The Suppression of Toll Like Receptors by Insulin

NCT ID: NCT01151605

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2013-12-31

Brief Summary

This study will help us understand the possible beneficial effects of insulin in inflammation. Inflamamtion is considered to be the cause of atherosclerosis and heart disease.

Detailed Description

Obesity and type 2 diabetes are major health problems in the United States and the world. Both conditions are characterized by increased inflammation and oxidative stress and are associated with increased risk of cardiovascular disease.

Our previous work shows that insulin exerts a prompt and powerful anti-inflammatory effect, on circulating blood cells and in plasma in healthy subjects and in critically ill patients.

Toll like receptors (TLRs) recognize bacterial and viral products like endotoxin and viruses and are major determinants of the inflammatory response against foreign pathogens. In view of the recent data showing that TLRs recognize a range of molecules and proteins that are not of pathogenic source like saturated lipids and that TLRs are involved in the pathogenesis of atherosclerosis which leads to cardiovascular disease and insulin resistance which leads to type 2 diabetes (DM) we hypothesized that insulin infusion suppresses TLRs expression.

Our preliminary data show that insulin infusion for 4 hours reduces the levels of many TLRs and thus might protect from inflammation induced conditions We therefore propose to investigate, in more detail, the effect of infusing different doses of insulin on TLRs mRNA and protein levels and its activity in obese and DM subjects over a longer infusion period and a larger number of subjects in circulating white blood cells and in fat tissue. Also we will be comparing the baseline levels of TLRs and TLRs related proteins as well as their modulation by insulin between normal, obese and DM subjects.

Conditions

Insulin Resistance

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

obese subjects

obese (BMI \>30Kg/m2) subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr

Group Type: EXPERIMENTAL

insulin infusion

Intervention Type: DRUG

insulin to be infused at 3.5 units/hour along with Dextrose 12.5% at a rate to achieve blood glucose levels between 80-120mg/dl

Dextrose infusion

Intervention Type: DRUG

Dextrose 12.5% will be infused at a rate to maintain blood glucose level 80-120mg/dl

Saline Infusion

Intervention Type: DRUG

Saline will be infused at 100ml/hr

Normal weight subjects

Normal weight subjects infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr

Group Type: ACTIVE_COMPARATOR

insulin infusion

Intervention Type: DRUG

insulin to be infused at 3.5 units/hour along with Dextrose 12.5% at a rate to achieve blood glucose levels between 80-120mg/dl

Dextrose infusion

Intervention Type: DRUG

Dextrose 12.5% will be infused at a rate to maintain blood glucose level 80-120mg/dl

Saline Infusion

Intervention Type: DRUG

Saline will be infused at 100ml/hr

obese type 2 diabetes subjects

obese (BMI \>30Kg/m2) subjects with type 2 diabetes infused with insulin dextrose or saline 1 week apart. Each infusion will continue for up to 14 hr

Group Type: EXPERIMENTAL

insulin infusion

Intervention Type: DRUG

insulin to be infused at 3.5 units/hour along with Dextrose 12.5% at a rate to achieve blood glucose levels between 80-120mg/dl

Dextrose infusion

Intervention Type: DRUG

Dextrose 12.5% will be infused at a rate to maintain blood glucose level 80-120mg/dl

Saline Infusion

Intervention Type: DRUG

Saline will be infused at 100ml/hr

Interventions

insulin infusion

insulin to be infused at 3.5 units/hour along with Dextrose 12.5% at a rate to achieve blood glucose levels between 80-120mg/dl

Intervention Type: DRUG

Dextrose infusion

Dextrose 12.5% will be infused at a rate to maintain blood glucose level 80-120mg/dl

Intervention Type: DRUG

Saline Infusion

Saline will be infused at 100ml/hr

Intervention Type: DRUG

Other Intervention Names

Intravenous regular insulin infusion; Intravenous dextrose solution infusion; normal saline infusion

Eligibility Criteria

Inclusion Criteria

Lean Group:

1. Age: 20 to 65 years of age inclusive

2. Sex: male or female

3. Normal fasting plasma glucose (65-100 mg/dl)

4. Normal BMI (20-25)

Obese Group:

1. Age: 20 to 65 years of age inclusive

2. Sex: male or female

3. Normal fasting plasma glucose (65-100 mg/dl)

4. BMI> 30

DM Group:

1. Type 2 Diabetes Mellitus

2. Age: 20 to 65 years of age inclusive

3. Sex: male or female

4. BMI >30

5. Hba1c < 8%

6. If on statins, angiotensin converting enzyme inhibitor, angiotensin receptor blocker or low dose aspirin, should be on a stable dose for one month.

Exclusion Criteria

1. Pregnancy

2. Congestive heart failure

3. Heart Rate <50 beats /minute

4. Sick Sinus Syndrome

5. Second or third degree heart block

6. Blood pressure <80 mm systolic or > 160/100 mmHg

7. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass surgery or coronary angioplasty) in the previous three months

8. Hepatic disease (transaminase > 3 times normal)

9. Renal impairment (serum creatinine > 1.5)

10. History of drug or alcohol abuse within past one year

11. Participation in any other concurrent clinical trial

12. Potassium (K+) values <3.5 meq/l to > 5.5 meq/l)

13. Any other life-threatening, non-cardiac disease

14. Use of an investigational agent or therapeutic regimen within 30 days of study

15. Type 2 diabetics on thiazolidinediones and/ or insulin

16. Subjects on steroids, NSAIDS or antioxidants

17. Patients taking exenatide or sitaglipin or loop diuretics

18. Anemia (Hemoglobin level less than 12gm/dl in females and 13gm/dl in males) 19)Allergy to lidocaine

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

University at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

Paresh Dandona

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paresh Dandona, MBBS

Role: PRINCIPAL_INVESTIGATOR

The Research foundation of SUNY at Buffalo

Locations

Millard Fillmore Gates Hospital

Buffalo, New York, United States

Countries

United States

Other Identifiers

708CR13

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1934

Identifier Type: -

Identifier Source: org_study_id