Sydney Diabetes centre's experience of the Australian Government's roll out of subsidised continuous glucose monitoring for children with type 1 diabetes mellitus.

AIM: To determine patient/carer expectations of continuous glucose monitoring (CGM) and short-term satisfaction, to assess the efficacy of CGM in improving: fear of hypoglycaemia and glycaemic control (HbA1c , ketosis, hypoglycaemia) and to determine time requirements of diabetes clinic staff in commencing and administering CGM. METHODS: We assessed CGM-naïve patients starting on CGM at a Sydney Diabetes Centre following the introduction of a nationwide government subsidy for CGM. A standardised questionnaire was administered collecting demographic and glycaemic information in addition to Likert scale assessment of expectations and satisfaction. Clinic staff reported time dedicated to CGM education, commencement and follow-up. RESULTS: A total of 55 patients or parents/carers completed baseline questionnaires, with 37 completing a 3-month follow-up questionnaire. There were high expectations of CGM prior to commencement and high satisfaction ratings on follow-up. CGM improved fear of hypoglycaemia, and total daily insulin dose increased after commencement of CGM. There was a trend towards lower HbA1c that was not statistically significant and no statistically significant reduction in ketosis or hypoglycaemia. Comments were mostly positive, with some concern raised regarding technical issues and a lack of subsidy after 21 years of age. Staff time requirements were substantial, with an estimated average of 7.7 h per patient per year. CONCLUSIONS: Patients and families have high expectations of CGM, and satisfaction levels are high in the short term. Total insulin delivery increased after CGM commencement. Time requirements by staff are substantial but are worthwhile if families' overall satisfaction levels are high.

Normal cortisol response on low-dose synacthen (1 microg) test in children with Prader Willi syndrome.

INTRODUCTION: It has been postulated that central adrenal insufficiency (CAI), resulting from hypothalamic dysfunction, may contribute to the increased unexplained death rates in Prader Willi syndrome (PWS). A study using the overnight metyrapone test reported a 60% prevalence of CAI in children with PWS. We used a low-dose Synacthen test to screen for CAI in children with PWS. METHODS: We studied 41 children with genetic diagnosis of PWS [20 males; mean age, 7.68 (±5.23) yr] in five pediatric endocrinology centers in Australasia. All participants were randomly selected, and none had a history of Addisonian crisis. Ten of the cohort were receiving sex hormone therapy, 19 were receiving GH, and four were receiving T4. Their mean body mass index z-score was +1.48 (±1.68). Baseline morning ACTH and cortisol levels were measured, followed by iv administration of 1 µg Synacthen. Post-Synacthen cortisol levels were measured at 30 min, and a cortisol level above 500 nmol/liter was considered normal. RESULTS: The mean baseline ACTH and cortisol were 15 (±14) ng/liter and 223 (±116) nmol/liter, respectively. The mean 30-min plasma cortisol was 690 (±114) nmol/liter, and the average increase from baseline was 201%. CONCLUSIONS: Our result suggests that CAI is rare in children with PWS.

Investigating maturity onset diabetes of the young.

Maturity Onset Diabetes of Young (MODY) is a monogenic and autosomal dominant form of diabetes mellitus with onset of the disease often before 25 years of age. It is due to dysfunction of pancreatic beta cells characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies. It is frequently mistaken for type 1 or type 2 diabetes mellitus. Diagnosis of MODY is important as the GCK subtype has better prognosis and may not require any treatment. Subtypes HNF1A and HNF4A are sensitive to sulfonylureas, however diabetes complications are common if not treated early. Moreover, there is genetic implication for the patient and family. Rare MODY subtypes can be associated with pancreatic and renal anomalies as well as exocrine dysfunction of the pancreas. So far there are six widely accepted subtypes of MODY described but the list has grown to nine. Although the majority of diabetes mellitus in youth remains type 1 and the incidence of type 2 is rising, MODY should be considered in patients with non-ketotic diabetes at presentation, and in patients with a strong family history of diabetes mellitus without pancreatic auto-antibodies. Furthermore the diagnosis must be confirmed by molecular studies. With advancement in genomic technology, rapid screening for MODY mutations will become readily available in the future.

The clinical and biochemical spectrum of congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency.

21-Hydroxylase Deficiency (21-OH Deficiency) represents the most common form of Congenital Adrenal Hyperplasia (CAH), a complex and heterogenous group of conditions, characterised by defects in one of the five enzymes involved in adrenal steroidogenesis. Defects in this steroidogenic enzyme, the product of the CYP21A2 gene, cause disruption in the pathway involved in cortisol and aldosterone production and consequently, the accumulation of their steroid precursors as well as a resulting adrenocorticotrophic hormone (ACTH)-driven overproduction of adrenal androgens. Treatment with glucocorticoid, with or without mineralocorticoid and salt replacement, is directed at preventing adrenal crises and ensuring normal childhood growth by alleviating hyperandrogenism. Conventionally, two clinical forms of 21-OH Deficiency are described - the classical form, separated into salt-wasting and simple-virilising phenotypes, and the non-classical form. They are differentiated by their hormonal profile, predominant clinical features and age of presentation. A greater understanding of the genotype-phenotype correlation supports the view that 21-OH Deficiency is a continuum of phenotypes as opposed to a number of distinct phenotypical entities. Significant advancements in technologies such as Tandem Mass Spectrometry (TMS) and improvements in gene analysis, such as complete PCR-based sequencing of the involved gene, have resulted in remarkable developments in the areas of diagnosis, treatment and treatment monitoring, neonatal screening, prenatal diagnosis and prenatal therapy.

The association between ketoacidosis and 25(OH)-vitamin D levels at presentation in children with type 1 diabetes mellitus.

BACKGROUND: There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D(3) and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM. OBJECTIVE: To determine the relationship between measured 25(OH)-vitamin D(3) levels and the degree of acidosis in children at diagnosis with T1DM. SUBJECTS: Children presenting with new-onset T1DM at a tertiary children's hospital. METHODS: 25(OH)-vitamin D(3) and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D(3) levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation. RESULTS: Fourteen of the 64 children had low 25(OH)-vitamin D(3) levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r(2) = 0.20, p < 0.001) and ethnic background a further 10% (partial r(2) = 0.10, p = 0.002). The levels of 25(OH)-vitamin D(3) increased in 10 of the 11 children with resolution of the acidosis. CONCLUSIONS: Acid-base status should be considered when interpreting 25(OH)-vitamin D(3) levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.