REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
18
VOLUME 11 NUMBER 1 • MARCH 2014
a mere chance finding. The current glycaemic target is HbA
1c
level
< 7% with individualisation of therapy (Table 2).
Hypoglycaemia and adverse CV events
In the ACCORD trial, which included diabetic patients with CVD or
high CV risk, symptomatic, severe hypoglycaemia was associated
with higher mortality rates in patients in both study arms.
4
The ADVANCE trial also showed that the occurrence of severe
hypoglycaemic episodes had a detrimental effect on CV outcome.
The ORIGIN trial also provided evidence corroborating
hypoglycaemia with adverse CV outcomes.
11
The trial randomised
12 537 people at high risk of CVD plus IGF, IGT or type 2 DM
to receive insulin glargine (with a target fasting blood sugar level
of < 95 mg%) versus standard care. After a median follow up of
6.2 years, the rates of incident CV outcome were similar in both
groups. In this population in the ORIGIN trial, severe hypoglycaemia
occurred in 5.7 and 1.8% of patients assigned to insulin glargine
and standard-therapy groups, respectively. Severe hypoglycaemia
was associated with a greater risk for primary outcome, mortality,
CV deaths and arrhythmia deaths.
Compensatory mechanisms induced by hypoglycaemia, such
as enhanced catecholamine release, may aggravate myocardial
ischaemia and provoke arrhythmia. It remains unclear whether
hypoglycaemia is simply a marker of disease severity or contributes
to the adverse outcomes. Hypoglycaemic episodes probably identify
patients at risk for other reasons such as malnutrition, heart failure
and renal dysfunction.
Cardiovascular effects of drugs used in diabetes
Few data are available regarding the net cardiovascular safety and
efficacy of medications used to control glucose level in diabetes.
Metformin has the best track record of safety, tolerability and low
hypoglycaemic risk. This drug remains the first drug of choice.
Concern always exists regarding the ability of sulfonylureas to
impair ischaemic preconditioning. However, the UKPDS trial has
been able to allay such fear to some extent.
Of the thiazolidinediones, rosiglitazone was withdrawn from
the market because of the fear of increased risk of myocardial
infarction. Recently, it has been reintroduced. Pioglitazone reduces
the risk of myocardial infarction but can cause fluid retention.
Dipeptidyl peptidase 4 inhibitors have so far shown no adverse
cardiovascular outcomes. Their safety track appears good.
Insulin increases the risk of hypoglycaemia, and retrospective
studies have shown adverse outcome when insulin is used in
diabetics with heart failure.
Conclusion
As the incidence of diabetes assumes alarming proportions and
threatens to become a modern pandemic, every effort should be
made to prevent diabetes-related cardiovascular complications.
Interventions to reduce fasting blood glucose levels have
unfortunately been not translated to better cardiovascular outcomes
in all individuals. Recent trials such as ACCORD, ADVANCE and
VADT challenged this proposition. However, meta-analysis of these
trials suggests that subgroups of diabetics with shorter duration of
illness receive benefit from tight glycaemic control (HbA
1c
< 7%).
Hypoglycaemia is always an issue when the the physician aims
for tight glycaemic control. As hypoglycaemia adversely affects
cardiovascular homeostasis, every effort should be made to avoid it
at all costs while going for tight glycaemic control.
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While an HbA
1c
target level of less than 7% to reduce microvascular disease
is a generally accepted level, the evidence for an HbA
1c
target in relation to
macrovascular risk is less compelling.
Consensus indicates that an HbA
1c
level of less than 7% should be targeted
but with acknowledgement of the need to pay attention to individual
requirements of the patient.
Fasting plasma glucose should be less than 120 mg% (7.2 mmol/l) and
postprandial less than 160–180 mg% (9–10 mmol/l) on an individualised
basis.
Ideally, tight glycaemic control should be started early in the course of the
disease in younger people and those without attendant co-morbidities.
Stringent targets of HbA
lc
= 6–6.5% may be considered in selected patients
with a short disease duration, long life expectancy and no CVD, if it can be
achieved without hypoglycaemia or other adverse effects.
For critically ill indoor patients, insulin therapy is indicated at a threshold of
no greater than 180 mg% (l0 mmol/l) (ADA 2008).
Once insulin therapy has been started in critically ill patients, a glucose
range of 140–180 mg% is recommended.
With the preferred method of intravenous insulin infusion, frequent glucose
monitoring is essential to minimise the occurrence of hypoglycaemia and to
achieve optimal glucose control.
Tight glucose control (80–110 mg%) has not been associated with mortality
benefit in many trials. In the past some trials have shown increased
mortality rates.
Table 2.
Current glycaemic targets (ESC/EASD guidelines).
1
