Cardiovascular Diseases, Diabetes, Hyperglycemia, Hypoglycemia, Sudden Cardiac Death
Conditions
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
Interventions
OTHERHyperglycemia 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).
OTHERHyperglycemia 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).
OTHERRebound 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)
OTHERRebound 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).
OTHERHypoglycemia 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)
OTHERHypoglycemia 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).
OTHERHypoglycemia 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).
OTHERHyperglycemia 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).
OTHERHyperglycemia 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
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the global work during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively. | 255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2) | Absolute change in the global work index measured by pressure-strain loop analysis during insulin-induced hypoglycemia compared to euglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively (Hypo-Heart 1 and Hypo-Heart 2). Study outcomes will be analyzed separately for each included study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary secondary outcome: Change in mechanical dyssynchrony during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively. | 255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2) | Absolute change in mechanical dyssynchrony (defined as the standard deviation of regional time to peak strain) measured by speckle tracking echocardiography measured by pressure-strain loop analysis during insulin-induced hypoglycemia compared to euglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively (Hypo-Heart 1 and Hypo-Heart 2). Study outcomes will be analyzed separately for each included study. |
| Change in the global work during recovery in individuals with type 1 diabetes. | 255 minutes | Absolute change in the global work index measured by pressure-strain loop analysis during recovery (post-hypoglycemic euglycemia and hyperglycemia) compared to euglycemia in individuals with type 1 diabetes (Hypo-Heart 1). Study outcomes will be analyzed separately for each included study. |
| Change in mechanical dyssynchrony during recovery in individuals with type 1 diabetes. | 255 minutes | Absolute change in mechanical dyssynchrony (defined as the standard deviation of regional time to peak strain) measured by speckle tracking echocardiography measured by pressure-strain loop analysis during recovery (post-hypoglycemic euglycemia and hyperglycemia) compared to euglycemia in individuals with type 1 diabetes (Hypo-Heart 1). Study outcomes will be analyzed separately for each included study. |
| Change in the global work during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively. | 255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2) | Absolute change in the global work index measured by pressure-strain loop analysis during hyperglycemia compared to euglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively (Rapid Heart and Hypo-Heart 2). Study outcomes will be analyzed separately for each included study. |
| Change in mechanical dyssynchrony during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively. | 255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2) | Absolute change in mechanical dyssynchrony (defined as the standard deviation of regional time to peak strain) measured by speckle tracking echocardiography measured by pressure-strain loop analysis during hyperglycemia compared to euglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively (Rapid Heart and Hypo-Heart 2). Study outcomes will be analyzed separately for each included study. |
Countries
Denmark
Outcome results
None listed