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.

Effect of GLP1R agonists taspoglutide and liraglutide on primary thyroid C-cells from rodent and man.

Glucagon-like peptide 1 (GLP1) analogs have been associated with an increased incidence of thyroid C-cell hyperplasia and tumors in rodents. This effect may be due to a GLP1 receptor (GLP1R)-dependent mechanism. As the expression of GLP1R is much lower in primates than in rodents, the described C-cell proliferative lesions may not be relevant to man. Here, we aimed to establish primary thyroid cell cultures of rat and human to evaluate the expression and function of GLP1R in C-cells. In our experiments, GLP1R expression was observed in primary rat C-cells (in situ hybridization) but was not detected in primary human C-cells (mRNA and protein levels). The functional response of the cultures to the stimulation with GLP1R agonists is an indirect measure of the presence of functional receptor. Liraglutide and taspoglutide elicited a modest increase in calcitonin release and in calcitonin expression in rat primary thyroid cultures. Contrarily, no functional response to GLP1R agonists was observed in human thyroid cultures, despite the presence of few calcitonin-positive C-cells. Thus, the lack of functional response of the human cultures adds to the weight of evidence indicating that healthy human C-cells have very low levels or completely lack GLP1R. In summary, our results support the hypothesis that the GLP1R agonist-induced C-cell responses in rodents may not be relevant to primates. In addition, the established cell culture method represents a useful tool to study the physiological and/or pathological roles of GLP1 and GLP1R agonists on normal, non-transformed primary C-cells from rats and man.