Adiponectin Polymorphisms, Insulin Resistance, and Pharmacokinetics in Obesity

Study Overview
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Brief Summary
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The primary objective of this study is to determine the influence of insulin resistance on drug metabolism and response in obese subjects. The investigators hypothesize that expression of adiponectin (a hormone secreted by fat tissue), and specific variants in the adiponectin gene can predict the insulin resistance and drug response among obese subjects.

Detailed Description
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The following study will hypothesizes that insulin resistance causes changes in drug metabolism, elimination, and effect. We will differentiate the insulin resistant phenotype amongst obese individuals on the basis of both laboratory (fasting insulin, triglycerides, fasting glucose) analysis, and quantitative and qualitative adiponectin expression. We will determine the effect of insulin resistance on the pharmacokinetics and pharmacodynamics of anesthetic induction agents and opioids, using propofol and fentanyl as examples.

Official Title
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Adiponectin Polymorphisms, Insulin Resistance, and Pharmacokinetics in Obesity

Conditions
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Obesity

Intervention / Treatment
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* Drug: Propofol and Fentanyl administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria include patients of adult age American Society of Anesthesiologists Class I, II, or III, and undergoing elective surgical procedures requiring general anesthesia Body mass index greater than 35 Exclusion Criteria: Patients with evidence of hepatic, renal, or cardiovascular dysfunction History of difficult tracheal intubation, or adverse reaction to anesthesia shall be excluded from the study Patients taking prescribed or over-the-counter anxiolytics, narcotics, or sleeping aids, will also be excluded

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propofol and Fentanyl administration<br>Propofol and Fentanyl will be administered to all subjects. All subjects will have blood drawn to determine pharmacokinetic variables. Processed EEG will be used to determine pharmacodynamics. Plasma samples will be used to ascertain adiponectin levels and for DNA sampling for analysis of adiponectin single nucleotide polymorphisms. | Drug: Propofol and Fentanyl administration<br>* Propofol will be administered to all patients via infusion at a dose of 2 mg/kg lean body weight/minute. The infusion will stop once loss of consciousness is reached. Fentanyl will be administered via target controlled infusion to achieve a plasma concentration of 2 ng/ml.<br>* Other names: anesthetic administration;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma concentration of drugs fentanyl and propofol | Plasma concentration over time will be measured and modeled in order to calculate drug clearance, volume of distribution, area under the curve, and micro rate constants. Knowledge of these variables will allow safer administration of anesthetic drug administration in the obese population. | measured for 12 hours (beginning of anesthesia to 12 hours after) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adiponectin plasma protein levels | The investigators will measure specific levels of the protein adiponectin in the blood, to determine if quantitative expression of adiponectin can predict insulin resistance in obesity and drug metabolism and response. | measured once (immediately before the operation) | 
| Adiponectin gene polymorphisms | The investigators will look at specific genetic variants of the adiponectin gene to determine if expression of specific variants can predict insulin resistance and changed in drug response and metabolism. | measured once per study (immediately before the operation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Insulin Resistance