Elevated PAI-1 Levels May Predict Type 2 Diabetes Before Blood Sugar Rises: Study Suggests

“After accounting for multiple factors, those with elevated baseline PAI-1 had a 1.87 times higher risk. The association was even stronger in individuals with normal glucose levels (OR: 2.68), highlighting the potential of PAI-1 as an early biomarker for assessing diabetes risk,” the researchers reported in Diabetology & Metabolic Syndrome.

Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system primarily secreted by adipose tissue, plays a crucial role in blood clot regulation. While it is well known for its association with cardiovascular disease, recent research has highlighted its potential involvement in metabolic disorders, including type 2 diabetes. Emerging evidence suggests that elevated PAI-1 levels may serve as an early risk marker for diabetes.

Lars Johansson, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden, and colleagues present findings from a large prospective analysis investigating the link between PAI-1 levels and the development of type 2 diabetes mellitus.

For this purpose, the researchers conducted a prospective case-referent study within the Västerbotten Intervention Programme (VIP). Between 1990 and 2005, data on cardiovascular risk factors, fasting plasma glucose (FPG), and 2-hour plasma glucose (2-hPG) were collected during baseline health examinations. Blood samples were stored for future analysis, and participants followed over time.

During the study period, 484 individuals developed type 2 diabetes. An equal number of referents without diabetes were matched based on sex, age, and year of participation. Baseline plasma samples were analyzed for PAI-1 levels, with a subgroup analysis conducted on 201 cases and 201 matched referents with normal baseline glucose levels (FPG <6.1 and 2-hPG <8.9 mmol/L).

The following were the key findings of the study:

• Higher baseline PAI-1 levels were linked to an increased risk of developing type 2 diabetes, even after adjusting for BMI, family history of diabetes, smoking status, hypertension, FPG, and 2-hPG (OR = 1.87).
• In a subgroup analysis of 201 participants with normal glucose levels at the time of the health examination, elevated PAI-1 levels were associated with an even higher risk of diabetes (OR = 2.68).

“The findings showed that elevated PAI-1 levels in individuals without diabetes may serve as an early indicator of type 2 diabetes, appearing before any detectable rise in fasting plasma glucose or 2-hour plasma glucose,” the researchers concluded.

Reference:

Hernestål-Boman, J., Öhman, T., Jansson, JH. et al. Elevated levels of PAI-1 precede the occurrence of type 2 diabetes mellitus. Diabetol Metab Syndr 17, 61 (2025). https://doi.org/10.1186/s13098-025-01629-4