METHODS
All patients with T1D who were seen at the Diabetes Centre of a regional
hospital were invited to participate in this study. Exclusion criteria
included patients who were pregnant, English illiterate or had
significant cognitive impairment that negated taking an informed
consent. Informed consent was obtained from subjects who agreed to
participate in the study, with ethics approval obtained from the
National Healthcare Group Domain Specific Review Board. This study
consisted of 3 components: review of medical records, a detailed
self-administered questionnaire (in English) and review of the blood
glucose profile based on prospectively performed self-monitoring of
blood glucose (SMBG) for 4 weeks.
Review of medical records included demographic data such as the
patient’s age, gender and ethnicity, body mass index (BMI), age of
diabetes diagnosis and the duration of diabetes, HbA1c values, results
of insulin autoantibodies, as well as the insulin type and doses. The
presence of diabetes-related complications – both microvascular
complications such as retinopathy, nephropathy, neuropathy and
macrovascular complications such as ischemic heart disease, stroke and
peripheral vascular disease; were included. All prior hospitalizations
or emergency department attendances for hypoglycaemia were also
reviewed.
The questionnaire included several categories of important information.
Firstly, diabetes self-management practices were assessed, which
included frequency of SMBG (at least 3 times/day), methods for dosing of
insulin (fixed or flexible insulin dosing), methods used to adjust
insulin doses (based on carbohydrate intake and/or blood glucose),
familiarity with carbohydrate counting and correction for
hyperglycaemia. Secondly, prior diabetes education was assessed
including the format, delivery and content covered. Thirdly, the Gold
score and Clarke score, which are screening tools for
IAH6,8,10, were assessed. The Gold score was obtained
using a single question “do you know when your hypoglycaemic episodes
are commencing?”, with the response graded on a 7-point Likert scale: 1
representing “always aware” and 7 representing “never
aware”6. A Gold score of >= 4 indicates
IAH6. The Clarke score comprises eight questions
assessing the exposure to hypoglycaemia, symptomatic responses to
hypoglycaemia and the glycaemic threshold8. A Clarke
score of >= 4 indicates IAH8. Last but
not least, the Problem Areas in Diabetes (PAID) questionnaire, a 20-item
scale consisting of emotional problems commonly seen in people with
diabetes mellitus, was administered.
The HYPO score, a useful indicator of the severity of problems with
hypoglycaemia, was computed11. This score comprised of
two components – the first component was based on historical recall of
hypoglycaemic events requiring assistance during the preceding one year
– assistance required to recognize hypoglycaemia, assistance required
to treat hypoglycaemia, glucagon administration required for
hypoglycaemia, and emergency medical services required for
hypoglycaemia, in the last one year11. Severe
hypoglycaemia was defined in our study as the occurrence of at least one
of the above four events in the preceding one year. This is consistent
with the American Diabetes Association definition of severe
hypoglycaemia as severe cognitive impairment requiring external
assistance for recovery2. The accuracy of self-recall
of severe hypoglycaemia was confirmed by Pedersen et al, who
demonstrated that 90% of subjects with confirmed episodes of severe
hypoglycaemia during a prospective one year period of monitoring were
able to successfully recall these episodes12. The
second component of the HYPO score was calculated based on the
prospective period of SMBG, as discussed in the next section.
Following administration of the questionnaire, subjects who consented
were provided with a standardized glucometer and 150 test strips and
instructed to perform SMBG before every meal and at bedtime, daily for 4
weeks. Clinically significant
hypoglycaemia was defined as an episode in which capillary blood glucose
was < 3 mmol/L during this prospective 4-week period of SMBG.
A glucose level of < 3 mmol/L was chosen as it is sufficiently
low to indicate serious, clinically important
hypoglycaemia13. During all episodes in which blood
glucose was < 3 mmol/L, subjects were asked to record the
absence or presence of symptoms and whether these were autonomic or
neuroglycopenic symptoms – this was the second component required for
calculation of the HYPO score.
Statistical analysis was performed using the Statistical Package for the
Social Sciences (SPSS) software. Descriptive statistics were presented
as median with interquartile range for quantitative variables and number
(percentages) for qualitative variables. Univariate analysis was
performed by using independent sample t-test, Pearson’s chi-square test,
Mann-Whitney-U test and Fisher exact test whenever appropriate to
compare demographic and clinical factors between subjects with impaired
and intact awareness of hypoglycaemia. A p-value of < 0.05 was
considered statistically significant and all p-values reported were
two-sided.