Can Maximising Time in Range Using Automated Insulin Delivery and a Low Carbohydrate Diet Restore the Glucagon Response to Hypoglycaemic in Type 1 Diabetes?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with Type 1 diabetes with C-peptide levels less than 200pmol/L.
- •Type 1 diabetes for 5 years or more.
- •HbA1c greater than or equal to 53 mol/mol.
- •Normal renal function.
- •Normal thyroid function.
- •Gold Score 4-7 (indicating impaired awareness of hypoglycaemia)
- •Willingness to monitor blood ketones daily.
- •Use of freestyle libre device is permitted at study entry and may be continued in participants in group 1
排除标准
- •Current use of a non-approved closed loop / AID system or those on a predictive low glucose suspend insulin pump.
- •Proliferative retinopathy
- •Regular use of real time CGM in the preceding 3 months.
- •History of Diabetic ketoacidosis in the preceding 6 months.
- •Severe hypoglycaemic episode requiring external assistance in the preceding 6 months.
- •Inability to safely use technology used in this study (e.g. impaired vision, memory or dexterity that prevents safe operation of CGM or insulin pump.)
- •Inability to support the technology requirements for the study (e.g. unable to upload study device at home)
- •History of Haemophilia, Cystic Fibrosis, pancreatic disease or complete pancreatectomy, ischaemic heart disease, epilepsy or hypoglycaemia induced seizure
- •History of severe reaction or allergy to adhesive necessary to this study.
- •Unable to adhere to study timetable.
- •Unable to give informed consent.
- •Pregnancy. We will perform a pregnancy test on all eligible participants at baseline.
- •Concurrent use of any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas. These may lower insulin requirements and predispose to diabetic ketoacidosis.
- •Concurrent use of medication that may affect blood glucose such as SSRIs
- •A condition, which in the opinion of the investigator, would put the patient or study at risk
- •HbA1c greater than or equal to 75 mmol/mol
研究组 & 干预措施
Group 1 - Standard Care
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.
干预措施: Stepped hyperinsulinaemic-hypoglycaemic clamp study (Procedure)
Group 1 - Standard Care
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.
干预措施: Blinded continuous glucose monitor (Device)
Group 1 - Standard Care
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.
干预措施: Stable isotope studies- D2 Glucose and D5 Glycerol (Procedure)
Group 2- Automated insulin delivery and low carbohydrate diet
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.
干预措施: Stepped hyperinsulinaemic-hypoglycaemic clamp study (Procedure)
Group 2- Automated insulin delivery and low carbohydrate diet
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.
干预措施: Insulin pump (Device)
Group 2- Automated insulin delivery and low carbohydrate diet
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.
干预措施: Continuous glucose monitor (Device)
Group 2- Automated insulin delivery and low carbohydrate diet
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.
干预措施: Low carbohydrate diet (Other)
Group 2- Automated insulin delivery and low carbohydrate diet
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.
干预措施: Blinded continuous glucose monitor (Device)
Group 2- Automated insulin delivery and low carbohydrate diet
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.
干预措施: Stable isotope studies- D2 Glucose and D5 Glycerol (Procedure)
结局指标
主要结局
The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia
时间窗: Clamp 1 at baseline and clamp 2 at 8 months
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.
次要结局
- Time in Glycaemic Range (3.9-10mmol/L)(Baseline (study entry), midpoint at 4 months and endpoint at 8 months)
- Time Spent Below the Target Glycaemic Range (<3.9mmol/L)(Baseline (study entry), midpoint at 4 months and endpoint at 8 months)
- Time Spent Above the Target Glycaemic Range (>10mmol/L)(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(Clamp 1 at baseline and clamp 2 at 8 months)
- The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia(Clamp 1 at baseline and clamp 2 at 8 months)
- The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia(Clamp 1 at baseline and clamp 2 at 8 months)
- Endogenous Glucose Production(Clamp 1 at baseline and clamp 2 at 8 months)
- HbA1c(Baseline (study entry) endpoint (8 months))
- Change in Quality of Life at Trial Entry and End.(Baseline (study entry) endpoint (8 months))
- Change in Emotional Distress Related to Diabetes at Trial Entry and End.(Baseline (study entry) endpoint (8 months))
- Change in Fear of Hypoglycaemic(Baseline (study entry) endpoint (8 months))
- Change in Confidence of Managing Hypoglycaemia(Baseline (study entry) endpoint (8 months))
- Hypoglycaemia Awareness(Clamp 1 - study entry, clamp 2 - 8 months)
- Trial Making Test(Clamp 1- study entry, clamp 2 - 8 months)
- Digit Span Test(Clamp 1- study entry, clamp 2 - 8 months)
- Digit Symbol Substitution Test(Clamp 1- study entry, clamp 2 - 8 months)
- Four Choice Reaction Time Test(Clamp 1- study entry, clamp 2 - 8 months)