to improve short‐term glycemic control in youth with T1D but HIIE was more enjoyable. Future work with a larger sample size is required to explore the potential for HIIE to improve health markers in youth with T1D.
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