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Diabetes and Hypertension physiopathology and therapeutics

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 Journal of Human Hypertension (2000) 14, Suppl 1, S26–S31
 2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00
www.nature.com/jhh
Diabetes and hypertension
physiopathology and therapeutics
F Contreras, M Rivera, J Vasquez, MA De la Parte and M Velasco
Faculty of Medicine, Central University of Venezuela
Diabetes mellitus by itself, is a frequent and increasing
public health problem. The prevalence in most Western
countries varies between 2 to 5% and it is rapidly
increasing in Asiatic countries due to changes in dietary
habits during the last years. The association between
diabetes mellitus and hypertension has been described
in 60 to 65% of diabetics. In hypertension we find insulin
resistance mainly in skeletal muscle involving the con-
version of glucose to glycogen independently of blood
flow. The degree of resistance is related to the severity
of hypertension and varies between races. States of
Keywords: diabetes mellitus; insulin resistance; endothelial dysfunction; atherosclerosis
Introduction
Diabetes mellitus and hypertension coexist more fre-
quently than reported in classic literature in studies
of large populations of developed countries yielding
values between 60 to 65% of coexistence.1 It is also
known that high blood pressure is two to three times
more frequent in diabetic patients. These patho-
logies are independent risk factors for cardiovascu-
lar disease and when they coexist there is an
increase of two to eight times in morbidity for car-
diovascular disease and the mortality for those dis-
eases is duplicated.1,2 The factors involved in this
association include: (1) the frequency for both dis-
eases increases with age; (2) they have the same pre-
disposing factors; (3) hypertension is secondary to
the diabetic complications, usually nephropathy in
type 1 diabetes; (4) hypertension in type 2 diabetics
could appear before, or could be related to, dia-
betic nephropathy.
Although it is not clear if the occurrence of hyper-
tension is higher in type 1 than in type 2 diabetes,
in diabetics type 1 the incidence of subjects with
hypertension is near 40%.1
Diabetes mellitus (DM) type 2I is a very frequent
illness whose occurrence has increased during the
last decades as a consequence of a series of factors;
we should mention among them the higher long-
evity of the population and a progressive increment
of obesity and sedentary life. Hypertension in type
2 diabetes mellitus has a negative effect on the velo-
city of appearance and progression of complications
of the disease such as nephropathy and retinopathy.
The risk of fatal and non-fatal cardiovascular
Correspondence: Professor Manuel Velasco, Torres Domus, Aven-
ida Abraham, Lincoln c/Olimpo, Piso 6, Ofic 6A, Sabana Grande,
Caracas, Venezuela
hyperinsulinaemia and insulin-resistance have been
postulated as causes and/or consequences of hyperten-
sion. Regardless of the type of diabetes, hypertension
is two to three times more common among diabetics
compared with non-diabetics. In this paper we propose
to review the essential physiopathological mechanisms
involved in this association that causes high morbidity
and mortality rates and increases disability among the
population involved. Journal of Human Hypertension
(2000) 14, Suppl 1, S26–S31.
events in people with DM type 2 is two to four times
higher than in non-diabetic patients. If we include
other risk factors such as hypertension, hyperlipid-
aemia, obesity, etc, we observe that the coexistence
of these factors with diabetes leads to a multiplying
effect of the risks for cardiovascular accidents.
Pathogenesis of arterial hypertension in
diabetes
Diabetes mellitus is a chronic disorder with a gen-
etic basis with a high influence from environmental
factors with three kinds of characteristic manifes-
tations: (1) a metabolic syndrome consisting of
hyperglycaemia, glycosuria, polyphagia, polydipsia,
polyuria and alterations of the lipid and protein
metabolisms due to a complete or partial deficiency
of the action of insulin and/or a peripheral resist-
ance to the insulin effect; (2) a vascular syndrome
including (a) macroangiopathic alterations affecting
all organs, particularly heart, brain and peripheral
circulation, kidney and retina, and (b) a microangio-
pathic component involving the microcirculation
producing mainly endothelial dysfunction; (3) a per-
ipheral or autonomous neuropathic syndrome caus-
ing vascular disfunction.3
It is known that the majority of hypertensive dia-
betics have type 2 DM, usually without nephro-
pathy. In type 1 DM blood pressure is not altered at
the beginning of the illness so that the appearance
of hypertension in type 1 DM is related to kidney
damage. Although, in both types of diabetes hyper-
insulinaemia is present, different mechanisms are
proposed for the appearance of hypertension. In the
following section we propose several suggested
mechanisms trying to explain the vascular problems
in diabetics.
The vascular changes described in the subject

with hypertension are: increase in thickness of the
media in all vessels (large, medium, small and
arterioles), as an adaptive response to the increased
resistance in the wall of the artery in order to regu-
late the local blood flow, a phenomenon observed
in the circulatory system as a whole, including large
vessels and even resistance arterioles what amplifies
and perpetuates arterial hypertension. However, in
animal models these structural changes show
hypertrophy in the large vessels and hyperplasia in
small arteries and arterioles.4
In addition to these mechanic changes, the
phenomenon of vascular rarefaction is described,
consisting of the effective loss of microvascular per-
fusion units, arterioles or capillaries, leading to a
decrease of blood flow to the skeletal muscle. Insu-
lin resistance is directly related to low perfusion and
loss of the capillary bed density in the skeletal mus-
cle. In diabetic subjects structural changes of the
vessels walls associated to hyperglycaemia have
been described.5
Today we know that the endothelium mediates
the ability of the blood vessels to modify their archi-
tecture in response to haemodynamic changes.5 The
normal endothelium reduces the vascular tonus pro-
ducing relaxation of the vascular wall and inhibiting
the growth of the smooth muscle, adhesion and
aggregation of platelets and leukocytes and thus pre-
venting thrombosis. It is easy to understand that an
alteration of the inhibitory function of the vascular
endothelium will lead to vasoconstriction with an
increase of the peripheral vascular resistance and a
rise of blood pressure, stimulation of the growth of
the vascular smooth muscle and elevation of the
adhesion and platelet aggregation, altogether leading
to thrombogenic accidents.
Many studies demonstrate that nitric oxide (NO)
produced by the endothelium largely contributes to
this vascular remodelling participating actively as a
negative regulator of the proliferation of vascular
smooth muscle in response to stimulation.6 A dys-
functional endothelium loses not only the capacity
to regulate vascular tone, but also its anti-thrombotic
and anti-aggregation properties for leukocytes and
platelets.7
Thromboxane A2, produced by the platelets, is
the most important agent producing vasoconstric-
tion, is increased in diabetics, and the smooth mus-
cle of the vessels has a higher susceptibility to it.
Other agents are endothelin-1, a vasoconstrictor
stimulated by hyperglycaemia. In these subjects the
concentrations of NO are low; this is the reason for
the alterations of the endothelium-dependent
phenomenon. Among the vasodilating substances
prostacycline is an endothelium agent, produced in
lower amounts in diabetics and exhibiting a contra-
dictory vasoconstricting action mediated by throm-
boxane A2.4
In diabetics NO is blocked by the products of
advanced glycosilation in a time-dependent way
beginning during the first 2 weeks and reaching a
maximum peak within 2 months. In that manner
glycosilated haemoglobin reduces the endothelium-
dependent relaxation mediated by NO. Diabetic
patients show an elevated oxidative stress produc-
Diabetes and hypertension
F Contreras
S27
ing a larger amount of free radicals that inactivates
the NO, and damage the coupling of the vasodilator
to the endothelium receptor.
The coexistence of hypertension and diabetes
enhances the loss of the endothelium-mediated
vasodilation, which could be explained by a lower
production of NO or by a decrease of the response
to the NO in the vascular smooth muscle.8 There are
several degrees and types of endothelial dysfunc-
tion: (1) damage to the Galphai proteins; (2) lower
release of NO, prostacyclines and/or endothelium-
derived hyperpolarizing factor, (EDHF); (3) increase
in the release of endoperoxidases; (4) increase in the
production of oxygen reactive species; (5) increase
of endotheline 1 (ET-1) production; and (6) decrease
of the vascular smooth muscle sensitivity to NO,
prostacyclines, and/or EDHF.
Different metabolic pathways related to hypergly-
caemia are involved in the higher production of free
radicals (anion super-oxyde hydroxyl). However,
none of the investigations carried out recently have
shown the limits where blood sugar levels are toxic
to the vascular system. When endothelial cells are
incubated in high glucose concentrations there is a
higher production of advanced glycosilated end-pro-
ducts (AGE), that could inactivate NO.
Nitrous oxide inhibits platelets adherence and
aggregation, reduces the adherence of monocytes to
the endothelium, the proliferation of the vascular
smooth muscle and eliminates the capacity of mono-
cytes to oxydize low-density lipoproteins (LDL).
The activation of the renin-angiotensin-aldos-
terone system also has an important role in the gen-
esis of endothelial dysfunction in hypertensive indi-
viduals. Levels of bradykinin and angiotensin II
inside the endothelial wall are controlled by the
angiotensin- converting-enzyme (ACE). ACE breaks
down bradykinin to produce angiotensin II. Brady-
kinin stimulates the endothelial cell to release vaso-
dilating substances. The action of kinines is main-
tained in spite of endothelial dysfunction except in
very severe arterial injuries. Angiotensin II could be
partly responsible for endothelial dysfunction
because it induces resistance to the vasodilatory
effect of the NO, so that by stopping the production
of angiotensin II the direct and indirect vasocon-
strictive effects of this peptide are blocked.9
Another possible contribution of DM to endo-
thelial dysfunction is the impairment of the lipid
profile; it has been demonstrated that hypercholest-
erolaemia accelerates the deficit of intracellular argi-
nine, reducing the activity of the NO synthetase,
lowering the production of NO and increasing endo-
thelin secretion predominating the vasoconstrictive
response. It is important to remark that the develop-
ment of the atherosclerotic process begins with an
initial injury produced either by a metabolic trauma
like diabetes, hypercholesterolaemia, smoking,
infections, ischaemia, etc; or by a physical trauma
such as hypertension and percutaneous coronary
angioplasty.4
Insulin and atherosclerosis
There is a relationship between the decrease of
sensitivity to the effect of insulin, secondary hyper-
Journal of Human Hypertension
 Diabetes and hypertension
F Contreras
S28
insulinism and predisposition to atherosclerosis.
High levels of insulin are related to elevated concen-
trations of plasminogen type I inhibitor (PAI-1), due
to an apparent direct effect of insulin on the PAI-
1 producing hepatocytes. Therefore, the atherogenic
effect of insulin is mediated partly by high levels of
PAI-1 with the ensuing inhibition of fibrinolysis.
PAI-1 is proportionally related to the triglycerides
levels in patients with ischaemic cardiopathy but in
addition it is found in high concentrations in the
atheromatous lesion. Obese patients with type II DM
show high levels of PAI-1 associated with hyper-
insulinism and hypertriglyceridaemia.
Resistance to insulin could be defined as a
decrease to the response or to the sensitivity of the
effectors to the hormone action. Insulin effectors
include principally, muscle cells, adipocytes, hepa-
tocytes and also the beta cells of the pancreatic
islets.10 Resistance to insulin could be divided in:
(1) decrease of the sensitivity to the hormone (post-
receptor failure); (2) decreased biological response
to insulin; and (3) decreased sensitivity and
response. The immediate results of insulin-resist-
ance is the compensating increment of pancreatic ␤
cell secretion, which leads to hyperinsulinism, with
high serum insulin concentrations without hypogly-
caemia.10
Insulin has direct and indirect atherogenic effects.
It acts directly as a mitogenic factor for the smooth
muscle cells contributing to their proliferation.
Additionally it acts as a migratory factor of the
smooth muscle cells from the media to the intima.
Also it increases the tubular sodium reabsorption in
the kidney and the sympathetic activity, all of which
could contribute to the development of arterial
hypertension. Indirectly, insulin has a large influ-
ence in the lipid profile acting on the catabolism of
triglyceride-rich lipoproteins increasing the concen-
tration of strongly atherogenic remnants. Insulin
participates in different processes of lipid catab-
olism. So, it is known that a low insulin efficiency
leads to a higher amount of strongly atherogenic gly-
cosilated LDL particles, the precursors of the foam
cells. Insulin also increases the number and activity
of the cell receptors for LDL stimulating the HMG-
CoA reductase, and regulates the synthesis of intra-
cellular cholesterol. In the high-density lipoprotein
(HDL) receptor insulin modulates the lecitin-choles-
terol-acil transferase. Hyperinsulinaemia also
increases the liver production of very low-density
lipoproteins (VLDL), causing hypertriglyceridaemia
since insulin resistance reduces the removal of tri-
glycerides.10 In addition it should be mentioned that
hyperinsulinaemia might decrease the levels of
dehydroepiandrosterone (DHEA) in men.
Recently it has been established that acute hyper-
insulinaemia strongly reduces protein degradation
in the myocardium of patients with cardiovascular
disease and resistance to the peripheral action of
insulin. This kind of antiproteolitic response rep-
resents a potential mechanism through which hy-
perinsulinaemia contributes to the development of
myocardial hypertrophy in patients with cardio-
vascular disorders.4
Hyperglycaemia, atherosclerosis and diabetes
Journal of Human Hypertension
associated vascular complications are linked by
another mechanism: the non-enzymatic glycosil-
ation of proteins, which include the serum lipopro-
teins. Non-enzymatic protein glycosilation is related
to several processes promoting atherosclerosis.11
The binding of glucose to proteins produces insol-
uble complexes called advanced glycosilated end
products (AGE),12 which are synthesized in higher
amounts in hyperglycaemia. The effects of the AGE
proteins include the following: (1) procoagulant
changes on the surface of endothelial cells and
higher oxydative stress due to binding to endothelial
cells; (2) a greater endothelium permeability because
of inhibition of the association of heparinsulphate
to the extracellular matrix; (3) alteration of the endo-
thelium-dependent vasodilation as a result of nitric
oxide depletion; (4) proliferation of smooth muscle
cells induced by cytokines resulting from binding of
AGE-bounded proteins to specific macrophages
receptors; (5) a higher secretion of platelet-derived
growth factor (PDGF) and a pronounced enhance-
ment of circulating monocytes chemotaxis.
Insulin’s theory for hypertension
It was Reaven, who first associated cardiovascular
accidents, obesity and intolerance to glucose using
the term X Syndrome, called later on Metabolic Syn-
drome. At present Assmann13 has proposed the term
Metabolic Cardiovascular Syndrome and estab-
lished defining diagnostic criteria that include: (1)
resistance to insulin with hyperinsulinaemia and
decreased glucose tolerance; (2) dislipidaemia, hy-
pertriglyceridaemia and decrease of HDL-col; (3)
thrombogenicity due to increase of coagulation fac-
tor VII and to the inhibitor of the plasminogen activ-
ating factor (PAI-1); (4) hypertension with sympath-
etic hyperactivity; (5) trunk obesity accompanied by
increase of free fatty acids (FFA) in the portal vein;
(6) hyperuricaemia.
Different direct findings could explain the pres-
ence of hypertension in insulin-resistant diabetic
patients, such as: (1) increase of sodium and water
reabsorption in the proximal renal tubuli increasing
the intravascular volume. (2) Activation of the sym-
pathetic nervous system with the ensuing rise in the
concentration of catecholamines, leading to an
increase of the heart rate, myocardial contractility
and cardiac output. It has been reported higher tone
of the great veins as well as vasoconstriction of the
resistance vessels together with an increment of tub-
ulo-renal sodium reabsorption and renin liber-
ation;2,4 (3) Alteration of the function of the insulin-
dependent transmembrane ionic pumps, which is
expressed in: (a) increase of the sodium-proton
pump activity, what causes a great deal of hydrogen
ions to leave the cells and rising of intracellular pH.
This has an easy vascular reactivity to noradrena-
line, angiotensin II and to salt overload and stimu-
lates the cell proliferation of the arteriole smooth
muscle; (b) reduction of the activity of the sodium-
potassium-ATPase insulin-dependent pump with
the subsequent increase of sodium and decrease of
potassium concentrations inside the cell; (c)
increased reactivity of smooth muscle due to cito-

solic Ca2+ increase as the Ca-ATPase becomes resist-
ant to insulin. (4) Enhancement of arteriolar vaso-
constriction because of greater sensitivity to
vasoconstrictor and lower sensitivity to vasodilator
stimuli. The impairment of the Na-K-ATPase insu-
lin-dependent pump disappears slowly by addition
of L-arginine, the precursor for NO. The synthesis of
NO is directly correlated to the sensitivity to insulin
in healthy patients.4,7 Additionally, acute hyper-
insulinaemia increases endothelin concentrations so
that diabetics show a higher response to noradrena-
line and angiotensin II. (5) Activation of insulin-
dependent growth factors (protooncogene e-myc,
IGF-1 and IGF-2) producing more hypertrophy of the
vessel wall. Recent studies have established that
such growth factors have an effect on the glucose
transporters of muscle and fat cells causing trans-
location of the transporter GLUT-4, the main glucose
transporter and insulin-dependent situated princi-
pally in skeletal muscle, heart and adipocytes.14
Abnormalities of lipids
Insulin, a classic anabolic hormone, has a high meta-
bolic activity in the adipose tissue, which promotes
the deposit of triglycerides in the adipocytes by dif-
ferent mechanisms: (a) induces the production of
lipoprotein lipase, which is bounded to the endo-
thelial vascular cells of the adipose tissue, breaking
down the circulating lipoproteins; (b) increases the
glucose transport into the fat cell augmenting the
use of alpha-glycero-phosphate for the esterification
of free fatty acids; (c) inhibits the intracellular
lipolisis.
Glycosilation of lipoproteins elevates its athero-
genic potential. Glycosilated LDL, not detected by
the classic LDL receptors, increases the synthesis of
cholesterol esters and the accumulation of macro-
phages. The formation of foam cells through captur-
ing of lipids by macrophages as well as cell prolifer-
ation in the smooth muscle is higher when
glycosilated LDL bind to the macrophage recep-
tors.11
In 1988 Randle et al15 proposed that the increase
of the free fatty acid oxidation limits the glucose
consumption in the muscle due to alteration of the
oxidation-reduction potential of the cell and to the
inhibition of many glycolisis enzymes. When large
amounts of fatty acids are oxidized acetylCoA
accumulates in the cell, a powerful inhibitor of the
pyruvate dehydrogenase complex. This complex is
activated when pyruvate is being used for the forma-
tion of acetyl-CoA. The activation is produced by
dephosphorylation of the inactive form of the
enzyme catalysed by the pyruvate phosphatase I and
II, which at the same time are stimulated by the Ca2+
and Mg2+ levels of the cell and by the binding of
insulin to its receptors. The results of these bio-
chemical disorders include the inhibition of insulin-
induced glucose processing increasing the free fatty
acid concentration and promoting in that way oxi-
dation of fats.10
The consequence of all these biochemical
phenomena is a decrease of the synthesis and
activity of the adipocyte lipoprotein lipase (LPL)
Diabetes and hypertension
F Contreras
S29
since insulin acts as its major regulator and
increases the activity of the liver lipase, which
accelerates the synthesis and secretion of hepatic
VLDL rich in triglycerides,16 producing hypertrigly-
ceridaemia, reduction of HDL-cholesterol, changes
in the composition of the LDL generating dense and
short LDL particles and accumulation of VLDL rem-
nants and chylomycrons, all of these factors con-
tributing to the genesis and persistence of hyperten-
sion in the diabetic patient.
Pharmacological treatment
The high rate of patients with DM forces us upon
maintaining an adequate level of metabolic control
and reduction of other cardiovascular risk factors
such as the lipid profile, arterial hypertension and
tobacco habits. This is the case of patients
presenting DM and hypertension, two morbid con-
ditions that together are present in 50% of patients
with type 1 and type 2 diabetes mellitus. It is known
that cardiovascular diseases are present in 75% of
all deaths associated with DM.17 Diabetes mellitus
and hypertension are closely related and predispose
the individual to arteriosclerosis and kidney failure.
The object of blood pressure control in diabetic
patients is to reduce as much as possible the number
of deaths and disabled people. The optimal level of
blood pressure in diabetic patients is still not estab-
lished but the statements of the VI JNC show that
130/85 mm Hg should be the values searched for.18
The efficiency of a hypertension treatment should
be measured not only by the reduction of blood
pressure but also by a lower excretion rate of urinary
albumin, the nephroprotective effect. The choice of
an antihypertensive drug ought to be based not only
on the reduction of blood pressure alone but also
on a better control of glycaemia, lipid profile and
thrombotic disorders.19
According to the literature control of blood press-
ure must be sufficient in order to reduce the velocity
and the extent of damage to kidney function. Among
the different antihypertensive drugs, the inhibitors
of the angiotensin-converting-enzyme (ACEI) are
recommended by the VI JNC. The ACEI delay the
progression of microalbuminuria and could reduce
the percentage of patients showing terminal renal
failure. Comparative studies between ACEI and cal-
cium channel blockers such as the Appropriate
Blood Pressure Control in Diabetes (ABCD), in
which enalapril was compared with nisoldipine, a
calcium channel blocker with long half-life, demon-
strating after 5 years that cardiac infarction was sig-
nificantly reduced in the group treated with enalap-
ril. In another study using fosinopril and
amlodipine, the Fosinopril and Amlodipine Cardiac
Events Trial (FACET) proved that cardiacaccidents
were duplicated in patients treated with calcium
channel blockers, but blood pressure was higher
using ACEI.18,20 This study suggested also that the
combined use of calcium channel blockers and an
ACE inhibitor was effective in the treatment of
hypertension, as supported by the findings of the
Systolic Hypertension meeting in Europe (Syst-
Eur).21
Journal of Human Hypertension
 Diabetes and hypertension
F Contreras
S30
More recently, the study Hypertension Optimal
Treatment (HOT) also demonstrated that the com-
bined use of calcium channel antagonists with ACEI
make a rational therapeutic choice for patients
presenting hypertension and diabetes.22
Other studies have established that the kidneys of
type 2 diabetics were structurally heterogeneous
with less than one-third of them showing typical
changes of diabetic nephropathy a decrease of kid-
ney function only in those patients with typical
structural changes.23
Additional comparative studies with ACEI and
beta-blockers, such as the United Kingdom Prospec-
tive Diabetes Study (UKPDS), found no difference in
the rate of cardiovascular or diabetic complications,
not even in the microalbuminuria or proteinuria in
patients treated with captopril or atenolol, and they
conclude that both drugs are equally effective and
safe, and could be used with great benefit for the
treatment of uncomplicated hypertensive type 2 dia-
betic patients.19,24
Other studies show improvement of retinal
arterial and brain blood flow with the use of ACEI
(perindopril 4 mg) compared with atenolol.25
When using the ACEI there are studies showing
fosinopril as one of the most adequate for its double
elimination route simplifying the use in patients
with nephropathy.26 Nevertheless other authors pre-
fer the use of quinalapril since it could attenuate
endothelial dysfunction in coronary disease, not
only for the inhibitory effect of the ACEI upon the
formation of angiotensin II but because of its
capacity to prevent bradykinin degradation.7
In the group of calcium channel blockers there
also exists the possibility of treatment with the non-
dihydropyridine calcium antagonists verapamil and
diltiazem that also decreases the excretion of albu-
min and proteins and apparently improves insulin
sensitivity.1
It is reported in some studies the use of candersar-
tan and cilexetil (angiotensin II receptor antagonist)
specific for AT1 receptors; these had no effect on the
homeostasis of glucose and serum lipids when used
in hypertensive patients and type 2 diabetics show-
ing a fairly good control of their blood pressure
values and a well tolerated.27
Diet, exercise, insulin and oral antidiabetic drugs
have been the most important resources for the treat-
ment of uncomplicated diabetes. At present when
an oral antidiabetic drug is required, the tendency
is to choose second generation sulphonilurea
(gliburide or gliclazida).28 The therapeutic system
glipizida GITS is a valid alternative.
During the treatment of the diabetic patient with
arterial hypertension, a good control of the blood
sugar reduces considerably the onset of new compli-
cations caused by the two processes that work on
the altered endothelium. Glicazide returns the lipid
peroxides and the activity of mononuclear cells to
normal levels,29 and reducing the levels of platelet
aggregation30 have a proven action on the cardio-
vascular system of diabetic patients, when they are
compared with other sulfonilureas. Even more, it
shows antioxidant actions compared with those of
the vitamin E.
Journal of Human Hypertension
There are other drugs such as the thiazolindine-
diones (Troglitazone) that does not only have an
improving effect in the peripheral sensitivity to
insulin but also in improving lipid profile, it does
not affect insulin secretion and blocks the release of
␣-tumor-necrosis-factor and produces vasodilation
by blocking calcium movement.31,32
Other possibilities of new antihypertensive drugs
could be Urapidil, a postsynaptic and peripheral
alpha-1 antagonist with central agonist effect on the
serotoninergic 5-HT1A receptors that does not affect
glucose and lipid metabolism.33
Likewise, the hypolipidic treatment with statins
and aspirin have been shown to be effective and
promise a better prognosis for diabetic patients with
cardiovascular disease. The efficacy of aspirin at low
dose (81–325 mg/day), was demonstrated by the
Anti-Platelet Trialists (APT), in which a reduction
of vascular accidents in diabetic and non-diabetic
patients was observed, corroborated by the Early
Treatment Diabetic Retinopathy Study (ETDRS).34,35
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