REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
8
VOLUME 7 NUMBER 1 • MARCH 2010
would seem perfectly sensible in normalbuminuric patients
with diabetes.
8
There are several important practical points about blood
pressure in diabetic patients which should be borne in mind.
Firstly, the nature of blood pressure is different in type 1 and
type 2 diabetic patients. Usually hypertension in patients with
type 1 diabetes is a reflection of renal parenchymal damage,
whereas in type 2 diabetes hypertension is usually a reflection
of the metabolic syndrome of which both glucose intolerance
and hypertension are integral parts. By the time patients with
type 2 diabetes are diagnosed, studies have demonstrated
that an abnormal circadian blood pressure profile is found
in 79% of patients.
9
Once nephropathy occurs in type 2
diabetes then hypertension tends to worsen, whereas this
relationship between renal dysfunction and hypertension is
less clear in type 1 diabetes.
10
In type 2 diabetes, because of
the high prevalence of obesity, the relevant blood pressure
measurement cuff size must be used in order to be able to
obtain and interpret the reading correctly.
The second major issue regarding blood pressure in
diabetic patients is the frequent occurrence of orthostatic
hypotension, which may mean blood pressure targets need
to be individualised. In these circumstances often the blood
pressure target should be set as the lowest standing blood
pressure at which the patient does not feel ill effects; in
practice this may be well above the NICE guideline. Diabetic
patients have a higher prevalence of nocturnal hypertension
(with loss of the normal circadian blood pressure profile)
than the general population. If needed, short acting
antihypertensive agents such as captopril can be taken once
daily as the patient goes to bed allowing some therapeutic
benefit to be achieved without unpleasant side effects from
orthostatic hypotension. A further comment on hypertension
in diabetic patients is that if the radial and brachial arteries are
heavily calcified then pseudohypertension may occur, with
high blood pressure measurements out of keeping with the
degree of target-organ damage. Patients with this clinically
rare phenomenon may suffer hypotensive symptoms on the
introduction of antihypertensive medication.
Two trials have demonstrated the benefit of ACE inhibitors
in normoalbuminuric patients for risk reduction of progression
to microalbuminuria. BENEDICT randomised 1 204 patients
with type 2 diabetes and hypertension to receive a minimum
of three years treatment with trandalopril, verapamil,
trandalopril plus verapamil, or placebo. Blood pressure control
was comparable across the groups. Trandalopril alone or in
combination with verapamil decreased the risk of developing
persistent microalbuminuria (defined as overnight albumin
excretion rate
≥
20
µ
g/min) by 50%, whereas the effect
of verapamil alone was similar to placebo.
11
More recently
the ADVANCE study randomised 11 140 patients with
type 2 diabetes to a fixed combination of perindopril plus
indapamide or placebo with a mean follow-up of 4.3 years.
Treatment was given irrespective of blood pressure with a
resulting 21% reduction in development of microalbuminuria
(19.6% versus 23.6%) for the treatment group compared
with placebo; there was also an 18% reduction in death
from cardiovascular disease seen in the treatment arm of the
ADVANCE study population.
12
In all such studies there is debate as to whether it is the
level of blood pressure achieved or the inhibition of the renin–
angiotensin system which has led to the observed benefit. In
many such studies the level of achieved blood pressure did
not differ between the groups treated with renin–angiotensin
system blocking agents and the other groups and therefore
it is generally accepted that these agents have additional
benefits beyond the lowering of blood pressure. It is certainly
true that ACE inhibitors and ARBs, by preventing the action of
angiotensin II, stop not only its vasoconstrictor action but its
remodelling effect on the left ventricle, its ability to modulate
renal endothelial function resulting in proteinuria and other
effects on the vasculature. Having accepted this, lowering
blood pressure in diabetic patients should be the primary
therapeutic target and which agents are used to achieve this
is a secondary matter.
Agents blocking the renin–angiotensin system
Much of the evidence cited in this article advocates blockade of
the renin–angiotensin systemwith ACE inhibitors, ARBs, both,
or a direct renin inhibitor. These medications are employed
with increasing regularity in diabetic patients. There is concern
about the safe use of such agents in patients who may have a
declining glomerular filtration rate despite the fact that such
patients, often with additional cardiac failure may, although
yet to be shown by any major trial, have the most to gain.
In view of the relative excess of angiotensin II receptors on
the efferent glomerular arteriole compared with the afferent
glomerulararteriole,vasoconstrictionoftheefferentglomerular
arteriole helps to maintain glomerular filtration pressure.
Agents blocking the renin–angiotensin system lead to
an increase of blood flow through the efferent glomerular
Abbreviations and acronyms
ACE
angiotensin-converting enzyme
ADVANCE Action in Diabetes and Vascular disease: PreterAx and
DiamicroN MR Controlled Evaluation
ARB
angiotensin II receptor blocker
BENEDICT
Bergamo Nephrologic Diabetes Complications Trial
CALM Candesartan and Lisinopril Microalbuminuria
CKD
chronic kidney disease
DETAIL
Diabetics Exposed to Telmisartan and Enalapril
HbA
1c
glycated haemoglobin
IDNT
Irbesartan in Diabetic Nephropathy Trial
INNOVATION INcipieNt to OVert: Angiotensin II receptor blocker,
Telmisartan, Investigation On type 2 diabetic Nephropathy
IRMA-2
Irbesartan in Patients with type 2 Diabetes and
Microalbuminuria
NICE
National Institute for Health and Clinical Excellence
RENAAL
Reduction of Endpoints in NIDDM with the
Angiotensin II Antagonist Losartan
SHARP
Study of Heart and Renal Protection
UKPDS
UK Prospective Diabetes Study
