Obesity
Conditions
Keywords
Obesity, Insulin Resistance
Brief summary
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
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.
Interventions
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.
Sponsors
National Institute of General Medical Sciences (NIGMS)
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma concentration of drugs fentanyl and propofol | measured for 12 hours (beginning of anesthesia to 12 hours after) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adiponectin plasma protein levels | measured once (immediately before the operation) | 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. |
| Adiponectin gene polymorphisms | measured once per study (immediately before the operation) | 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. |
Countries
United States
Outcome results
None listed