Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus

Gestational diabetes (GDM) is a significant clinical and public health burden, affecting over
400,000 pregnant women in the United States each year. Without adequate treatment, women with
GDM and their infants are at risk for substantial morbidity. Because of this, experts
recommend treatment focused on normalization of hyperglycemia to improve outcomes. However,
providers have limited capacity to predict which treatment will achieve glycemic goals. This
results in a choice based on provider and patient preference and a trial and error approach,
which can create delays in glycemic control within the short (8-10 weeks) window between
diagnosis and delivery. Maternal and fetal morbidity may be related to a mismatch between
glycemic pathophysiology and the mechanism of action of glucose-lowering agents. In fact, GDM
is heterogeneous, with predominant insulin resistance (IR) in 50%, insulin secretion deficit
(ISD) in 30%, and a combination of both in 20% of women as underlying mechanisms of
hyperglycemia. This variation in GDM pathophysiology and clinical outcomes supports the use
of an individualized treatment approach. The overall goal of this project is to investigate
an individualized treatment approach for GDM where treatment is based on each woman's GDM
mechanism. The study will employ the same treatment in both arms, but choice of treatment
will differ based on study arm (matched or unmatched to GDM mechanism).