1474-P: Identification and Management of MODY2 Pregnancy Patients

Abstract

Precise differentiation of glucokinase (GCK) monogenic diabetes, MODY2, from gestational diabetes mellitus (GDM) is critical for accurate management of the pregnancy outcome. We screened MODY2 complicating pregnancies in Chinese GDM patients, explored the pathogenesis of novel GCK mutations, and evaluated the patients’ pregnancy outcome and management. The GCK gene from 411 GDM patients was screened with PCR-direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and 15 GCK mutations were identified. We also retrospectively analyzed a total of 65 pregnancies from 21 MODY2 families, wherein 41 were from 15 maternal families and 24 were from six paternal families. Bioinformatic analysis and biochemical functional study were conducted to identify novel GCK mutations. In total, we identified 21 GCK mutations: 15 from the 411 GDM patients and six from 24 fathers. Of the Asp78Asn (GAC → AAC), Met87Arg (ATG → AGG), Leu451Val (CTT → GTT), Leu451Pro (CTG → CCG) and 1019 + 20G > A mutations, five, i.e., were novel and deleterious, with markedly decreased enzyme activity and thermal stability. The unaffected offspring of GCK mutation affected mothers were heavier than affected offspring (p<0.001). Of 21 insulin-treated affected mothers, 10 had maternal hypoglycemia (47.6%) and seven had perinatal complications (33.3%), and the affected offspring of the insulin-treated affected mothers had significantly lower birth weights than that of the 20 diet-control affected mothers (p=0.031). In this study, the prevalence of MODY2 complicating pregnancy in Chinese GDM patients was 3.6% (15/411). The defective GCK may contribute to the hyperglycemia in MODY2. Insulin therapy is not beneficial for MODY2 complicating pregnancy and therefore should not be recommended. Disclosure L.Liu: None. Y.Jiang: None. Y.Chen: None. C.Liu: None. T.Li: None. Funding National Natural Science Foundation of China (81970686, 81770791, 81471012, 82070823, 81270876); Interdisciplinary Program of Shanghai Jiao Tong University (YG2019ZDA08); Shanghai Leading Talent (SLJ15055); National Institutes of Health (SC1DK104821); Tobacco-Related Disease Research Program (T31IR1603)