Plasminogen Activator Inhibitor—1 in Nonobese Subjects with Non-Insulin-Dependent Diabetes Mellitus

Abstract

Abstract

Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to be a risk factor for the development of vascular complications in obese and hyperinsulinemic non-insulin-dependent diabetes (NIDDM) patients. To clarify whether PAI-1 also plays an essential role in the development of such complications in NIDDM patients without obesity or hyperinsulinemia, PAI-1 was analyzed in relation to blood pressure, fasting plasma levels of glucose (FPG), hemoglobin A_1c (HbA_1c), immunoreactive insulin (F-IRI), C-peptide (CPR), total cholesterol (TC), triglyceride (TGL), and HDL-cholesterol (HDL-C) in 77 NIDDM patients and 10 healthy control subjects. The NIDDM patients were not obese (body mass index [BMI]: <26 kg/m²) or hyperinsulinemic, and BMI in the controls was between 19 and 24 kg/m². In addition, parameters of insulin secretion reserve, including ΣIRI, insulinogenic index, and CPR at 5 min after glucagon loading, were evaluated simultaneously. Plasma levels of PAI-1 were higher in the NIDDM group (9.3 ± 0.9 ng/ml) than in the controls (4.3 ± 0.7 ng/ml; P < 0.01). Levels of FPG and HbAic were also elevated in the NIDDM group (P < 0.05 for each), but F-IRI did not differ between the two groups. However, multiple regression analysis revealed no significant correlation in the NIDDM between PAI-1 and F-IRI or the parameters of insulin secretion reserve. Regardless of the presence or absence of vascular complications, PAI-1 did not vary significantly in the NIDDM. These findings suggest that the effects of PAI-1 on the development of diabetic complications in NIDDM patients may not proceed in the same way in those with versus those without obesity or hyperinsulinemia, because no correlation was found between PAI-1 and insulin secretion reserve, while plasma levels of PAI-1 were higher in the NIDDM group than in the controls.