0
0
A groundbreaking study from the University of Pittsburgh has unveiled three distinct molecular pathways that drive the progression from gestational diabetes to type 2 diabetes in women, highlighting potential targets for precision medicine approaches. Published in Diabetes/Metabolism Research and Reviews, the research focuses on the critical period post-pregnancy, where women with a history of gestational diabetes face an increased risk of developing type 2 diabetes within the years following delivery.
Gestational diabetes, a condition affecting pregnant women, significantly raises the likelihood of later developing type 2 diabetes. However, the exact molecular mechanisms underlying this transition have remained unclear. The new study, led by Dr. Saifer Khan and his team at the Vascular Medicine Institute and the VA Medical Center in Pittsburgh, sheds light on these mechanisms by identifying three “clusters” of women, each driven by different molecular factors.
Dr. Khan explains, “In type 2 diabetes research, many pathways emerge repeatedly, and understanding the cause-and-effect interactions can be complex. By focusing on this high-risk population, we could target the early stages of the disease and simplify the pathways involved.”
The research team examined data from 225 women who developed type 2 diabetes within 12 years after a diagnosis of gestational diabetes. The women were selected from The Study of Women, Infant Feeding and Type 2 Diabetes After Gestational Diabetes (The SWIFT Study). Using a combination of metabolomic, proteomic, and genomic data, alongside clinical measures such as triglycerides, insulin, and glucose levels, the team identified three distinct molecular drivers:
- Pancreatic Beta-Cell Dysfunction: In this cluster, the primary driver was a failure of the pancreatic beta cells, responsible for producing insulin.
- Insulin Resistance: In a second cluster, insulin resistance played the leading role in the development of type 2 diabetes.
- Mixed Mechanism: The third group exhibited a combination of both beta-cell dysfunction and insulin resistance, accounting for roughly 50% of the participants.
This study builds on previous research published by the team in Science Advances, which was the first to identify molecular mechanisms of the progression from gestational diabetes to type 2 diabetes.
The researchers aim to develop methods that will allow healthcare providers to easily categorize women into these molecular clusters and offer targeted early interventions to prevent the development of type 2 diabetes.
The study involved contributions from Dr. Zhang Xiangyu, Dr. Babak Razani of Pitt and the VA Medical Center, Dr. Juile Van and Dr. Michael B. Wheeler of the University of Toronto, Dr. Stacey Alexeeff and Dr. Erica P. Gunderson of Kaiser Permanente Northern California, and the Kaiser Permanente Bernard J. Tyson School of Medicine.
This research represents a significant step forward in understanding the molecular origins of post-pregnancy type 2 diabetes and paves the way for personalized treatment strategies that could prevent the onset of the chronic disease in women who are most at risk.
For more information, refer to the study: Saifur R. Khan et al., Early Postpartum Metabolic Heterogeneity Among Women Who Progressed to Type 2 Diabetes After Gestational Diabetes: A Prospective Cohort, Diabetes/Metabolism Research and Reviews (2025). DOI: 10.1002/dmrr.70027.
