Insulin ResistanceNCT01151605
The Suppression of Toll Like Receptors by Insulin
A study testing insulin infusion, Dextrose infusion and Saline Infusion in people with Insulin Resistance, run by University at Buffalo at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- insulin infusion, Dextrose infusion and Saline Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Dec 2013
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Lean Group:
- Age: 20 to 65 years of age inclusive
- Sex: male or female
- Normal fasting plasma glucose (65-100 mg/dl)
- Normal BMI (20-25)
- Obese Group:
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- Age: 20 to 65 years of age inclusive
- Sex: male or female
- Normal fasting plasma glucose (65-100 mg/dl)
- BMI> 30
- DM Group:
- Type 2 Diabetes Mellitus
- Age: 20 to 65 years of age inclusive
- Sex: male or female
- BMI >30
- Hba1c < 8%
- If on statins, angiotensin converting enzyme inhibitor, angiotensin receptor blocker or low dose aspirin, should be on a stable dose for one month.
Who cannot join
- Pregnancy
- Congestive heart failure
- Heart Rate <50 beats /minute
- Sick Sinus Syndrome
- Second or third degree heart block
- Blood pressure <80 mm systolic or > 160/100 mmHg
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- Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass surgery or coronary angioplasty) in the previous three months
- Hepatic disease (transaminase > 3 times normal)
- Renal impairment (serum creatinine > 1.5)
- History of drug or alcohol abuse within past one year
- Participation in any other concurrent clinical trial
- Potassium (K+) values <3.5 meq/l to > 5.5 meq/l)
- Any other life-threatening, non-cardiac disease
- Use of an investigational agent or therapeutic regimen within 30 days of study
- Type 2 diabetics on thiazolidinediones and/ or insulin
- Subjects on steroids, NSAIDS or antioxidants
- Patients taking exenatide or sitaglipin or loop diuretics
- Anemia (Hemoglobin level less than 12gm/dl in females and 13gm/dl in males) 19)Allergy to lidocaine
Trial locations and contacts
1 site in 1 country.
United States1 site
Millard Fillmore Gates Hospital
Buffalo, New York, 14209
About this study
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.
Read the 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
- Being tested
- insulin infusion, Dextrose infusion, Saline Infusion
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
insulin infusionDrug
Also called Intravenous regular 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 infusionDrug
Also called Intravenous dextrose solution infusion
Dextrose 12.5% will be infused at a rate to maintain blood glucose level 80-120mg/dl
Saline InfusionDrug
Also called normal saline infusion
Saline will be infused at 100ml/hr
| Study group | Role | What they receive |
|---|---|---|
| obese subjects | Experimental | obese (BMI >30Kg/m2) subjects infused with insulin, dextrose and saline in this specific sequence 1 week apart. Each infusion will continue for up to 24 hr Receives: Drug: insulin infusion; Drug: Dextrose infusion; Drug: Saline Infusion |
| Normal weight subjects | Active comparator | Normal weight subjects infused with insulin, dextrose and saline in this specific sequence 1 week apart. Each infusion will continue for up to 24 hr Receives: Drug: insulin infusion; Drug: Dextrose infusion; Drug: Saline Infusion |
| obese type 2 diabetes subjects | Experimental | obese (BMI >30Kg/m2) subjects with type 2 diabetes infused with insulin, dextrose and saline in this specific sequence 1 week apart. Each infusion will continue for up to 24 hr Receives: Drug: insulin infusion; Drug: Dextrose infusion; Drug: Saline Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Suppression of Toll Like Receptor (TLR) 2 mRNA by Insulin
percent change from baseline (0hrs) in TLR2 mRNA in mononuclear cells (MNC) following up to 24 hrs of 3.5U/hr insulin infusion (II) adjusted to the similar average change following up to 24hr infusion of dextrose (DI) and saline (SI) control groups. The correction is calculated as follows: Corrected percent change from baseline following II= change from baseline following II - (average change from baseline following DI and SI)*100. Changes from baseline are calculated as: (expression at 24hrs-expression at 0hr)/expression at 0hr.
Measured: 24 hours
Secondary outcomes (3)
Change in TLR4 mRNA in MNC
percent change from baseline (0hrs) in TLR4 mRNA in mononuclear cells (MNC) following up to 24 hrs of 3.5U/hr insulin infusion (II) adjusted to the same change following up to 24hr infusion of dextrose (DI) and saline (SI) control groups in this order. The correction is conducted as follows: Corrected percent change from baseline following II= change from baseline following II - (average change from baseline following DI and SI)*100. Changes from baseline are calculated as: (expression at 24hrs-expression at 0hr)/expression at 0hr.
2- For each PCR measurement of specific target gene, relative expression of 3 housekeeping genes (beta-actin, ubiquitin C and cyclophilin A) from the same cDNA is assessed, and normalization factor (based on the 3 genes) is calculated and entered into PCR software to automatically adjust/normalize target gene expression
Measured: 24 hours
Change in CD14 Expression in MNC
percent change from baseline (0hrs) in CD14 mRNA in mononuclear cells (MNC) following up to 24 hrs of 3.5U/hr insulin infusion (II) adjusted to the similar average change following up to 24hr infusion of dextrose (DI) and saline (SI) control groups in this specific order. The correction is conducted as follows: Corrected percent change from baseline following II= change from baseline following II - (average change from baseline following DI and SI)*100. Changes from baseline are calculated as: (expression at 24hrs-expression at 0hr)/expression at 0hr. For each PCR measurement of specific target gene, relative expression of 3 housekeeping genes (beta-actin, ubiquitin C and cyclophilin A) from the same cDNA is assessed, and normalization factor (based on the 3 genes) is calculated and entered into PCR software to automatically adjust/normalize target gene expression.
Measured: 24hrs
Fasting TLR2 mRNA Expression Levels in the 3 Cohorts
Comparison of TLR2 mRNA expression in MNC in fasting condition. Fasting TLR2 mRNA expression is measured using real-time PCR at baselines of the 3 visits (II, DI, SI visits) is averaged and reported as arbitrary units. For each PCR measurement of specific target gene, relative expression of 3 housekeeping genes (beta-actin, ubiquitin C and cyclophilin A) from the same cDNA is assessed, and normalization factor (based on the 3 genes) is calculated and entered into PCR software to automatically adjust/normalize target gene expression.
Measured: baseline/fasting
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2010 (estimated)
- Study startSep 2008
- Primary completionJul 2012
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All subjects in each cohort (normal weight, obese and obese with type 2 diabetes) received the 3 interventions (insulin, followed by dextrose, and then Saline) in a fixed sequence.
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University at Buffalo
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Principal investigator, Paresh Dandona, University at Buffalo
- Investigators
- Paresh Dandona, MBBS, Principal investigator, The Research foundation of SUNY at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01151605
- Sponsor's protocol ID
- 1934
- Other IDs
- 708CR13
- Status last verified
- Aug 2026
- First submitted
- 25 Jun 2010
- Last updated
- 11 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No