Clinical trial NCT03150030: Hypoglycaemia and Cardiac Arrhythmias in Type 2 Diabetes
Official title: Hypoglycaemia and Cardiac Arrhythmias in Type 2 Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 2
Arrhythmia, Cardiac
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2017-05-11
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patiens with insulin-treated type 2 diabetes with complications and healthy controls

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

Patients with type 2 diabetes

* Arrhythmia diagnosed prior to or at the time of inclusion
* 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)
* 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)
* Arrhythmia diagnosed prior to or at the time of inclusion
* 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)
* Anemia (male: hemoglobin \< 8.0; female: hemoglobin \< 7.0 mmol/l)

Primary outcomes:
measure: Part 1: Clinically relevant arrhythmias
timeFrame: 0-240 min during the combined hyper- and hypoglycaemic clamp
measure: Part 2: Prevalence of clinically relevant arrhythmias as defined above
timeFrame: Within 12 months
measure: Part 2: Clinically relevant arrhythmias during hypoglycaemia compared to euglycaemia
timeFrame: Within 12 months
measure: Part 2: Difference in MAGE
timeFrame: Within 12 months
Secondary outcomes:
measure: Part 1: Differences in mean corrected QT interval (QTc)
timeFrame: 0-240 min during the combined hyper- and hypoglycaemic clamp
measure: Part 1: Difference in counter regulatory hormonal response
timeFrame: 0-240 min during the combined hyper- and hypoglycaemic clamp
measure: Part 1: Differences in haemodynamic regulation
timeFrame: 0-240 min during the combined hyper- and hypoglycaemic clamp
measure: Part 2: Clinical relevant arrhythmias during low glucose variability compared to high glucose variability.
timeFrame: Within 12 months
measure: Part 2: The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
timeFrame: Within 12 months
measure: Part 2: The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
timeFrame: Within 12 months
measure: Part 2: The relationship between diabetes complication status at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
timeFrame: Within 12 months
measure: Part 2: Correlation between prevalence and total duration of hypoglycaemia and risk of clinically relevant arrhythmias
timeFrame: Within 12 months
measure: Part 2: Correlation between plasma glucose variation and risk of clinical relevant arrhythmias
timeFrame: Within 12 months
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Gentofte Hospital
Study officials:
References:
citation: 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.