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The investigators decided not to perform the study. No participants have been enrolled.
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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.
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]
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intact Day | Placebo Comparator | The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of saline at 48 ml/hr IV |
|
| Blocked Day | Experimental | The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of trimethaphan (4mg/min) IV. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trimethaphan | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Endogenous Glucose Production | Amount of label glucose appearance | Duration of the study (4 hours) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D014294 | Trimethaphan |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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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
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| Saline | Other | 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 |
|
| D002712 |
| Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |