VOLUME 11 NUMBER 2 • JUNE 2014
91
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
interpreting the results. CV sympathetic function is assessed by
measuring the blood pressure response to standing.
92
PWA may contribute to assessment of CV risk in patients with
type 1 diabetes.
78
In a study, greater augmentation pressure was
independently associated with prevalent CAD and estimated
myocardial perfusion with low ABI (< 0.90).
78
Screening patients for
silent myocardial ischaemia is controversial but seems reasonable in very
high-risk patients, in particular in those with long duration of diabetes
and proteinuria or evidence of peripheral artery disease, and in those
who wish to start a vigorous exercise programme. Measurement of
CAC score may be suggested as a first-line investigation, leading to a
stress test if the score is higher than 400.
93,94
Treatment
Gycaemic control
Intensive insulin therapy has been strongly demonstrated to reduce
the onset as well as progression of all diabetes-related microvascular
complications.
58,60,95-98
The DCCT/ EDIC study found in approximately
1 200 patients with type 1 diabetes a relative CVD risk reduction of
40%, adjusted for other risk factors including albuminuria, when
comparing intensive versus standard treatment (mean HbA
1c
7.4 vs
9.1%) for 11 years.
58
In adolescent patients, intensive treatment
(HbA1c = 8.1%) compared to conventional treatment (HbA
1c
= 9.8%) has been shown to reduce the risk and progression of
background retinopathy by 53%, clinical neuropathy by 60%, and
microalbuminuria by 54%.
60
A prolonged effect of early intensive
approaches was also seen in a four-year follow up of intensively
treated adolescent type 1 diabetic patients.
99
Several studies confirmed the association between poor
glycaemic control and an increasing risk for nephropathy,
100-102
retinopathy,
95,103,104
and neuropathy.
105-109
A large proportion of
patients, however, fail to achieve glycaemic targets.
110-112
GLP-1-based treatment as an add-on to insulin
Due to their action on insulin secretion and glucose regulation,
glucagone-like peptide 1 (GLP-1)-based treatment approaches
have been established in the treatment of type 2 diabetes. Based
on
in vitro
and animal studies, GLP-1-based drugs additionally may
be effective in preserving and even expanding the beta-cell mass.
113
In a small study on 15 patients with newly detected type 1 diabetes,
the addition of exenatide at onset of diabetes has been shown to
decrease insulin requirement.
113
Three groups of patients have been
formed: group1 (insulin alone), group 2 (insulin and exenatide) and
group 3 (insulin and sitagliptin).
After one year, a decrease in insulin requirement of 16.7±12.5,
39.8±17.2, 21.2±9.6 units in groups 1, 2 and 3, respectively
(
p
=0.0431) was detected. A mean stimulated c-peptide secretion
of 0.34±0.12, 0.45±0.34, 0.44±0.5 ng/ml was found (
p
=0.8656).
The maximum percentage preservation in c-peptide was observed in
the patients of group 2.
113
Of relevance is the evidence that GLP-1 can
protect type 1 diabetes patients from both acute hyperglycaemia-
or hypoglycaemia-induced endothelial dysfunction, oxidative stress
and inflammation.
114
Approaches beyond glycaemic control
In contrast to DCCT/EDIC, some trials did not confirm the association
between glycaemic control and CVD risk.
115-117
Discrepancies
are suggested to be based on differences between the study
populations.
118
With a view to prevention and treatment of CAD,
it is recommended to focus not only on glycaemic control.
118
Traditional risk factors such as albuminuria, the metabolic syndrome
and inflammatory markers should also be addressed.
118
International guidelines recommend lowering blood pressure in
diabetes to prevent macro- and microvascular outcomes. However,
most evidence from randomised clinical trials refers to type 2
diabetes. A goal of blood pressure < 130 and < 80 mmHg has
been recommended.
90,119
The most recent recommendations of the
American Diabetes Association (ADA) set a blood pressure goal of
< 140/< 80 mmHg for persons with diabetes and hypertension;
lower targets (such as < 130 mmHg) may be appropriate in patients
if the specific target can be achieved without an additional burden
of treatment.
90
Pharmacological therapy in people with diabetes and
hypertension should be with a regimen that includes either an
angiotensin converting enzyme (ACE) inhibitor or an angiotensin
receptor blocker (ARB).
90
Generally, two or more drugs are required to
achieve blood pressure targets in diabetics. Preferred combinations
are either ACE inhibitors or ARBs (not together) with a calcium-
channel blocker or a diuretic. For the latter, both thiazide
90
and,
more recently, thiazide-like diuretics
120
are recommended. However,
more recent appraisal of the evidence indicates lack of evidence to
support systolic blood pressure targets < 130 mmHg and suggests
optimal diastolic blood pressure between 80 and 85 mmHg.
72
In studies among patients with diabetes, regular physical
activity has been demonstrated to reduce CVD-related and total
mortality.
11
Early treatment of hypertension has been reported to
prevent end-stage kidney disease in patients with type 1 diabetes.
121
ACE inhibitors have been demonstrated to be effective and safe
in in reducing microalbuminuria.
122
In adolescent patients with
persistent microalbuminuria, the use of ACE inhibitors
91,100,123
or
angiotensin II receptor blockers
91
is recommended to prevent the
progression to macroalbuminuria. Furthermore, in order to reduce
progression of microalbuminuria, cessation of smoking is strongly
recommended.
117,124,125
Lifestyle modification is recommended for the improvement
of lipid profile. In diabetic patients with overt CVD, statins should
be added irrespective of lipid levels.
90
Statin therapy is also
recommended in diabetic patients without CVD aged>40 years
and≥one other CVD risk factor (family history of CVD, hypertension,
smoking, dyslipidaemia, albuminuria).90 In patients with lower CV
risk, statin therapy should be considered if LDL cholesterol remains
above 100 mg/dl.
90
In diabetic patients without overt CVD, the goal
for LDL cholesterol is 100 mg/dl (2.6 mmol/l). In patients with overt
CVD, an LDL cholesterol goal of 70 mg/dl (1.8 mmol/l) using a high
dose of statin may be considered.
90
Discussion
Despite a remarkable improvement in life expectancy, type 1
diabetes patients are confronted with an increased risk of CV
mortality, often under-recognised evidence. Further improvement
may base on consequent risk assessment and management of
risk factors. Estimation of CV risk including the role of surrogate
markers deserves more attention in the future. Currently, optimised
glycaemic control is considered to be the most promising approach.
Recent research on a small group of patients suggests the addition
of exenatide at onset of diabetes to decrease insulin requirement.
These results, however, need to be confirmed by further investigation
on larger groups of patients.
