Diabetes mellitus is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
Cross-talk between the rennin-angiotensin system (RAS) and insulin signaling
has been demonstrated. The rennin angiotensin system (RAS) may regulate
pancreatic islet blood flow, oxygen tension, and islet (pro) insulin biosynthesis.
The present study was designed to evaluate the effect of low doses captopril and
losartan, as adjunct treatment in uncontrolled type 2 DM patients treated with
oral hypoglycemic agents alone.
This double-blind placebo-controlled clinical trial was conducted on 75
patients with uncontrolled type 2 diabetes mellitus; they are randomized into
three groups:
Group A: includes (25) patients treated with placebo formula containing lactose
only in addition to glibenclamide (10 mg/kg) for 4 months; group B: includes
(25) patients treated with 12.5 mg captopril given once daily at bed time, for 4
months; group C: includes (25) patients treated with 25 mg losartan given as a
single daily dose at bed time for 4 months; all patients take the test drugs in
addition to the routinely administered oral hypoglycemic drug (glibenclamide 10
mg/kg). After 12 hours fasting, blood samples were collected from all patients to
measure fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), Cpeptide,
triglyceride (TG), total cholesterol, low density lipoprotein (LDL-c),
high density lipoprotein (HDL-c), serum urea and creatinine, alanine
transaminase, aspartate transaminase, alkaline phosphatase (ALP) and gamma
glutamine transferees (GGT), and urine samples were obtained for assessment of
microalbuminuria (MAU), before starting drug treatment (as zero time sample)
and then after 4 months of treatment to follow the changes in the studied
parameters.
Adjuvant use of low doses of captopril or losartan with the currently used
oral hypoglycemic agents (glibenclamide) results in significant reduction in FPG
and HbA1c levels associated with increase in C-peptide level compared to those
treated with the oral hypoglycemic agents and placebo; additionally, lipid
profile, MAU, renal and liver functions were significantly improved after 4
months of treatment.
Inhibition of RAS by ACEIs or AT1 antagonists (ARBs) increases insulin
sensitivity and improves insulin secretion, where treatment of poorly controlled
type 2 DM patients with captopril or losartan resulted in improving the response
of target tissues to glibenclamide.
Key words: Captopril, Losartan, Glycemic control, Type 2 DM |