SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 11 NUMBER 1 • MARCH 2014
11
Treatment
The mainstay of prevention and treatment of impaired hypo-
glycaemia awareness is to prevent hypoglycaemia. In patients
without diabetic neuropathy, avoidance of hypoglycaemia for three
weeks is sufficient for recovery from unawareness, whereas three
to six months is required for recovery in patients with diabetic
neuropathy.
25
Patient education
Patient education has two broad aims. Firstly to assist the patient to
recognise symptoms of low glucose levels and institute preventative
steps to avoid severe hypoglycaemia, and secondly to equip them to
avoid hypoglycaemic episodes by managing and, when necessary,
appropriately adjusting their diet and insulin treatment regimen
(Table 4).
2,12,19,26
Even with intensive insulin treatment, structured patient
educational programmes have proven not only to significantly
improve HbA
1c
levels, reduce the risk and occurrence of
hypoglycaemia and restore hypoglycaemia awareness, but also
to reduce psychological distress and improve perceived well-
being.
27
However, there is also evidence that some patients with
severe hypoglycaemia unawareness remain poorly compliant
with therapeutic decisions despite regular clinical contact and
attendance at diabetes education programmes, and make little
attempt to modify their behaviour in order to avoid hypoglycaemia.
Such patients may benefit from psychological counselling to help
them modify their approach to management of their illness.
10
Frequent blood glucose monitoring
Frequent self-monitoring of blood glucose (SMBG) is necessary
to identify periods of low glucose levels and to prevent them
through adjustments of diet and insulin regimens. This is especially
important as the treatment regimen becomes more complex. Four
to seven measurements a day are typically required in patients with
hypoglycaemia unawareness.
12,19,25,28
Reducing the risk of treatment-related hypoglycaemia
Intensive glucose control improves microvascular outcomes in
diabetes.
29,30
Therefore a long-term treatment strategy should
aim for an optimal balance of glucose-lowering efficacy and
durability, but with a low propensity for hypoglycaemia.
31
Efforts
to prevent hypoglycaemia should begin from the clinical onset of
the disease.
2
In patients receiving oral therapy for type 2 diabetes, hypogly-
caemia is relatively infrequent early in treatment, but it becomes
significantly more limiting to glycaemic control as the disease
progresses and endogenous secretion of insulin diminishes.
Because therapeutic hyperinsulinaemia is a prerequisite for
iatrogenic hypoglycaemia, insulin secretagogues, such as
sulphonylureas or ‘glinides’, are more likely to be associated with
hypoglycaemic events than other oral agents that do not raise
blood insulin levels, or do so only during hyperglycaemia. These
include metformin and dipeptidyl-peptidase 4 (DPP-4) inhibitors
(sitagliptin, vildagliptin, saxagliptin), which are appropriate oral
options either as monotherapy or in combination with each
other to minimise the risk of hypoglycaemia.
28,31
Similarly, when
added to metformin or basal insulin, the subcutaneously injected
glucagon-like peptide 1 (GLP-1) agonists, liraglutide and exenatide,
significantly improve glucose control without increasing the risk of
severe hypoglycaemia.
32-35
Because hypoglycaemia increases in frequency with duration
of diabetes and of insulin therapy, in insulin-dependent type 2
diabetes, combining a GLP-1 agonist with basal insulin may be
beneficial, because it allows intensification of glucose control
while maintaining lower doses of insulin and a reduced risk of
hypoglycaemia.
36,37
In insulin-requiring patients, in comparison with regular insulin,
the long-acting basal insulin analogues (glargine and detemir) exhibit
improved time-action profiles and reduced day-to-day glucose
variability, which are associated with a lower risk of hypoglycaemia.
Similarly, the rapid-acting prandial insulin analogues (lispro, aspart,
glulisine) are associated with a lower incidence of postprandial and
nocturnal hypoglycaemia.
19,28,38,39
Insulin degludec is a new long-acting basal insulin, which
is expected to be available soon in South Africa. It forms long
subcutaneous multihexamers that delay absorption and provide
a flat and stable action profile with of action greater than 42
hours. In clinical trials comparing insulin degludec with insulin
glargine, at similar levels of glycaemic control, insulin degludec was
associated with lower rates of nocturnal hypoglycaemia in patients
with type 1 diabetes and less overall hypoglycaemia and nocturnal
hypoglycaemia in patients with type 2 diabetes.
39,40
In a large observational study of patients with type 2 diabetes
starting insulin therapy, at one year, basal or basal-plus-mealtime
insulin was associated with a lower risk of overall and nocturnal
hypoglycaemia than premix insulin. The risk for nocturnal but not
overall hypoglycaemia was lower with basal plus mealtime insulin
than with basal insulin alone, suggesting that some individuals
use too much basal insulin when short-acting insulin is required,
increasing the risk of hypoglycaemia during the night.
41
Continuous subcutaneous infusion (CSII) pumps make it
possible to match insulin administration with daily fluctuating
requirements and reduce the dosing errors that may occur with
multiple daily insulin injections. In comparison with multiple daily
insulin injections in both patients with type 1 and type 2 diabetes,
the use of CSII is associated with maintenance or improvement of
HbA
1c
levels with significantly fewer (if any) episodes of nocturnal
or severe hypoglycaemia. Furthermore, with long-term use, CSII
restores awareness of hypoglycaemia in patients who are unaware
before transitioning to the pump.
42-44
Adjustment of glycaemic goal
Lower glycaemic goals are associated with a greater risk of
hypoglycaemia. Diabetes treatment guidelines recommend
relaxation of HbA
1c
targets to < 7.5% or even up to 8% in patients
Table 4.
Patient education to avoid hypoglycaemia.
Recognition of hypoglycaemia
Risk factors and the importance of avoiding and timeously correcting
hypoglycaemia (consequences of recurrent hypoglycaemia)
Dietary education (may require discussion about use of fad diets, e.g. for
weight loss or bulking)
Regular snacks at the right times
Self-management and adjustment of flexible insulin dosing depending on
variation in diet and activity levels
How and when to test blood glucose levels
How to manage symptomatic and asymptomatic low blood glucose levels
Awareness of delayed hypoglycaemia, e.g. after heavy alcohol intake or
exercise
