Permanent neonatal diabetes: combining sulfonylureas with insulin may be an effective treatment

Abstract

What's new?• KCNJ11 mutations causing permanent neonatal diabetes are treated with sulfonylureas, but not all individuals are able to transfer completely from insulin to sulfonylureas.• Our data highlight that combining sulfonylurea treatment with insulin in those who are unable to fully transfer may still lead to clinically meaningful outcomes.• We demonstrate improvements in endogenous insulin production, HbA 1c , glycaemic variability and hypoglycaemia awareness.• These changes were not observed at initial doses of glibenclamide and improvements required higher sustained doses of glibenclamide.• Combining insulin and sulfonylureas should be considered in those with permanent neonatal diabetes who are not able to transfer to sulfonylurea therapy alone. AbstractBackground Permanent neonatal diabetes caused by mutations in the KCNJ11 gene may be

Monogenic diabetes: a gateway to precision medicine in diabetes

“…The Journal of Clinical Investigation patients could switch from insulin therapy to sulfonylurea successfully (79,83), with mutation severity (77,84,85) and diabetes duration before the transition (86) predicting the likelihood of success. For patients who cannot completely transfer to sulfonylurea, combining insulin and sulfonylurea has shown favorable results (87).…”

New insights into KATP channel gene mutations and neonatal diabetes mellitus

“…In some individuals, the insulin dose can be reduced when sulphonylureas are introduced, but cannot be discontinued completely. It is recommended that both insulin and sulphonylurea are used to treat these patients 78 . In contrast to type 2 diabetes mellitus, where sulphonylurea failure is observed in ~44% of individuals after 5 years of treatment 79 , excellent glycaemic control remained after 10 years of sulphonylurea therapy in all patients with K ATP mutations examined 68 .…”

Precision Medicine: Long-Term Treatment with Sulfonylureas in Patients with Neonatal Diabetes Due to KCNJ11 Mutations

“…Patients who are older at the time of transition may have had more time for beta-cell destruction or dedifferentiation, and thus less ability to respond to SU. For patients that are unable to fully transition onto SU after a trial with sufficiently high SU dose, the addition of other glucose-lowering medications may assist with lowering HbA1c, reducing insulin requirements, decreasing risk for hypoglycemia, and even improving hypoglycemic awareness [50]. It is imperative to continue SU at a maximal dose even after other medications are utilized to help achieve glycemic targets, as the endogenous insulin secretion is only possible through high-dose SU and the resulting benefits include reducing the dose of any exogenous insulin that may still be required, as well as possible beneficial effects on brain function (such as those discussed above) [34,51,52].…”