HETEROGENEITY OF GESTATIONAL DIABETES MELLITUS

Abstract

Gestational diabetes mellitus (GDM) is a complex, heterogeneous disorder. As the prevalence of GDM increases, it is increasingly important to identify subgroups of women within the GDM umbrella whose pathophysiology and associated pregnancy risk necessitates a different management approach in order to optimise maternal and neonatal outcomes. Glucokinase maturity-onset diabetes of the young (GCK-MODY) and islet autoimmunity are two such clinical entities. Recently, new pregnancy-specific screening criteria (NSC) for GCK-MODY were proposed to identify women with GDM who warrant GCK genetic testing. We tested the NSC and HbA1c in a multiethnic GDM cohort. The prevalence of GCK-MODY in women with GDM was ~1%. The NSC performed well for Anglo-Celtic women, but less well for women from other ethnic backgrounds. Antepartum HbA1c was not higher in those with GCK-MODY. We report the first two cases of antepartum fetal GCK genotyping and demonstrate how knowledge of fetal GCK genotype guides the management of maternal hyperglycaemia. We examined the prevalence, clinical significance and antepartum to post-partum trajectory of glutamic acid decarboxylase autoantibodies (GADA), insulinoma-associated antigen-2 autoantibodies (IA-2A), insulin autoantibodies (IAA) and zinc transporter 8 autoantibodies (ZnT8A) in a multiethnic GDM cohort. 9.9% of women were positive for one islet autoantibody antepartum. No participant had multiple islet autoantibodies. ZnT8A were the most common islet autoantibody. For women with positive GADA, IA-2A or IAA antepartum, islet autoantibody positivity typically persisted post-partum and 20% of women had post-partum glucose levels consistent with diabetes. In contrast, women with positive ZnT8A antepartum typically demonstrated normal ZnT8A titres post-partum and normal post-partum glucose tolerance. ZnT8A may be a marker for islet autoimmunity in a proportion of women with GDM, but the clinical relevance of ZnT8A in GDM needs further research.