Trial Outcomes & Findings for Maximising Time With a Normal Blood Glucose to Restore the Glucagon Response in Type 1 Diabetes (NCT NCT04614168)
NCT ID: NCT04614168
Last Updated: 2025-12-17
Results Overview
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.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
NA
Target enrollment
24 participants
Primary outcome timeframe
Clamp 1 at baseline and clamp 2 at 8 months
Results posted on
2025-12-17
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
11
|
|
Overall Study
COMPLETED
|
5
|
11
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Group 1 - Standard Care
n=8 Participants
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.
|
Group 2- Automated Insulin Delivery and Low Carbohydrate Diet
n=11 Participants
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.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.9 Years
STANDARD_DEVIATION 11.3 • n=8 Participants
|
42.9 Years
STANDARD_DEVIATION 9.5 • n=11 Participants
|
39.95 Years
STANDARD_DEVIATION 10.63 • n=19 Participants
|
|
Sex/Gender, Customized
Female
|
6 participants
n=8 Participants
|
4 participants
n=11 Participants
|
10 participants
n=19 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United Kingdom
|
8 participants
n=8 Participants
|
11 participants
n=11 Participants
|
19 participants
n=19 Participants
|
|
Age Diagnosed (Years)
|
7 Years
n=8 Participants
|
20 Years
n=11 Participants
|
16.5 Years
n=19 Participants
|
|
Time since diagnosis (Years)
|
19.2 Years
n=8 Participants
|
25.5 Years
n=11 Participants
|
24.67 Years
n=19 Participants
|
|
HbA1c
|
63 mmol/mol
n=8 Participants
|
61 mmol/mol
n=11 Participants
|
63 mmol/mol
n=19 Participants
|
|
Weight
|
84.5 Kg
STANDARD_DEVIATION 11.9 • n=8 Participants
|
77.33 Kg
STANDARD_DEVIATION 7.8 • n=11 Participants
|
80.35 Kg
STANDARD_DEVIATION 10.14 • n=19 Participants
|
|
BMI
|
29.34 kg^m2
STANDARD_DEVIATION 4.1 • n=8 Participants
|
26.18 kg^m2
STANDARD_DEVIATION 2.99 • n=11 Participants
|
27.51 kg^m2
STANDARD_DEVIATION 3.76 • n=19 Participants
|
|
Insulin Pump User
|
4 participants
n=8 Participants
|
3 participants
n=11 Participants
|
7 participants
n=19 Participants
|
|
Time in range (3.9-10 mmol/L)
|
49.05 Percentage time spent 3.9-10 mmol/L
STANDARD_DEVIATION 12.47 • n=8 Participants
|
53.55 Percentage time spent 3.9-10 mmol/L
STANDARD_DEVIATION 14.48 • n=11 Participants
|
50.39 Percentage time spent 3.9-10 mmol/L
STANDARD_DEVIATION 13.83 • n=19 Participants
|
|
Time <3.9 mmol/L
|
0.71 Percentage
n=8 Participants
|
0.65 Percentage
n=11 Participants
|
0.71 Percentage
n=19 Participants
|
|
Time <3.0 mmol/L
|
0.12 Percentage
n=8 Participants
|
0.13 Percentage
n=11 Participants
|
0.13 Percentage
n=19 Participants
|
|
Time >10 mmol/L
|
25.12 Percentage
STANDARD_DEVIATION 11.73 • n=8 Participants
|
33.64 Percentage
STANDARD_DEVIATION 12.42 • n=11 Participants
|
30.05 Percentage
STANDARD_DEVIATION 12.57 • n=19 Participants
|
|
Time >13.9 mmol/L
|
21.7 Percentage
STANDARD_DEVIATION 8.77 • n=8 Participants
|
15.25 Percentage
STANDARD_DEVIATION 13.75 • n=11 Participants
|
17.97 Percentage
STANDARD_DEVIATION 12.07 • n=19 Participants
|
|
CV Glucose
|
38.24 Percentage
STANDARD_DEVIATION 6.8 • n=8 Participants
|
35.06 Percentage
STANDARD_DEVIATION 4.94 • n=11 Participants
|
36.4 Percentage
STANDARD_DEVIATION 5.85 • n=19 Participants
|
PRIMARY outcome
Timeframe: Clamp 1 at baseline and clamp 2 at 8 monthsPopulation: Three participants withdrew from group 1 after the 1st clamp study visit. They were excluded from the study analysis.
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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia
Delta Clamp 1 (P3-P1)
|
1.34 pmol/L
Interval 0.46 to 4.52
|
1.68 pmol/L
Interval 0.96 to 3.35
|
|
The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia
Delta Clamp 2 (P3-P1)
|
2.26 pmol/L
Interval 0.52 to 3.64
|
0.31 pmol/L
Interval 0.0 to 1.53
|
SECONDARY outcome
Timeframe: Baseline (study entry), midpoint at 4 months and endpoint at 8 monthsPercentage time spent in target glycaemic range.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Time in Glycaemic Range (3.9-10mmol/L)
Baseline
|
51.46 Percentage
Standard Deviation 13.63
|
53.55 Percentage
Standard Deviation 14.48
|
|
Time in Glycaemic Range (3.9-10mmol/L)
Midpoint
|
44.26 Percentage
Standard Deviation 11.5
|
78.01 Percentage
Standard Deviation 6.32
|
|
Time in Glycaemic Range (3.9-10mmol/L)
Endpoint
|
39.64 Percentage
Standard Deviation 20.15
|
76.85 Percentage
Standard Deviation 9.61
|
SECONDARY outcome
Timeframe: Baseline (study entry), midpoint at 4 months and endpoint at 8 monthsPercentage of time spent below the target glycaemic range
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Time Spent Below the Target Glycaemic Range (<3.9mmol/L)
Endpoint
|
2.18 Percentage
Standard Deviation 3.85
|
0.74 Percentage
Standard Deviation 0.57
|
|
Time Spent Below the Target Glycaemic Range (<3.9mmol/L)
Midpoint
|
2.25 Percentage
Standard Deviation 3.50
|
0.94 Percentage
Standard Deviation 0.55
|
|
Time Spent Below the Target Glycaemic Range (<3.9mmol/L)
Baseline
|
1.02 Percentage
Standard Deviation 0.62
|
2.13 Percentage
Standard Deviation 3.17
|
SECONDARY outcome
Timeframe: Baseline (study entry), midpoint at 4 months and endpoint at 8 monthsPercentage of time spent above the target glycaemic range
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Time Spent Above the Target Glycaemic Range (>10mmol/L)
Endpoint
|
23.42 Percentage
Standard Deviation 17.23
|
19.06 Percentage
Standard Deviation 5.87
|
|
Time Spent Above the Target Glycaemic Range (>10mmol/L)
Baseline
|
21.94 Percentage
Standard Deviation 13.93
|
33.64 Percentage
Standard Deviation 12.42
|
|
Time Spent Above the Target Glycaemic Range (>10mmol/L)
Midpoint
|
21.67 Percentage
Standard Deviation 13.55
|
18.93 Percentage
Standard Deviation 4.66
|
SECONDARY outcome
Timeframe: Clamp 1 at baseline and clamp 2 at 8 monthsDelta cortisol from P1 (5.0 mmol/L) to P3 (2.5 mmol/L)
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia
Delta P3-P1 Clamp 1
|
146 ng/mL
Standard Error 126
|
72.52 ng/mL
Standard Error 91.48
|
|
The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia
Delta P3-P1 Clamp 2
|
195.2 ng/mL
Standard Error 115.9
|
11.31 ng/mL
Standard Error 37.14
|
SECONDARY outcome
Timeframe: Clamp 1 at baseline and clamp 2 at 8 monthsDelta adrenaline from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L)
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia
Clamp 1
|
260 Delta pg/mL
Interval 78.5 to 499.0
|
187 Delta pg/mL
Interval 27.25 to 658.5
|
|
The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia
Clamp 2
|
413 Delta pg/mL
Interval 267.5 to 524.5
|
252.5 Delta pg/mL
Interval 172.8 to 696.5
|
SECONDARY outcome
Timeframe: Clamp 1 at baseline and clamp 2 at 8 monthsThe change in noradrenaline concentration from plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L).
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia
Delta noradrenaline (P3-P1) Clamp 1
|
49 pg/mL
Interval -132.0 to 225.0
|
-10.56 pg/mL
Interval -50.25 to 38.75
|
|
The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia
Delta noradrenaline (P3-P1) Clamp 2
|
-43 pg/mL
Interval -133.0 to 56.0
|
90.5 pg/mL
Interval 3.75 to 172.3
|
SECONDARY outcome
Timeframe: Clamp 1 at baseline and clamp 2 at 8 monthsThe change in the glucose rate of appearance from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L)
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Endogenous Glucose Production
Delta glucose rate of appearance P3-P1 Clamp 1
|
-0.16 mg/kg/minute
Standard Deviation 0.21
|
-0.12 mg/kg/minute
Standard Deviation 0.16
|
|
Endogenous Glucose Production
Delta glucose rate of appearance P3-P1 Clamp 2
|
-0.22 mg/kg/minute
Standard Deviation 0.16
|
-0.8 mg/kg/minute
Standard Deviation 0.16
|
SECONDARY outcome
Timeframe: Baseline (study entry) endpoint (8 months)Delta HbA1c from baseline to study endpoint.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
HbA1c
|
0 mmol/mol
Interval -4.5 to 4.0
|
-12 mmol/mol
Interval -18.0 to -4.0
|
SECONDARY outcome
Timeframe: Baseline (study entry) endpoint (8 months)Measured using the EQ5D-5L- -VAS. Number on scale of 0-100 to assess wellbeing on that day. 100 being the most well.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Change in Quality of Life at Trial Entry and End.
Baseline
|
81 Number
Standard Deviation 6.52
|
79.36 Number
Standard Deviation 12.33
|
|
Change in Quality of Life at Trial Entry and End.
Endpoint
|
82 Number
Standard Deviation 11.51
|
80.27 Number
Standard Deviation 9.96
|
SECONDARY outcome
Timeframe: Baseline (study entry) endpoint (8 months)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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Change in Emotional Distress Related to Diabetes at Trial Entry and End.
Baseline
|
2.18 Numerical score
Standard Deviation 0.64
|
2.2 Numerical score
Standard Deviation 1.15
|
|
Change in Emotional Distress Related to Diabetes at Trial Entry and End.
Endpoint
|
1.96 Numerical score
Standard Deviation 0.66
|
1.58 Numerical score
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: Baseline (study entry) endpoint (8 months)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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Change in Fear of Hypoglycaemic
Worry Scale Endpoint
|
21.4 Numerical score
Standard Deviation 15.39
|
12.88 Numerical score
Standard Deviation 9.78
|
|
Change in Fear of Hypoglycaemic
Behaviour Scale Baseline
|
22 Numerical score
Standard Deviation 4.24
|
20.55 Numerical score
Standard Deviation 4.03
|
|
Change in Fear of Hypoglycaemic
Behaviour Scale Endpoint
|
19.2 Numerical score
Standard Deviation 8.11
|
18.82 Numerical score
Standard Deviation 4.79
|
|
Change in Fear of Hypoglycaemic
Worry scale Baseline
|
24 Numerical score
Standard Deviation 9.34
|
24.25 Numerical score
Standard Deviation 15.85
|
SECONDARY outcome
Timeframe: Baseline (study entry) endpoint (8 months)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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Change in Confidence of Managing Hypoglycaemia
Baseline
|
27.2 Numerical score
Standard Deviation 5.17
|
27.64 Numerical score
Standard Deviation 7.63
|
|
Change in Confidence of Managing Hypoglycaemia
Endpoint
|
29.2 Numerical score
Standard Deviation 5.31
|
31.27 Numerical score
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: Clamp 1 - study entry, clamp 2 - 8 monthsMeasured 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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Hypoglycaemia Awareness
Clamp 2 Plateau 1
|
34 Numerical score
Interval 23.5 to 36.0
|
28 Numerical score
Interval 22.0 to 36.0
|
|
Hypoglycaemia Awareness
Clamp 2 Plateau 2
|
34 Numerical score
Interval 27.0 to 64.5
|
29 Numerical score
Interval 24.0 to 60.0
|
|
Hypoglycaemia Awareness
Clamp 1 Plateau 1
|
24 Numerical score
Interval 22.5 to 31.5
|
27 Numerical score
Interval 18.0 to 32.0
|
|
Hypoglycaemia Awareness
Clamp 1 Plateau 2
|
35 Numerical score
Interval 29.5 to 60.5
|
25 Numerical score
Interval 19.0 to 50.0
|
|
Hypoglycaemia Awareness
Clamp 1 Plateau 3
|
39.64 Numerical score
Interval 30.5 to 62.5
|
34 Numerical score
Interval 24.0 to 64.0
|
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Hypoglycaemia Awareness
Clamp 2 Plateau 3
|
46 Numerical score
Interval 29.5 to 71.0
|
47 Numerical score
Interval 26.0 to 76.0
|
SECONDARY outcome
Timeframe: Clamp 1- study entry, clamp 2 - 8 monthsMeasured 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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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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|---|---|---|
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Trial Making Test
Trail making A delta clamp 1
|
-3.05 Minutes
Interval -4.55 to 0.4
|
0.00 Minutes
Interval -12.0 to 1.5
|
|
Trial Making Test
Trail making A delta clamp 2
|
-2.6 Minutes
Interval -4.55 to 0.05
|
-1.9 Minutes
Interval -7.2 to 2.4
|
|
Trial Making Test
Trail making B delta clamp 1
|
11.5 Minutes
Interval -10.35 to 22.8
|
-7.8 Minutes
Interval -10.0 to 1.0
|
|
Trial Making Test
Trail making B delta clamp 2
|
0.7 Minutes
Interval -2.98 to 5.5
|
-5.6 Minutes
Interval -23.9 to -0.9
|
SECONDARY outcome
Timeframe: Clamp 1- study entry, clamp 2 - 8 monthsMeasured 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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Digit Span Test
Digit span forwards clamp1
|
-1 Correct responses
Interval -2.0 to 0.0
|
-1 Correct responses
Interval -1.0 to 1.0
|
|
Digit Span Test
Digit span backwards clamp 2
|
0 Correct responses
Interval -1.0 to 2.0
|
0 Correct responses
Interval 0.0 to 1.0
|
|
Digit Span Test
Digit span forwards clamp 2
|
0 Correct responses
Interval -1.5 to 1.5
|
0 Correct responses
Interval -1.0 to 0.0
|
|
Digit Span Test
Digit span backwards clamp 1
|
0 Correct responses
Interval -1.0 to 0.0
|
0 Correct responses
Interval -1.0 to 0.0
|
SECONDARY outcome
Timeframe: Clamp 1- study entry, clamp 2 - 8 monthsMeasured 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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Digit Symbol Substitution Test
Delta score clamp 1
|
-4.4 Correct responses
Standard Deviation 5.4
|
0.82 Correct responses
Standard Deviation 6.56
|
|
Digit Symbol Substitution Test
Delta score clamp 2
|
-6.6 Correct responses
Standard Deviation 13.7
|
-4.0 Correct responses
Standard Deviation 7.1
|
SECONDARY outcome
Timeframe: Clamp 1- study entry, clamp 2 - 8 monthsMeasured 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.
Outcome measures
| Measure |
Group 1 - Standard Care
n=5 Participants
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 Participants
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.
|
|---|---|---|
|
Four Choice Reaction Time Test
Clamp 1
|
15.4 Time (ms)
Standard Deviation 7.4
|
38.45 Time (ms)
Standard Deviation 63.21
|
|
Four Choice Reaction Time Test
Clamp 2
|
52.9 Time (ms)
Standard Deviation 20.43
|
57.78 Time (ms)
Standard Deviation 60.63
|
Adverse Events
Group 1 - Standard Care
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group 2- Automated insulin delivery and low carbohydrate diet
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1 - Standard Care
n=5 participants at risk
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.
|
Group 2- Automated insulin delivery and low carbohydrate diet
n=11 participants at risk
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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|---|---|---|
|
Eye disorders
Proliferative retinopathy
|
0.00%
0/5 • From recruitment of participant to study completion (8 months per participants).
|
9.1%
1/11 • Number of events 1 • From recruitment of participant to study completion (8 months per participants).
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place