Title: Improving glucose control in patients with diabetes following myocardial infarction: The role of a novel glycaemic monitoring strategy
Funder: Department of Health and Social Care

Abstract: Background Patients with diabetes are at increased risk of myocardial infarction (MI) and their outcome following cardiac ischaemia remains poor with repeated hospital admissions and high mortality, particularly in insulin-treated individuals. A multifactorial approach is key to improving clinical outcomes in diabetes patients following MI. Blood pressure and lipid targets are relatively easy to address, whereas glycaemia continues to be difficult to control for a number of reasons including: i) frequent glucose testing (currently by finger pricking) is required to safely and effectively adjust hypoglycaemic therapy, a source of major inconvenience to patients, ii) daily activities induce large fluctuations in glucose levels, which are not always identified by sporadic capillary glucose testing and iii) difficulties in interpreting results of capillary glucose tests. Hyperglycaemia is associated with adverse clinical outcome and is usually quantified by assessing glycated haemoglobin (HbA1c), a medium term glycaemic marker. Treatment of high glucose levels can result in hypoglycaemia which is associated with increased mortality and morbidity, resulting in higher health care expenditure. Quantification, or even detection, of hypoglycaemia can be difficult with current glycaemic monitoring strategies and therefore this complication of therapy remains under-reported. Research aim Investigate whether an alternative glucose monitoring strategy, that does not require finger prick testing and gives a more comprehensive overview of glucose levels, improves glycaemic control in diabetes following MI. Exploratory analyses will include the role of the new glycaemic monitoring strategy in improving clinical outcomes/quality of life and cost effectiveness. Design This is a phase II, randomised, three centre, two arm study to compare an approved glucose sensor, which is replaced fortnightly and has the ability to provide 96 glucose readings/day, against standard self-monitoring of blood glucose (SMBG). Inclusion criteria are patients with recent MI and known diabetes who are being treated with a sulphonylurea and/or insulin. Exclusion criteria include newly diagnosed diabetes, active malignancy or unable/unwilling to consent. Consenting adults will be randomised 1:1 within 5 days of MI admission to: i) Control group using SMBG to assess glycaemia. This group will also have masked continuous glucose monitoring using Libre Pro device during the first month and between study days 76-90. ii) Intervention group employing Freestyle Libre and ambulatory glucose profile (AGP) readings to assess glycaemia. Freestyle Libre devices will be worn from start of the study to day 90. SMBG and AGP, for control and intervention arm respectively, will be reviewed by the research nurse/investigators at four study visits: day 14&plusmn;2, day 30&plusmn;2, day 76&plusmn;2 and day 90&plusmn;2 after randomisation. Changes in treatment will be allowed between days 30-76 in case patients are concerned about their glucose readings. A structured approach with clear cut-off values will be used to optimise treatment according to 4 glycaemic parameters: HbA1c, fasting glucose, postprandial glucose and hypoglycaemia. The primary end point is the difference in time spent in euglycaemia per day (defined as glucose levels between 3.9-10.0 mmol/l) between two study arms in the two weeks between days 76-90 post randomisation. Secondary and exploratory end points are: Time spent in euglycaemia between days 16-30, Time in hypoglycaemia or hyperglycaemia between days 76-90, HbA1c at day 90, Health-related quality of life, Hospital admissions and one year mortality, Economic impact of the intervention Outcomes This study will assess an alternative and convenient glucose testing method following MI in patients with diabetes. Data generated will have immediate implications for glycaemic monitoring in this population and may transform patient care by optimising glycaemia and improving quality of life. Results will also inform large scale multicentre studies to investigate the effect of this glycaemic monitoring strategy on clinical outcomes including mortality, recurrent MI and hospital readmission.

Lay abstract: Background People with diabetes do less well after a heart attack compared to people without diabetes. One reason may be because they have large swings in blood sugar (glucose) levels, which are not picked up by standard finger prick testing. This research study will test a new way to measure glucose (not requiring repeated finger pricking) which may lead to more stable glucose levels. It may also lead to less complications and better survival rates after a heart attack. Study details The study involving 150 diabetes patients will take place at hospitals in Leeds, Sheffield and Hull. Using a random process, patients who consent to the study will be allocated within 5 days of their hospital admission with a heart attack to one of two groups: i) Glucose testing using standard finger pricks ii) Glucose testing based on a sensor that sits on the arm, avoids finger pricks and provides detailed feedback of sugar levels, giving up to 96 glucose readings/day. Patients will be seen in hospital at 14, 30, 76 and 90 (&plusmn;2) days after starting in the study. Glucose levels, quality of life and patient satisfaction will be measured both at the start and 90 days. Patients will also be contacted one year later by telephone to record admissions to hospital and survival. Research outcomes The study will help us to understand whether monitoring using a glucose sensor increases the time that sugar levels remain in target compared with standard finger prick testing within the first 90 days after a heart attack. We will also find out whether glucose sensors improve quality of life, admissions to hospital and survival. If the glucose sensors turn out to have beneficial effects, we could provide them to people with diabetes after a heart attack, improving their care and quality of life.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: METABOLIC AND ENDOCRINE;CARDIOVASCULAR