Abstract
Angiogenesis is a multistep process implicated in the pathophysiology and
progression of diabetic nephropathy (DN). Angiotensin-converting enzyme
inhibitors (ACEI) and calcium channel blockers (CCB) have an important role in
DN. We performed a randomized-controlled trial of lisinopril alone (an ACEI) or
in combination with verapamil (a CCB) as a therapy for DN in type 2 diabetes
mellitus (T2DM) patients with hypertension (HTN) and urinary albumin creatinine
ratio (UACR) (30–300 mg/g) also to evaluate their effect
on UACR, the angiogenic proteins: Angiopoietin 2 (Ang-2) and Endostatin (EST).
Forty T2DM patients with microalbuminuria, aged 45–65 years were
included. Patients were randomly assigned into group 1 receiving oral lisinopril
and group 2 receiving oral lisinopril and verapamil once daily. After 3 months
follow-up fasting blood glucose (FPG), HbA1c, lipid profile, UACR, serum urea
and creatinine levels were assessed. EST and Ang-2 were measured using ELISA
technique. Baseline Ang-2 and EST levels were elevated in both groups compared
with controls (p<0.001). After follow-up, group 2 had significantly
decreased FPG, HbA1c, UACR, EST and Ang-2 compared with their baseline levels
(p<0.001 for all comparisons) and with group 1 (p<0.001). No
adverse reactions were reported. Baseline EST and Ang-2 were positively
correlated to UACR (r=0.753, p<0.001) (r=0.685,
p<0.001). Lisinopril/verapamil combination enhanced glycemic
control and kidney function via diminishing EST and Ang-2. This combination can
be considered as a safe and effective approach for early stage nephropathy
therapy in T2DM.
Key words
diabetic nephropathy - lisinopril - verapamil - angiopoietin - endostatin