Clinical care and other categories posters: Maturity onset diabetes of the young (MODY)

Ten-year follow-up of an international series of patients with permanent neonatal diabetes due to ABCC8 mutations shows excellent long-term glycaemic response to sulphonylureas and high frequency of neurological features

P Bowman¹, MH Shepherd¹, F Barbetti², F Mathews¹, Neonatal Diabetes International Collaboration, E Rawlins¹, J Sanchez³, S Ellard¹, SE Flanagan¹, AT Hattersley¹

¹Medical Research, University of Exeter Medical School, Exeter, UK, ²Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy, ³Miller School of Medicine, University of Miami, Miami, Florida, USA

Aims Mutations in the KATP-channel genes ABCC8 and KCNJ11 are the commonest cause of permanent neonatal diabetes (PNDM); 90% can be treated with oral sulphonylureas (SU) instead of insulin. Previous studies have suggested that people with ABCC8-NDM require lower SU doses and have a milder neurological phenotype than those with KCNJ11-NDM. However, many studies included mixtures of permanent and transient forms of ABCC8-NDM, and none assessed long-term treatment response. We aimed to assess the 10-year glycaemic and neurological outcomes in SU-treated ABCC8-PNDM.

Methods Individuals with ABCC8-PNDM diagnosed in the UK, Italy, France or USA who transferred from insulin to SU before May 2010 were eligible for inclusion. Data on glycaemic control, SU dose and neurological features were collected from the clinical notes and analysed using non-parametric statistical methods.

Results Long-term data were obtained for 20/24 individuals. 90% remained on SU without insulin at most recent follow-up (median (range) 9.8 (4.1–12.6)years). Glycaemic control improved on SU (pre-SU vs one-year HbA1c 7.0% vs 5.7%, p=0.002) and remained stable long-term (one-year vs 10-year HbA1c 5.7% vs 6.2%, p=0.06), n=15. High doses of SU were required (one-year vs 10-year dose 0.34 vs 0.26mg/kg/glibenclamide, p=0.36), n=15. Neurological features occurred in 12/20: improvement after starting SU was reported in 7/12. Developmental delay, learning difficulties and ADHD were common (all reported in ≥40% at most recent follow-up).

Conclusions High-dose SU treatment of ABCC8-PNDM results in excellent long-term glycaemic control. Overt neurological features occur more frequently than previously described; some improvement may occur with SU therapy, therefore multidisciplinary assessment is advisable.

Pregnancy in women with MODY has excellent maternal and fetal outcomes

E Harris¹, G Thanabalasingham², JE Hirst³, KO Owen²

¹Medical School, University of Oxford, Oxford, UK, ²OCDEM, University of Oxford, Oxford, UK, ³Nuffield Department of Obstetrics & Gynaecology, John Radcliffe Hospital, Oxford, UK

Background and Aims Pregnancy in women with MODY may affect those with pre-existing diabetes or present as gestational diabetes (GDM). Little information exists on their outcomes. We describe maternal and fetal outcomes in women with MODY from our centre.

Methods We examined data on key pregnancy outcomes for women with MODY who completed a pregnancy from 2009 to 2019. This was compared to local 2014–2016 National Diabetes in Pregnancy Audit data.

Results Thirteen women (8 HNF1A, 3 HNF4A and 2 GCK–MODY) with 26 pregnancies and 23 live births were included. Seven women had known MODY and 2 each were labelled as type 1, type 2 and GDM. One case of GDM was reassigned as GCK-MODY during her 4^th pregnancy.

All pregnancy losses were first trimester. Median HbA1c during the first trimester for MODY was 5.9% (IQR 5.3–6.1%). 81% of MODY achieved the first trimester HbA1c target of 6.5%, compared to 18.5% of type 1 and 39.5% of type 2 cases. Median (IQR) HbA1c in the 3^rd trimester was 5.6% (5.4–5.9%), and 100% were below 6.5%, compared to 43.1% and 70.7% of type 1 and type 2 respectively.

Two babies (9%) were delivered <37 weeks, compared to 46% of type 1 and 19% of type 2 pregnancies. 16% were large for gestational age (>90th centile) compared to 50% and 42% of babies of mothers with type 1 and type 2 diabetes respectively.

Removing 5 GCK-MODY pregnancies did not significantly alter these results.

Conclusions In this large case series, women with MODY have excellent pregnancy outcomes compared to other forms of diabetes.