Pregnancy Complicated by Maternal MODY 3 and Paternal MODY 2 Diabetes and Subsequent Rapidly Falling Insulin Requirement
Table 2
MODY subtypes and pregnancy implications (4 most common subtypes in descending order of frequency).
Gene and MODY subtype in the mother
Gene Function + Phenotype
Prognosis
Associated pregnancy implication
HNF1-alpha gene (MODY 3)
Regulates insulin gene transcription Reduced insulin secretion/diabetes and marked sensitivity to sulfonylurea
Progressive May require insulin May develop secondary complications
Not associated with increased birthweight
Glucokinase (GCK) gene (MODY 2)
Catalyses conversion of glucose to glucose-6-phosphate Reduced glucose sensing by beta cells – Mild diabetes
Generally non or slowly progressive Complications rare
Unaffected fetus—Excess fetal growth if no GCK mutation Affected fetus—maternal hyperglycemia will be sensed as normal and result in normal growth
HNF4-alpha gene (MODY 1)
Nuclear transcription factor that regulates hepatic and pancreatic beta cell gene expression Reduced insulin secretion/diabetes and marked sensitivity to sulfonylurea
Progressive May require insulin May develop secondary complications
Associated with increased birth weight (50% of babies), can cause neonatal hyperinsulinaemic hypoglycaemia
Progressive beta-cell failure with diabetes onset around puberty Insulin resistance without obesity Insulin dependence
In affected mother—possible pregnancy complications associated with genital and uterine malformations, such as recurrent miscarriages or preterm labour For affected fetus—Urogenital malformations may be visible on prenatal ultrasound