Hypoglycaemia is the commonest side-effect of insulin treatment for diabetes mellitus.
Appreciation of the risk factors for hypoglycaemia and early recognition of its symptoms can
help the affected individual with prompt self-treatment of hypoglycaemia, preventing
progression to severe hypoglycaemia. The proposed MD project will consist of three major
studies to investigate the risks for, symptoms of, and rate of recovery from, hypoglycaemia.
STUDY ONE:
This study will examine the alleged association between severe hypoglycaemia and serum
angiotensin converting enzyme (ACE) levels. While many patients rarely experience severe
hypoglycaemia, a small subgroup experiences recurrent episodes. These are very disruptive
to daily life and may be dangerous, for example if they occur when the individual is driving.
It is therefore of clinical importance to identify risk factors for severe hypoglycaemia.
Scandinavian studies have reported an association between elevated serum ACE activity and
an increased risk of severe hypoglycaemia in type 1 diabetes. A hypothetical explanation for
these findings is that lower ACE activity confers increased ability for cerebral function to be
maintained despite metabolic substrate deprivation. It is possible that in diabetes, this could
manifest as greater impairment of mental ability during hypoglycaemia in people with high
ACE activity. This would explain their increased risk of severe hypoglycaemia for a given
level of blood glucose as they would be more incapacitated, and therefore less able to self-treat.
However these studies have methodological limitations and these findings have not yet
been reproduced outside Scandinavia.
In this study, it is proposed to examine the relationship between serum ACE levels and the
incidence of severe hypoglycaemia. Blood will be sampled for serum ACE activity and the
self-estimated frequency of severe hypoglycaemia will be recorded in 300 people with type 1
diabetes attending diabetes clinics at the Royal Infirmary of Edinburgh.
STUDY TWO:
This study will examine the variability of hypoglycaemia symptom reporting. It is known
that the symptoms of hypoglycaemia are idiosyncratic and age-specific. However, no studies
have assessed the extent of any intra-individual variability in symptom reporting.
A cohort of 350 people with type 1 and type 2 diabetes, with different disease durations and
varying treatment modalities, will be recruited and the symptoms associated with each
hypoglycaemic episode will be recorded prospectively over a 12 month period. The reported
symptom clusters will be analysed to assess the consistency of symptom reporting for each
individual. Regression analysis will be used to assess whether an individual's consistency
coefficient is related to any other factors such as disease duration or treatment modality. The
ability to predict which individuals will report a consistent group of symptoms and which
individuals will experience an erratic pattern of symptoms would assist patient education and
allow clinicians to inform patients about how to anticipate and recognise hypoglycaemia.
STUDY THREE:
This study will examine the time taken for full cognitive recovery from hypoglycaemia and
the possible effect of the clinical syndrome of impaired awareness of hypoglycaemia on this
process. The effects of acute insulin-induced hypoglycaemia on cognitive function have been
investigated extensively but the recovery period after hypoglycaemia has not been rigorously
assessed. Previous studies examining recovery have had multiple limitations.
The objective of this third study is to measure the recovery time for various domains of
cognitive function in a large group of patients with type 1 diabetes who have either normal
(n=20) or impaired (n=l 6) awareness of hypoglycaemia. A hyperinsulinaemic glucose clamp
technique will be used to induce controlled hypoglycaemia and a battery of cognitive tests
will be applied at baseline, at the beginning and end of a one hour period of hypoglycaemia,
then at ten minute intervals during a 90 minute recovery period. Each subject will act as their
own control by undergoing a euglycaemic clamp on a separate occasion. Test scores will be
compared using general linear modelling with awareness of hypoglycaemia as a betweensubjects
factor. The findings of this study will have important clinical implications and help
to advise patients how long to wait after restoration of euglycaemia before resuming activities
such as driving.
