Background: We established a neonatal section of the Ukrainian Pediatric Diabetes Registry (UPDR) to identify cases of neonatal diabetes (ND).
Objective and hypotheses: We investigated the genetic etiology and treatment of patients with ND.
Method: According to the UPDR the number of children (017 y.o) with DM1 in 2015 was 8388 (a prevalence of one in 907), with DM2 36 (one in 211519) and with ND 52 (one in 146436). We studied 48 probands with permanent or transient diabetes diagnosed within the first 6 months of life (n=27) and 21 probands with permanent diabetes diagnosed between 6 and 9 months of age. KCNJ11, INS and ABCC8 were sequenced in all patients. For those diagnosed before 6 months who were negative in the initial screening, we also tested for 6q24 and used targeted next generation sequencing (tNGS) to screen other known genes.
Results: We determined the genetic etiology in 28 of 48 (58.3%) probands diagnosed with diabetes before 9 months: in 88.9% of those diagnosed before 6 months and in 19% diagnosed between 6 and 9 months. KATP channel mutations were the commonest cause of ND accounting for 50% of cases. All of these patients transferred from insulin to sulfonylureas (SU). After 1 year of SU treatment all had a HbA1c level <48 mmol/mol (<6.5%), P=0.01. The daily dose of SU after 1 year of treatment decreased to 0.15 [0.08;0.19] mg/kg per day, P=0.03. C-peptide increased from 0.13 [0.06;0.6] to 1.1 [0.5;1.7] ng/ml, P=0.01 (Table 1).
|Onset <6 months (n=27)||11.1%||7.4%||11.1%||3.7%||3.7%||3.7%|
|Onset 69 months (n=21)||||14.3%|||||||||
Conclusion: Every child with diabetes onset <9 months should undergo genetic testing for ND. tNGS increased the number of patients with a confirmed genetic etiology of ND.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology