A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Impact of intercurrent illness on calcium homeostasis in children with hypoparathyroidism: a case series.

BACKGROUND: Hypoparathyroidism is characterised by hypocalcaemia, and standard management is with an active vitamin D analogue and adequate oral calcium intake (dietary and/or supplements). Little is described in the literature about the impact of intercurrent illnesses on calcium homeostasis in children with hypoparathyroidism. METHODS: We describe three children with hypoparathyroidism in whom intercurrent illnesses led to hypocalcaemia and escalation of treatment with alfacalcidol (1-hydroxycholecalciferol) and calcium supplements. RESULTS: Three infants managed with standard treatment for hypoparathyroidism (two with homozygous mutations in GCMB2 gene and one with Sanjad-Sakati syndrome) developed symptomatic hypocalcaemia (two infants developed seizures) following respiratory or gastrointestinal illnesses. Substantial increases in alfacalcidol doses (up to three times their pre-illness doses) and calcium supplementation were required to achieve acceptable serum calcium concentrations. However, following resolution of illness, these children developed an increase in serum calcium and hypercalciuria, necessitating rapid reduction to pre-illness dosages of alfacalcidol and oral calcium supplementation. CONCLUSION: Intercurrent illness may precipitate symptomatic hypocalcaemia in children with hypoparathyroidism, necessitating increase in dosages of alfacalcidol and calcium supplements. Close monitoring is required on resolution of the intercurrent illness, with timely reduction of dosages of active analogues of vitamin D and calcium supplements to prevent hypercalcaemia, hypercalciuria and nephrocalcinosis.

The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.

OBJECTIVE: In children with congenital hyperinsulinism (CHI), K(ATP) channel genes (ABCC8 and KCNJ11) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI. DESIGN: Follow-up observational study at two CHI referral hospitals. METHODS: Clinical outcomes such as subtotal pancreatectomy, (18)F-Dopa positron emission tomography-computed tomography (PET-CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI. RESULTS: In total, 32 (32%) children had pathogenic mutations in K(ATP) channel genes (27 in ABCC8 and five in KCNJ11), of which 11 (34%) were novel. In those negative at initial screening, other mutations (GLUD1, GCK, and HNF4A) were identified in three children. Those with homozygous/compound heterozygous ABCC8/KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with (18)F-Dopa PET-CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy. CONCLUSIONS: Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require (18)F-Dopa PET-CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.

The effect of biopsy-positive silent coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in children with Type 1 diabetes.

OBJECTIVE: To determine the effect of coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in asymptomatic children with Type 1 diabetes. METHODS: Data were compared in children with coeliac disease diagnosed by annual antibody screening and jejunal biopsy and treated with a gluten-free diet (n = 49) against individuals who were antibody negative (n = 49) matched for age, sex and duration of diabetes. RESULTS: No differences in growth were observed. In the years prior to diagnosis of coeliac disease, mean glycated haemoglobin (HbA(1c)) was lower in cases compared with control subjects [8.3 +/- 1.1% vs. 8.7 +/- 0.9%, P = 0.02 (mean +/- sd)]. In cases, HbA(1c) deteriorated 12 months from the start of a gluten-free diet to levels similar to control subjects (8.9 +/- 1.5% vs. 8.8 +/- 1.5%, P-value for analysis of variance = 0.9). In regression analysis, the diagnosis of coeliac disease and start of a gluten-free diet was associated with a rise in HbA(1c) in the first year of treatment [odds ratio 1.56 (95% confidence intervals 1.16-2.10), P = 0.003] after adjusting for insulin dose and regimen and other variables. CONCLUSIONS: In children with Type 1 diabetes, lower HbA(1c) prior to diagnosis of silent coeliac disease rises following treatment with a gluten-free diet to levels similar to those without coeliac disease. Although unproven, these observations may relate to abnormalities at the small bowel mucosa before the appearance of circulating coeliac antibodies.