In the general population, the incidence of myocardial infarction (MI) peaks in the morning. This high point is preceded by the diurnal peak in the plasma level of the MI risk factor plasminogen activator inhibitor-1 (PAI-1). Contrastingly, type 2 diabetes (T2D) patients exhibit higher rates and an altered temporal distribution in MI onset. Previous research has demonstrated both morning and evening MI peaks, as well as no maximum at all. Therefore, we hypothesize that individuals with prediabetes have an altered diurnal variation in the level of PAI-1 compared to controls.

We invited 12 young, healthy, lean (YHL) male volunteers (age ± SD: 22.2 ± 2.3 y, BMI: 22.4 ± 2.0 kg/m2) and 12 older and overweight men with prediabetes (65 ± 9 y, 30.3 ± 2.7 kg/m2) into our metabolic research unit for 1.5 days. During their stay, we provided them with standard meals and a set activity routine. At 10.00, 14.00, 22.00, and 04.00, we obtained blood samples to quantify PAI-1 around the clock using ELISA.

The average daily PAI-1 level was significantly higher in prediabetic than YHL men (mean ± SEM: 1105.04 ± 127.92 pg/mL vs. 557.48 ± 120.21 pg/mL, p<0.0001). In YHL, the PAI-1 peak occurred at 10.00 (824.79 ± 138.89 pg/mL) with a trough at 22.00 (332.77 ± 40.06 pg/mL). In older and overweight men with prediabetes, PAI-1 peaked earlier at 04.00 (1376.06 ± 130.81 pg/mL) and dropped earlier at 14.00 (941.46 ± 127.47 pg/mL).

Our data demonstrate that the PAI-1 levels are higher and phase-advanced in older, overweight men with prediabetes compared to YHL. This disturbed diurnal PAI-1 pattern could contribute to higher MI rates and the altered MI onset timing in T2D. More broadly, our findings highlight the crucial role the timing of sample acquisition plays in clinical practice and health research.