Clinical trial NCT03956173: Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes
Official title: Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes type1
Hypoglycemia
Arrhythmias, Cardiac
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: University Hospital, Gentofte, Copenhagen
name: Hillerod Hospital, Denmark
First posted: 2019-05-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 24 patients with type 1 diabetes with insulin treatment for ≥ 3 years.

Brief summary: The investigators hypothesise that following episodes of hypoglycemia, rebound hyperglycemia may result in a prolonged period of increased QTc and, thereby, increased susceptibility to serious cardiac arrhythmias in patients with type - 1 diabetes.

Detailed description: In this study, changes in cardiac rhythm, haemodynamic regulation, and hormonal response will be evaluated during insulin-induced hypoglycemia followed by hyperglycemia and euglycemia, respectively, on two separate experimental days. Twenty-four patients with type-1 diabetes are included. Patients are randomised 1:1 to start with either the combined hypo- and hyperglycemic or the hypo- and euglycemic clamp. After an overnight 10 hour fast, participants are admitted for a 255 minute clamp. An individualised insulin infusion will be initiated targeting a plasma glucose level of 5.0-8.0 mmol/l. When the targeted plasma glucose level is achieved, the hyperinsulinemic euglycemic clamp will be initiated at time 0. The insulin infusion will be fixed at an infusion rate 80 mU/m2/min and a 20% glucose infusion will be initiated in order to regulate plasma glucose levels. After 45 min of monitoring at euglycemic plasma glucose level, plasma glucose will be decreased over a period of 30 minutes, targeting 2.5 mmol/l for a period of 60 min in a hyperinsulinemic hypoglycemic clamp. From 135 min to 195 min, plasma glucose levels will be increased to either hyperglycemic level or euglycemic level and will be kept constant for 105 minutes. Echocardiography is performed at baseline, at hypoglycemic level and at hyper-or normoglycemic level. Blood samples are taken every 15 minutes throughout the entire clamp, however bedside plasma glucose is analysed every fifth minute. A Holter-ECG is obtained throughout the entire clamp.

Eligibility criteria: Inclusion Criteria:

* Informed and written consent
* Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
* Age 18-70 years
* Insulin treatment for ≥3 years

Exclusion Criteria:

* Arrhythmia diagnosed prior to the screening visit
* Implantable cardioverter defibrillator (ICD) or pacemaker at the time of inclusion
* Severe heart failure (left ventricular ejection fraction \<25%)
* Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
* Thyroid dysfunction (except for well-regulated eltroxin substituted myxoedema)
* Anemia (male: hemoglobin \<8.0; female: hemoglobin \<7.0 mmol/l)

Primary outcomes:
measure: QTc prolongation.
timeFrame: 255 minutes
Secondary outcomes:
measure: QTd dispersion.
timeFrame: 255 minutes
measure: Atrial ectopic beats.
timeFrame: 255 minutes
measure: Bradycardia
timeFrame: 255 minutes
measure: Ventricular premature beats
timeFrame: 255 minutes
measure: Glucagon response
timeFrame: 255 minutes
measure: Catecholamine response
timeFrame: 255 minutes
measure: Growth hormone response
timeFrame: 255 minutes
measure: Cortisol response
timeFrame: 255 minutes
measure: Haemodynamic regulation.
timeFrame: 255 minutes
measure: Inflammatory response
timeFrame: 255 minutes
measure: Oxidative stress markers (8-iso-PGF2α)
timeFrame: 255 minutes
measure: Oxidative stress markers (8-oxoGuo)
timeFrame: 255 minutes
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Clinical Metabolic Physiology, SDCC
Study officials:
affiliation: Steno diabetic centre (SDCC)
name: Tina Vilsbøll, MD, DMSc
role: STUDY_DIRECTOR
References: