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VOLUME 9 NUMBER 2 • JUNE 2012
93
SA JOURNAL OF DIABETES & VASCULAR DISEASE
HANDS ON
Pathophysiology of ‘stress’ hyperglycAemia
2,3
At the 2012 International Symposium on Intensive Care and Emergency
Medicine (ISICEM) meeting in Brussels, Krinsley made some important
observations. Diabetic patients respond differently from non-diabetics.
They will have higher HbA
1c
levels on admission and will tolerate higher
glucose levels in the acute setting without adverse effect. The aim then
is to avoid tight control (< 6.1 mmol/l) in the patient with diabetes in the
in-patient setting.
A better determinant of mortality is the glucose variability or ‘lability’,
i.e. swinging from high to low to high over the in-patient period. This
has been shown to be independently associated with an increased mor-
tality. Hypoglycaemic events are associated with a 2.5-times increased
mortality rate. Hypo- and hyperglycaemic episodes are associated with a
4.8-times increased mortality rate, but with glucose variability, there is a
six-fold increased mortality rate associated with the difference between
the highest and lowest glucose levels.
To avoid this glucose lability, high-concentration glucose infusions
(50%) should be avoided and a more stable caloric intake should be
maintained. Possibly consider using a basal insulin as ‘background’
therapy in a stable patient, with associated lower short-acting insulin
dosage requirements. Increase the frequency of measurements and
rather use smaller dosages of short-acting insulin at one time to avoid
wide fluctuations in glucose levels.
In the presence of a stress response, as most ICU patients will experi-
ence, hyperglycaemia results from gluconeogenesis and glycogenolysis
when stress hormones such as cortisol, adrenaline, glucagon and growth
hormone are released. Hyperglycaemia directly affects the mitochondrial
function of cells in the liver, kidneys and lungs. Compensatory responses
in the cells (autophagy) are impaired and circulatory glucose can cause
direct cellular damage.
Hyperglycaemia is also pro-inflammatory with the release of
NF-k
β
and interleukins. A reduction in endothelial nitric oxide
will affect vasoconstriction and alter organ perfusion. There is an
activation of the coagulation pathway with a risk of thrombosis and
it adversely affects the efficacy of neutrophil activation in the presence
of sepsis.
4
Hyperglycaemia in hospital can occur due to previously diagnosed
diabetes, previously undiagnosed diabetes or iatrogenic hyperglycaemia
(fasting sugar level ≥ 7 mmol/l; random glucose level ≥ 11.1 mmol/l),
which will revert to normoglycaemia post discharge. Stress, decompen-
sation of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus
(T2DM) or other types of diabetes, e.g. gestational diabetes, causes such
as withholding of diabetic medication, such as pre-operatively, or the
administration of drugs such as glucocorticoids or vasopressors, may all
precipitate hyperglycaemia.
Specific in-hospital settings
Diabetic and non-diabetic non-critically ill patients
No evidence exists for specific targets for glucose control in non-critically
ill patients. A safe level would be fasting levels of < 7.8 mmol/l. Post-meal
levels should be maintained below 10 mmol/l. Patient safety is crucial.
Clear guidelines are needed to detect and treat hypoglycaemic events.
If a previously diagnosed diabetic patient is admitted, a baseline
HbA
1c
level will give an indication of the adequacy of his/her control.
(Patients who are going for surgery will be discussed separately.) In
most instances the patient could continue his/her out-patient treat-
ment and supplementary insulin can be given before meals to avoid
excessive glucose excursions.
A simple supplementary scale using subcutaneous short-acting insulin
analogues is effective, safe and easy to administer (Table 1). The short-
acting insulin analogues are preferred as they act quickly, can be admin-
istered immediately pre-meal, which is crucial in the hospital setting, and
do not have a lag response, with less risk of hypoglycaemia.
If no insulin is to be given, monitor for hypoglycaemia if the glucose
levels are below 3.9 mmol/l. There are differing opinions as to what the
safe lower limit of glucose must be. It is prudent to use 3.9 mmol/l in our
setting, as recommended by the ADA.
If the patient is not a known diabetic, glucose levels should be moni-
tored in any setting where hyperglycaemia may occur, which could affect
the outcome of the hospitalisation and illness. Examples include glucocor-
ticoid therapy, enteral or parenteral nutrition and immune suppressives.
Persistent hyperglycaemia must be treated to the same targets as those
with pre-existent diabetes until the precipitating event has resolved.
It is crucial not to miss follow up of patients with persistent, unexplained
hyperglycaemia as out-patients once the acute event has resolved, as
they may be newly diagnosed or previously undiagnosed diabetics. There
must be a planned follow up within six weeks of discharge, when a fast-
ing glucose test and possibly an HbA
1c
assay should be performed. If the
HbA
1c
level is > 6.5%, it may be diagnostic of diabetes mellitus.
Table 1.
Protocol example of supplementary subcutaneous insulin pre-meal
(NovoRapid/Humalog/Apidra).
Glucose level
(mmol/l)
Insulin-resistant
patient e.g.
obese (units)
Normal
(units)
Insulin-sensitive
patient e.g.
elderly (units)
< 3.9
Monitor for
hypoglycaemia,
no insulin
Monitor for
hypoglycaemia,
no insulin
Monitor for
hypoglycaemia,
no insulin
4–5.9
2
0
0
6–7.9
4
2
0
8–9.9
6
4
2
10–11.1
8
6
4
12–13.9
10
8
6
> 14
12
10
8