Multifactorial risk factor intervention in patients with Type 2 diabetes improves arginine bioavailability ratios

Endothelial dysfunction is defined by reduced bioavailability of nitric oxide and has been shown to be associated with cardiovascular risk. The global arginine bioavailability ratio and the arginine to ornithine ratio have recently been shown to be associated with cardiovascular outcome in patients with coronary artery disease. The aim of our study was to investigate the impact of a multifactorial risk factor intervention in subjects with Type 2 diabetes on these two potential new cardiovascular surrogate parameters.

In a single-centre and prospective study, we investigated 41 patients with Type 2 diabetes not reaching treatment targets according to current local diabetes guidelines in two out of three of the following measurements: HbA(1c) LDL cholesterol 2.6 or blood pressure. Within 3 months, therapy was intensified according to current guidelines aiming to reach the treatment targets. At baseline and 3 months, arginine, ornithine and citrulline were chromatographically determined after pre-column-derivatization followed by fluorescent detection, and arginine bioavailability ratios were calculated.

Intensified risk factor management significantly improved the global arginine bioavailability ratio (0.33 ± 0.12 at baseline vs. 0.38 ± 0.14 after 3 months; P = 0.018). A significant improvement was only seen in patients with short diabetes duration (< 5 years), whereas in patients with longer diabetes duration improvement did not reach statistical significance.

In patients with Type 2 diabetes, intensified risk factor management improves arginine bioavailability ratios. Duration of diabetes seems to be an important factor influencing the capacity of the global arginine bioavailability ratio improvement.