A laboratory study in rats shows that compound Y improves insulin sensitivity by affecting liver enzyme Z. Which human measurements would best translate this mechanistic evidence into a feasible human follow-up study?

• A. Rely solely on animal organ histology endpoints and assume the same histological changes occur identically in humans without measuring metabolic markers
• B. Measure fasting glucose, fasting insulin, HOMA-IR, and perform an oral glucose tolerance test in humans randomized to compound Y or placebo to check whether the mechanism translates to improved insulin sensitivity
• C. Measure only body weight as the primary outcome because insulin sensitivity changes are irrelevant for translation from animals
• D. Only collect self-reported food frequency questionnaires because mechanistic enzyme changes cannot be captured in humans

Answer: (B)