Diabetes Mellitus
Conditions
Keywords
Glucose, Insulin
Brief summary
Determine the effect of aldosterone on how the body handles glucose (sugar).
Detailed description
Determine the effect of aldosterone on glucose metabolism in humans.
Interventions
DRUGAldosterone infusion (A)
Infusion of exogenous aldosterone (0.7 mcg/kg/hr for 12.5 hrs)
DRUGVehicle Infusion (V)
Vehicle infusion for 12.5 hours
OTHERHigh Sodium Diet (HS)
160 mmol/d sodium diet for 7 days
OTHERLow Sodium Diet (LS)
20 mmol/d sodium diet for 9 days
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Ambulatory subjects, 18 to 70 years of age, inclusive 2. 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 3. 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
1. 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. 2. Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride). 3. Screening plasma potassium \<3.5 mmol/L or use of chronic potassium supplements for the treatment of hypokalemia 4. Use of hormone replacement therapy 5. If on statin therapy for hypercholesterolemia, a change in dose within the past 6 months. 6. Breast-feeding 7. 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 8. Treatment with anticoagulants 9. History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack 10. History or presence of immunological or hematological disorders 11. Diagnosis of asthma requiring use of inhaled beta agonist \>1 time per week 12. Clinically significant gastrointestinal impairment that could interfere with drug absorption 13. Impaired hepatic function \[aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) \>2.0 x upper limit of normal range\] 14. 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: 15. eGFR \<60 ml/min 16. Hematocrit \<35% 17. 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 18. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) 19. Treatment with lithium salts 20. History of alcohol or drug abuse 21. Treatment with any investigational drug in the 1 month preceding the study 22. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study 23. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Secretion | 3 hours | Acute Insulin response during Hyperglycemic clamp (delta insulin uU/mL, t=0-10) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 3 hours | 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. |
Countries
United States
Participant flow
Pre-assignment details
11 participants did not start the study (5 Participants did Not Meet inclusion or exclusion criteria, 6 declined participation)
Participants by arm
| Arm | Count |
|---|---|
| HS-V/A; LS-V/A High Sodium diet- Vehicle then Aldosterone Low Sodium diet- Vehicle then Aldosterone | 7 |
| HS-A/V; LS-A/V High Sodium diet- Aldosterone then Vehicle Low Sodium diet- Aldosterone then Vehicle | 5 |
| LS-V/A; HS-V/A Low Sodium diet- Vehicle then Aldosterone High Sodium diet- Vehicle then Aldosterone | 6 |
| LS-A/V; HS-A/V Low Sodium diet- Aldosterone then Vehicle High Sodium diet- Aldosterone then Vehicle | 5 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 |
| Overall Study | scheduling | 4 | 4 | 2 | 1 |
Baseline characteristics
| Characteristic | HS-V/A; LS-V/A | HS-A/V; LS-A/V | LS-V/A; HS-V/A | LS-A/V; HS-A/V | Total |
|---|---|---|---|---|---|
| Age, Continuous | 25.1 years | 29.2 years | 32.5 years | 27.2 years | 28.4 years |
| Glucose (mg/dL) | 85.3 mg/dL STANDARD_DEVIATION 7.6 | 85.4 mg/dL STANDARD_DEVIATION 7.2 | 85.3 mg/dL STANDARD_DEVIATION 7.6 | 85.4 mg/dL STANDARD_DEVIATION 7.2 | 85.3 mg/dL STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 18 | 4 / 14 | 3 / 18 | 4 / 14 |
| serious Total, serious adverse events | 0 / 18 | 0 / 14 | 0 / 18 | 0 / 14 |
Outcome results
Primary
Insulin Secretion
Acute Insulin response during Hyperglycemic clamp (delta insulin uU/mL, t=0-10)
Time frame: 3 hours
Population: Three subjects were excluded or withdrew after infusion but before hyperglycemic clamp due to low potassium, loss of IV access, burning at IV site. These 3 participants were not included in final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle, HS | Insulin Secretion | 48.9 uU/mL | Standard Deviation 34.8 |
| Vehicle, LS | Insulin Secretion | 37.6 uU/mL | Standard Deviation 30.9 |
| Aldosterone, HS | Insulin Secretion | 51.8 uU/mL | Standard Deviation 40.2 |
| Aldosterone, LS | Insulin Secretion | 34.4 uU/mL | Standard Deviation 20.9 |
Secondary
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.
Time frame: 3 hours
Population: Three subjects were excluded or withdrew after infusion but before hyperglycemic clamp due to low potassium, loss of IV access, burning at IV site. These 3 participants were not included in final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle, HS | Insulin Sensitivity | 25.2 mg/kg/min per uU/mL*100 | Standard Deviation 15.4 |
| Vehicle, LS | Insulin Sensitivity | 24.8 mg/kg/min per uU/mL*100 | Standard Deviation 16.4 |
| Aldosterone, HS | Insulin Sensitivity | 23.4 mg/kg/min per uU/mL*100 | Standard Deviation 17.3 |
| Aldosterone, LS | Insulin Sensitivity | 24.7 mg/kg/min per uU/mL*100 | Standard Deviation 13.4 |