A new study from the University of Pittsburgh has identified three distinct molecular drivers of type 2 diabetes in women who developed the condition following gestational diabetes. Published in Diabetes/Metabolism Research and Reviews, the research reveals that these women can be categorized into three “clusters,” each driven by a unique molecular pathway. These findings could pave the way for precision-medicine approaches to prevent type 2 diabetes in this high-risk population.
The study, led by Dr. Saifur Khan, Ph.D., at the Vascular Medicine Institute at Pitt and the VA Medical Center in Pittsburgh, examined 225 women who developed type 2 diabetes within 12 years of having gestational diabetes. The cohort was selected from The SWIFT Study (The Study of Women, Infant Feeding, and Type 2 Diabetes After Gestational Diabetes). By analyzing blood samples taken throughout the progression to type 2 diabetes, along with clinical data, the research team employed advanced computational modeling and machine learning to analyze metabolomic, proteomic, and genomic data.
The study identified three distinct clusters of women based on the molecular drivers behind their type 2 diabetes:
Pancreatic Beta-Cell Dysfunction: In this group, diabetes was driven by the failure of insulin-producing cells in the pancreas.
Insulin Resistance: This cluster exhibited insulin resistance as the primary driver of the disease.
Mixed Pathway: Around 50% of the participants fell into this cluster, where both pancreatic beta-cell dysfunction and insulin resistance contributed to the disease progression.
These findings build on previous research by the team that identified molecular mechanisms linking gestational diabetes to the onset of type 2 diabetes, as published in Science Advances. The goal of future research is to develop tools to easily identify which cluster a woman falls into and provide early interventions to prevent the progression to type 2 diabetes.
The research team includes Zhang Xiangyu, Ph.D., Babak Razani, M.D., Ph.D., from Pitt and the VA Medical Center, Michael B. Wheeler, Ph.D., Julie Van from the University of Toronto, and experts from Kaiser Permanente Northern California, including Stacey Alexeeff, Ph.D., and Erica P. Gunderson, Ph.D., M.P.H.
This study represents a crucial step toward understanding and preventing the progression of type 2 diabetes in women post-pregnancy, with potential implications for precision medicine in diabetes care.
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