Acute Changes in Plasma Glucose and Cardiovascular Disease in Diabetes

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.

Conditions

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

Interventions

OTHER

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).

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).

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)

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).

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)

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).

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).

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).

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).

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen

  lead OTHER

Principal Investigators

• Tina Vilsbøll · Steno Diabetes Center Copenhagen, Denmark

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-07-01

Primary Completion

2023-05-01

Completion

2023-12-01

Countries

• Denmark

Study Locations