SA JOURNAL OF DIABETES & VASCULAR DISEASE
DRUG TRENDS
VOLUME 10 NUMBER 1 • MARCH 2013
41
clinically overt cardiovascular disease. The
results showed an unequivocal decrease in
cardiovascular events with the administration
of atorvastatin over placebo.
Dr Blom used these data and those from
a meta-analysis of all major statin trials to
substantiate an across-the-board statin
strategy for T2DM, even in the absence
of cardiovascular disease or increased LDL
cholesterol levels. He further stated, ‘Statins
reduce almost all cardiovascular outcomes
except haemorrhagic stroke and are the
number one workhorse in LDL cholesterol
lowering.’ Other LDL cholesterol-lowering
agents include ezetimibe, which combines
well with statins.
Bile acid sequestrants are not frequently
used in South Africa but are interesting agents
to consider in those with T2DM, as they
have been shown to not only reduced LDL
cholesterol but can also improve glycaemic
control.Unfortunatelycholestyramineispoorly
tolerated due to frequent gastrointestinal side
effects. Colesevelam is better tolerated but is
not available in South Africa. Colesevelam
has more extensive data on glycaemic control
than cholestyramine and reduces HbA
1c
levels
by approximately 0.5%.
Aggressive
management
of
LDL
cholesterol unfortunately does not prevent
all cardiovascular events. This residual risk
is a major target of on-going research
and therapeutic efforts. More aggressive
management of dyslipidaemia may be
one way to reduce residual risk. Dr Blom
considered two potential management
strategies. The first is to focus harder on LDL
cholesterol lowering, as current interventions
are often too little, too late. Earlier and
more aggressive statin therapy could bring
substantial benefits.
The second strategy is often referred
to as comprehensive lipid management.
This strategy targets other components of
the atherogenic lipid phenotype, such as
elevated triglycerides, low high-density (HDL)
cholesterol and the presence of small, dense
LDL particles.
Of the agents used in comprehensive
lipid management, Dr Blom discussed
fibrates and niacin, as well as some agents
still in development. Data from trials of
fibrate monotherapy indicate that fibrates
reduce cardiovascular event rates in patients
with atherogenic dyslipidaemia, but are
not efficacious in high vascular-risk patient
without atherogenic dyslipidaemia. Sub-
group analysis of the ACCORD trial, which
enrolled T2DM patients with particularly
high vascular risk, indicated some benefit
from adding fenofibrate to simvastatin for
patients with marked dyslipidaemia, defined
as triglycerides > 2.30 mmol/l and HDL <
0.88 mmol/l.
TheAIM-HIGHstudy,examiningtheefficacy
of niacin in atherosclerotic dyslipidaemia, was
abandoned as it was seen as futile, with no
improved cardiovascular outcomes evident
from adding niacin as a second agent to
statins. Results from the larger HPSII-THRIVE
trial are pending.
In summary, Dr Blom recommended early,
aggressive statin therapy. In the case of severe
hypertriglyceridaemia (> 10 mmol/l) a fibrate
is often required to prevent pancreatitis.
There is no benefit from adding fibrates to
statins in patients with T2DM who do not
have marked dyslipidaemia, as defined in the
ACCORD study. Dr Blom also warned against
therapeutic inertia, as several surveys show
that many patients remain on their initial
statin dose despite not reaching their LDL
cholesterol targets.
Portions of portions: the diet
debacle
Dr Wayne May, endocrinologist, Cape Town
From as early as the 17th century, individuals
with type 1 diabetes (T1DM) have been
placed on low-carbohydrate diets to better
manage their health. Diet, despite being the
oldest tool in the health arsenal, remains a
controversial issue and the debate around
low-carbohydrate diets is currently of
particular interest in South Africa, with much
discussion being generated in the practice
of medicine and in the social media.
Low-carbohydrate diets can be stratified
according to daily carbohydrate intake. A
ketogenic diet is defined as carbohydrate
intake of less than 50 g daily, whereas a
non-ketogenic diet may be defined as low in
carbohydrates (50–130 g daily) or moderate
(130–225 g daily).
Low-fat diets became popularised in the
1950s with the hypothesis that fat is the
cause of heart disease, after associations were
made between dietary fat and heart disease
mortality. By 1986, a blood cholesterol level
above 200 mg/dl was treated as a disease.
Despite being a molecule that is essential
throughout the body, many epidemiological
studies have indicated that as levels of
cholesterol and saturated fat increase, the
risk of coronary death over 10 years also
increases.
MigrationalstudiesofJapaneseimmigrants
to the USA have shown increased risk of
heart disease accompanying the change
to a Western diet, however no consistent
evidence exists. Some dietary-intervention
studies have indicated that interventional
lowering of cholesterol and saturated fats
in the diet is associated with a decreased
risk of heart disease. In terms of the patient
with diabetes, UKPDS data rates cholesterol
as the strongest predictor for heart disease.
The CARD study indicates that statin therapy
alone can reduce the risk of heart disease in
the patient with diabetes.
Dr May went on to compare benefits of
low-carbohydrate and low-fat diets for the
patientwithdiabetes. Obesity reviews indicate
that in terms of weight loss, low-carbohydrate
diets show better results in the short term (at
six months), but within a year, weight loss will
be equivalent in both low-carbohydrate and
low-fat diets. Low-carbohydrate diets have
the advantage of raising HDL cholesterol
levels; however, at both six and 12 months,
low-fat diets had the advantage in terms of
LDL cholesterol levels.
Trials on the dietary prevention of
diabetes have indicated that a diet low
in fat and saturated fats, and high in
fibre (Mediterranean diet) will delay the
progression to diabetes. Why this is the case
remains in the realmof speculation, although
weight loss could be the predominant
driving factor. Similarly, pharmaceutical
agents that decrease fat intake show a delay
in progression to diabetes, with associated
cardiovascular benefits.
A study by Shai and colleagues
1
comparing low-carbohydrate, low-fat, and
Mediterranean diets indicated that the
Mediterranean diet was best for fasting
sugar levels. At 24 months, weight loss
was superior in the low-carbohydrate and
Mediterranean dietary arms.
However, adherence toa low-carbohydrate
diet over the long term is difficult, with a
six-year follow up indicating equivalency to
low-fat diets in terms of weight loss. Low-
carbohydrate diets were also found to exhibit
a short-term benefit in HbA
1c
levels, although
this was lost over time, with equivalent levels
with low-fat diets at 12 months. No diet
has currently shown any benefit in terms
of macro- and microvascular reduction or
promoting a longer life.
Fewdataexist for low-carbohydratediets in
T1DM. Existing studies show improved HbA
1c
levels, reduction in hypoglycaemic episodes
and a lowering of insulin-replacement
requirements. Improved HbA
1c
level has also
been noted in low-carbohydrate diets in
the young; however, there are no data on
