SummaryBackgroundKCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients.MethodsIn this multicentre, international cohort study, all 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 Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817.Findings90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had 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, median sulfonylurea dose at 1 year was 0·30 mg/kg per day (0·14–0·53) and at most recent follow-up visit was 0·23 mg/kg per day (0·12–0·41; p=0·03). No reports of severe hypoglycaemia were recorded in 809 patient-years of follow-up for the whole cohort (n=81). 11 (14%) patients reported mild, transient side-effects, but did not need to stop sulfonylurea therapy. Seven (9%) patients had microvascular complications; these patients 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). Initial improvement was noted following transfer to sulfo...

Objective: To investigate rates and risk factors of hospital admission for diabetic ketoacidosis (DKA) or severe hypoglycemia in young patients with established type 1 diabetes. Design: In total, 31 330 patients with type 1 diabetes (median age 12.7 years) from the Diabetes Patienten Verlaufsdokumentation (DPV) Prospective Diabetes Registry treated between 2011 and 2013 in Germany were included. Methods: Admission rates for DKA (pH !7.3 or bicarbonate !15 mmol/l) and severe hypoglycemia (requiring assistance from another person) were calculated by negative binomial regression analysis. Associations of DKA or hypoglycemia with patient and treatment characteristics were assessed by multivariable regression analysis. Results: The mean admission rate for DKA was 4.81/100 patient-years (95% CI, 4.51-5.14). The highest DKA rates were observed in patients with HbA1c R9.0% (15.83 (14.44-17.36)), age 15-20 years (6.21 (5.61-6.88)) and diabetes duration of 2-4.9 years (5.60 (5.00-6.27)). DKA rate was higher in girls than in boys (5.35 (4.88-5.86) vs 4.34 (3.95-4.77), PZ0.002), and more frequent in migrants than in non-migrants (5.65 (4.92-6.49) vs 4.57 (4.23-4.93), PZ0.008). The mean admission rate for severe hypoglycemia was 1.45/100 patient-years (1.30-1.61). Rates were higher in migrants compared to non-migrants (2.13 (1.72-2.65) vs 1.28 (1.12-1.47), P!0.001), and highest in individuals with severe hypoglycemia within the preceding year (17.69 (15.63-20.03) vs patients without preceding hypoglycemia 0.42 (0.35-0.52), P!0.001). Differences remained significant after multivariable adjustment. Conclusions: The identification of at-risk individuals for DKA (patients with high HbA1c, longer diabetes duration, adolescents, girls) and for severe hypoglycemia (patients with preceding severe hypoglycemia, migrants) may facilitate targeted diabetes counselling in order to prevent these complications.

Transition from child to adult-oriented care is widely regarded a challenging period for young people with kidney transplants and is associated with a high risk of graft failure.We analyzed the existing transition structures in Germany and Austria using a questionnaire and retrospective data of 119 patients transferred in 2011 to 2012.Most centers (73%) confirmed agreements on the transition procedure. Patients’ age at transfer was subject to regulation in 73% (18 years). Median age at transition was 18.3 years (16.5–36.7). Median serum creatinine increased from 123 to 132 μmol/L over the 12 month observation period before transfer (P = 0.002). A total of 25/119 patients showed increased creatinine ≥20% just before transfer. Biopsy proven rejection was found in 10/119 patients. Three patients lost their graft due to chronic graft nephropathy.Mean coefficient of variation (CoV%) of immunosuppression levels was 0.20 ± 0.1. Increased creatinine levels ≥20% just before transfer were less frequently seen in patients with CoV < 0.20 (P = 0.007).The majority of pediatric nephrology centers have internal agreements on transitional care. More than half of the patients had CoV of immunosuppression trough levels consistent with good adherence. Although, 20% of the patients showed increase in serum creatinine close to transfer.