Acute Changes in Plasma Glucose and Cardiovascular Disease in Diabetes

Steno Diabetes Centers

Status: Active, not recruiting

Conditions: Hypoglycemia; Diabetes; Hyperglycemia; Cardiovascular Diseases; Sudden Cardiac Death

Treatments: Other: Hyperglycemia with slow decline in plasma glucose in type 1 diabetes; Other: Hyperglycemia in type 2 diabetes; Other: Hypoglycemia in healthy controls; Other: Rebound euglycemia in type 1 diabetes; Other: Hyperglycemia in healthy controls; Other: Rebound hyperglycemia in type 1 diabetes; Other: Hypoglycemia in type 1 diabetes; Other: Hypoglycemia in type 2 diabetes; Other: Hyperglycemia with rapid decline in plasma glucose in type 1 diabetes

Study type: Interventional

Funder types: Other

Identifiers

NCT05500352

H18034040_part2

Details and patient eligibility

About

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.

Full 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

Enrollment: 86 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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86 participants in 9 patient groups

Cardiovascular effects of slowly declining plasma glucose in type 1 diabetes

Experimental group

Treatment:

Other: Hyperglycemia with slow decline in plasma glucose in type 1 diabetes

Cardiovascular effects of rapidly declining plasma glucose in type 1 diabetes

Experimental group

Treatment:

Other: Hyperglycemia with rapid decline in plasma glucose in type 1 diabetes

Cardiovascular effects of rebound hyperglycemia in type 1 diabetes

Experimental group

Treatment:

Other: Rebound hyperglycemia in type 1 diabetes

Cardiovascular effects of rebound euglycemia in type 1 diabetes

Experimental group

Treatment:

Other: Rebound euglycemia in type 1 diabetes

Cardiovascular effects of hypoglycemia in type 1 diabetes

Experimental group

Treatment:

Other: Hypoglycemia in type 1 diabetes

Cardiovascular effects of hypoglycemia in type 2 diabetes

Experimental group

Treatment:

Other: Hypoglycemia in type 2 diabetes

Cardiovascular effects of hypoglycemia in healthy controls

Experimental group

Treatment:

Other: Hypoglycemia in healthy controls

Cardiovascular effects of hyperglycemia in type 2 diabetes

Experimental group

Treatment:

Other: Hyperglycemia in type 2 diabetes

Cardiovascular effects of hyperglycemia in healthy controls

Experimental group

Treatment:

Other: Hyperglycemia in healthy controls