VOLUME 11 NUMBER 1 • MARCH 2014
9
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Hypoglycaemia unawareness: practical avoidance and
management
DAVID WEBB, ALKESH MAGAN
Introduction
In diabetic patients requiring insulin, hypoglycaemic events are
inevitable and severe hypoglycaemia is one of the most feared
complications of the disease. It is associated with not only physical
discomfort, cognitive dysfunction and loss of personal control,
but sometimes more severe consequences, including coma and
death.
In comparison with conventional glucose targets, iatrogenic
hypoglycaemia is up to six times more common with intensive
therapy and remains the most important barrier to sustained good
glucose control.
1-4
Neural tissue is dependent on a continuous supply of glucose
for maintenance of function. Consequently, the development
of symptoms in response to low glucose levels is essential for
recognising impending neuroglycopenia and to provoke timeous
corrective measures to restore glucose balance. Unawareness of
hypoglycaemia and failure to develop warning symptoms therefore
increases the risk of severe hypoglycaemia and its associated
morbidity.
Causes of hypoglycaemia
Conventional risk factors for acute hypoglycaemia include missed
meals, excess insulin administration, alcohol consumption and
increased physical activity without adjustment of carbohydrate
intake. However, perhaps most importantly, the unphysiological
nature of insulin therapy itself predisposes to defective glucose
regulation.
In non-diabetic individuals, insulin secretion is stimulated as
needed in response to ingestion of carbohydrate or other causes
of increased blood glucose levels. Before reaching the periphery,
insulin passes through the liver where it stimulates the synthesis of
glycogen and inhibits gluconeogenesis. Due to hepatic metabolism,
only approximately half of its initial concentration reaches the
systemic circulation, from where it stimulates peripheral glucose
uptake into the tissues and inhibits lipolysis.
By contrast, therapeutic insulin is injected into subcutaneous
tissue, from where it is slowly released directly into the systemic
circulation, regardless of plasma glucose level, until the depot is
depleted. Furthermore, absorption is variable, such that the same
doses may be too little or too much to maintain normoglycaemia
at different times.
1
Correspondence to: Dr David Webb
Pattacus Medical Consulting, Johannesburg
e-mail:
Dr Alkesh Magan
Specialist physician/endocrinologist, Centre for Integrative Health,
Sandton Medi-Clinic, Johannesburg
S Afr J Diabetes Vasc Dis
2014;
11
: 9–13
Consequences of hypoglycaemia
Hypoglycaemia has profound consequences on the health and
well-being of patients with diabetes. Some of these are listed in
Table 1.
Hypoglycaemia unawareness
Hypoglycaemia unawareness (HA) is defined as the onset of
neuroglycopenia before the appearance of autonomic warning
symptoms.
1
Clinically, it presents with an inability to perceive
the symptoms associated with falling glucose levels, resulting in
uncorrected and severe symptomatic hypoglycaemia that requires
external assistance.
Normal and defective responses to hypoglycaemia
Under normal circumstances, a reduction in plasma glucose level
will set in motion a series of predictable physiological responses
to maintain normal glucose levels and glucose supply to the brain.
When glucose falls to approximately 4.5 mmol/l, insulin secretion
from pancreatic beta-cells is inhibited. Lower-than-normal levels
(approximately 3.6–3.9 mmol/l) are initially associated with secretion
of glucagon frompancreatic alpha-cells, and later increased secretion
of adrenalin. These responses promote hepatic glucose production
through glycogenolysis and gluconeogenesis and inhibit peripheral
glucose uptake. Recovery from acute hypoglycaemia relies mainly
on these three sequential protective processes.
Further prolonged hypoglycaemia is associated with the secretion
of various other neurotransmitters and hormones, including cortisol
and growth hormone, although these are not protective during
acute insulin-induced hypoglycaemia. Neurological symptoms and
disorders of mental function start to appear when glucose levels
fall below 3.0 mmol/l (Table 2). Symptoms resolve after the glucose
concentration is restored to normal.
Table 1.
Possible consequences of hypoglycaemia.
4-10
Medical
Social
Psychological
Treatment-
related
Cardiovascular
complications
Loss of
consciousness
Increased risk
of dementia
Increased risk
of seizures
Defensive eating
leading to
weight gain
Trauma from falls
Coma and death
Interferes with
social life
Interferes with
relationships
Interferes
with work
Increased risk of
accidents, e.g.
in traffic
Fear
Guilt
Anxiety
Low levels of
overall
happiness
Reduced
compliance
with
treatment
