Permanent Neonatal Diabetes Mellitus: Same Mutation, Different Glycemic Control with Sulfonylurea Therapy on Long-Term Follow-up

Abstract

Permanent neonatal diabetes mellitus (PNDM) is a rare condition presenting before six months of age. Mutations in the genes encoding the ATP-sensitive potassium (KATP) channel are the most common causes. Sulfonylurea (SU) therapy leads to dramatic improvement in diabetes control and quality of life in most patients who carry these mutations. Here, we report the long-term follow-up results of two siblings with PNDM who were treated with insulin until ABCC8 gene mutation was identified, and were successfully transferred to oral SU therapy. After 3.5 years of follow-up on SU, one patient had a very good response, while the other one had a poor response. Bad compliance to diet was thought to be the most probable reason for poor glycemic control in this patient. In conclusion, molecular genetic diagnosis in all patients with PNDM is recommended. Compliance to treatment should be an important aspect of the follow-up of these patients. Conflict of interest:None declared.

Sulfonylurea vs insulin therapy in individuals with sulfonylurea‐sensitive permanent neonatal diabetes mellitus, attributable to a KCNJ11 mutation, and poor glycaemic control

“…The first is to increase the sulfonylurea dosage; however, as in the study by Aydin et al . , the sulfonylurea dosage increase in SVK1 had no significant effect on her HbA 1c levels during the second part (fifth to eleventh year) of the follow‐up (Fig. a), probably because the plateau in the dose–response curve was reached.…”

“…We do not think, therefore, that insulin resistance was a significant factor in the poor glycaemic control. Furthermore, SVK1 adhered well to her medication, but she consumed sweets, which may have influenced the therapeutic outcomes [4]. The latest data from SVK1 support this theory, as after omitting sweets her HbA 1c levels decreased from 76 mmol/mol (9.1%) to 57 mmol/mol (7.4%).…”

“…Previously, all people with PNDM have been treated with insulin, until it was shown that sulfonylurea might be a more appropriate treatment for the majority of individuals with KCNJ11 mutations, depending on the type of mutation . Moreover, only a few individuals who initially responded to sulfonylurea therapy showed worsening glycaemic control during the long‐term follow‐up . Individuals with other types of diabetes who have poor glycaemic control on oral antidiabetes agents usually benefit from insulin therapy ; therefore, we aimed to compare sulfonylurea therapy with insulin therapy in two sulfonylurea‐sensitive people with PNDM resulting from a KCNJ11 mutation, who failed to maintain good glycaemic control on sulfonylurea monotherapy during long‐term follow‐up.…”

Neonatal diabetes caused by the heterozygous Pro1198Leu mutation in the ABCC8 gene in a male infant: 6‐year clinical course

“…Oral sulfonylurea therapy is reportedly responsive in patients with diabetes caused by the ABCC8 gene mutation. Furthermore, the treatment has been reported as safe and effective until 13 months in one study, and 3.5 years in another study after the start. The long‐term clinical course of such patients, however, has not been detailed.…”

Stability of Three Different Galenic Liquid Formulations Compounded from Tablet Containing Glibenclamide

“…The PND occurs typically in the first months of life and needs insulin treatment. In recent years has been discovered the connection between PND and the mutation of a gene affecting potassium channels KIR 6.2 of pancreatic beta cells [1][2][3][4][5] (Figure 1).…”