the Diabetic Process
Conditions
Keywords
unacylated ghrelin, beta cell function
Brief summary
Use of human unacylated ghrelin (UAG, also called des-octanoyl ghrelin) to study physiology in healthy subjects. The proposed research is an investigator-initiated study funded by the National Institutes of Health designed to examine the effect of physiologic levels of UAG on the regulation of glucose homeostasis as well as beta cell function.
Interventions
DRUGunacylated ghrelin
IV, UAG (4.0 µg/kg/hr), one time, duration of study visit (approximately 5 hours)
DRUGacyl ghrelin
IV, AG (1.0 µg/kg/hr), one time, duration of study visit (approximately 5 hours)
DRUGcombined acyl and desacyl ghrelin
IV, the combination of AG (1 µg/kg/hr) and UAG (4 µg/kg/hr), one time, for the duration of the study visit (approximately 5 hours)
DRUGsaline
IV, saline, one time, for the duration of the study visit(approximately 5 hours)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
David Dalessio
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Apparently healthy men and women. Only premenopausal women who are using an adequate method of contraception at Screening and who agree to continue the contraception during the study will be included. Male subjects do not need to use on birth control. 2. Ages between 18 and 50 years, inclusive. 3. BMI between 18.5 and 29.9 kg/m2, inclusive
Exclusion criteria
1. History or clinical evidence of impaired fasting glucose or impaired glucose tolerance or diabetes mellitus, myocardial infarction, history or symptoms of congestive heart failure, history of cancer or anorexia nervosa, history or active liver or renal disease (AST or ALT \>2x upper limits of normal, calculated glomerular filtration rate \[GFR\] \<60). 2. A baseline resting systolic blood pressure of less than 100 mm Hg. 3. History of growth hormone deficiency or excess disorders (acromegaly, pituitary gigantism, panhypopituitarism); history of adrenal insufficiency or Cushing's disease/syndrome; history of neuroendocrine tumors. 4. Anemia defined as hematocrit \<33%. 5. Use of medications that alter insulin sensitivity: niacin, glucocorticoids, metformin, thiazolidinediones, exenatide, or atypical anti-psychotics. 6. Pregnancy or lactation. 7. BMI \<18 kg/m2 or BMI \>30 kg/m2; fasting plasma glucose \>100 mg/dl and/or 2 hr plasma glucose \>140 mg/dl on a 75 g oral glucose tolerance test. 8. Electrocardiogram (ECG) abnormalities: specifically, myocardial ischemia, previous myocardial ischemia, atrial fibrillation, second or third degree heart block and complete right or left bundle branch block. 9. Females who are on progesterone-only contraception and those who have irregular menses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| acute insulin release (AIRg) | one year | The primary outcome measure will be AIRg. This is calculated as the incremental insulin release,following IV glucose administration. (For the first ten minutes of the study visit.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | one year | 1\. Insulin sensitivity is quantified as the insulin sensitivity index (SI) using Bergman's minimal model of glucose kinetics from the glucose and insulin results obtained from a FSIGT. |
| Disposition index | one year | 2\. The disposition index (DI) is a measure of β-cell function. It accounts for the modulating effect of insulin sensitivity on β-cell responses. It is calculated as the product of the SI and AIRg |
| glucose tolerance | one year | 3\. Glucose tolerance is measured by glucose disappearance constant. This is calculated as the slope of the natural log of glucose during the study visit, during a set time frame. |
Countries
United States
Outcome results
None listed