Acute hyperosmolar hyperglycaemic state in cystic fibrosis-related diabetes caused by glucocorticoid and itraconazole interaction.

Hyperosmolar hyperglycaemic state (HHS) has not previously been reported in cystic fibrosis-related diabetes (CFRD). We report the case of a 15-year old boy with stable CFRD who developed acute HHS after treatment with glucocorticoids and itraconazole for presumed allergic broncho-pulmonary aspergillosis (ABPA). This case highlights the dangerous and preventable combination of high glucose intake, glucocorticoids and itraconazole inhibition of CYP3A4 (with resultant glucocorticoid accumulation) that can result in a state of life- threatening HHS in an adolescent with previously stable CFRD.

Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.

INTRODUCTION: The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. ß-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines. Recent international paediatric guidelines did not address adaptations to care for patients from Indigenous backgrounds. MAIN RECOMMENDATIONS: This guideline provides advice on paediatric type 2 diabetes in relation to screening, diagnosis, diabetes education, monitoring including targets, multicomponent healthy lifestyle, pharmacotherapy, assessment and management of complications and comorbidities, and transition. There is also a dedicated section on considerations of care for children and adolescents from Indigenous background in Australia and New Zealand. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: Published international guidelines currently exist, but the challenges and specifics to care for children and adolescents with type 2 diabetes which should apply to Australasia have not been addressed to date. These include: recommendations regarding care of children and adolescents from Indigenous backgrounds in Australia and New Zealand including screening and management; tighter diabetes targets (glycated haemoglobin, ≤ 48 mmol/mol [≤ 6.5%]) for all children and adolescents; considering the use of newer medications approved for adults with type 2 diabetes under the guidance of a paediatric endocrinologist; and the need to transition adolescents with type 2 diabetes to a diabetes multidisciplinary care team including an adult endocrinologist for their ongoing care.

Insulin resistance is not due to persistently elevated serum tumor necrosis-alpha levels in small for gestational age, premature, or twin children.

BACKGROUND: In pregnancies with small for gestational age (SGA) fetuses, elevated amniotic fluid tumor necrosis factor-alpha (TNF-alpha) levels have been reported. TNF-alpha has been shown to induce insulin resistance in rodents and humans. We hypothesized that an adverse fetal or early neonatal environment for SGA, twin, and premature children leads to persistently elevated TNF-alpha levels that induce insulin resistance in each of these groups. METHODS: The study group consisted of 16 SGA, 14 premature, 53 twin subjects, and the control group of 40 normal subjects (10 short-stature and 30 normal-stature). All subjects were prepubertal and non-obese. Insulin sensitivity (S(I)) was measured in all but the normal-statured control subjects. Fasting plasma TNF-alpha and cortisol levels were measured in all subjects. RESULTS: The study group had reduced S(I)[SGA 18.5 +/- 3, premature 17.8 +/- 2, twin 12.7 +/- 0.7 (x10(-4)/min/ microU/mL)] compared to the short normal control subjects (43 +/- 8 x 10(-4)/min/ microU/mL, p < 0.001). Plasma TNF-alpha levels were lower in the insulin-resistant study group when compared to the control group (2.9 +/- 0.1 vs. 5.0 +/- 0.2 pg/mL, p < 0.001). An association was present between reduced S(I) and low plasma TNF-alpha levels in the study group (p = 0.01, r = 0.4). Fasting plasma cortisol was lower in the study compared to the control group (266 +/- 16 vs. 341 +/- 28 nmol/L, p < 0.01) due to the influence of the twin study subgroup. There was no relationship between plasma cortisol and TNF-alpha levels (p = 0.3). CONCLUSION: SGA, premature, and twin children are insulin resistant and have low plasma TNF-alpha and cortisol levels. We speculate that the mechanism leading to insulin resistance in these subjects is also suppressing plasma TNF-alpha and cortisol concentrations.