Low prevalence of GCK gene mutations in Chinese patients with gestational diabetes mellitus

Accumulating evidence suggests maturity onset diabetes of the young (MODY) caused by GCK gene mutations (GCK-MODY) is often misdiagnosed as Gestational Diabetes Mellitus (GDM) in pregnant women. This study investigated the prevalence and diagnostic value of GCK gene mutations in Chinese GDM patients.

A retrospective analysis was conducted on 3394 pregnant women undergoing prenatal care or delivery at Beijing Jishuitan Hospital between April and December 2019. GDM was diagnosed in 474 women (14.0%) using the International Association of Diabetes and Pregnancy Study Groups (IADPSG, 2010) criteria via a 75 g Oral Glucose Tolerance Test (OGTT). Among these, 177 GDM patients with fasting blood glucose ≥5.1 mmoL/L underwent targeted GCK gene sequencing.

Targeted sequencing identified eight rare GCK variants in nine individuals. None of the variant carriers met definitive diagnostic criteria for GCK-MODY. The prevalence of rare GCK variants in the screened GDM subgroup was 1.9% (9/474).

The low prevalence (1.9%) of rare GCK variants and absence of confirmed GCK-MODY cases indicate limited utility of fasting glucose-based screening for GCK-MODY in Chinese GDM populations. These findings highlight challenges in distinguishing GCK-MODY from GDM through conventional glucose thresholds.