Insulin Resistance
Conditions
Brief summary
The investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. To test this hypothesis, the investigators propose to determine the role of the autonomic nervous system in hepatic insulin resistance.
Detailed description
In this study, the investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. The investigators will measure EGP at baseline (EGPBsl) and during the last 30 minutes of a hyperinsulinemic euglycemic clamp (EGPClamp) on two different occasions (intact and Blocked study days). A double blinded randomize cross-over design will be used. Subjects will be randomized to either the intact or blocked days and a month later will be crossed-over to the other arm. The investigator performing the analysis will also be blinded to the treatments received. At baseline in both study days it is expected to see any differences since the same subject will serve as his own control. During the clamp, insulin suppresses EGP. In obese insulin resistant subjects this suppression should be blunted. If the hypothesis is correct, it is expected an improvement in the suppression by insulin of EGP during autonomic blockade only. For this study, the primary endpoint therefore, will be the EGP during the clamp between the intact and blocked days. H0= {(EGPClamp)Blocked - (EGPClamp)Intact}=0\]
Interventions
DRUGTrimethaphan
Trimethaphan 4 mg/min IV will be given as a pharmacological tool to study the role of the autonomic nervous system on the regulation of endogenous glucose production by the liver.
OTHERSaline
IV saline at a rate of 48 mL/hr, will be given during the insulin clamp to resemble the volume infused in the intact day
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Subjects will be studied twice, randomly assigned to star on the intact day (saline) or the blocked day (trimethaphan) and after 1 month cross to the other arm
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Males and females of all races between 18 and 60 years of age * Hypertension defined by two or more properly measured seated blood pressure readings \>130/85 mmHg or currently on antihypertensive medication. This will allow us to include subjects with pre-hypertension. * Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2. * Insulin resistance will be defined as a HOMA2 IR index ≥1.6 * Able and willing to provide informed consent
Exclusion criteria
* Pregnancy or breast feeding * Current smokers or history of heavy smoking (\>2 packs/day) * History of alcohol or drug abuse * Previous allergic reaction to study medications * Evidence of type I or type II diabetes (i.e. fasting glucose \>126 mg/dl, use of anti-diabetic medications) * Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy * History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack * History or presence of immunological or hematological disorders * Impaired renal function * Anemia * Treatment with phosphodiesterase 5 inhibitors * Treatment with anticoagulants * Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) * Treatment with any investigational drug in the 1 month preceding the study * Inability to give, or withdraw, informed consent * Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e., clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol, inability to find IV access)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endogenous Glucose Production | Duration of the study (4 hours) | Amount of label glucose appearance |
Countries
United States
Outcome results
None listed