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VOLUME 9 NUMBER 1 • MARCH 2012
45
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REPORT
Diabetic dyslipidaemia: new therapies
Prof Derick Raal
A typical diabetes lipogram: small, dense LDL-C, low HDL-C and high triglyceride
•
levels.
Statin’s main effect is reduction of LDL-C levels.
•
Fibrate’s main effect is reduction of triglyceride and increased HDL-C levels.
•
Niacin reduces triglyceride and raises HDL-C levels.
•
There is still a substantial residual risk of cardiovascular disease, even when the LDL-C
•
level has been greatly reduced.
Triglycerides: no clear cardiovascular risk (if one corrects for other factors). FIELD and
•
ACCORD LIPID trials showed no cardiovascular benefit with the addition of fibrate
to statin therapy.
HDL-C has multiple physiological functions. Low HDL-C levels have a clear associa-
•
tion with increased cardiovascular risk. New drugs target HDL-C.
Niacin raises HDL-C levels, decreases carotid intima–media thickness but does not
•
reduce cardiovascular events (AIM-HIGH study). Side effects are a problem.
Reconstituted high-density lipoprotein (rHDL) intravenous infusions can reverse
•
atheroma in the acute setting.
Cholesterylester transfer protein (CETP) inhibitors: torcetrapib raises HDL-C levels,
•
but increases death rate. New drugs in this class are being developed.
More aggressive lowering of LDL-C levels is still the best way of reducing cardiovas-
•
cular risk. One should aim for very low levels (< 1.8 mmol/l in high-risk patients). For
every 2 mmol/l lowering of LDL-C levels, there is a 40% reduction in cardiovascular
event rate.
New therapy to lower LDL-C levels will soon be available as PSK9 inhibitors
•
and there is a progressive and probably
meaningful weight loss.
‘There is considerable interest in the
non-glycaemic potential benefits of GLP-1
agonists with regard to their neuro- and
cardioprotective effects. A real-life study
in medically insured patients, the Life-Link
study, has recently shown a 16% reduc-
tion in cardiovascular events in patients on
exenatide.’ Dr Distiller noted.
‘With regard to the ultimate promise of
these agents, the increased proliferation
and reduced apoptosis of
β
-cells, which
was shown in early experimental laboratory
studies, there is some evidence from HOMA
studies that, for example, liraglutide is
β
-cell
sparing compared to TZDs and basal insu-
lin’. ‘At this juncture, liraglutide appears the
better option in this class of agents, but this
situation is dynamic and may change with
the advent of once-weekly exenatide’, Dr
Distiller noted.
With regard to the DPP-4 inhibitors, Dr
Distiller noted ‘they work, they are mild, and
do not change the world; but they do work.
They are weight neutral, drop HbA
1c
levels on
average by 0.7%, and there is a suggestion
that they preserve
β
-cell function. Overall,
their cardiovascular effects are not yet as well
researched as the GLP-1 agonists’, he noted.
With regard to when to use these
agents,
10
Dr Distiller noted that early use
when there is still
β
-cell function is taken
up in many algorithms as an alternative for
sulphonylureas with metformin. They are
also used in combination with insulin, fol-
lowing acceptable trials and registration for
use of the particular agent with insulin.
As DPP-4 receptors are widespread in the
body, and despite the claimed specificity of
these inhibitors, Dr Distiller noted a general
acceptance that these drugs have a subtle
effect on the immunosurveillance system,
leading to increased incidence of bronchitis,
for example.
With regard to the GLP-1 analogues and
their risk of pancreatitis, pancreatic and thy-
roid cancer, there is an alert but not yet an
alarm, despite the much-commented article
on post-marketing surveillance’,
11
he con-
cluded.
Is type 2 diabetes a cardiovascular
risk equivalent?
Dr AD Horak, Dr Hoosen Randeree
A stimulating debate concluded the pres-
entations, with Dr AD Horak (Cape Town)
presenting the view that diabetes is worse
than a cardiovascular risk equivalent, while
Dr Hoosen Randeree (Parklands Hospital,
Durban) felt that diabetes is less than a car-
diovascular risk equivalent because future
risk is confounded by the patient’s ethnicity,
age, gender and age of onset of diabetes.
The type of therapy used in the treatment of
type 2 diabetes also confounds the assess-
ment of the condition as a cardiovascular
risk equivalent.
The conclusion of the participants was
that the clinician needs to focus on those
diabetic patients who will benefit most from
preventative therapy, so as to reduce the
cardiovascular and vascular consequences
of type 2 diabetes.
Dr F Mohamed and J Aalbers
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