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VOLUME 10 NUMBER 2 • JUNE 2013
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
although the ALP is characterized by multiple lipid abnormalities.
The recently updated SEMDSA guidelines
19
for the management of
T2DM suggest the following two LDL-C targets:
1. 1.8 mmol/l is the target for most patients with T2DM.
2. Patients who fulfil all of the following criteria can be treated
to a LDL-C of 2.5 mmol/l: No cardiovascular disease or chronic
kidney disease, no other cardiovascular risk factors, less than
forty years old or duration of diabetes less than 10 years.
ApoB levels of 0.8 g/l and 1.0 g/l correspond to the LDL-C targets
of 1.8 mmol/l and 2.5 mmol/l respectively. The non-HDL-C targets
are 0.8 mmol/l higher than the LDL-C targets, i.e. 2.6 mmol/l and
3.3 mmol/l respectively. Triglycerides should ideally be less than 1.7
mmol/l, while HDL-C should be more than 1.2 mmol/l in females
and more than 1.0 mmol/l in men.
6,19
The choice of statin and starting dose depends on the baseline
LDL-C, the risk of interaction with other drugs the patient may be
taking and individual tolerability. Following statin initiation, patients
require regular follow-up (at 6-12 weekly intervals) and statin dose
adjustment if they have not reached their target LDL-C. Patients
who are unable to reach target despite high doses of potent statins
such as atorvastatin or rosuvastatin, or who are unable to tolerate
the statin dose required to reach target, can be treated with the
combination of a statin and ezetimibe. Stable patients at LDL-C
goal can be followed up annually for their lipids.
Although statins are highly effective therapy they do not
prevent all vascular events (residual risk). Statins do not deal with
all the components of the ALP and there has been much interest
in combining statins with other lipid lowering therapies that
more specifically address issues such as hypertriglyceridaemia and
low HDL-C. A full review of these studies is beyond the scope
of this article. The two therapies that have been best studied in
combination with statins are fibrates and niacin. The ACCORD
study examined the utility of adding fenofibrate or placebo in
simvastatin treated type 2 diabetics with added vascular risk,
irrespective of baseline lipids. The study overall failed to show any
benefit from adding fenofibrate. In a post-hoc analysis, a subgroup
of patients with high TGs (defined as TG > 2.30 mmol/l) and low
HDL-C (defined as HDL-C < 0.88 mmol/l) seemed to benefit from
fibrate therapy.
20
The HPS-THRIVE II study examined the utility of
adding modified release niacin with laropiprant to simvastatin (+
ezetimibe if required) based aggressive lipid lowering therapy (the
baseline LDL-C before randomization was 1.64 mmol/l) in high-risk
patients. About 32% of patients included had T2DM. Niacin did
not improve cardiovascular outcomes and was associated with a
significant excess of adverse events.
21,22
The role of combination therapy in diabetes is thus currently
not well defined and there are no clear guidelines when, and if,
a second lipid lowering agent should be added to statin based
therapy. Controlling the LDL-C remains critical and additional
therapy should only be considered once the LDL-C is adequately
controlled. Good glycaemic control and lifestyle changes may aid in
improving hypertriglyceridaemia and increasing HDL-C.
Acute Pancreatitis
Severe hypertriglyceridaemia (TG > 10-15 mmol/l) may trigger acute
pancreatitis. Acute pancreatitis occurs unpredictably in patients
with severe hypertriglyceridaemia. The correlation between the
severity of hypertriglyceridaemia and the onset of acute pancreatitis
is not clear cut. Some patients with severe hypertriglyceridaemia
never develop pancreatitis while others may have recurrent attacks.
Hypertriglyceridaemic pancreatitis is associated with significant
morbidity and mortality.
Clinical clues that help identify patients with severe hypertrig-
lyceridaemia include eruptive xanthomata (figure 1), a lipaemic
specimen (figure 2) or a very high TC value on screening. Severe
hypertriglyceridaemia is secondary to accumulation of chylomi-
crons and VLDL, which do contain cholesterol in addition to TG,
and marked accumulation of these lipoproteins can thus raise TC
substantially. Many, but not all, diabetics with severe hypertriglyc-
eridaemia have poorly controlled diabetes.
Eruptive xanthomata
Legend:
Eruptive xanthomata are associated with severe hypertriglyceridaemia.
They are usually asymptomatic and found on the flexor surfaces of the elbows
and knees. They also commonly occur on the buttocks, thighs and flanks.
Lipaemic plasma
Legend:
Lipaemia is caused by the accumulation of large, TG-rich lipoproteins
(chylomicrons and VLDL) and indicates that patients are at risk of developing
hypertriglyceridaemic pancreatitis.
