Clinical trial NCT05500352: Acute Changes in Plasma Glucose and Cardiovascular Disease in Diabetes
Official title: Myocardial Work and Left Ventricular Mechanical Dyssynchrony During Acute Changes in Plasma Glucose in Individuals With Type 1 Diabetes, Type 2 Diabetes and Without Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes
Hypoglycemia
Hyperglycemia
Cardiovascular Diseases
Sudden Cardiac Death
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2022-08-15
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The present echocardiographic study includes participants from three experimental clamp studies; the Hypo-Heart 1 (Study 1), Hypo-Heart 2 (Study 2) and Rapid-Heart (Study 3).
Primary purpose: BASIC_SCIENCE

Brief summary: Patients with diabetes have an increased risk of sudden cardiac death compared to the general population. Severe hypoglycemia is associated with an increased risk of cardiovascular (CV) disease (CVD) and events, including cardiac arrhythmias and sudden cardiac death; likewise, increased glycemic variability is associated with macrovascular complications and increased mortality. The physiological mechanisms linking hypoglycemia and glycemic variability to CVD and CV events remain unclear.

Myocardial work and mechanical dyssynchrony will be measured by speckle tracking echocardiography during euglycemia, hypoglycemia and hyperglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes. Echocardiographic images from three experimental clamp studies - Hypo-Heart 1 (sub-study 1), Hypo-Heart 2 (sub-study 2) and Rapid-Heart - will be included in this study.

Detailed description: The results of this study may be compiled into one or more manuscripts for publication.

Study ID's:

Hypo-Heart 1 (sub-study 1): NCT03956173 Hypo-Heart 2 (sub-study 2): NCT03150030 Rapid-Heart: NCT04800536

Eligibility criteria: The present echocardiographic study includes 86 participants from three experimental clamp studies; the Hypo-Heart 1 (Study 1), Hypo-Heart 2 (Study 2) and Rapid-Heart (Study 3), including patients with type 1 diabetes (Hypo-Heart 1 and Rapid-Heart), patients with type 2 diabetes (Hypo-Heart 2) and healthy controls (Hypo-Heart 2).

Hypo-Heart 1:

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)

Hypo-Heart 2:

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

Inclusion Criteria: 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)

Exclusion Criteria: 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)

Rapid-Heart:

Inclusion criteria - chronic hyperglycaemia cohort

* Informed and written consent
* Type 1 diabetes
* Age ≥18 years
* C-peptide negative (\<0.2 nmol/l)
* Insulin treatment for ≥1 year
* HbA1C ≥63 mmol/mol

Inclusion criteria - well-controlled cohort

* Informed and written consent
* Type 1 diabetes
* Age ≥18 years
* C-peptide negative (\<0.2nmol/l)
* Insulin treatment for ≥1 year
* HbA1C ≤53 mmol/mol

Exclusion criteria - both cohorts

* Arrhythmia diagnosed prior to or at the time of the screening visit
* ECG with left or right bundle branch block diagnosed prior to the screening visit.
* Implantable cardioverter defibrillator or pacemaker at the time of inclusion
* Heart failure diagnosed prior to the screening visit (left ventricular ejection fraction \< 45%)
* Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
* Thyroid dysfunction (except for well-regulated myxoedema)
* Anaemia (male: haemoglobin \<8.0 mmol/l; female: haemoglobin \<7.0 mmol/l)
* Treatment with anticoagulant or antiplatelet treatment
* Bleeding disorder diagnosed prior to the screening visit

Primary outcomes:
measure: Change in the global work during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively.
timeFrame: 255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2)
Secondary outcomes:
measure: Primary secondary outcome: Change in mechanical dyssynchrony during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively.
timeFrame: 255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2)
measure: Change in the global work during recovery in individuals with type 1 diabetes.
timeFrame: 255 minutes
measure: Change in mechanical dyssynchrony during recovery in individuals with type 1 diabetes.
timeFrame: 255 minutes
measure: Change in the global work during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively.
timeFrame: 255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2)
measure: Change in mechanical dyssynchrony during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively.
timeFrame: 255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2)
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen, Denmark
name: Tina Vilsbøll
role: PRINCIPAL_INVESTIGATOR
References: