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Title: Hypoglycaemia in type 1 diabetes : risk factors, symptoms and recovery
Author: Zammitt, Nicola Naomi
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2012
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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 selftreat. 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available