Maximising Time With a Normal Blood Glucose to Restore the Glucagon Response in Type 1 Diabetes

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.

Conditions

• Type 1 Diabetes
• Type 1 Diabetes Mellitus With Hypoglycemia
• Hypoglycemia
• Hypoglycemia Unawareness
• Glucagon Deficiency
• Insulin Hypoglycemia

Interventions

PROCEDURE

Stepped hyperinsulinaemic-hypoglycaemic clamp study

Participants will commence on a primed insulin infusion at a constant rate of 60mU/m2/min along with a variable rate 20% glucose infusion. Participants will have their blood glucose monitored every 5 minutes. The glucose infusion will be altered to achieve the desired blood glucose plateaus of: 5mmol/l, 3mmol/l and 2.5mmol/l. Each plateau will be held for 40 minutes. During each plateau blood samples will be taken on three occasions for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On two occasions during each plateau participants will complete the Edinburgh hypoglycaemia scale and the following cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be discontinued and the blood glucose will be allowed to rise to the normal range. Participants will consume lunch before leaving the clinical research facility.

DEVICE

Insulin pump

Insulin pump with a built-in algorithm that allows it to work with a CGM device to adjust insulin delivery based on CGM readings.

DEVICE

Continuous glucose monitor

Continuous glucose monitoring device that sends data to the insulin pump to allow the algorithm to adjust insulin delivery. Participants are able to see the glucose data from the device when it is used in open mode.

OTHER

Low carbohydrate diet

30-40g of carbohydrate per main meal portion.

DEVICE

Blinded continuous glucose monitor

Allows data on blood glucose to be collected without values altering the behaviour of the participant. Participants have to continue to monitor their own blood glucose while wearing the device in the blinded mode.

PROCEDURE

Stable isotope studies- D2 Glucose and D5 Glycerol

These studies will take place at the same time as the hyperinsulinaemic hypoglycaemic clamp studies. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.

Sponsors & Collaborators

• NHS Lothian

  collaborator OTHER_GOV

• The Leona M. and Harry B. Helmsley Charitable Trust

  collaborator OTHER

• Tandem Diabetes Care, Inc.

  collaborator INDUSTRY

• DexCom, Inc.

  collaborator INDUSTRY

• University of Edinburgh

  lead OTHER

Principal Investigators

• Shareen Forbes, MBChB, PhD · University of Edinburgh

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-07-26

Primary Completion

2023-09-22

Completion

2025-12-26

FDA Device

Yes

Countries

• United Kingdom

Study Locations