Bowman P, et al. - In this 10-year multicenter follow-up study, researchers assessed long-term effectiveness and safety of sulfonylureas in a large international cohort of patients with KCNJ11 permanent neonatal diabetes. In treating patients with KCNJ11 permanent neonatal diabetes, high-dose sulfonylurea therapy is suitable from diagnosis. Moreover, this therapy proved to be highly efficacious and safe and helped maintain excellent glycemic control for at least 10 years.

Methods

• Researchers performed this multicenter, international cohort study including patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before November 30, 2006.
• They assessed clinical characteristics and annual data relating to glycemic control, sulfonylurea dose, severe hypoglycemia, side-effects, diabetes complications, and growth.
• They mainly focused on sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA_1c and sulfonylurea dose.
• They also evaluated neurological features related to KCNJ11 permanent neonatal diabetes.

Results

• Inclusion criteria was met by 90 patients, and 81 registered with the study, offering long-term (> 5.5 years cut-off) outcome data.
• For the whole cohort, the duration of median follow-up was 10.2 years (IQR 9.3–10.8).
• At most recent follow-up (between December 1, 2012 and October 4, 2016), sulfonylurea therapy alone was maintained in 75 (93%) of 81 participants.
• Excellent glycemic control was sustained in patients for whom researchers paired data on HbA1c and sulfonylurea at all time points (ie, pre-transfer [for HbA1c], year 1, and most recent follow-up; n=64)—median HbA1c was 8.1% (IQR 7.2–9.2; 65.0 mmol/mol [55.2–77.1]) before transfer to sulfonylureas, 5.9% (5.4–6.5; 41.0 mmol/mol [35.5–47.5]; p<0.0001 vs pre-transfer) at 1 year, and 6.4% (5.9–7.3; 46.4 mmol/mol [41.0–56.3]; p<0.0001 vs year 1) at most recent follow-up (median 10.3 years [IQR 9.2–10.9]).
• In the same patients, 0.30 mg/kg per day (0.14–0.53) was documented as the median sulfonylurea dose at 1 year and 0.23 mg/kg per day (0.12–0.41; p=0.03) at most recent follow-up visit.
• For the whole cohort (n=81), 809 patient-years of follow-up contained no reports of severe hypoglycemia.
• Mild, transient side-effects were experienced by 11 (14%) patients, but did not lead to cessation of sulfonylurea therapy.
• Microvascular complications were reported in seven (9%) patients who had been taking insulin longer than those without complications (median age at transfer to sulfonylureas 20.5 years [IQR 10.5–24.0] vs 4.1 years [1.3–10.2]; p=0.0005).
• After transfer to sulfonylureas, 18 (47%) of 38 patients with CNS features demonstrated initial improvement.
• CNS features were seen in 52 (64%) of 81 patients who had long-term therapy with sulfonylureas.