The Suppression of Toll Like Receptors by Insulin

Insulin Resistance Clinical Trial

Official title:

The Suppression of Toll Like Receptors by Insulin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01151605
• Other study ID #: 1934
• Secondary ID: 708CR13
• Status: Completed
• Phase: N/A
• Start date: September 2008
• Est. completion date: December 2013

Study information

• Verified date: January 2024
• Source: University at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Drug:
• 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
• Dextrose infusion
Dextrose 12.5% will be infused at a rate to maintain blood glucose level 80-120mg/dl
• Saline Infusion
Saline will be infused at 100ml/hr

Locations

Country	Name	City	State
United States	Millard Fillmore Gates Hospital	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
University at Buffalo	American Diabetes Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Suppression of Toll Like receptors by Insulin	Expression of TLR2, TLR4, TLR7 and TLR9 mRNA in mononuclear cells and adipose tissue	24 hours
Secondary	TLR expression	Basal TLR expression in obese and type 2 diabetic subjects as compared to lean subjects	0 hours