Urinary angiotensin converting enzyme 2 increases in patients with type 2 diabetic mellitus

Background/aims: Angiotensin converting Enzyme 2 (ACE2) is highly expressed in the kidney and recognized to be renoprotective by degrading Angiotensin II to Angiotensin (1-7) in diabetic nephropathy. However, little is known about the role of urinary ACE2 (UACE2) in diabetes. The present study was performed to evaluate UACE2 levels in type 2 diabetic patients with various degrees of albuminuria and its associations with metabolic parameters. The effect of Ras inhibitors on UACE2 excretion was also assessed.

Methods: A total of 132 type 2 diabetic patients with different degrees of albuminuria and 34 healthy volunteers were studied. UACE2 levels and activity were measured.

Results: Compared to healthy controls, UACE2 to creatinine (UACE2/Cr) levels were significantly increased in both albuminuric and non-albuminuric diabetic patients. UACE2/Cr levels were much higher in hypertensive diabetic patients compared with their normotensive counterparts and treatment with Ras inhibitors markedly attenuated the augmentation. Furthermore, UACE2/Cr was positively correlated with fasting blood glucose, hemoglobin A1C (HbA1C), triglyceride, and total Cholesterol. In multiple regression analysis, UACE2/Cr was independently predicted by HbA1C and Ras inhibitors treatment.

Conclusions: UACE2 increased in type 2 diabetic patients with various degrees of albuminuria and Ras inhibitors suppresses UACE2 excretion. UACE2 might potentially function as a marker for monitoring the metabolic status and therapeutic response of Ras inhibitors in diabetes.