Clinical trial NCT01440439: Comparing Long-acting Insulins During Exercise in Type 1 Diabetes
Official title: Impact of Insulin Detemir Versus Insulin Glargine on Glycaemic Control and Metabolism During Exercise in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Keywords: insulin glargine
insulin detemir
hypoglycaemia
metabolism
Exercise
Lead sponsor: Buckinghamshire Healthcare NHS Trust
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2011-09-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Exercise is an important part of a healthy lifestyle, and many people with Type 1 Diabetes like to take part in regular sport and exercise. The majority of people with Type 1 Diabetes are treated with a "basal bolus" insulin regimen, with background insulin provided by long-acting "basal" insulin doses, and "bolus" doses of short-acting insulin used to accompany food intake. Evidence shows that the main factor preventing people with diabetes from pursuing a more active lifestyle is fear of low blood glucose (hypoglycaemia). A previous study has shown that the type of background insulin affects the likelihood of an individual suffering hypoglycaemia during exercise and for 2 and a half hours afterwards. The aim of this study is to examine this further.

The two most commonly used long-acting insulins, insulin glargine and insulin detemir, will be compared. Previous data suggests that there is a greater likelihood of hypoglycaemia with insulin glargine than insulin detemir. Exercise intensity can have an influence on the likelihood of hypoglycaemia, and in this previous study exercise intensity was measured using heart rate. This study will use a more formal definition of exercise intensity. The investigators will study blood glucose during exercise, but also metabolism as measured by hormones affecting blood glucose levels as well as markers of fat metabolism. The investigators will also use a continuous glucose monitoring system (CGMS) to consider hypoglycaemia on thei night following exercise as this is a recognised consequence of exercise in type 1 diabetes.

The null hypothesis to be tested in this study is that there is no difference between the two insulins in their effect on blood glucose levels and metabolism during exercise and rates of nocturnal hypoglycaemia after exercise.

Detailed description: A1: At the first appointment, potential participants will be screened regarding the inclusion criteria, and if eligible to take part the study information sheet will be discussed with them in detail. Written, informed consent will be obtained if participants are willing to take part in the study. Participants will be given advice and support from this point in order to optimise basal insulin therapy using their usual basal insulin.

A2: Following a period of at least 3 weeks from recruitment into the study, participants will have their maximal oxygen uptake (VO2 MAX - a measure of capacity for physical exercise) assessed.

A3: After at least 4 weeks following recruitment , to allow time for optimisation of basal insulin therapy, and at least one week following A2, the participant's metabolism will then be assessed during and after 60 minutes of exercise at 50% VO2 MAX. Participants will be fitted with a continuous glucose monitoring system (CGMS) to monitor glucose levels for the 24 hours after exercise finishes.

A4: At least 24 hours and no more than 7 days after A3 the participant will switched to using the other trial insulin for basal insulin therapy. Again, participants will be provided with advice and support in order to optimise treatment.

A5: At least 4 weeks following A4, the participant's metabolism will once again be assessed during and after 60 minutes of exercise at 50% VO2 MAX. Participants will again be fitted with CGMS to monitor glucose levels for the 24 hours after exercise finishes.

A6: Once the 24 hours after exercise are complete, the study finishes and participants re-start their usual basal insulin.

Eligibility criteria: Inclusion Criteria:

* Participant is willing and able to give informed consent for participation in the study.
* Male or Female, aged between 18 and 65 years
* Diagnosed with Type 1 Diabetes Mellitus (T1DM)
* HbA1c \< 10% or 86 mmol/mol
* Treated with a basal bolus regimen using either insulin glargine or insulin detemir as the basal insulin
* Exercising regularly for at least 1 hour per week on average

Exclusion Criteria:

* People with any one of the following complications of diabetes:

  * stage 2+ diabetic retinopathy
  * renal impairment (with creatinine \>150micromol/l)
  * known history or symptoms of cardiovascular disease
  * foot ulceration
  * peripheral vascular disease
* Pregnancy or breastfeeding
* Untreated or unstable respiratory disease
* Known hypoglycaemia unawareness
* Treatment with drugs known to interfere with glucose metabolism
* Known or suspected allergy to or intolerance of any of the trial drugs or related products
* Receipt of any investigational drug within four months prior to Visit 0
* Known or suspected abuse of alcohol, narcotics or illicit drugs
* Any clinically significant disease or disorder which in the investigator's opinion could interfere with the results of the trial

Primary outcomes:
measure: Glucose excursion (which, as defined below, is the change in blood glucose between the start and finish of one hour of exercise)
timeFrame: Between baseline and 1 hour
Secondary outcomes:
measure: Lactate
timeFrame: 0, 60 and 90 minutes
measure: NEFA (Non-esterified fatty acids)
timeFrame: 0, 60 and 90 minutes
measure: B-OHB (beta-hydroxybutyrate)
timeFrame: 0, 60 and 90 minutes
measure: Catecholamines
timeFrame: 0, 60 and 90 minutes
measure: Glucagon
timeFrame: 0, 60 and 90 minutes
measure: Human growth hormone (hGH)
timeFrame: 0, 60 and 90 minutes
measure: Cortisol
timeFrame: 0, 60 and 90 minutes
measure: IL-6 (interleukin 6)
timeFrame: 0, 60 and 90 minutes
measure: High sensitivity CRP (Hs-CRP)
timeFrame: 0, 60 and 90 minutes
measure: RQ (Respiratory Quotient)
timeFrame: Baseline and 1 hour
measure: Frequency of hypoglycaemic events
timeFrame: 24 hours
measure: Time spent in hypoglycaemia
timeFrame: 24 hours
measure: Blood glucose
timeFrame: 0, 10, 20, 30, 40, 50, 60, 70, 80, 90 minutes
Other outcomes:
Locations:
city: High Wycombe
country: United Kingdom
facility: Wycombe Hospital
state: Buckinghamshire
Study officials:
affiliation: Bcukinghamshire Healthcare NHS Trust
name: Ian W Gallen, MD FRCP
role: PRINCIPAL_INVESTIGATOR
References: