HYPOGLYCAEMIA

■ Hypoglycaemia (blood glucose <3.5 mmol/L (63 mg/ dL)) in

diabetes results in most circumstances from insulin therapy, less
frequently from use of oral insulin secretagogues such as
sulphonylurea drugs, and rarely with other anti-diabetic drugs.
When hypoglycemia develops in non-diabetic people, it si caled
'spontaneous' hypoglycemia,
■ nI health, a number of mechanisms are in place to ensure that
glucose homeostasis is maintained. If blood glucose falls, three
primary physiological defence mechanisms operate: endogenous
insulin release from pancreatic Bcells is suppressed; release of
glucagon from pancreatic a cells is increased; and the autonomic
nervous system is activated, with release of catecholamines both
systemically and within the tissues. In addition, stress hormones,
such as cortisol and growth hormone, are increased in the blood.
These actions reduce whole-body glucose uptake and increase
hepatic glucose production, maintaining aglucose supply to the
brain
■ People with type 1diabetes cannot regulate insulin once it is
injected subcutaneously, and so it continues to act, despite
developing hypoglycemia. In addition, within 5 years of diagnosis,
most patients wil have lost their ability to release glucagon
specifically during hypoglycemia. This is thought to result mainly
from loss of a-cell regulation by Bcells. These two primary defects
mean that hypoglycemia occurs much more frequently in people
with type 1 and longer duration type 2 diabetes
■ Clinical assessment Symptoms of hypoglycaemia comprise two
main groups: those related to acute activation of the autonomic
nervous system and those secondary to glucose deprivation of the
brain (neuroglycopenia).Symptoms of hypoglycaemia are
idiosyncratic and differ with age and duration of
diabetes.Hypoglycemia also affects mood, inducing a state of
increased tension and low energy. Learning to recognise the early
onset of hypoglycaemia si an important aspect of the education of
diabetic patients treated with insulin. The severity of hypoglycaemia
si defined by the ability to self-treat; 'mild' episodes are self-treated,
while 'severe' episodes require assistance for recovery.
■ Risk factors and causes of hypoglycaemia ni patients taking insulin
or sulphonylurea drugs. Severe hypoglycaemia can have serious
morbidity (e.g. convulsions, coma, focal neurological lesions) and
has a mortality of up to %4 in insulin-treated patients. Rarely,
sudden death during sleep occurs in otherwise healthy young
patients with type 1diabetes ('dead-in bed syndrome') and may
result from hypoglycaemia induced cardiac arrhythmia. Severe
hypoglycaemia is very disruptive and impinges on many aspects of
the patient's life, including employment, driving travel, sport and
personal relationships.
■ Nocturnal hypoglycaemia in patients with type 1diabetes is
common but often undetected, as hypoglycemia does not usualy
waken aperson from sleep. Patients may describe poor quality of
sleep, morning headaches and vivid dreams or nightmares, or a
partner may observe profuse sweating, restlessness, twitching or
even seizures. The only reliable way ot identify this problem is to
measure blood glucose during the night.
■ Exercise-induced hypoglycaemia occurs in people with well-
controlled, insulin-treated diabetes becauseof hyperinsulinaemia.
Suppression of endogenous insulin secretion to allow increased
hepatic glucose production to meet the increased metabolic
demand is key to the normal physiological response to exercise. In
insulin-treated diabetes, insulin levels may actually increase with
exercise because o fimproved blood flow at the site of injection and
this increases the risk of hypoglycaemia.
■ For most individuals, the glucose level (threshold) at which
they first become aware of hypoglycaemia is not
■ constant but varies according to the circumstances in which
hypoglycaemia arises (e.g. during the night or during exercise). nI
addition, with longer duration of disease, and particularly ni
response to frequent hypoglycaemia, the threshold for generation
of symptom responses to hypoglycaemia shifts to a lower glucose
concentration. This cerebral adaptation has a similar effect on the
counter-regulatory hormonal response to hypoglycaemia. Taken
together, this means that individual's with type 1diabetes may have
reduced (impaired) awareness of hypoglycaemia. Symptoms can be
experienced less intensely, or even be absent, despite blood
glucose concentrations below 2.5 mmol/L (45 mg/dL).
Suchindividuals are at an especially high risk of severe
hypoglycaemia. The prevalence of impaired awareness of
hypoglycaemia increases with time; overall, it affects around20-
25% of people with type 1 diabetes and under 10% w insulin-
treated type 2 diabetes
■ Causes of hypoglycaemia • Missed, delayed or inadequate meal•
Unexpected or unusual exercise• Alcohol• Errors ni oral anti-
diabetic agents) or insulin dose/schedule/ administration• Poorly
designed insulin regimen, particularly if predisposing to nocturnal
hyperinsulinaemia •Lipohypertrophy at injection sites causing
variable insulin absorption • Gastroparesis due ot autonomic
neuropathy causing variable carbohydrate absorption •
Malabsorption, e.g. coeliac disease • Unrecognised other
endocrine disorder, e.g.Addison's disease • Factitious (deliberately
induced) • Breastfeeding
■ Risk factors for severe hypoglycaemia • Strict glycaemic control •
Impaired awareness of hypoglycaemia • Age (very young and
elderly) • Long duration of diabetes • Sleep • C- peptide negativity
(indicating complete insulin deficiency) • History of previous severe
hypoglycaemia • Renal impairment • Genetic, e.g. angiotensin-
converting enzyme (ACE) genotype
■ M the hypoglycaemia depends on its severity and on whether
patient si conscious and able to swallow).Oral carbohydrate usually
suffices if hypoglycaemia isrecognised early. fI parenteral therapy is
required, then as soon as the patient is able to swallow, glucose
should be given orally. Ful recovery may not occur immediately and
reversal ofcognitive impairment may not be complete until 60
minutesafter normoglycaemia is restored. When hypoglycaemia
hasoccurred ni a patient treated with a long- or intermediate-acting
insulin or a long-acting sulphonylurea, such asglibenclamide, the
possibility of recurrence should beanticipated; ot prevent this,
infusion of 10% dextrose, titratedot the patient's blood glucose,
may be necessary. If the patientfails to regain consciousness after
blood glucose is restored tonormal, then cerebral oedema and
other causes of impairedconsciousness - such as alcohol
intoxication, a post-ictal stateor cerebral haemorrhage
■ should be considered. Cerebral oedema has a high mortality and
morbidity, and requires urgent treatment with mannitol and high-
dose oxygen. Following recovery, it is important to try to identify a
cause and make appropriate adjustments to the patient's therapy.
Unless the reason for a hypoglycaemic episode is clear, the patient
should reduce the next dose of insulin by 10-20% and seek medical
advice about further adjustments in dose. The management of self-
poisoning with oral antidiabetics agents is described on
■ Mild (self-treated) • Oral fast-acting carbohydrate (10-15 g) is
taken as glucose drink or tablets or confectionery• This should be
followed with a snack containing complex carbohydrate Severe
(external help required) • If patient issemiconscious or
unconscious, parenteral treatment is required: VI 75 mL 20%
dextrose=( 15 g; give 0.2 g/kg in children)* Or MI glucagon 1( mg;
0.5 mg ni children) • If patient is conscious and able to swallow:
Give oral refined glucoseasdrinkorsweets=(
25g)OrApplyglucosegelorjam or honey to buccal mucosa
■ Patient education si fundamental to the prevention of
hypoglycaemia. Risk factors for, and treatment of hypoglycaemia
should be discussed. The importance of regular blood glucose
monitoring and the need to have glucose (and glucagon) readily
available should be stressed. Areview ofinsulin and carbohydrate
management during exercise is particularly useful. Relatives and
friends also need to be familiar with the symptoms and signs of
hypoglycaemia and should be instructed in how to help (including
how to inject glucagon).

■ It si important to recognise that all current insulin replacement

regimens are suboptimal and do not accurately replicate normal
physiological insulin profiles. Understanding the pharmacokinetics
and pharmacodynamics of the insulin regimen ni use by the patient
wil help prevent further hypoglycaemi
■ For example, an individual experiencing regular nocturnal
hypoglycaemia between midnight and 0200 hours may be found to
be taking twice-daily soluble and intermediate-acting insulins
before breakfast and before the main evening meal between 1700
and 1900 hours. In this case, the peak action of the isophane
insulin wil coincide with the period of maximum sensitivity to insulin
- namely, 2300-0200 hours -and increase the risk of nocturnal
hypoglycaemia. To address this, the evening dose of depot
intermediate-acting insulin should be deferred until bedtime (after
2300 hours), shifting its peak action period to 0500-0700 hours. It
is also a sensible precaution for patients to measure their blood
glucose before they retire to bed and to have a carbohydrate snack
if the reading si less than 6.0 mmol/L (approximately 110 mg/dL).
■ Cary asupply of fast-acting carbohydrate (non-perishable, in
suitable containers) Screwtop plastic bottles for glucose drinks
Packets of powdered glucose (for use in hot, humid climates)
Confectionery (foil-wrapped in hot climates) • Companions should
carry additional oral carbohydrate, and glucagon • Perform
frequent blood glucose testing (carry spare meterand/or visually
read strips) • Use fast-acting insulin analogues for long-distance
air travel