14
VOLUME 11 NUMBER 1 • MARCH 2014
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Trinath Kumar Mishra
Department of Cardiology, SCB Medical College, Odisha, India
e-mail:
Previously published in
J Diabetes Metab
2014;
5
: 336.
S Afr J Diabetes Vasc Dis
2014;
11
(1): 14–18
Glycaemic control and cardiovascular outcomes in diabetes
BISWAJIT DAS, TRINATH KUMAR MISHRA
Abstract
While type 1 diabetes mellitus (DM) is characterised by insulin
deficiency due to pancreatic beta-cell destruction, type 2 DM
is characterised by a state of longstanding insulin resistance
(IR), compensatory hyperinsulinaemia and varying degrees
of elevated plasma glucose levels (PG), associated with
clustering of cardiovascular (CV) risk and the development
of macrovascular disease prior to the diagnosis of DM.
Coronary artery disease (CAD) accounts for 70% of mortality
and morbidity in patients with diabetes.
Studies in diabetes care have helped prevent or reduce
microvascular complications in type 1 and 2 diabetes.
However the same cannot be said about macrovascular
disease. Despite all data concerning the association between
diabetes and cardiovascular disease (CVD), the exact
mechanism by which diabetes is linked to atherosclerosis is
incompletely understood, and this is especially true in the
case of hyperglycaemia. The positive effect of intensive
glucose management in comparison to non-intensive glucose
control is far from proven.
The DCCT and UKPDS studies have shown that while
glycaemic control is important for preventing long-term
macrovascular complications, early glucose control is far more
rewarding (metabolic memory). Later trials such as ACCORD,
ADVANCE and VADT do not advocate tight glycaemic control.
In fact, the ACCORD trial has shown increased mortality
with tight glucose control. Tight glucose control may be
beneficial in selected patients with short disease duration,
long life expectancy and no CVD. In critically ill patients, a
blood glucose target of 140–180 mg% is fairly reasonable
and achievable. The ESC/EASD guidelines of October 2013,
like those of the ADA, AHA and ACC, continue to endorse
a treatment target for glucose control in diabetes of HbA
lc
level < 7%, based predominantly on microvascular disease
with acknowledged uncertainty regarding the effect of the
intensive glucose control on CVD risk.
Management of hyperglycaemia in diabetics should not
be considered in isolation; diabetics require multifactorial
intervention for hypertension, dyslipidaemia and microalbu-
minuria besides hyperglycaemia. In fact, the combined use of
antihypertensives, aspirin and lipid-lowering agents makes it
difficult to discern the beneficial effects of antihyperglycae-
mic therapy.
Keywords:
diabetes, glycaemic control, hyperglycaemia
Introduction
Diabetes mellitus (DM) is a condition defined by an elevated level
of blood glucose. Type 1 diabetes is characterised by a deficiency
in insulin due to progressive destruction of pancreatic beta-
cells, progressing to absolute insulin deficiency. Type 2 diabetes
is a combination of insulin resistance and beta-cell failure in
association with obesity and a sedentary lifestyle. However, not
all overweight/obese individuals have diabetes and vice versa.
The increased prevalence of diabetes worldwide has led to a
situation where approximately 360 million people had diabetes in
2011, of which 95% would have had type 2 DM.
1
This number
was estimated to have increased to 552 million by 2013 and it is
presumed that half of these would be unaware of their diabetes
status.
The prevalence of diabetes is increasing worldwide and more
people with diabetes will die or be disabled as a consequence
of vascular complications. Prospective studies have shown
unambiguous associations of blood glucose and glycated
haemoglobin levels with the risk of major cardiovascular events.
In the case of subjects with type 1 diabetes, in spite of the fact
that the rate of cardiovascular disease (CVD) is significantly lower
compared with a population with type 2 diabetes, their relative
risk for coronary heart mortality is seven-fold higher than in
matched counterparts without disease.
In spite of all these data concerning the association between
diabetes and CVD, the exact mechanism by which diabetes is linked
to atherosclerosis remains incompletely understood. This is especially
true in the case of hyperglycaemia. The role of non-glycaemic
factors accompanying the majority of patients with diabetes,
such as hypertension, dyslipidaemia and haemorrheological
abnormality, are better understood and appear to be independent
of hyperglycaemia. There have also been data regarding the future
impact of statins, aspirin, ACE inhibitors and aggressive control of
blood pressure on the progression of CVD. By contrast, the positive
effect of intensive glucose management on CVD outcome is far
from proven. Some studies even show a negative influence.
The objective of this article was to analyse trials related to gly-
caemic control in diabetics and assess their impact on CV out-
comes.
Glycaemic continuum and CVD
Type 2 DM develops following a prolonged period of euglycaemic
insulin resistance (IR), which progresses with the development
of beta-cell failure to frank diabetes with increased risk of
vascular complications. While microvascular complications such
as retinopathy, nephropathy and neuropathy develop with overt
hyperglycaemia, macrovascular complications such as coronary
artery disease, cerebrovascular disease and peripheral arterial
disease appear earlier, during the stage of impaired fasting
glucose (IFG) and impaired glucose tolerance (IGT). Therefore
these complications are already established by the time type 2 DM
is diagnosed. Over 60% of patients with type 2 DM develop CVD,
which is a more severe and costly complication than retinopathy.
