20
VOLUME 10 NUMBER 1 • MARCH 2013
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
a fat tolerance test should be ≤ 2.5 mmol/l.
20
The Joint British
Societies’ guidelines recommend increasing CVD risk by a factor
of 1.3 when using the charts in patients with fasting triglycerides
> 1.7 mmol/l.
21
Therefore, a triglyceride level of 1.7 mmol/l seems
to be a suitable threshold for intervention.
Managing hypertriglyceridaemia in diabetes
Finding hypertriglyceridaemia should alert clinicians to search for
secondary causes, such as hypothyroidism, renal impairment, liver
inflammation (particularly from alcohol abuse) and poor blood
glucose control.
22
Indeed, some oral hypoglycaemics may attenuate
the rise in triglyceride levels. For example, a relatively small study of
treatment-naïve type 2 diabetic patients found that glibenclamide
reduced postprandial hypertriglyceridaemia compared with placebo
(AUC 687 and 821 mM/h respectively). However, glibenclamide
attenuated the increase in chylomicron triglycerides only compared
with placebo (AUC 344 and 487 mM/h respectively) rather than
VLDL. Therefore, a reduction in triglycerides of intestinal origin
seems to account for most of the decrease in postprandial levels
induced by glibenclamide. Further studies need to ascertain whether
the reduction in triglyceride levels is a pharmacodynamic effect of
glibenclamide or a reflection of improved postprandial glycaemia
and increased insulin-induced lipoprotein lipase activity.
11
Lifestyle changes
Clinicians should encourage diabetic patients with hypertri-
glyceridaemia to implement lifestyle changes, such as controlling
body weight, taking regular physical activity, avoiding tobacco and
high-carbohydrate foods, and eating a diet low in saturated fat and
sugar.
23,24
Patients with triglyceride levels > 11.30 mmol/l should
immediately start a very low-fat diet, in which fat accounts for
≤ 15% of calories.
24
There is currently no standardised treatment protocol for severe
hypertriglyceridaemia (e.g. > 10 mmol/l). In patients with diabetes,
fenofibrate may be the preferred treatment, usually combined with
a statin.
8
According to NICE, patients at high risk of pancreatitis
should commence treatment with a fibrate before starting a
statin.
22
Omega-3 PUFAs, which can reduce triglyceride levels by
up to 45% in patients with severe hypertriglyceridaemia, enrolled
patients who had fasting triglycerides < 4.5 mmol/l. Nicotinic acid
(niacin) and fibric acid derivatives (fibrates) are more effective,
reducing triglycerides by up to 50 and 60% respectively. The choice
depends on other considerations, such as the need to reduce and
increase concentrations of LDL and HDL cholesterol respectively.
(Bile acid sequestrants either produce no in change or increase
triglycerides.)
23,24
Fibrates
Statins are the mainstay of treatment for diabetic dyslipidaemia.
19
However, NICE suggests prescribing a fibrate (fenofibrate first-line)
if triglyceride levels remain above 4.5 mmol/l despite addressing
secondary causes.
22
Clinicians could consider adding a fibrate
if triglyceride levels remain between 2.3 and 4.5 mmol/l after 6
months of treatment with a statin and optimal glucose control,
especially in patients at high cardiovascular risk – which is usually
the case in type 2 diabetes.
22
Fibric acid derivatives (fibrates) reduce
triglycerides by up to 60%.
24
However, fenofibrate did not significantly reduce the primary
endpoint in the FIELD study
25
and ‘considerable controversy’
still surrounds fibrates’ clinical efficacy.
26
FIELD enrolled 9 795
patients with type 2 diabetes (37% women; mean age at baseline
62.2 years), total cholesterol levels of 3.0–6.5 mmol/l and a total-
cholesterol/HDL ratio of ≥ 4.0, or plasma triglyceride concentrations
of between 1.0 and 5.0 mmol/l. Of these, 59% showed low HDL
levels (< 1.03 mmol/L in men and < 1.29 mmol/l in women), 52%
high triglyceride levels (> 1.7 mmol/l) and 38% both. At baseline,
triglyceride levels were 1.93 mmol/l (standard deviation [SD] 0.88)
in the placebo arm, and 1.95 mmol/l in the micronised fenofibrate
(200 mg daily) arm. Four months after the start of treatment
fenofibrate reduced triglycerides by 0.56 mmol/l (–28.6%)
compared with placebo, which was broadly maintained until the
end of the study (median five years; –0.41 mmol/l; –21.9%).
25
Fenofibrate reduced the RR of a coronary event by 11%
compared with placebo (5.2 and 5.9% respectively;
p
= 0.16),
this difference was not statistically significant. The risk of non-fatal
MI (RR 0.76;
p
= 0.010), total CVD events (RR 0.89;
p
= 0.035)
and coronary revascularisation (RR 0.79;
p
= 0.003) significantly
declined in the fenofibrate arm.
25
Nevertheless, whether adding
a fibrate to statin reduces cardiovascular risk in type 2 diabetic
patients ‘remains unproven’, although the possibility of a clinically
relevant improvement in those with elevated triglyceride and low
HDL levels cannot be excluded.
26
As mentioned above, in patients with low HDL cholesterol VLDL
triglycerides were independently associated with CHD events.
6
A
meta-analysis of five studies, including FIELD, found that in patients
with dyslipidaemia (defined as triglyceride ≥ 2.3 mmol/l and HDL
≤ 0.9 mmol/l) fibrates reduced the rate of coronary heart disease by
35% (95% CI 22–46). In contrast, in patients who failed to meet
the criteria for dyslipidaemia, fibrates reduced the rate of coronary
heart disease by 6%, which was not statistically significant (95%
CI –5–16).
27
Therefore, fibrates may be effective in patients with the
combination of low HDL and high triglycerides.
Nicotinic acid preparations
Nicotinic acid (niacin) reduces triglyceride levels by up to 50%.
23,24
However, NICE advises against using nicotinic acid preparations
and derivatives routinely in type 2 diabetes. Nicotinic acid may
be suitable for some people intolerant of other therapies who
have ‘more extreme disorders’ of lipid metabolism. Such patients
should be managed by specialists.
22
Specialist referral may also
be appropriate in cases of acute pancreatitis, difficult-to-manage
Table 1.
Effect of lipid lowering medication on triglyceride, LDL and
HDL levels
23,24
Author
Triglyceride
reduction
(%)
LDL change
(%)
HDL
increase
(%)
Statins
Oh
et al
.
Solano
et al.
20 – 40
7 – 30
18 – 55
i
18 – 55
i
5 – 15
5 – 15
Ezetimibe
Solano
et al
.
5 – 10
15 – 20
i
1 – 4
Fibrates
Oh
et al
.
Solano
et al
.
40 – 60
20 – 50
5 – 30
5 – 20
i
15 – 25
10 – 20
Nicotinic acid Oh
et al
.
Solano
et al
.
30 – 50
20 – 50
5 – 25
i
5 – 25
i
20 – 30
15 – 35
Fish oil
Oh
et al
.
30 – 50
5 – 10
5 – 10
Key:
HDL = high-density lipoprotein; LDL = low-density lipoprotein
