48
VOLUME 10 NUMBER 2 • JUNE 2013
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Dr Dirk Blom
Lipid Laboratory
5th Floor Chris Barnard Building
UCT Health Sciences Faculty
Anzio Road
7925 Observatory
Cape Town
Fax: + 27 21 4066396
E-mail:
Tel: +27 21 4066055
S Afr J Diabetes Vasc Dis
2013;
10
: 48–50
Dyslipidaemia in Type 2 Diabetes
DIRK J. BLOM
Abstract
Cardiovascular disease is the commonest cause of death in
patients with type 2 diabetes (T2DM) and dyslipidaemia is
an important atherosclerotic risk factor. Dyslipidaemia is very
common in T2DM and is characterized by mild to moderate
hypertriglyceridaemia, lowhighdensity lipoproteincholesterol
(HDL-C) andthepresenceof small dense lowdensity lipoprotein
(LDL) particles. Almost all patients with T2DM will require
lipid lowering therapy with statins aiming for a target LDL-
cholesterol of 1.8 mmol/l in the majority of patients. Younger
patients with a shorter duration of diabetes and no other risk
factors can be treated to a target of 2.5 mmol/l. The role of
statin and fibrate combination therapy in reducing residual
risk by ameliorating hypertriglyceridaemia and low HDL-
cholesterol that may persist despite statin monotherapy is not
well definedand is not included inguideline recommendations.
Diabetes is the commonest secondary cause of severe
hypertriglyceridaemia that may trigger acute pancreatitis.
Patients with severe hypertriglyceridaemia require good
glycaemic control, a very low fat diet and a fibrate.
Introduction
Conventionally, doctors have viewed T2DM primarily as a disorder
of glucose metabolism and hyperglycaemia as the central defining
feature. An alterative viewpoint would be to think of T2DM primarily
as a vascular disorder in which high blood glucose is an essential,
but not the sole defining component. The pathophysiology of T2DM
is complex (and not uniform in all patients) but dyslipidaemia and
hypertension often result from the same pathophysiological processes
that lead to hyperglycaemia. The combination of dyslipidaemia,
hyperglycaemia, hypertension and other factors creates a ‘toxic’
vascular environment that damages both small and large vessels.
Microvascular damage leads to retinopathy, nephropathy and
neuropathy while macrovascular damage causes atherosclerotic
cardiovascular disease (ASCVD). ASCVD is responsible for the highest
number of life years lost in T2DM when compared to age matched
controls without diabetes; and is, in fact, the major cause of death
accounting for about 50-75% of all deaths in those with T2DM.
1,2
Dyslipidaemia is an important contributor to the pathogenesis of
ASCVD in patients with T2DM. This article will review dyslipidaemia
in diabetes, focussing on patients with T2DM.
Atherosclerosis in type 2 diabetes
Atherosclerosis in T2DM is often diffuse and extensive. Studies have
shown that the coronary arteries of those with T2DM are smaller,
have a higher plaque burden and show inadequate compensatory
remodelling when compared to those of non-diabetic patients with
coronary artery disease.
3
It is thus not surprising that patients with
T2DM have poorer outcomes following acute myocardial infarction
or other acute coronary syndromes. Vascular interventions are
associated with a higher complication rate which is at least in
part due to the smaller vessels and the diffuse atherosclerosis that
characterizes T2DM. Although the short term risk of coronary
artery bypass grafting (CABG) is higher than that of percutaneous
intervention (PCI) with stenting, a recent study has confirmed that
CABG should be the preferred option for many diabetics requiring
coronary revascularization as PCI only deals with a discrete focal
area of disease while CABG bypasses multiple diseased vascular
segments.
4
Dyslipidaemia and atherosclerosis
Dyslipidaemia is an important contributor to the pathogenesis of
atherosclerosis and extensive basic sciences, epidemiological and
clinical evidence supports the causative role of elevated levels
of apolipoprotein B100 (apoB)-containing lipoproteins in the
development of atherosclerosis. ApoB-containing lipoproteins
range in size and density from very low density lipoproteins (VLDL)
to intermediate density lipoproteins (IDL) to low density lipoproteins
(LDL). VLDL are large, triglyceride (TG)-rich lipoproteins secreted by
the liver. In the circulation, VLDL undergo progressive delipidation
(TG removal) and are transformed into IDL and subsequently LDL.
The latter two lipoproteins are smaller and relatively enriched in
cholesterol when compared to VLDL.
LDL account for the majority of circulating apoB-containing
lipoproteins in humans due to their long half life of around 3-4
days. LDL are thus the major circulating pro-atherosclerotic apoB-
containing lipoproteins and in clinical practice the contribution
of other apoB-containing lipoproteins is often ignored. This is a
reasonable approach as long as VLDL and IDL are not elevated.
Patients with elevated levels of VLDL and IDL usually have elevated
TGs as these lipoproteins are TG enriched when compared to LDL.
LDL-C reflects the amount of cholesterol carried in LDL particles
in a given volume of serum or plasma. Because LDL particles may
differ in size, and therefore the amount of cholesterol they carry, the
correlation of LDL-C with LDL particle number is only approximate.
The same amount of cholesterol may be carried in many small
LDL particles or fewer large LDL particles. Particle size influences
atherosclerotic risk as smaller particles penetrate the endothelium
more readily, have longer plasma half lives and are more prone to
oxidative damage.
5
Head of Division of Lipidology, Department of Medicine, University of Cape Town
Submitted 6/5/2013, accepted 1/6/2013
