N/A
N=19
Maximising Time With a Normal Blood Glucose to Restore the Glucagon Response in Type 1 Diabetes
Type 1 Diabetes · Type 1 Diabetes Mellitus With Hypoglycemia · Hypoglycemia · Hypoglycemia Unawareness · Glucagon Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT04614168 ↗Enrolled (actual)
19
Serious AEs
6.3%
Results posted
Dec 2025
Primary outcome: Primary: The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia — 1.34; 1.68; 2.26; 0.31 pmol/L — p=>0.99
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Stepped hyperinsulinaemic-hypoglycaemic clamp study (Procedure); Insulin pump (Device); Continuous glucose monitor (Device); Low carbohydrate diet (Other); Blinded continuous glucose monitor (Device); Stable isotope studies- D2 Glucose and D5 Glycerol (Procedure)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- University of Edinburgh
- Primary completion
- Sep 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia |
1.34; 1.68; 2.26; 0.31 | >0.99 |
| SECONDARY Time in Glycaemic Range (3.9-10mmol/L) |
51.46; 53.55; 44.26; 78.01; 39.64; 76.85 | 0.37 |
| SECONDARY Time Spent Below the Target Glycaemic Range (<3.9mmol/L) |
1.02; 2.13; 2.25; 0.94; 2.18; 0.74 | 0.20 |
| SECONDARY Time Spent Above the Target Glycaemic Range (>10mmol/L) |
21.94; 33.64; 21.67; 18.93; 23.42; 19.06 | 0.58 |
| SECONDARY The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia |
146; 72.52; 195.2; 11.31 | 0.13 |
| SECONDARY The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia |
260; 187; 413; 252.5 | 0.63 |
| SECONDARY The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia |
49; -10.56; -43; 90.5 | 0.44 |
| SECONDARY Endogenous Glucose Production |
-0.16; -0.12; -0.22; -0.8 | 0.38 |
| SECONDARY HbA1c |
0; -12 | 0.0094 sig |
| SECONDARY Change in Quality of Life at Trial Entry and End. |
81; 79.36; 82; 80.27 | >0.99 |
| SECONDARY Change in Emotional Distress Related to Diabetes at Trial Entry and End. |
2.18; 2.2; 1.96; 1.58 | 0.13 |
| SECONDARY Change in Fear of Hypoglycaemic |
22; 20.55; 19.2; 18.82; 24; 24.25 | 0.25 |
| SECONDARY Change in Confidence of Managing Hypoglycaemia |
27.2; 27.64; 29.2; 31.27 | 0.25 |
| SECONDARY Hypoglycaemia Awareness |
24; 27; 35; 25; 39.64; 34 | 0.77 |
| SECONDARY Trial Making Test |
-3.05; 0.00; -2.6; -1.9; 11.5; -7.8 | 0.88 |
| SECONDARY Digit Span Test |
-1; -1; 0; 0; 0; 0 | 0.5 |
| SECONDARY Digit Symbol Substitution Test |
-4.4; 0.82; -6.6; -4.0 | 0.88 |
| SECONDARY Four Choice Reaction Time Test |
15.4; 38.45; 52.9; 57.78 | 0.38 |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT04614168). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.