Hypoglycaemia (Low Blood Sugar) in Adults With Diabetes and Adrenal Failure

Study Overview
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Brief Summary
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The purpose of this study is to measure how often low blood sugars occur in people who live with both adrenal insufficiency (AI) and diabetes and need to take insulin. People who live with AI need to take steroid replacement tablets every day, for life. Two of the most common types of steroid replacement tablets are called prednisolone and hydrocortisone. Low blood sugar (hypoglycemia) is a very common side effect of taking insulin and can often be unpleasant, frightening and dangerous. People who have adrenal failure are also at risk of hypoglycaemia, although this is rare. It is not known whether taking steroids affects how often hypoglycaemia happens. The study has three aims: To measure how often low blood sugars occur at night in people who live with with both adrenal insufficiency (AI) and insulin-treated diabetes To compare how often low blood sugars occur in people taking prednisolone for their AI versus those taking hydrocortisone. To compare the patterns throughout the day for low blood sugars in those taking prednisolone versus those taking hydrocortisone. The study will compare this information with results in people who have AI without diabetes. Participants will be given continuous glucose monitoring systems (Dexcom G6 devices) which are small wearable devices that measure glucose levels throughout the day and night. They will be asked to wear a device for 30 days. Participants will not be asked to make any changes to their usual medications or their diet.

Detailed Description
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PURPOSE OF THE STUDY The purpose of this study is to measure how often hypoglycaemia occurs in people who take steroid tablets for adrenal insufficiency and insulin for diabetes compared to individuals with adrenal insufficiency on steroid tablets without diabetes. To do this, participants will be given a continuous glucose monitoring (CGM) system, which is an effective and accurate way of measuring blood sugars throughout the day and night. This study will assess how often hypoglycaemia occurs, especially at night, and whether the type of steroid tablet people take affects how often hypoglycaemia happens. STUDY AIMS To measure how often low blood sugars occur at night in people with both AI and insulin-treated diabetes using CGM, and in people without diabetes who are matched in age, sex and steroid replacement (hydrocortisone or prednisolone). To compare the frequency of low blood sugars in people taking prednisolone for their AI versus those taking hydrocortisone. To compare the patterns throughout the day for low blood sugars in those taking prednisolone versus those taking hydrocortisone. STUDY DESIGN This study will observe 16 adults with both insulin-treated diabetes and adrenal insufficiency and 16 adults without diabetes who are matched for age, sex and steroid replacement. The investigators will aim to recruit 32 participants in total. Participants will spend 30 days in the study. RECRUITMENT Recruitment will be undertaken in endocrinology and diabetes clinics at Imperial College Healthcare NHS Trust. Participant information sheets will be given to potential participants and following any questions, informed consent will be taken. Participants will be given as much time as they require (at least 24 hours) to decide whether or not to take part - this can vary on a per participant basis.

Official Title
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Frequency of Nocturnal Hypoglycaemia in Adults With Insulin-treated Diabetes and Adrenal Failure Using Prednisolone or Hydrocortisone: a Pilot Study

Conditions
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Diabetes Mellitus, Type 1, Adrenal Insufficiency, Diabetes Mellitus Type 2 - Insulin-Treated

Intervention / Treatment
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* Device: Continuous Glucose Monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: for test group: Confirmed diagnoses of adrenal insufficiency and insulin-treated diabetes for more than one year. Adults aged above 18 years for matched control group: Diabetes mellitus excluded on baseline blood review Adults aged above 18 years Exclusion Criteria: Measured eGFR ≤ 30 Acute illness Abnormal thyroid function Admission to hospital Pregnant or planning pregnancy Breastfeeding Enrolled in other clinical trials, except at the discretion of the chief investigator Have active malignancy or under investigation for malignancy Severe visual impairment Reduced manual dexterity Unable to participate due to other factors, as assessed by the Chief Investigators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Participants who live with insulin- treated diabetes and adrenal insufficiency. | Device: Continuous Glucose Monitoring<br>* Continuous Glucose Monitoring using a Dexcom G6 Continuous Glucose Monitoring Device<br>|
| Control group<br>Participants who live with adrenal insufficiency and NOT with insulin-treated diabetes. | Device: Continuous Glucose Monitoring<br>* Continuous Glucose Monitoring using a Dexcom G6 Continuous Glucose Monitoring Device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent in hypoglycaemia | Percentage time spent in hypoglycaemia (glucose levels < 3.0mmol/L, 55mg/dL). Glucose levels will be measured by a continuous glucose monitoring device (CGM). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent in hypoglycaemia (glucose levels < 3.9mmol/L, 70mg/dL) | Percentage time spent in hypoglycaemia (glucose levels < 3.9mmol/L, 70mg/dL) | 30 days | 
| Time spent in target glucose levels | Percentage time spent in target (glucose levels 3.9-10mmol/L, 70-180mg/dL) | 30 days | 
| Time spent in hyperglycaemia | Percentage time spent in hyperglycaemia (glucose levels >10mmol/L, 180mg/dL) | 30 days | 
| Hypoglycaemic excursions | Number of hyperglycaemic excursions. This will comprise the number of times glucose sugar levels are recorded as below 3.9mmol/L, 70mg/dL | 30 days | 
| Gold questionnaire score | The Gold questionnaire asks individuals to report their experience in detecting hypoglycemic events with scores ranging from minimum score of 1 (always aware) to a maximum score of 7 (never aware). The minimum score refers to the individual never being aware of hypoglycaemia, and an increasing score refers to greater awareness of hypoglycaemia. | Baseline | 
| Hypoglycaemia Fear Survey-II (HFS-II) score | This 33-item questionnaire assesses fear of hypoglycaemia. The minimum score is 0 and the maximum score is 132. A higher score indicated greater fear of hypoglycaemia. | Baseline | 
| Hospital Anxiety and Depression (HADS) Score | A questionnaire assessing levels of anxiety and depression. The questionnaire consists of 14 questions: 7 questions assess for anxiety and 7 questions assess for depression. Each question can score between 0 and 3. Two scores are calculated separately for anxiety and depression. The minimum score is 0 and maximum score is 21 for both anxiety and depression. A greater score denotes greater severity of anxiety or depression. | Baseline |