Identification and management of GCK-MODY complicating pregnancy in Chinese patients with gestational diabetes.
Mol Cell Biochem
; 477(5): 1629-1643, 2022 May.
Article
em En
| MEDLINE
| ID: mdl-35229243
ABSTRACT
Precise differentiation of glucokinase (GCK) monogenic diabetes from gestational diabetes mellitus (GDM) is critical for accurate management of the pregnancy outcome. We screened GCK-MODY 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 GCK-MODY 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 th Asp78Asn (GAC â AAC), Met87Arg (ATG â AGG), Leu451Val (CTT â GTT), Leu451Pro (CTG â CCG) and 1019 + 20G > A e 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 GCK-MODY complicating pregnancy in Chinese GDM patients was 3.6% (15/411). The defective GCK may contribute to the hyperglycemia in GCK-MODY. Insulin therapy is not beneficial for GCK-MODY complicating pregnancy and therefore should not be recommended.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gravidez em Diabéticas
/
Diabetes Gestacional
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Pregnancy
País/Região como assunto:
Asia
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China