Gestational Diabetes Mellitus: Early Risk Factors, Prevention, Optimal Treatment, and Long-term Consequences for Mothers and Offspring: Reflections on 25 Years of Research: The 2025 Norbert Freinkel Award Lecture.

Gestational diabetes mellitus (GDM) has long been viewed as a metabolic condition first recognized during pregnancy. However, research now demonstrates that underlying metabolic abnormalities are detectable during the preconception period in individuals who subsequently develop GDM and that GDM carries long-term implications for both mothers and offspring. In this article, I provide an overview of the work that my colleagues and I have conducted over the past 25 years, aimed at understanding when GDM risk emerges, how risk can be modified, and how intrauterine exposure to hyperglycemia and its treatment influences health across the life course. This work spans population-based epidemiology, preconception biomarker studies, efficacy prevention trials, and pragmatic interventions embedded within an integrated health care system. Together, these findings affirm Norbert Freinkel's concept of fuel-mediated teratogenesis and underscore the need for precision prevention and treatment strategies that address biological, behavioral, and social determinants of health risk factors.