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| Name | Class |
|---|---|
| NHS Lothian | OTHER_GOV |
| The Leona M. and Harry B. Helmsley Charitable Trust | OTHER |
| Tandem Diabetes Care, Inc. | INDUSTRY |
| DexCom, Inc. |
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Almost all people who have had type 1 diabetes for 5 years have a defect in secretion of the hormone Glucagon. This hormone is involved in the body's response to low blood glucose (hypoglycaemia). It works by releasing glucose stores from the liver to bring the blood glucose back to normal. This defect therefore increases the risk of severe hypoglycaemia. The reason for this Glucagon defect in people with Type 1 diabetes is currently unknown.
This study aims to look at the Glucagon response to hypoglycaemia in 24 people with type 1 diabetes to ascertain whether tight blood glucose control over a period of time improves this response. The investigators aim to achieve good blood glucose control using new generation Automated Insulin Delivery systems (AIDs). This system is made of: an insulin pump, a continuous glucose monitor (CGM) and an algorithm that allows adjustment of insulin delivery based on the blood glucose readings from the CGM. This is the most up to date technology that there is in the management of type 1 diabetes. However, people using this technology often still have problems with high blood glucose after eating. To ensure a very good blood glucose control participants will also follow a low carbohydrate diet to prevent this blood glucose rise after meals.
The Glucagon response to low blood glucose will be measured at zero and eight months using the hyperinsulinaemic hypoglycaemic clamp technique.
This is a feasibility pilot study involving 24 participants with type 1 diabetes. Participants will be recruited from the local type 1 diabetes clinic and insulin pump waiting list. Each participant will enter the trial for a period of 8 months. The investigators aim to test if maximising time in glycaemic range (blood glucose 3.9-10 mmol/L) will restore the glucagon response to insulin-induced hypoglycaemia.
After signing informed consent participants will be screened for eligibility against the inclusion and exclusion criteria.
Those who are eligible will have an initial 20-day period of baseline blood glucose data collection. This will be achieved using a blinded continuous glucose monitoring (CGM) device. Participants will continue on their pre-trial diabetes care during this period and will be required to monitor their own blood glucose as normal.
The participants will be split into two groups using stratified sampling to match for: age, gender and BMI.
Group 1 will be the control group. Participants in this group will continue on standard diabetes care for the duration of the trial. Participants will be required to undertake two further periods of blinded CGM monitoring at 4 and 8 months.
Group 2 will be the intervention group. Participants in this group will be placed on the automated insulin delivery (AID) system and asked to follow a low carbohydrate diet of 30-40g of carbohydrate per main meal portion. The AID system will consist of: a Tandem t:slim X2 insulin pump with control IQ technology and a Dexcom G6 continuous glucose monitor. After receiving training on the use of the devices these participants will enter a 2 week study run-in period to become accustomed to the devices and so that device settings can be optimised. As a safety measure these participants will be asked to measure blood ketones at least once daily throughout the trial. Study staff will monitor the data from the participants study devices throughout the trial and adjust settings as required to maximise time in glycaemic range.
At the beginning and end of the trial all participants will undergo a hyperinsulinaemic hypoglycaemic clamp study to measure their counterregulatory hormone response to hypoglycaemic. Participants will also undergo cognitive tests and assessment of hypoglycaemic awareness during each clamp study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 - Standard Care | Active Comparator | This group will continue on their standard diabetes care. They will be required to undergo three periods of blinded continuous glucose monitoring each lasting 20-days at: baseline, 4 months and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months. They will also complete quality of life and diabetes treatment questionnaires at baseline and 8 months. |
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| Group 2- Automated insulin delivery and low carbohydrate diet | Experimental | This group will be placed on an automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ technology and Dexcom G6 continuous glucose monitor. They will also be asked to follow a low-carbohydrate diet of 30-40g of carbohydrate per main meal. At baseline they will have a 20-day period of blinded continuous glucose monitoring. Participants in this group will undergo a stepped hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months. They will also complete quality of life and diabetes treatment questionnaires at baseline and 8 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stepped hyperinsulinaemic-hypoglycaemic clamp study | Procedure | Participants will commence on a primed insulin infusion at a constant rate of 60mU/m2/min along with a variable rate 20% glucose infusion. Participants will have their blood glucose monitored every 5 minutes. The glucose infusion will be altered to achieve the desired blood glucose plateaus of: 5mmol/l, 3mmol/l and 2.5mmol/l. Each plateau will be held for 40 minutes. During each plateau blood samples will be taken on three occasions for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On two occasions during each plateau participants will complete the Edinburgh hypoglycaemia scale and the following cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be discontinued and the blood glucose will be allowed to rise to the normal range. Participants will consume lunch before leaving the clinical research facility. |
| Measure | Description | Time Frame |
|---|---|---|
| The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia | The delta glucagon concentration (pmol/L) from plateau 1 (normoglycaemia- 5.0 mmol/L) to plateau 3 (hypoglycaemia- 2.5 mmol/L). The physiological response in health would be for an increase in glucagon secretion from normo- to hypoglycaemia. | Clamp 1 at baseline and clamp 2 at 8 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time in Glycaemic Range (3.9-10mmol/L) | Percentage time spent in target glycaemic range. | Baseline (study entry), midpoint at 4 months and endpoint at 8 months |
| Time Spent Below the Target Glycaemic Range (<3.9mmol/L) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shareen Forbes, MBChB, PhD | University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Edinburgh Royal Infirmary/University of Edinburgh | Edinburgh | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36600427 | Derived | Baxter F, Baillie N, Forbes S. Study protocol: a randomised controlled proof-of-concept real-world study - does maximising time in range using hybrid closed loop insulin delivery and a low carbohydrate diet restore the glucagon response to hypoglycaemia in adults with type 1 diabetes? BMJ Open. 2022 Dec 20;12(12):e054958. doi: 10.1136/bmjopen-2021-054958. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 - Standard Care | Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped. Blinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode. Stable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 28, 2022 |
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| INDUSTRY |
Participants will be divided into two groups using stratified sampling to match for age, sex and BMI.
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| Insulin pump | Device | Insulin pump with a built-in algorithm that allows it to work with a CGM device to adjust insulin delivery based on CGM readings. |
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| Continuous glucose monitor | Device | Continuous glucose monitoring device that sends data to the insulin pump to allow the algorithm to adjust insulin delivery. Participants are able to see the glucose data from the device when it is used in open mode. |
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| Low carbohydrate diet | Other | 30-40g of carbohydrate per main meal portion. |
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| Blinded continuous glucose monitor | Device | Allows data on blood glucose to be collected without values altering the behaviour of the participant. Participants have to continue to monitor their own blood glucose while wearing the device in the blinded mode. |
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| Stable isotope studies- D2 Glucose and D5 Glycerol | Procedure | These studies will take place at the same time as the hyperinsulinaemic hypoglycaemic clamp studies. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study. |
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Percentage of time spent below the target glycaemic range
| Baseline (study entry), midpoint at 4 months and endpoint at 8 months |
| Time Spent Above the Target Glycaemic Range (>10mmol/L) | Percentage of time spent above the target glycaemic range | Baseline (study entry), midpoint at 4 months and endpoint at 8 months |
| The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia | Delta cortisol from P1 (5.0 mmol/L) to P3 (2.5 mmol/L) | Clamp 1 at baseline and clamp 2 at 8 months |
| The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia | Delta adrenaline from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) | Clamp 1 at baseline and clamp 2 at 8 months |
| The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia | The change in noradrenaline concentration from plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L). | Clamp 1 at baseline and clamp 2 at 8 months |
| Endogenous Glucose Production | The change in the glucose rate of appearance from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) | Clamp 1 at baseline and clamp 2 at 8 months |
| HbA1c | Delta HbA1c from baseline to study endpoint. | Baseline (study entry) endpoint (8 months) |
| Change in Quality of Life at Trial Entry and End. | Measured using the EQ5D-5L- -VAS. Number on scale of 0-100 to assess wellbeing on that day. 100 being the most well. | Baseline (study entry) endpoint (8 months) |
| Change in Emotional Distress Related to Diabetes at Trial Entry and End. | Diabetes Distress Scale (DDS-1)- a 28-item self-reporting scale. Each item can be scored from 1 (not a problem) to 6 (a very serious problem). This questionnaire will be completed at study entry and study end. Data presented is the DDS total score. | Baseline (study entry) endpoint (8 months) |
| Change in Fear of Hypoglycaemic | Measured using the Hypoglycaemia Fear Survey (HFS)- this survey consists of two subscales- Baseline (study entry) endpoint (8 months) Behaviour and Worry. There are 28 items in the survey that the participant ranks from Never (0) to Almost Always (4). Higher scores indicate fear of hypoglycaemia. In the Behaviour subscale the lowest possible score in 0 and the highest possible score is 60. In the Worry subscale the lowest possible score is 0 and the highest is 72. Participants will complete this questionnaire at study entry and study end. | Baseline (study entry) endpoint (8 months) |
| Change in Confidence of Managing Hypoglycaemia | Measured using the Hypoglycaemic Confidence Scale- this is a 9 item scale. The participant rates each item from Not Confident at All to Very Confident. Participants will complete this questionnaire at study entry and study end. Higher scores mean more confidence. 'Not confident' at lower end of scale scored as 1 and 'very confident' at top of the scale scored as 4. Min score is 9 and max score is 36. | Baseline (study entry) endpoint (8 months) |
| Hypoglycaemia Awareness | Measured during each clamp study using the Edinburgh Hypoglycaemic Scale- this is a 17 item scale of symptoms of hypoglycaemia. The participant ranks on a scale from Not at all (1) to A Great Deal (7) whether they are experiencing each symptom at the time of the questionnaire being completed. Higher scores mean more hypoglycaemia symptoms. The lowest possible score is 0 and the highest possible score is 119. | Clamp 1 - study entry, clamp 2 - 8 months |
| Trial Making Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Delta score plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Participants are timed completing the test. Higher scores indicate a longer time to complete the test. | Clamp 1- study entry, clamp 2 - 8 months |
| Digit Span Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in change in score from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Lower scores mean more errors. Forwards- participant repeats the numbers as read. Backwards- the participant repeats the numbers backwards. | Clamp 1- study entry, clamp 2 - 8 months |
| Digit Symbol Substitution Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0 mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Given 90 seconds to complete as many items as possible. Higher scores mean more items completed in the allotted time. | Clamp 1- study entry, clamp 2 - 8 months |
| Four Choice Reaction Time Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Higher scores mean more time taken to complete the task. | Clamp 1- study entry, clamp 2 - 8 months |
| FG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 - Standard Care | Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped. Blinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode. Stable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study. |
| BG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex/Gender, Customized | Number | participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Age Diagnosed (Years) | Median | Inter-Quartile Range | Years |
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| Time since diagnosis (Years) | Median | Inter-Quartile Range | Years |
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| HbA1c | Median | Inter-Quartile Range | mmol/mol |
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| Weight | Mean | Standard Deviation | Kg |
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| BMI | Mean | Standard Deviation | kg^m2 |
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| Insulin Pump User | Number | participants |
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| Time in range (3.9-10 mmol/L) | Mean | Standard Deviation | Percentage time spent 3.9-10 mmol/L |
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| Time <3.9 mmol/L | Median | Inter-Quartile Range | Percentage |
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| Time <3.0 mmol/L | Median | Inter-Quartile Range | Percentage |
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| Time >10 mmol/L | Mean | Standard Deviation | Percentage |
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| Time >13.9 mmol/L | Mean | Standard Deviation | Percentage |
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| CV Glucose | Mean | Standard Deviation | Percentage |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia | The delta glucagon concentration (pmol/L) from plateau 1 (normoglycaemia- 5.0 mmol/L) to plateau 3 (hypoglycaemia- 2.5 mmol/L). The physiological response in health would be for an increase in glucagon secretion from normo- to hypoglycaemia. | Three participants withdrew from group 1 after the 1st clamp study visit. They were excluded from the study analysis. | Posted | Median | Inter-Quartile Range | pmol/L | Clamp 1 at baseline and clamp 2 at 8 months |
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| Secondary | Time in Glycaemic Range (3.9-10mmol/L) | Percentage time spent in target glycaemic range. | Posted | Mean | Standard Deviation | Percentage | Baseline (study entry), midpoint at 4 months and endpoint at 8 months |
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| Secondary | Time Spent Below the Target Glycaemic Range (<3.9mmol/L) | Percentage of time spent below the target glycaemic range | Posted | Mean | Standard Deviation | Percentage | Baseline (study entry), midpoint at 4 months and endpoint at 8 months |
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| Secondary | Time Spent Above the Target Glycaemic Range (>10mmol/L) | Percentage of time spent above the target glycaemic range | Posted | Mean | Standard Deviation | Percentage | Baseline (study entry), midpoint at 4 months and endpoint at 8 months |
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| Secondary | The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia | Delta cortisol from P1 (5.0 mmol/L) to P3 (2.5 mmol/L) | Posted | Mean | Standard Error | ng/mL | Clamp 1 at baseline and clamp 2 at 8 months |
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| Secondary | The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia | Delta adrenaline from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) | Posted | Median | Inter-Quartile Range | Delta pg/mL | Clamp 1 at baseline and clamp 2 at 8 months |
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| Secondary | The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia | The change in noradrenaline concentration from plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L). | Posted | Median | Inter-Quartile Range | pg/mL | Clamp 1 at baseline and clamp 2 at 8 months |
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| Secondary | Endogenous Glucose Production | The change in the glucose rate of appearance from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) | Posted | Mean | Standard Deviation | mg/kg/minute | Clamp 1 at baseline and clamp 2 at 8 months |
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| Secondary | HbA1c | Delta HbA1c from baseline to study endpoint. | Posted | Median | Inter-Quartile Range | mmol/mol | Baseline (study entry) endpoint (8 months) |
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| Secondary | Change in Quality of Life at Trial Entry and End. | Measured using the EQ5D-5L- -VAS. Number on scale of 0-100 to assess wellbeing on that day. 100 being the most well. | Posted | Mean | Standard Deviation | Number | Baseline (study entry) endpoint (8 months) |
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| Secondary | Change in Emotional Distress Related to Diabetes at Trial Entry and End. | Diabetes Distress Scale (DDS-1)- a 28-item self-reporting scale. Each item can be scored from 1 (not a problem) to 6 (a very serious problem). This questionnaire will be completed at study entry and study end. Data presented is the DDS total score. | Posted | Mean | Standard Deviation | Numerical score | Baseline (study entry) endpoint (8 months) |
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| Secondary | Change in Fear of Hypoglycaemic | Measured using the Hypoglycaemia Fear Survey (HFS)- this survey consists of two subscales- Baseline (study entry) endpoint (8 months) Behaviour and Worry. There are 28 items in the survey that the participant ranks from Never (0) to Almost Always (4). Higher scores indicate fear of hypoglycaemia. In the Behaviour subscale the lowest possible score in 0 and the highest possible score is 60. In the Worry subscale the lowest possible score is 0 and the highest is 72. Participants will complete this questionnaire at study entry and study end. | Posted | Mean | Standard Deviation | Numerical score | Baseline (study entry) endpoint (8 months) |
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| Secondary | Change in Confidence of Managing Hypoglycaemia | Measured using the Hypoglycaemic Confidence Scale- this is a 9 item scale. The participant rates each item from Not Confident at All to Very Confident. Participants will complete this questionnaire at study entry and study end. Higher scores mean more confidence. 'Not confident' at lower end of scale scored as 1 and 'very confident' at top of the scale scored as 4. Min score is 9 and max score is 36. | Posted | Mean | Standard Deviation | Numerical score | Baseline (study entry) endpoint (8 months) |
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| Secondary | Hypoglycaemia Awareness | Measured during each clamp study using the Edinburgh Hypoglycaemic Scale- this is a 17 item scale of symptoms of hypoglycaemia. The participant ranks on a scale from Not at all (1) to A Great Deal (7) whether they are experiencing each symptom at the time of the questionnaire being completed. Higher scores mean more hypoglycaemia symptoms. The lowest possible score is 0 and the highest possible score is 119. | Posted | Median | Inter-Quartile Range | Numerical score | Clamp 1 - study entry, clamp 2 - 8 months |
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| Secondary | Trial Making Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Delta score plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Participants are timed completing the test. Higher scores indicate a longer time to complete the test. | Posted | Median | Inter-Quartile Range | Minutes | Clamp 1- study entry, clamp 2 - 8 months |
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| Secondary | Digit Span Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in change in score from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Lower scores mean more errors. Forwards- participant repeats the numbers as read. Backwards- the participant repeats the numbers backwards. | Posted | Median | Inter-Quartile Range | Correct responses | Clamp 1- study entry, clamp 2 - 8 months |
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| Secondary | Digit Symbol Substitution Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0 mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Given 90 seconds to complete as many items as possible. Higher scores mean more items completed in the allotted time. | Posted | Mean | Standard Deviation | Correct responses | Clamp 1- study entry, clamp 2 - 8 months |
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| Secondary | Four Choice Reaction Time Test | Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Higher scores mean more time taken to complete the task. | Posted | Mean | Standard Deviation | Time (ms) | Clamp 1- study entry, clamp 2 - 8 months |
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From recruitment of participant to study completion (8 months per participants).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 - Standard Care | Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped. Blinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode. Stable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study. | 0 | 5 | 0 | 5 | 0 | 5 |
| EG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. | 0 | 11 | 1 | 11 | 0 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Proliferative retinopathy | Eye disorders | Systematic Assessment | 3 month eye screening one participant HCL group was diagnosed with proliferative retinopathy in their left eye (R1 to R4). They were referred to ophthalmology. Repeat screening by ophthalmology showed R1 in both eyes. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Shareen Forbes | University of Edinburgh | 0131 242 6740 | shareen.forbes@ed.ac.uk |
| Dec 2, 2025 |
| Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D007003 | Hypoglycemia |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D007332 | Insulin Infusion Systems |
| D050528 | Diet, Carbohydrate-Restricted |
| ID | Term |
|---|---|
| D016503 | Drug Delivery Systems |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D007260 | Infusion Pumps |
| D004864 | Equipment and Supplies |
| D001187 | Artificial Organs |
| D013523 | Surgical Equipment |
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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| Superiority |
| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 |
| Group 2- Automated Insulin Delivery and Low Carbohydrate Diet |
Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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| OG001 | Group 2- Automated Insulin Delivery and Low Carbohydrate Diet | Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires. Stepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. Insulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment. CGM: CGM sends data to the insulin pump to allow automatic insulin adjustment. Low carbohydrate diet: 30-40g of carbs/meal. Blinded CGM: data on BG collected without values altering behaviour. Stable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp. |
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