SAN ANTONIO, Sept. 11, 2025 – Researchers at The University of Texas at San Antonio Health Science Center have made a groundbreaking discovery, identifying physiological changes that precede the onset of Type 2 diabetes long before current prediabetes diagnostic thresholds are met. This pioneering study, published in The Journal of Clinical and Applied Research and Education: Diabetes Care, introduces a new risk category termed “pre-prediabetes.”
The study challenges conventional medical understanding by revealing that individuals with normal glucose tolerance can exhibit severe insulin resistance, early beta cell dysfunction, and measurable cardiovascular disease. “We’ve shown that long before you develop diabetes, and even before you meet the criteria for prediabetes, people can be severely insulin resistant,” stated Ralph DeFronzo, MD, professor of medicine and chief of the Diabetes Division at the Health Science Center. “Diabetes is a continuous disease; you don’t just wake up one day with prediabetes or diabetes.”
Rethinking Diagnostic Criteria
The American Diabetes Association (ADA) currently defines diabetes using three criteria: fasting glucose levels, two-hour glucose levels during an oral glucose tolerance test (OGTT), and hemoglobin A1c levels. Prediabetes is similarly defined with slightly lower thresholds. However, these measures often miss at-risk patients until the disease has progressed significantly.
In their study, DeFronzo’s team, in collaboration with the Translational Research Department of the Dasman Diabetes Institute in Kuwait, found that one-hour glucose levels during an OGTT are a more accurate predictor of future disease. A value between 120 and 155 mg/dL can identify individuals likely to develop prediabetes, and eventually Type 2 diabetes, years before they meet standard criteria.
“The one-hour glucose is far superior to the two-hour glucose test for predicting who will progress,” DeFronzo emphasized. “Using this measure, we can see insulin resistance and beta cell problems well before the current definitions kick in.”
The Case for Early Intervention
Despite this compelling evidence, the ADA does not currently recommend routine treatment for prediabetes, and no drugs are approved by the Food and Drug Administration for its treatment. In high-risk cases, the ADA suggests considering metformin, a drug that DeFronzo helped introduce to the United States but now considers outdated.
DeFronzo advocates for the use of more effective treatments for Type 2 diabetes, prediabetes, and potentially “pre-prediabetes.” He highlights the insulin sensitizer pioglitazone, which has been shown to reduce the progression from prediabetes to diabetes by 75%—more than double the effect of metformin. Additionally, newer GLP-1 receptor agonists and dual agonists like semaglutide and tirzepatide can reduce Type 2 diabetes progression rates by up to 85%.
He argues that high-risk patients, especially those with a strong family history of diabetes or early cardiovascular disease, should be screened early and offered treatment well before the onset of Type 2 diabetes.
Early Detection, Early Intervention
Through continued research, patient education, and off-label prescribing by endocrinologists and other specialists, DeFronzo hopes healthcare providers will eventually shift toward earlier detection and intervention for insulin resistance, prediabetes, and Type 2 diabetes. He believes this study’s findings should prompt more clinicians to consider OGTTs, especially in high-risk populations, and recognize that significant metabolic and vascular disease can be present long before traditional thresholds for prediabetes.
“Insulin resistance can lead to diabetes, beta cell failure, heart failure, atherosclerosis, liver disease, and kidney disease,” DeFronzo noted. “We can see it and measure it years before overt diabetes becomes manifest. The sooner we act, the better prepared we are to prevent these outcomes.”
The study, titled “One-Hour Plasma Glucose Predicts the Progression From Normal Glucose Tolerance to Prediabetes,” was conducted by a team including Abdul-Ghani M, Abu-Farha M, Abdul-Ghani T, Chavez-Velazquez A, Merovci A, DeFronzo RA, Alajmi F, Stern M, and Al-Mulla F, and was published on July 1, 2025. The full study can be accessed at https://pubmed.ncbi.nlm.nih.gov/40377532/.
UT Health San Antonio, the clinical care, clinical research, and health system enterprise of The University of Texas at San Antonio, offers a comprehensive network of inpatient and outpatient care facilities. It is the region’s only academic health center and one of the nation’s leading health sciences institutions. To learn more about their work, visit UTHealthSA.org.
