Impact of Exercise Training on Dipeptidyl Peptidase 4 and Insulin-Like Growth Factor Binding Protein 1 in Patients with Coronary Artery Disease: Relationship to Nitric Oxide Response

Dipeptidyl peptidase 4 (DPP4) is a proteolytic enzyme, involved in a wide range of different cellular functions and expressed on the surface of most cell types, including the endothelium. The circulating level of insulin-like growth factor (IGF) binding protein 1(BP1) is associated with insulin resistance and diabetes, but it also affects the prognosis and mortality of CV diseases. The aim of the study was to evaluate the effects of exercise training on DPP4 and circulating IGF BPI, and to assess their relationship to nitric oxide (NOx), a circulating marker of endothelial function, in patients with stable coronary artery disease (CAD). An overall of 48 subjects was involved in the study, including 28 patients with stable CAD (CAD group, 59.2 +/- 8.2 years) and 20 healthy controls (C group, 57.1 +/- 8.2 years). At baseline, DPP4, IGF BP1 and NOx, as well as an exercise test, were performed in both groups. After the initial study, CAD group underwent a supervised three-week exercise training at a residential center, and after that period DPP4, IGF BPI, NOx and exercise tolerance were determined again. At baseline, both DPP4 and IGF BP1 were significantly (p = 0.023 and p = 0.021) higher in CAD group, compared to the C group. Since both DPP4 and IGF BP1 significantly decreased in CAD group (p = 0.002 and p = 0.026, respectively) after three weeks of exercise, there were no significant differences between CAD and C groups in DPP4 and IGF BP1 at the end of the study. NOx was significantly lower in CAD group at baseline compared to the C group (p = 0.032). Since it significantly increased in CAD group (p = 0.028), there were no significant differences between groups after three weeks of exercise. Exercise capacity was significantly lower in CAD group at baseline compared to the C group (p < 0.001). However, it significantly increased in CAD group during the study (p<0.001) and therefore, at the end of the study there were not registered any significant differences between CAD and C group. The DPP4 decrease positively correlated with IGF BP1 decrease (r= 0.920, p < 001), NOx increase (r = 0.965, p < 0.001) and exercise capacity increase (r = 0.818, p < 0.001); IGF BP1 decrease significantly correlated with NOx increase (r = 0.890, p < 0.001) and exercise capacity increase (r = 0.878, p < 0.001), and NOx increase significantly correlated with exercise capacity increase (r = 0.827, p < 0.001). Regular exercise significantly improves exercise tolerance and endothelial function in stable CAD patients, since it significantly reduces DPP4 and IGF BP1 and increases NOx after three weeks of supervised exercise.