Pioglitazone decreases plasma angiotensin II concentration in type 2 diabetes.

Aim: Adipocytes express all components of the renin-angiotensin system (RAS), and adipocyte RAS regulates adipocyte differentiation and metabolism. Plasma angiotensin II (AII) is a putative marker of adipocyte RAS production. The aim of this study was to investigate the effect of pioglitazone on plasma AII in type 2 diabetes (T2D).

Methods: Fifty Japanese subjects with T2D were randomly allocated to two groups. One group was administered pioglitazone 30 mg/day (pioglitazone group) and the other group was not given pioglitazone (control group) for 16 weeks. Lipoprotein lipase mass in preheparin serum (LPL mass) was measured as an adipocyte-derived factor and a marker of insulin sensitivity.

Results: In the pioglitazone group, the mean HbA1c decreased (p<0.0001), LPL mass increased (p<0.0001), and plasma AII decreased (p=0.0007), whereas these parameters were unchanged in the control group. The change in plasma AII correlated negatively with the change in LPL mass (r=-0.312) in the pioglitazone group. In the pioglitazone group, the decrease in plasma AII was higher (p=0.0002) and the increase in LPL mass tended to be higher (p=0.0941) in the subgroup with higher baseline plasma AII than that with lower plasma AII.

Conclusions: The present study indicates that pioglitazone decreases plasma AII associated with an increase in LPL mass in T2D. The insulin-sensitizing effect of pioglitazone may be involved in suppressing adipocyte RAS.