Beneficial Effects of Rosiglitazone on Novel Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus

Aim: Impaired exercise capacity, adiponectin, MMPs and TIMPs have all been implicated in the development of cardiovascular disease. The aim of our study was to determine the effects of rosiglitazone on these factors in diabetic patients.

Methods: Seventy individuals with Type 2 diabetes were assigned randomly to either a rosiglitazone group (8 mg/day, RG) or a control group (CG) for 6 months. All participants took gliclazide 160 mg plus metformin 1700 mg in stable dose. None of the individuals had diabetic complications or had previously participated in an exercise programme. Anthropometric parameters, VO2 peak, oxygen pulse, glycaemic indices, lipid profile, adiponectin, insulin resistance, blood pressure and serum MMP-9, TIMP-1, TIMP-2 levels were assessed at baseline and at the end of the study. After Bonferroni adjustment, a P-value < 0.017 was assumed to be statistically significant.

Results: Rosiglitazone treatment significantly increased VO2 peak (P < 0.0001), the duration of the exercise test (P < 0.0001), oxygen pulse (P = 0.010) and TIMP-2 levels (P = 0.008) in comparison with CG. Insulin resistance, hyperglycaemia, diastolic blood pressure and MMP-9 levels were also reduced (P < 0.017). Fat mass, lipid profile, TIMP-1 levels and MMP9 : TIMP-1 ratio were unaltered after rosiglitazone treatment. There were no significant changes in these parameters in control subjects. In univariate analysis, the rosiglitazone-induced increment of VO2 peak was associated with alterations in plasma adiponectin (r = 0.691), HOMA-IR (r = -0.782) and HbA(1c) (r = -0.676) (P < 0.017). These relationships retained significance after multiple regression analysis (P = 0.005).

Conclusions: Rosiglitazone treatment increases cardiorespiratory fitness and modulates favourably serum adiponectin, MMP-9 and TIMP-2 levels. Whether these effects produce cardiovascular benefits in the long term requires further investigation.