Aldosterone and Glucose Homeostasis

Study Overview
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Brief Summary
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Determine the effect of aldosterone on how the body handles glucose (sugar).

Detailed Description
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Determine the effect of aldosterone on glucose metabolism in humans.

Official Title
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Aldosterone and Glucose Homeostasis

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Aldosterone infusion (A)
* Drug: Vehicle Infusion (V)
* Other: High Sodium Diet (HS)
* Other: Low Sodium Diet (LS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory subjects, 18 to 70 years of age, inclusive For female subjects, the following conditions must be met: a postmenopausal status for at least 1 year, or b status-post surgical sterilization, or c if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing prior to drug treatment and on every study day Metabolic Syndrome as defined by the presence of > 3 of the following: a Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg. b Glucose Intolerance (Fasting Plasma Glucose > 100 mg/dL) c Increased triglyceride level > 150mg/dL (1.7mmol/L) d Decreased levels of HDL cholesterol For males, less than 40 mg/dL For females, less than 50 mg/dL e Waist circumference For males, greater than 40 inches (102 cm) For females, greater than 35 inches (89 cm). Exclusion Criteria: Previously diagnosed Type I Diabetes , or the use of anti-diabetic medication. Subjects with type II diabetes not on medication will be allowed to participate if fasting blood glucose is <200mg/dL. Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride). Screening plasma potassium <3.5 mmol/L or use of chronic potassium supplements for the treatment of hypokalemia Use of hormone replacement therapy If on statin therapy for hypercholesterolemia, a change in dose within the past 6 months. Breast-feeding Cardiovascular disease such as prior myocardial infarction, 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 Treatment with anticoagulants History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack History or presence of immunological or hematological disorders Diagnosis of asthma requiring use of inhaled beta agonist >1 time per week Clinically significant gastrointestinal impairment that could interfere with drug absorption Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) >2.0 x upper limit of normal range] Impaired renal function [estimated glomerular filtration rate (eGFR) of <60ml/min] as determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine (Scr) is expressed in mg/dl and age in years: eGFR <60 ml/min Hematocrit <35% Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult, such as arthritis treated with non-steroidal antiinflammatory drugs Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) Treatment with lithium salts History of alcohol or drug abuse Treatment with any investigational drug in the 1 month preceding the study Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-V/A; LS-V/A<br>High Sodium diet- Vehicle infusion then Aldosterone infusion Low Sodium diet- Vehicle infusion then Aldosterone infusion | Drug: Aldosterone infusion (A)<br>* Infusion of exogenous aldosterone (0.7 mcg/kg/hr for 12.5 hrs)<br>* Other names: placebo;Drug: Vehicle Infusion (V)<br>* Vehicle infusion for 12.5 hours<br>Other: High Sodium Diet (HS)<br>* 160 mmol/d sodium diet for 7 days<br>Other: Low Sodium Diet (LS)<br>* 20 mmol/d sodium diet for 9 days<br>|
| Experimental: HS-A/V; LS-A/V<br>High Sodium diet- Aldosterone infusion then Vehicle infusion Low Sodium diet- Aldosterone infusion then Vehicle infusion | Drug: Aldosterone infusion (A)<br>* Infusion of exogenous aldosterone (0.7 mcg/kg/hr for 12.5 hrs)<br>* Other names: placebo;Drug: Vehicle Infusion (V)<br>* Vehicle infusion for 12.5 hours<br>Other: High Sodium Diet (HS)<br>* 160 mmol/d sodium diet for 7 days<br>Other: Low Sodium Diet (LS)<br>* 20 mmol/d sodium diet for 9 days<br>|
| Experimental: LS-V/A; HS-V/A<br>Low Sodium diet- Vehicle infusion then Aldosterone infusion High Sodium diet- Vehicle infusion then Aldosterone infusion | Drug: Aldosterone infusion (A)<br>* Infusion of exogenous aldosterone (0.7 mcg/kg/hr for 12.5 hrs)<br>* Other names: placebo;Drug: Vehicle Infusion (V)<br>* Vehicle infusion for 12.5 hours<br>Other: High Sodium Diet (HS)<br>* 160 mmol/d sodium diet for 7 days<br>Other: Low Sodium Diet (LS)<br>* 20 mmol/d sodium diet for 9 days<br>|
| Experimental: LS-A/V; HS-A/V<br>Low Sodium diet- Aldosterone infusion then Vehicle infusion High Sodium diet- Aldosterone infusion then Vehicle infusion | Drug: Aldosterone infusion (A)<br>* Infusion of exogenous aldosterone (0.7 mcg/kg/hr for 12.5 hrs)<br>* Other names: placebo;Drug: Vehicle Infusion (V)<br>* Vehicle infusion for 12.5 hours<br>Other: High Sodium Diet (HS)<br>* 160 mmol/d sodium diet for 7 days<br>Other: Low Sodium Diet (LS)<br>* 20 mmol/d sodium diet for 9 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion | Acute Insulin response during Hyperglycemic clamp (delta insulin uU/mL, t=0-10) | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | Insulin sensitivity index (ISI) was calculated by dividing the average glucose infusion rate (mg glucose infusion/kg body weight/min) by the average insulin concentration (uU/mL) from 90 to 120 minutes. This was multiplied by 100 (thus, x100 in units description), per reporting convention in literature. | 3 hours | 

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