Acute Changes in Plasma Glucose and Cardiovascular Disease in Diabetes

NCT ID: NCT05500352

Last Updated: 2022-08-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2023-12-01

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Cardiovascular effects of slowly declining plasma glucose in type 1 diabetes

Group Type: EXPERIMENTAL

Hyperglycemia with slow decline in plasma glucose in type 1 diabetes

Intervention Type: OTHER

Acute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Slow plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l).

Cardiovascular effects of rapidly declining plasma glucose in type 1 diabetes

Group Type: EXPERIMENTAL

Hyperglycemia with rapid decline in plasma glucose in type 1 diabetes

Intervention Type: OTHER

Acute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Rapid plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l).

Cardiovascular effects of rebound hyperglycemia in type 1 diabetes

Group Type: EXPERIMENTAL

Rebound hyperglycemia in type 1 diabetes

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in hyperglycemia (20.0 mmol/L)

Cardiovascular effects of rebound euglycemia in type 1 diabetes

Group Type: EXPERIMENTAL

Rebound euglycemia in type 1 diabetes

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in euglycemia (PG: 5-8 mmol/L).

Cardiovascular effects of hypoglycemia in type 1 diabetes

Group Type: EXPERIMENTAL

Hypoglycemia in type 1 diabetes

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in hyperglycemia (20.0 mmol/L) or euglycemia (PG: 5-8 mmol/L)

Cardiovascular effects of hypoglycemia in type 2 diabetes

Group Type: EXPERIMENTAL

Hypoglycemia in type 2 diabetes

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Cardiovascular effects of hypoglycemia in healthy controls

Group Type: EXPERIMENTAL

Hypoglycemia in healthy controls

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Cardiovascular effects of hyperglycemia in type 2 diabetes

Group Type: EXPERIMENTAL

Hyperglycemia in type 2 diabetes

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Cardiovascular effects of hyperglycemia in healthy controls

Group Type: EXPERIMENTAL

Hyperglycemia in healthy controls

Intervention Type: OTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Interventions

Hyperglycemia with slow decline in plasma glucose in type 1 diabetes

Acute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Slow plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l).

Intervention Type: OTHER

Hyperglycemia with rapid decline in plasma glucose in type 1 diabetes

Acute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Rapid plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l).

Intervention Type: OTHER

Rebound hyperglycemia in type 1 diabetes

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in hyperglycemia (20.0 mmol/L)

Intervention Type: OTHER

Rebound euglycemia in type 1 diabetes

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in euglycemia (PG: 5-8 mmol/L).

Intervention Type: OTHER

Hypoglycemia in type 1 diabetes

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in hyperglycemia (20.0 mmol/L) or euglycemia (PG: 5-8 mmol/L)

Intervention Type: OTHER

Hypoglycemia in type 2 diabetes

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Intervention Type: OTHER

Hypoglycemia in healthy controls

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Intervention Type: OTHER

Hyperglycemia in type 2 diabetes

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Intervention Type: OTHER

Hyperglycemia in healthy controls

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Intervention Type: OTHER

Other Intervention Names

Experimental clamp; Experimental clamp; Experimental clamp; Experimental clamp; Experimental clamp; Experimental clamp; Experimental clamp

Eligibility Criteria

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

• 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

• HbA1c ≤42 mmol/mol
• Fasting plasma glucose ≤6.1 mmol/l

• 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

• 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

• 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:

• 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)

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tina Vilsbøll

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Copenhagen, Denmark

Locations

Steno Diabetes Center Copenhagen

Herlev, , Denmark

Countries

Denmark

Other Identifiers

H18034040_part2

Identifier Type: -

Identifier Source: org_study_id