Background: Studies have suggested that sirolimus might be diabetogenic, mostly in kidney transplant recipients. Sirolimus has now been shown to be effective in the management of patients with congenital hyperinsulinism (CHI). However to date, there are no publications regarding the diabetogenic effect of Sirolimus in CHI patients.
Objective and hypotheses: To report the first case of sirolimus precipitating diabetes in a CHI patient with known genetic mutation.
Method: Prospective follow up of patient with CHI who has a dominant ABCC8 gene mutation
Results: A patient with CHI due to autosomal dominant ABCC8 mutation on high dose (15 mg/kg per day) of diazoxide was switched to sirolimus (4.25 mg/m2 per day) therapy at the age of 16.6 years, as she developed severe hypertrichosis. Four months later, whilst receiving concomitant treatment with clarithromycin for folliculitis, she was found to be hyperglycaemic. Her mother carried the same mutation and spontaneously developed diabetes during adulthood (30 years). Despite reduction in the dose of sirolimus (and eventually stopping), investigations revealed persistent hyperglycaemia on the 24 hour blood glucose profile, and increased HbA1c (70H mmol/mol). She was started on a sulphonylurea, with the plan to increase it to the maximum dose and if no response to introduce metformin and if still hyperglycaemic to consider introducing other insulin sensitising agents. In the long term it is possible that she may require subcutaneous insulin injections.
Conclusion: Dominant ABCC8 mutations are prone to diabetes at a later stage in life, but the timing may be influenced by medications such as m-TOR inhibitors. The diabetogenic impact of Sirolimus treatment in CHI patients should be confirmed in prospective studies.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology