Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes (Hypo-Heart-1)

The investigators hypothesise that patients with type 1 diabetes have clinically relevant, but often unrecognised, episodes of arrhythmias linked to episodes of hypoglycaemia and/or clinically significant fluctuations in plasma glucose.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Hyperglycaemia (Diabetic); Arrythmia, Cardiac; Hypoglycemia (Diabetic); Blood Glucose Fluctuations

Detailed Description

30 patients with type 1 diabetes will be recruited for a one-year observational study employing CGM (Continuous glucose monitor) and ILR (Implantable loop recorder). Patients will be scheduled for a three-week run-in period to ensure that the implanted ILR provides reliable data. Patient visits are planned for 0, 3, 6, 9, and 12 months and will include clinical examination, blood and urine samples, echocardiography (only first and last visit) and implant/explant of CGM. After 12 months, the participants will continue with an extended observation period of 2 years employing ILR and clinical examination.

Device: Loop recorder (Reveal LINQ, Medtronic, Minneapolis, MN, USA) Implantation of a loop-recorder

Device: Continuous glucose monitoring (Eversense XL, Senseonics, USA) Monitoring with a continuous glucose monitor

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2900
    • Clinical Metabolic Physiology, SDCC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with type 1 Diabetes recrutted in collaboration with Hillerod hospital, Gentofte hospital and Steno Diabetes Centre.

Description

Inclusion Criteria:

• Informed and written consent
• Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
• Age 18-80 years

• Fulfilling at least one of the below criteria*:

  1. Recurrent hypoglycaemia (defined as >1 episode/week with a plasma glucose measurement ≤3.9 mmol/l within the last 4 weeks)
  2. An episode of severe hypoglycaemia within the last year (according to the ADA definition, an event requiring assistance of another person to actively administer carbohydrates and/or glucagon, or take other corrective actions)
  3. Hypoglycaemic symptom unawareness (history of impaired autonomic response during hypoglycaemia)

(*The aim is that all patients will fulfil criteria a or b. If the targeted sample size cannot be recruited, patients fulfilling criteria c will be included)

• Insulin treatment

• One or more clinical relevant complications to diabetes defined as**:

  1. Nephropathy (creatinine >130 μmol/l and/or microalbuminuria)
  2. Macrovascular disease defined as coronary disease (stable angina pectoris. previous unstable angina pectoris or myocardial infarction), cerebrovascular disease (previous stroke or transitional cerebral ischaemia), and peripheral vascular disease (previous intermittent claudication or prior acute ischemia)
  3. Peripheral neuropathy with vibration perception threshold of >25 volt determined by biothesiometry
  4. Moderate to severe retinopathy
• Well-functioning ILR during run-in period (acceptable readings judged by an arrhythmologist)
• Participation in the extended study

(**The aim is that all patients will fulfil criteria a or b. If the targeted sample size cannot be recruited, patients fulfilling criteria c or d will be included)

Exclusion Criteria:

• Arrhythmia diagnosed prior to the screening visit
• 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 eltroxine substituted myxoedema)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of cardiac arrhythmias during hypoglycaemia, euglycaemia, hyperglycaemia.	Incidence of clinically relevant arrhythmias during hypoglycaemia (plasma glucose ≤3.9 mmol/l) compared to euglycaemia and hyperglycaemia.	Within 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of cardiac arrhythmias	Prevalence of clinically relevant arrhythmias	Within 12 months
Cardiac arrhythmias during LGV, HGV.	Clinical relevant arrhythmias during low glucose variability (LGV), defined as variations in plasma glucose below or equal to 5 mmol/l within two hours preceding an arrhythmic event, compared to high glucose variability (HGV), defined as variations in plasma glucose above 5 mmol/l within two hours preceding an arrhythmic event.	Within 12 months
The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV	The relationship between cardiovascular disease (heart failure and ischaemic heart disease) at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV	Within 12 months
The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV	The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV	Within 12 months
The relationship between diabetes complication status at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV	The relationship between diabetes complication status (neuropathy, nephropathy, retinopathy) at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV	Within 12 months
Hypoglycaemia and cardiac arrhythmia	The correlation between prevalence and total duration of hypoglycaemia and risk of clinically relevant arrhythmias	Within 12 months
Plasma glucose variation and cardiac arrhythmias	The correlation between plasma glucose variation (variation in plasma glucose (Δ mmol/l) within two hours of the event) and risk of clinically relevant arrhythmias	Within 12 months
CV, SD, ADRR, LBGI, HBGI, CONGA-1 and cardiac arrhythmias	The correlation between measures of glycaemic variability (coefficient of variation (CV), standard deviation (SD), average daily risk range (ADRR), low blood glucose index (LBGI), high blood glucose index (HBGI) and continuous overlapping net glycaemic action (CONGA-1)) and risk of clinically relevant arrhythmias	Within 12 months
Mean amplitude of glycaemic excursions (MAGE) and cardiac arrhythmia.	Difference in mean amplitude of glycaemic excursions (MAGE) two hours preceding an arrhythmic event versus MAGE during non-event	Within 12 months

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: University of Copenhagen; Hillerod Hospital, Denmark; University Hospital, Gentofte, Copenhagen
• Investigators: Study Director: Tina Vilsbøll, MD, Professor, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2018
• Primary Completion (ACTUAL): December 20, 2021
• Study Completion (ACTUAL): December 20, 2021

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: July 5, 2019
• First Posted (ACTUAL): July 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Arrhythmias, Cardiac
• Other Study ID Numbers: H-18034040_part2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No