Possible synergistic effect of ACE inhibition and calcium-channel blockade on insulin sensitivity in insulin-resistant type II diabetic hypertensive patients.

Abstract

So-called insulin resistance is a frequent phenomenon and a marker of increased risk for both type II diabetes mellitus and atherosclerosis. Today, insulin resistance is widely understood as a tissue- and pathway-specific defect of insulin-stimulated glucose uptake into skeletal muscle that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. Additional defects of insulin-stimulated muscle blood flow and cellular kation balance are presently attracting increasing awareness. Clinical and experimental evidence suggests that angiotensin-converting enzyme (ACE) inhibition ameliorates both insulin-stimulated skeletal-muscle glucose uptake and blood flow in insulin-resistant states by a direct stimulation of cellular glucose uptake, which appears to be kinin-mediated. This improvement of insulin sensitivity could mean not only improvement of glucose metabolism, but also reduction of chronically elevated serum insulin and the ensuing atherogenic consequences (hyper- and dyslipidemia, sympathetic overactivity, growth of vascular smooth-muscle cells, hypertension, etc.). Ca(2+)-channel blockers that do not increase heart rate appear to exert direct antiatherogenic effects while being metabolically neutral. Thus, the combination of Ca(2+)-channel blockade by sustained release verapamil and ACE inhibition by trandolapril in insulin-resistant type II diabetic patients with essential hypertension appears to be promising in terms of possible synergistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)