2014 Pathway Accelerator Awardee Kathleen A. Page, MD

Examining how the brain controls obesity

Project title: Neural Mechanisms in Maternal-Fetal Programming for Obesity and Diabetes
Institution: University of Southern California
Delivered 5 invited lectures related to the pathway project
Serves as ADA Research Grant Review Committee Reviewer, ADA Scientific Sessions Pregnancy Sub-Committee Member and ADA Abstract Reviewer

Major accomplishments:

The goal of this project is to understand how conditions in the womb influence the risk for obesity and type 2 diabetes in offspring later in life. To date, we have completed 3-hour oral glucose tolerance tests on 66 (46 gestational diabetes mellitus (GDM) exposed and 20 unexposed) children and we have completed fMRI studies on 63 (44 GDM exposed and 19 unexposed) of these children.

We performed a preliminary analysis to examine the independent effects of in utero exposure to gestational diabetes and maternal pre-pregnancy BMI on adiposity during childhood. Our findings among 71 children showed that BMI and total body fat were similar between GDM exposed and unexposed children. However, exposure to maternal GDM and higher maternal pre-pregnancy BMI were independently associated with greater waist to hip ratios in children. Our results suggest that central adiposity in children may be the most sensitive target to measure the impact of intrauterine exposure to GDM and maternal adiposity on offspring obesity risk.

We also recently discovered that both maternal pre-pregnancy BMI and GDM exposures are independently associated with a reduced hypothalamic response to glucose ingestion, findings suggestive of impaired glucose-linked satiety signaling. These findings support animal studies suggesting that fetal exposure to an abnormal nutrient environment can result in changes in brain appetite pathways. We are currently writing the manuscript to describe these novel findings. 
We have built one of the world's largest studies on links between neurodevelopment and metabolism in early childhood. We are submitting a proposal for an R01 grant to the National Institutes of Health in June to continue to build and investigate the biological underpinnings for maternal-fetal programming for risk of obesity and diabetes.

Impact statement:

As a physician, my practice focuses on patients with type 2 diabetes. I see a growing number of patients who were diagnosed with type 2 diabetes at a young age. My goal is to identify markers of disease in children at highest risk for diabetes, whether related to exposure to gestational diabetes or other environmental influences, and to develop and test interventions to prevent obesity and type 2 diabetes.

The Pathway award will allow me to break new ground in diabetes research by using novel methods that will advance our understanding of early life determinants of obesity and diabetes.