Acute Changes in Plasma Glucose and Cardiovascular Disease in Diabetes

August 15, 2022 updated by: Steno Diabetes Center Copenhagen

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
86

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Herlev, Denmark, 2920
        • Steno Diabetes Center Copenhagen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cardiovascular effects of slowly declining plasma glucose in type 1 diabetes
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).
Experimental: Cardiovascular effects of rapidly declining plasma glucose in type 1 diabetes
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).
Experimental: Cardiovascular effects of rebound hyperglycemia in type 1 diabetes
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 Names:
  • Experimental clamp
Experimental: Cardiovascular effects of rebound euglycemia in type 1 diabetes
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 Names:
  • Experimental clamp
Experimental: Cardiovascular effects of hypoglycemia in type 1 diabetes
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 Names:
  • Experimental clamp
Experimental: Cardiovascular effects of hypoglycemia in type 2 diabetes
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 Names:
  • Experimental clamp
Experimental: Cardiovascular effects of hypoglycemia in healthy controls
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 Names:
  • Experimental clamp
Experimental: Cardiovascular effects of hyperglycemia in type 2 diabetes
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 Names:
  • Experimental clamp
Experimental: Cardiovascular effects of hyperglycemia in healthy controls
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).
Other Names:
  • Experimental clamp

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the global work during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively.
Time Frame: 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.
255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Primary secondary outcome: Change in mechanical dyssynchrony during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively.
Time Frame: 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.
255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2)
Change in the global work during recovery in individuals with type 1 diabetes.
Time Frame: 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.
255 minutes
Change in mechanical dyssynchrony during recovery in individuals with type 1 diabetes.
Time Frame: 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.
255 minutes
Change in the global work during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively.
Time Frame: 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.
255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2)
Change in mechanical dyssynchrony during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively.
Time Frame: 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.
255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Steno Diabetes Center Copenhagen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tina Vilsbøll, Steno Diabetes Center Copenhagen, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 6, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 10, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H18034040_part2

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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