Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus

November 9, 2016 updated by: Rambam Health Care Campus

Acute Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus

Our investigation studies the role of acute insulin administration on the diabetic heart, its corresponding effective blood-insulin level and the time-course applicability of insulin in a routine clinical setting.

A case series of six male (48.1 ± 4.9 y/o) patients with controlled diabetes (HbA1c of 6.6 ± 0.3%, disease duration of 14.4 ± 6.7 yr). Each subject was evaluated for glucose homeostatic, hemodynamic and echocardiographic systolic and diastolic parameters at baseline and following two successive insulin-load steps of a euglycemic hyperinsulinemic clamp study, each 2 h in duration. Results are presented as a mean ± SEM and analysed using the student's t-test.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients:

Six male diabetic (five type 2 and one type 1) patients, 30-65 year old, with an established diagnosis of diabetes mellitus for ≥2 years, who were free of significant valvular heart disease, atrial arrhythmia or cardiac pacing comprised the study population. Patients' characteristics are summarized in table 1.

Each patient served as his or her own control. The study protocol was approved by the ethics committee at Rambam Medical Center, Haifa, Israel. Prior to the study, patients gave written informed consent after receiving a detailed explanation as to the purpose of the study, the technique, its side effects and the study protocol.

Patients were studied within a clinical research facility at the Rambam Medical Center, Haifa, Israel. Baseline evaluation was conducted at 8:00 am after 12 h of fasting, followed by two hyperinsulinemic euglycemic clamp (EHC) steps (2 h each step); The following vital signs were monitored during the study protocol: manual heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and baseline 12-lead electrocardiogram (ECG) recording. Glucose consumption rates against changing insulin levels were measured by the EHC technique. Cardiac function parameters were measured in the last 10 min of each step by tissue Doppler echocardiography. Results are presented as a mean ± SEM.

Clamp technique:

Each patient underwent an EHC study according to the protocol described previously, and implemented in our institute. Baseline measurements of blood insulin and glucose levels were collected. Thereafter, two insulin loads were initiated. The blood glucose level was kept near euglycemia (90 ± 5 mg/dl) throughout 2 h period of each insulin load step. Intravenous (iv) insulin loads were administered by 1- and 10-mU/kg·min at steps 1 and 2 of insulin loading (Lispro Insulin, Eli Lilly, France), respectively. Dexstrose in water 50% (DW50) was infused at variable infusion rates, titrated to maintain euglycemia. Concomitant saline 0.45% was used to dilute the DW50 in order to prevent hypertonicity-induced irritation of the cannuled vein. During the baseline period, saline 0.45% infusion rates were 0.75 ml/min to keep the iv cannule open. Every patient was given a chance to urinate before step 2.

Glucose and insulin homeostatic parameters of the study group were compared to those of healthy controls we studied earlier.

Cardiac function assessment:

Transthoracic echocardiography was performed by a qualified echocardiographer using a General Electric Vivid 3 machine (Tirat HaCarmel, Israel). Parameters were assessed as the mean of three consecutive heart beats.

Systolic echocardiographic parameters:

LV fractional shortening (LVFS) derived from end diastolic and end systolic LV dimensions; LV ejection fraction (LVEF) derived from end diastolic and end systolic LV volumes.

Diastolic echocardiographic parameters:

  1. Mitral valve diastolic flow parameters by pulse wave Doppler: E wave, represents early diastolic filling; A wave, represents late diastolic filling concomitant with the atrial kick, E/A ratio and E wave deceleration time (DT).
  2. Tissue Doppler-derived velocities of the mitral annulus: E' represents early diastolic velocity synchronous to the mitral inflow E wave, measured close to the interventricular septum (E' medial) and lateral wall (E' lateral); E' mean, derived from E' lateral and E' medial. A' represents late diastolic velocity to the synchronous mitral inflow A wave, measured close to the septum (A' medial) and lateral wall (A' lateral). A' mean is derived from A' lat. and A' med. A' reflects mitral annulus movement during atrial contraction. The E to E' ratio represents diastolic LV compliance.

Results are presented as mean ± SEM and analyzed using the student's t-test. Statistical significance considered when p value less than 0.05.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

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

  • Israel
      • Haifa, Israel
        • Rambam Medical Center

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

Ages Eligible for Study

30 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Diabetes mellitus duration of 2 years and over.

Exclusion Criteria:

  • Previous cardiac disease: valvular, Pacing, Arrhythmias, Primary Cardiomyopathy.

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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diabetic patients

Diabetic patients were treated with insulin loads, left ventricle functional parameters were compared to those of healthy persons.

Metabolic indices of insulin effect: blood insulin levels, glucose disposal rates under insulin infusion, were compared to respective group of healthy persons, studied earlier at our institution Insulin LISPRO intravenous loading
Drug: Insulin LISPRO intravenous loading
intravenous infusion of insulin Lispro.
Other Names:
  • Humalog Insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Left ventricle ejection fraction (%)
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time needed to exert insulin effect on myocardial function (hour)
Time Frame: 1 year
Describe the shortest time required for insulin to change myocardial function.
1 year

Other Outcome Measures

Outcome Measure
Time Frame
Blood insulin levels (μU/ml: micro international unit per milliliter)
Time Frame: 1 year
1 year
Left ventricle fractioning shortening (%)
Time Frame: 1 year
1 year
E wave (centimeter per second)
Time Frame: 1 year
1 year
A wave (centimeter per second)
Time Frame: 1 year
1 year
E deceleration time (seconds)
Time Frame: 1 year
1 year
E' (centimeters)
Time Frame: 1 year
1 year
A' (centimeters)
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

Rambam Health Care Campus

Investigators

  • Study Chair: Eddy Karnieli, MD, Professor emeritus, Faculty of medicine, Technion. Haifa, Israel
  • Principal Investigator: Ronen Bar Yoseph, MD, Pediatric Pulmonary Institute
  • Principal Investigator: Sergey Yalonetsky, MD, Cardiology Division

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

February 1, 2003

Primary Completion (Actual)

May 1, 2003

Study Completion (Actual)

November 1, 2004

Study Registration Dates

First Submitted

September 10, 2016

First Submitted That Met QC Criteria

November 9, 2016

First Posted (Estimate)

November 15, 2016

Study Record Updates

Last Update Posted (Estimate)

November 15, 2016

Last Update Submitted That Met QC Criteria

November 9, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1558-RMB-CTIL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

First we need to learn how to share data

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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