ACE Inhibitors Prevent Diabetes
and Cardiovascular Disease by Different Mechanisms
Angiotensin-converting enzyme (ACE) inhibitors
improve markers of cardiovascular disease and
prevent diabetes, renal disease, and cardiovascular
disease.
That, according to a review of the latest data
that explores the potential mechanisms of this
class of antihypertensives.
Samy I. McFarlane, MD, State University of New
York, Health Science Center, Brooklyn, New York,
United States, and colleagues describe in their
article the mechanisms whereby ACE inhibitors
influence the cardiometabolic syndrome, the symptoms
of which include central obesity, insulin resistance/hyperinsulinaemia,
dyslipidaemia, hypercoagulability, enhanced cardiovascular
inflammation, hypertension, and albuminuria.
ACE inhibitors inhibit the conversion of angiotensin
I to angiotensin II, and thereby block the actions
of the renin-angiotensin system (RAS). Angiotensin
II increases the production of reactive oxygen
species and has several vasoconstrictive effects,
including opposition of the vasorelaxant actions
of nitric oxide and stimulation of plasminogen
activator inhibitor-1, according to Dr. MacFarlane
and colleagues. In turn, increased plasminogen
activator inhibitor-1 production impairs fibrinolysis,
"which may help explain why ACE inhibitor
therapy has been demonstrated to improve the fibrinolytic
balance in high-risk patients," the authors
note.
Angiotensin II, furthermore, increases arterial
stiffness by a variety of mechanisms. "The
most positive data on vascular compliance come
from studies with ACE inhibitors," Dr. McFarlane
and colleagues point out, adding that: "study
findings showed ACE inhibition therapy improved
arterial compliance, primarily by increasing distensibility."
In contrast, fewer studies have evaluated the
effects of angiotensin receptor blockers (ARBs),
although these agents may also exert beneficial
effects and may act synergistically with ACE inhibitors.
The researchers next discussed the role of ACE
inhibitors in diabetes prevention. They note that
interruption of the RAS system may improve insulin
sensitivity. Several trials, beginning with the
Captopril Prevention Project (CAPPP), demonstrate
that ACE inhibitors reduce the incidence of type
2 diabetes in hypertensive patients.
Two large randomized trials of antihypertensive
are currently underway in patients with type 2
diabetes: the Diabetes Reduction Assessment with
Ramipril and Rosiglitazone medications (DREAM)
trial and the Nateglinide and Valsartan in Impaired
Glucose Tolerance Outcomes Research (NAVIGATOR)
trial. These trials will evaluate the benefits
of an ACE-inhibitor and an ARB, respectively,
in combination with antidiabetic drugs.
The authors note that, regarding the role of
ACE inhibitors in diabetic renal disease, with
the exception of ARBs, ACE inhibitors "have
been shown to be more effective in reducing proteinuria
than any other antihypertensive agents."
"Thus, therapeutic strategies that interrupt
the RAS reduce both cardiovascular disease and
renal disease in type 2 diabetes," the authors
conclude. Am J Cardiol. 2003;91:12A:30H-37H
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FACT:
Children who are large for gestational age and
exposed to either gestational diabetes or maternal
obesity are at increased risk for developing insulin
resistance syndrome during their childhood, Dr.
Charlotte Boney reported at the annual meeting
of the Pediatric Academic Societies.
Findings from a prospective, observational study
suggest that being large for gestational age is
a marker for fetal hyperinsulinemia in an environment
of either gestational diabetes or maternal obesity,
and possibly glucose intolerance.
