Fructose: Substrate, Stimulus, or Both?

This objective of this study is to use sensitive methodology under controlled conditions to investigate the mechanisms by which fructose consumption contributes to excess fatty acid synthesis and elevations in blood glucose levels following consumption of meals containing fructose.

Inclusion Criteria: * Body Mass Index 22 to 35 kg/m2 * Prediabetic (HbA1c 5.7% to 6.5%) or hyperinsulinemic (fasting insulin ≥12 µIU/mL) but non-diabetic (fasting glucose \<126mg/dL and HbA1c \< 6.5%) ; or normal control (fasting insulin \<10 µIU/mL, fasting glucose \<100 mg/dL, and HbA1c \< 5.7%) Exclusion Criteria: * Pregnancy or lactation within the past six months * Type 1 or 2 diabetes mellitus * History of liver disease or aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2x the upper limit of normal (ULN); * Fasting triglyceride or total cholesterol levels above 95th percentile for age and sex; * Hemoglobin or hematocrit below the lower limit of normal for sex; * Report of hepatitis or HIV infection; * History of cancer, use of any anti-diabetic medications or hypolipidemic agents in the past six months; * History of surgical procedure for obesity; * Self-reported change in body weight \>5% in the past six months; * History of other conditions known to affect insulin sensitivity and lipid metabolism; * Known intolerance to acetaminophen or components of the liquid test meals.