Hypoglycaemia and Cardiac Arrhythmias in Type 2 Diabetes

NCT03150030 | Completed DMC

• 1 other identifier: H-16046212
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Twenty-one patients with insulin-treated type 2 diabetes with diabetic complications will be recruited to Part 1 of the study, a three-hour combined hyper- and hypoglycaemic clamp, along with a control group of twenty-one individuals with normal glucose tolerance matched for age, gender, and body mass index. Patients with type 2 diabetes will be scheduled for a three-week run-in period with LR and CGM prior to participation in Part 1. Only patients with a well-functioning loop-recorder and who can comply with CGM will be included. Patients with type 2 diabetes will continue in part 2 of the study, a one year observational study employing CGM and LR and clinical examination after 1, 3, 6, 9, and 12 months and an extended observation period of 2 years employing LR and clinical examination.

Conditions

Diabetes Mellitus, Type 2; Arrhythmia, Cardiac

Outcome Measures

Primary Outcomes (4)

• Part 1: Clinically relevant arrhythmias

  Composite endpoint including atrial fibrillation, brady-arrhythmias and tachy-arrhythmias. Clinically relevant brady-arrhythmias are defined as sinus arrest for more than 3 seconds, frequency below 30 beats per minute (bpm), or high grade atrioventricular (AV) block including Mobitz Type II and third-degree AV block. Clinically relevant tachy-arrhythmias are defined as sustained ventricular tachycardia (duration \>30 seconds), and non-sustained ventricular tachycardia.

  0-240 min during the combined hyper- and hypoglycaemic clamp

• Part 2: Prevalence of clinically relevant arrhythmias as defined above

  Prevalence of clinically relevant arrhythmias as defined above

  Within 12 months

• Part 2: Clinically relevant arrhythmias during hypoglycaemia compared to euglycaemia

  Clinically relevant arrhythmias during hypoglycaemia compared to euglycaemia

  Within 12 months

• Part 2: Difference in MAGE

  Difference in mean amplitude of glycaemic excursions (MAGE) two hours preceding an arrhythmic event versus MAGE during non-event

  Within 12 months

Secondary Outcomes (9)

• Part 1: Differences in mean corrected QT interval (QTc)

  0-240 min during the combined hyper- and hypoglycaemic clamp

• Part 1: Difference in counter regulatory hormonal response

  0-240 min during the combined hyper- and hypoglycaemic clamp

• Part 1: Differences in haemodynamic regulation

  0-240 min during the combined hyper- and hypoglycaemic clamp

• Part 2: Clinical relevant arrhythmias during low glucose variability compared to high glucose variability.

  Within 12 months

• Part 2: The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV

  Within 12 months

Study Arms (2)

Patients with type 2 diabetes

Insulin-treated type 2 diabetes with diabetic complications

Other: Combined hyper- and hypoglycaemic clamp; Device: Loop recorder (Reveal LINQ, Medtronic, Minneapolis, MN, USA); Device: Continuous glucose monitoring (iPro2, Medtronic, Minneapolis, MN, USA)

Healthy controls

Healthy control subjects

Other: Combined hyper- and hypoglycaemic clamp

Interventions

Combined hyper- and hypoglycaemic clamp OTHER

During the entire clamp, participants will be monitored by ECG, pulse oximetry, and blood pressure and plasma glucose will be measured bedside every fifth minute. Additionally, patients with type 2 diabetes will be monitored by a loop recorder (LR) and a continuous glucose monitor (CGM). Comparison of LR and CGM recordings with the recordings obtained by ECG Holter monitor and blood sampling will be used for validation of the method used in Part 2 of the study. Blood samples will be drawn and analysed for changes in electrolytes, insulin, glucagon, catecholamines and cortisone. A cardiac haemodynamic evaluation will be performed by echocardiography at baseline, hyperglycaemia, and hypoglycaemia.

Healthy controls; Patients with type 2 diabetes

Loop recorder (Reveal LINQ, Medtronic, Minneapolis, MN, USA) DEVICE

Implantation of a loop-recorder

Patients with type 2 diabetes

Continuous glucose monitoring (iPro2, Medtronic, Minneapolis, MN, USA) DEVICE

Monitoring with a continuous glucose monitor

Patients with type 2 diabetes

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patiens with insulin-treated type 2 diabetes with complications and healthy controls

You may qualify if:

• Patients with type 2 diabetes
• Informed and written consent
• Type 2 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
• Treatment with insulin
• Glycated haemoglobin A1c (HbA1c) ≤58 mmol/mol
• One or more clinical relevant complications to diabetes defined as: peripheral neuropathy with vibration perception threshold of \> 25 volt determined by biothesiometry, moderate to severe retinopathy, nephropathy (creatinine \>130 μmol/l and/or albuminuria), and/or macrovascular disease. Macrovascular disease is defined as coronary disease (stable angina pectoris or previous unstable angina pectoris or myocardial infarct), cerebrovascular disease (previous stroke or transitional cerebral ischaemia), and peripheral vascular disease (previous intermittent claudication or prior acute ischemia)
• Well-functioning LR during run-in period (acceptable readings judged by an arrhythmologist)
• Participation in the extended study
• Healthy individuals
• HbA1c ≤42 mmol/mol
• Fasting plasma glucose ≤6.1 mmol/l

You may not qualify if:

• Patients with type 2 diabetes
• Severe heart failure (left ventricular ejection fraction \<25%)
• Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
• Insulin naïve patients with type 2 diabetes
• Thyroid dysfunction (except for well-regulated eltroxine substituted myxoedema)
• Unable to comply with daily CGM during run-in period
• Anemia (male: hemoglobin \< 8.0; female: hemoglobin \< 7.0 mmol/l)
• Healthy individuals
• Type 1 or type 2 diabetes
• Prediabetes (HbA1c \>42 mmol/l and/or fasting plasma glucose \>6.1 mmol/l)
• Family history of diabetes (type 1 og type 2 diabetes)
• 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)
• Anemia (male: hemoglobin \< 8.0; female: hemoglobin \< 7.0 mmol/l)

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Gentofte Hospital

Hellerup, 2900, Denmark

Location

Related Publications (1)

• Andersen A, Bagger JI, Sorensen SK, Baldassarre MPA, Pedersen-Bjergaard U, Forman JL, Gislason G, Lindhardt TB, Knop FK, Vilsboll T. Associations of hypoglycemia, glycemic variability and risk of cardiac arrhythmias in insulin-treated patients with type 2 diabetes: a prospective, observational study. Cardiovasc Diabetol. 2021 Dec 24;20(1):241. doi: 10.1186/s12933-021-01425-0.

  PMID: 34952579 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Arrhythmias, Cardiac

Interventions

Continuous Glucose Monitoring

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD-student

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: May 11, 2017
• Study Start: February 1, 2017
• Primary Completion: January 6, 2020
• Study Completion: January 6, 2020
• Last Updated: November 2, 2020

Record last verified: 2020-10

Locations

DK (1)