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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 3, May/June 2020
160
AFRICA
Consequences of elevated blood glucose
levels
ACS-induced hyperglycaemia is associated with increased risk
for in-hospital deaths, congestive heart failure and cardiogenic
shock.
6
The relative risk of in-hospital deaths for non-diabetic
ACS hyperglycaemic patients [admission blood glucose
≥
110
mg/dl (6.11 mmol/l)] is several fold higher versus matched
normoglycaemic counterparts.
6
This hyperglycaemia in
non-diabetic individuals is likely a combination of three factors:
previously undiagnosed diabetes, impaired glucose tolerance and
the acute stress response.
Whether elevated glucose levels are markers or direct
mediators of damaging outcomes following an acute myocardial
infarction (AMI) remains unresolved, although pre-clinical and
clinical data suggest harmful effects. For example, clinical trials
and epidemiological studies support a causative role because
intensive glycaemic control with insulin lowers the incidence of
cardiovascular complications.
7
High blood glucose availability
may also lead to ‘glucotoxic’ effects in cardiac endothelial cells,
to a much greater extent than in cardiomyocytes where increased
uptake is more dependent on the insulin-responsive glucose
transporter, GLUT-4. However, enhanced glycolytic flux also
has potential benefits: first, the membrane protection afforded
by increased flux and production of glycolytic ATP, and, second,
the enhanced oxidation of pyruvate with a decreased production
of harmful protons.
Here we propose that glucose–fatty acid interactions in the
ischaemic heart (FFA-induced lowering of glucose metabolism)
would not be restricted to only cardiomyocytes in this instance.
In support of this hypothesis, hyperglycaemia is associated with
impaired microvascular function, leukocyte capillary plugging,
enhanced platelet activation, larger infarct sizes and worse
functional recovery in AMI patients.
7
Key molecular mechanisms
whereby hyperglycaemia exerts such toxic effects include
higher intracellular oxidative stress, downstream metabolic
perturbations and activation of inflammatory pathways.
Clinical management
It is our viewpoint that one should routinely determine the
metabolic status (FFA, glucose, insulin) of suspected and
confirmedAMI patients (non-diabetic and diabetic) at the time of
admission, and thereafter monitor this in the ICU (for example,
to check for persistent hyperglycaemia). Which easily available
metabolic therapeutic options would be most appropriate under
such circumstances? The selection of a metabolically favourable
β
-blocker may be useful as in conjunction to its well-known
effects on haemodynamic parameters,
β
-blockers also inhibit
adipose lipolysis and limit subsequent FFA-mediated damaging
effects.
Modulating blood glucose levels is another therapeutic
option by employing the glucose–insulin–potassium (GIK)
cocktail originally proposed by Sodi-Pallares in 1969.
8
Indeed,
pharmacodynamic doses of insulin improve cardiac pump
function without increasing myocardial oxygen consumption
in acute ischaemic heart failure.
9
Lastly, FFA reduction and
stimulation of glucose metabolism in the ischaemic myocardium
by GIK treatment is able to blunt metabolic derangements.
7
However, such treatment must be initiated early, within the first
hours of symptom onset, because the relatively weak benefit of
most prior GIK studies is attributed to delayed infusion when
the ischaemic heart has already undergone substantial damage.
10
The major protective component of this cocktail is likely
to be insulin, which is known to lower FFA mobilisation,
to decrease circulating FFA levels and to promote glucose
uptake, thereby alternating dangerously high circulating blood
glucose levels. Insulin administration is also linked to additional
cardioprotective actions, independent of its ability to lower
systemic blood glucose levels.
7
Interestingly, when insulin was
infused at doses high enough to overcome stress-induced insulin
resistance, the subsequent lowering of FFA levels and restoration
of normoglycaemia were associated with cardioprotection in
patients undergoing coronary bypass grafting.
11
However, among
patients with suspected ACS, out-of-hospital administration
of intravenous GIK did not reduce progression to myocardial
infarction.
12
This study requires independent confirmation.
We agree with the American Heart Association (AHA) that
insulin treatment be initiated for ACS patients as soon as blood
glucose levels exceed 180 mg/dl (10 mmol/l), regardless of prior
diabetes history.
13
This option may easily be overlooked in ACS
patients with no history of diabetes in the ICU. The AHA
also recommends that ACS patients without diabetes should
be further evaluated at the time of hospitalisation (fasting
blood glucose and HbA
1c
levels) to assess a persistent severity
of metabolic derangements. However, clinicians must also be
mindful of hypoglycaemia and the associated adverse prognosis
with intensive insulin treatment, and frequent blood sugar
testing is required.
14
Conclusion
Metabolic dysregulation is a frequent and actionable event in
ACS. Modulation of hyperglycaemia and increased circulatory
FFA levels call for diverse pharmacological interventions.
Additional studies and further refinement of current guidelines
are needed.
We thank Dr Heinrich Taegtmeyer, McGovern Medical School at UTHealth
Houston, TX for helpful discussions.
References
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4.
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