Characterization of the Variability Of Insulin Secretory Parameters in the Meal Tolerance and the Maximal Stimulation Tests of Subjects With Prediabetes
Characterization of the Variability Of Insulin Secretory Parameters in the Meal Tolerance and the Maximal Stimulation Tests of Subjects With Prediabetes
A multi-year clinical study to improve tools for measuring the function of insulin-producing
 beta cells in people with type 2 diabetes mellitus.
A three-year observational study to standardize the meal tolerance and maximum stimulational
 tests for measuring beta cell function in the clinical setting. It also aims to improve
 methods for the early prediction of the long-term response to an intervention and for
 identification of patients at risk for rapid beta cell function deterioration, thereby
 enabling future clinical studies that examine diabetes progression.
Inclusion Criteria:

 1. Ability to give informed consent and comply with all study requirements

 2. Overweight and obese, generally healthy men and women. Healthy is defined as no
 clinically relevant abnormalities identified by a detailed medical history (with the
 exception of glucose tolerance, see below), full physical examination, including blood
 pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests.

 3. Glucose Parameters:

 1. Fasting plasma glucose ≥100 mg/dL and <126 mg/dL

 2. 2h post-OGTT glucose of ≥140 and <200 mg/dL

 3. HbA1c<6.5%

 4. Women of child-bearing potential are allowed (but must agree to use non-hormonal
 contraception and not plan to become pregnant for the duration of the study). Must
 agree to maintain the same contraceptive measures throughout the study. Acceptable
 contraceptive methods for female subjects of childbearing potential include one of the
 following:

 -  Abstinence.

 -  One (1) of the following methods:

 -  Tubal ligation

 -  Copper-containing intrauterine device (IUD)

 -  Condom AND spermicidal foam/gel/film/cream/suppository

 -  Male partner who has had a vasectomy for at least 6 months.

 5. It is required that all male subjects use an acceptable method of contraception (as
 outlined below), starting from the first dose of study medication and continuing for
 at least 28 days after the last dose of study drug:

 1. Abstinence

 2. A condom AND one of the following:

 -  Vasectomy for more than 6 months.

 -  Female partner who meets one of the following conditions:

 -  Has had a tubal ligation, hysterectomy, or bilateral oophorectomy; or

 -  Is post menopausal (menopause is defined as over the age of 60 years,
 or between 45 and 60 years being amenorrheic for at least 2 years with
 plasma (FSH) level > 30 UI/L) or

 -  Or for female partners of the male participants, in addition to
 hysterectomy, oophorectorectomy, or post-menopausal status, that the
 use of a spermicidal gel or foam will constitute adequate protection in
 conjunction with use of a condom by the male.

 6. BMI 27-40; stable weight (less than 3% change in past 3 months) Age Range: 30-65

 7. No history of diabetes mellitus

 8. Other conditions may be allowed, if medically stable and controlled for at least four
 weeks within acceptable limits, including: hypertension, dyslipidemia, osteoarthritis,
 osteoporosis

 9. Smokers allowed, but must be able to participate on inpatient stay and not smoke

 Exclusion Criteria:

 Subjects presenting with any of the following will not be included in the study:

 1. Evidence or history of clinically significant hematological, renal, endocrine,
 pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic,
 neoplastic, or allergic or clinical findings at Screening (seasonal allergies OK).

 2. Any condition possibly affecting absorption (eg, gastrectomy, malabsorption syndromes,
 abdominal surgery other than appendectomy, cholecystectomy or hysterectomy).

 3. Use of unacceptable medications

 4. A positive urine drug screen.

 5. History of regular alcohol consumption exceeding 7 drinks/week for females or 14
 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer
 or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.

 6. Treatment with an investigational drug within 30 days or 5 half-lives preceding the
 first dose of study medication.

 7. 12 lead ECG demonstrating QTc >450 msec at Screening for males, 470 msec for females.
 If QTc exceeds 450/470 msec, the ECG should be repeated two more times and the average
 of the three QTc values should be used to determine the subject's eligibility. An ECG
 with evidence for possible old myocardial infarction will need to have prior ECGs to
 document stability of finding.

 8. Supine blood pressure >=140 mm Hg (systolic) or 90 mm Hg (diastolic), on a single
 measurement. If elevated, confirm by a single repeat, following at least 10 minutes of
 rest.

 9. Screening serum alanine transaminase (ALT) or serum aspartate transaminase (AST)
 greater than 2X the upper limit of the laboratory reference range.

 10. Elevated fasting triglycerides at screening (>500 mg/dL), confirmed by a single repeat
 if deemed necessary.

 11. Pregnant or nursing females; inability to use effective contraception.

 12. Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.

 13. Participation in a clinical biomedical research study within prior two months may be
 excluded, depending on study type and details.

 14. History of sensitivity to heparin or heparin-induced thrombocytopenia, if utilized by
 the site for blood draws.

 15. Unwilling or unable to comply with directions and procedures described in this
 protocol.

 16. Subject is the Investigator or a sub-Investigator, research assistant, pharmacist,
 study coordinator, other staff, or a relative of study personnel directly involved
 with the conduct of the study.

 17. Other severe acute or chronic medical or psychiatric condition or laboratory
 abnormality that may increase the risk associated with study participation or
 investigational product administration or may interfere with the interpretation of
 study results and, in the judgment of the investigator, would make the subject
 inappropriate for entry into this study.