Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes

Hypoglycemia Clinical Trial

— Hypo-Heart-1  

Official title:

Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03956173
• Other study ID #: H-18034040
• Status: Completed
• Start date: December 1, 2018
• Est. completion date: December 1, 2021

Study information

• Verified date: July 2022
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes type1
• Hypoglycemia

Intervention

Other:
• Hypoglycemic combined with either normo or hyperglycemic clamp.
Twenty-four patients with type 1 diabetes has been recruited for a cross-over study including two experimental days, a combined hypo- and hyperglyemic clamp and a combined hypo- and euglycemic clamp, respectively. Patients will be randomised 1:1 to start with either the combined hypo- and hyperglycemic or the hypo- and euglycemic clamp. The hypo- and hyperglycemic or the hypo- and euglycemic clamp are estimated to last 255 minutes. The two clamp days will be separated by at least 30 days.

Locations

Country	Name	City	State
Denmark	Clinical Metabolic Physiology, SDCC	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	Hillerod Hospital, Denmark, University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	QTc prolongation.	Difference in mean corrected QT interval (QTc) prolongation during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia	255 minutes
Secondary	QTd dispersion.	Difference in QT dispersion (QTd) during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia	255 minutes
Secondary	Atrial ectopic beats.	Difference in atrial ectopic beats (prematurity threshold 30%),during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia	255 minutes
Secondary	Bradycardia	Difference in non-clinically significant bradycardia (=45 bpm for 5 seconds) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia	255 minutes
Secondary	Ventricular premature beats	Difference in ventricular premature beats during hyperglycaemia compared to euglycaemia both preceded by insulin-induced hypoglycaemia	255 minutes
Secondary	Glucagon response	Differences in glucagon response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia	255 minutes
Secondary	Catecholamine response	Differences in catecholamine response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia	255 minutes
Secondary	Growth hormone response	Differences in growth hormone response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia	255 minutes
Secondary	Cortisol response	Differences in cortisol responses during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia	255 minutes
Secondary	Haemodynamic regulation.	Differences in haemodynamic regulation (measured by echocardiography) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia	255 minutes
Secondary	Inflammatory response	Differences in markers of inflammation (high-sensitive C-reactive peptide (hs-CRP) and interleukin 6 (IL-6)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia	255 minutes
Secondary	Oxidative stress markers (8-iso-PGF2a)	Differences in markers of oxidative stress (8-iso prostaglandin F2a (8-iso-PGF2a)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia	255 minutes
Secondary	Oxidative stress markers (8-oxoGuo)	Differences in markers of oxidative stress (8-oxo-7,8-dihydroguanosine (8-oxoGuo)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia	255 minutes