Cardiovascular Effects of Exercise-related Hypoglycaemia in Patients With Type 1 Diabetes (Hypo Heart Exercise)

NCT04650646 | Completed DMC

• 1 other identifier: H-20023688
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with type 1 diabetes are recommended to perform at least 150 minutes of accumulated physical activity each week, however fear of hypoglycaemia is a well-known barrier to exercise in these patients. Previous experimental studies have almost exclusively focused on investigating cardiovascular effects of hypoglycaemia under resting conditions, however other underlying circumstances prior to or during a hypoglycaemic event, (e.g. exercise) are rarely discussed in the literature but might, nevertheless, be of significant clinical importance. In this study, the investigators aim to investigate the QT interval dynamics and prothrombotic factors during exercise-related hypoglycaemia in comparison with hypoglycaemia under resting conditions, in patients with type 1 diabetes. Fifteen patients with type 1 diabetes will be recruited for a crossover study including two test days, a combined euglycaemic- hypoglycaemic clamp combined with an exercise session and an euglycaemic- hypoglycaemic clamp during bed rest, respectively. Furthermore, the participants will be schedueled for a 24-hours followup visit after each test day for the purpose of investigating prolonged prothrombotic effects of hypoglycaemia. Patients will be randomised 1:1 to start with the combined exercise-clamp or the resting-clamp. The two test days will be separated by at least 4 weeks to minimise carry-over effects. A group of fifteen healthy individuals with normal glucose tolerance matched for age, gender and body mass index, will be recruited for a single blood test aiming to compare baseline coagulation status with patients with type 1 diabetes.

Conditions

Diabetes Mellitus, Type 1; Arrhythmia

Keywords

Type 1 diabetes; Cardiovascular disease; Hypoglycaemia; Exercise-related hypoglycaemia

Outcome Measures

Primary Outcomes (1)

• Hypoglycaemia and QTc interval prolongation

  Mean QTc interval prolongation from baseline during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.

  0-180minutes

Secondary Outcomes (13)

• Key secondary outcome: Hypoglycaemia and coagulation and fibrinolysis

  0-24hours

• Hypoglycaemia and QT dispersion (QTd)

  0-180minutes

• Hypoglycaemia and heart rate variability (HRV)

  0-180minutes

• Hypoglycaemia and bradycardia

  0-180minutes

• Hypoglycaemia and ectopic beats

  0-180minutes

Study Arms (2)

Hypoglycaemic clamp i combination with exercise

EXPERIMENTAL

A 180 minutes hyperinsulinaemic euglycaemic-hypoglycaemic clamp in combination with an exercise session. The participants will be monitored with Holter-ECG throughout the entire clamp and plasma glucose will be measured every 5 minutes. Blood samples will be drawn and analysed for changes in electrolytes, counterregulatory hormones, coagulation status, inflammation, endothelial damage and oxidative stress.

Other: Exercise-related hypoglycaemia

Hypoglycaemic clamp in combination with bed rest

EXPERIMENTAL

A 180 minutes hyperinsulinaemic euglycaemic-hypoglycaemic clamp in combination with bed rest. The participants will be monitored with Holter-ECG throughout the entire clamp and plasma glucose will be measured every 5 minutes. Blood samples will be drawn and analysed for changes in electrolytes, counterregulatory hormones, coagulation status, inflammation, endothelial damage and oxidative stress.

Other: Hypoglycaemia under resting conditions

Interventions

Exercise-related hypoglycaemia OTHER

Hypoglycaemia induced by intravenous insulin and exercise on a vertical cycle ergometer.

Hypoglycaemic clamp i combination with exercise

Hypoglycaemia under resting conditions OTHER

Hypoglycaemia induced by intravenous insulin during bed rest.

Hypoglycaemic clamp in combination with bed rest

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed and written consent
• Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
• Age ≥ 18 years
• Insulin treatment for ≥1 year

You may not qualify if:

• Arrhythmia diagnosed prior to the screening visit.
• Ischaemic heart disease or myocardial infarction diagnosed prior to the screening visit.
• Heart failure (left ventricular ejection fraction \<45%) diagnosed prior to the screening visit.
• Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
• ECG with left or right bundle branch block diagnosed prior to the screening visit.
• Thyroid dysfunction (except for well-regulated levothyroxine-substituted myxoedema)
• Anaemia (male: haemoglobin \<8.0; female: haemoglobin \<7.0 mmol/l)
• Treatment with anticoagulant or antiplatelet treatment.
• Bleeding disorder diagnosed prior to the screening visit.
• Withdrawal criteria
• \- The participants may withdraw at will at any time

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead

Study Sites (1)

Clinical Research, Steno Diabetes Center Copenhagen-Gentofte

Copenhagen, 2900, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Arrhythmias, Cardiac; Cardiovascular Diseases; Hypoglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tina Vilsbøll, MD, DMSc

  Steno diabetic centre (SDCC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: December 2, 2020
• Study Start: September 1, 2020
• Primary Completion: June 3, 2021
• Study Completion: December 1, 2021
• Last Updated: January 21, 2022

Record last verified: 2022-01

Locations

DK (1)