FGF21 and Fructose Challenge in Humans

Participation in this study involves fasting overnight, drinking a sweet beverage, and several blood draws through an IV line. Each subject may drink up to 10 different sweet beverages, separated by 2 weeks.

Inclusion criteria

for lean subjects:

• Men and women ages 18-60
• BMI 19-25 kg/m2; 19-23 for Asian subjects
• Stable weight (variation < 3 kg within 6 months of screening visit)
• Ability to give informed consent
• Ability to follow verbal and written instructions in English
• Use of medically approved form of contraception (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods)

Specific exclusion criteria for lean subjects:

• Fasting blood glucose >100; 2 hr OGTT blood glucose >140
• Fasting triglycerides >150

Inclusion criteria

for metabolic syndrome subjects:

3 or more of the following (based on joint scientific statement by Alberti et al, 2009:

• Fasting triglycerides >150 mg/dl (or on treatment for elevated triglycerides)
• HDL cholesterol <40 mg/dl in men or <50 mg/dl in women
• Blood pressure > 130/85 (or antihypertensive treatment in a subject with history of hypertension)
• Fasting BG >100
• Elevated waist circumference ** see below for race and ethnic specifications

Men Women

• Asian or Central, South or Native American > 90 cm > 80 cm
• Non-Asian, Non-Latino United States > 102 cm > 88 cm

General Exclusion criteria

• Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria
• Coronary heart disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure)
• Uncontrolled hypertension (BP > 160/100 mmHg on or off antihypertensive medication)
• Marijuana or intravenous drug use
• Recent weight loss (> 3 kg within 6 months of the screening visit)
• Gastroparesis
• Inflammatory or irritable bowel disease
• Malignancy treated with chemotherapy within the past 3 years
• Depression or psychosis requiring hospitalization
• Renal insufficiency (creatinine clearance < 40 ml/min)
• Transaminases > 2x above the normal range
• Known liver disease
• Pregnancy within 6 months of the screening visit
• Lactation
• Failure to use medically approved contraceptive methods
• History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling)
• Change in dose of thyroid hormone or antithyroidal medication within 3 months of screening visit
• History of alcohol abuse within the past 5 years
• Fructose intolerance

Exclusionary medications:

• Oral steroids
• Metformin
• Weight loss medications including nonprescription supplements