90
VOLUME 11 NUMBER 2 • JUNE 2014
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
measured at baseline or during follow up, was associated with
increased risk for incident hypertension. Older age, male gender,
family history of hypertension, greater baseline BMI, weight gain,
and greater albumin excretion rate were independently associated
with increased risk of hypertension. These data show that
hyperglycaemia is a risk factor for incident hypertension in type 1
diabetes and that intensive insulin therapy reduces the long-term
risk of developing hypertension.
In a recently published Brazilian study on approximately
1 300 patients with type 1 diabetes, however, body size and blood
pressure were not correlated to lipid levels and glycaemic control.
77
Correlation of serum lipids with HbA
1c
level was shown to be
heterogeneous across the spectrum of glycaemic control. Several
pathophysiological factors were suggested based on the HbA
1c
level. These results, therefore, do not support a unified explanation
for cardiovascular risk in type 1 diabetes patients.
77
Cardiovascular risk markers
As demonstrated in 144 participants of the Pittsburgh EDC study,
pulse-wave analysis (PWA) may contribute to assessment of CV
risk in patients with type 1 diabetes.
78
Arterial stiffness index,
augmentation index, augmentation pressure, sub-endocardial
viability ratio (serving as an estimate of myocardial perfusion),
electron beam computed tomography-measured coronary artery
calcification (CAC) and ankle-brachial index (ABI) were determined.
In the analysis of cross-sectional associations, greater augmentation
pressure was independently associated with prevalent CAD and
estimated myocardial perfusion with low ABI (< 0.90).
78
In the DCCT/EDIC study the stiffness/distensibility of the ascending
thoracic aortawasmeasuredwithmagnetic resonance imaging in 879
patients.
79
After adjusting for gender and cohort, aortic distensibility
was lower with increasing age, mean systolic blood pressure, low-
density lipoprotein (LDL) cholesterol and HbA
1c
level measured over
an average of 22 years. Patients with macroalbuminuria had 25%
lower aortic distensibility compared with those without, and lower
distensibility was also associated with greater ratio of left ventricular
mass to volume. This data stand in favour of strong adverse effects
of hypertension, chronic hyperglycaemia and macroalbuminuria on
aortic stiffness in type 1 diabetes.
After 15 years additional follow up in EDIC, left ventricular indices
were measured by cardiac magnetic resonance imaging in 1 017 of
the 1 371 members of the DCCT cohort.80 Mean DCCT/EDIC HbA
1c
level over time was associated with end-diastolic volume, stroke
volume, cardiac output, left ventricular mass, LV mass/EDV, and
aortic distensibility. These associations persisted after adjustment
for CVD risk factors. Therefore cardiac function and remodelling
in the EDIC cohort was associated with prior glycaemic exposure
(glycaemic memory).
As part of the EDIC study, 1 229 patients with type 1 diabetes
underwent ultrasonography of the internal and common carotid
arteries from 1994 to 1996 and again from 1998 to 2000.81 At
year 1 of the EDIC study, the carotid intima–media thickness (IMT)
was similar to that in an age- and gender-matched non-diabetic
population. After six years, the IMT was significantly greater in the
diabetic patients than in the controls. The mean IMT progression was
significantly less in the group that had received intensive therapy
during the DCCT than in the group that had received conventional
therapy after adjustment for other risk factors. IMT progression was
associated with age, and the EDIC baseline systolic blood pressure,
smoking, the LDL/HDL ratio, and urinary albumin excretion rate and
with the mean HbA
1c
value during the mean duration of the DCCT.
Therefore, intensive therapy during the DCCT resulted in decreased
progression of IMT six years after the end of the trial, which again
stands in favour of the effect of glycaemic memory.
As found by the 10-year follow-up examination of the Pittsburgh
EDC study cohort, CAC is related to clinical CAD independent of
other risk factors.
82
This association, however, was stronger in
men than in women.
82
In a cohort of patients with type 1 diabetes
(aged 22–50 years), progression of CAC, as identified by electron
beam computed tomography (EBCT), was strongly associated with
suboptimal glycaemic control (HbA
1c
> 7.5%).
83
In a study assessing CAC with multi-slice spiral computed
tomography (MSCT), nearly one-third of asymptomatic long-term
type 1 diabetes patients presented with coronary calcifications.
84
In patients with coronary calcifications, both cardiac autonomic
neuropathy and retinopathy were detected more frequently than
in those without (64 vs 29%,
p
<0.02; 59 vs 31%;
p
<0.02).
Additionally, duration of diabetes was longer in patients with than
without coronary calcification.
84
In a small cohort of adolescent, non-obese type 1 diabetes
patients, an increased carotid intima–media thickness was found to
be associated with insulin resistance. A causal relationship, however,
cannot be concluded.
85
According to a prospective longitudinal
study in children and adolescents with type 1 diabetes, systolic
blood pressure and body mass index are related to increased carotid
intima–media thickness. Control of these risk factors is presumed
to contribute to prevention of progression of carotid intima–media
thickness.86 In patients with long-term type 1 diabetes, sexual
dysfunction was demonstrated to be independently associated
with CVD and to potentially predict CVD.
87
Results on the predictive value of plasminogen activator
inhibitor-1 (PAI-1) are inconsistent. One study found PAI-1 levels to
be independently related to CAC in younger (< 45 years) patients
with type 1 diabetes.
88
According to another analysis, neither PAI-1
nor tPA-PAI-1 was an independent predictor of CAD.
89
Diagnosis/screening
In type 1 diabetes, hypertension is often the result of nephropathy.
Blood pressure measurement is recommended at every routine
visit.
90
In most adult patients with diabetes, a fasting lipid profile
is recommended at least once a year.
90
Low-risk lipid values (LDL
cholesterol <100 mg/dl, HDL>50 mg/dl, triglycerides <150 mg/dl)
provided, assessment may be repeated bi-annually.
90
In type 1 diabetes patients with diabetes duration≥five years, the
screening for nephropathy should include an annual assessment of
urine albumin excretion.
90
Irrespective of the degree of urine albumin
excretion, in all adults with diabetes serum creatinine should be
measured at least annually.
90
The creatinine value is useful for estimation
of glomerular filtration rate (GFR).
90
In children and adolescent
patients, annual screening both for nephropathy and retinopathy is
recommended to start at age 11 years in case of two years’ diabetes
duration and at age nine years with five years duration, respectively.
91
Screening for signs and symptoms of CV autonomic neuropathy
should be started five years after the diagnosis of type 1 diabetes.
16,90
CV reflex tests are the gold standard in clinical autonomic testing.
The most widely used tests assessing cardiac parasympathetic
function are based on the time-domain heart rate response to
deep breathing, Valsalva manoeuvre and postural change. Age is a
strong modulator of these tests and needs to be considered when
