Technical Abstract: Background: Metabolic phenotyping has potential utility as a diagnostic tool. While clinical parameters are commonly used in disease diagnosis, tools that enhance diagnosis of metabolic dysfunctions are needed. Objective: To identify typical and atypical metabolite temporal patterns in response to paired meal challenge tests. Design: Metabolic responses to high and low glycemic index (GI) meals were tested in 24 healthy pre-menopausal women, aged 18-35y, with BMI of 20-30Kg/m2 using a cross-over design. On test days, blood glucose, insulin, leptin and non-esterified fatty acids were measured at fasting, and for 8hr following test meal consumption. The data were range scaled and analyzed to assess the presence of distinct response phenotypes to the meal challenge tests. Results: Participants showed higher circulating glucose and insulin in response to the high GI compared to the low GI meal challenge. Using range-scaling and Principal Component Analysis three distinct groups were identified based on differential responses to the paired challenges. Members of the most populated phenotype (n=18) displayed little deviation from the expected response to the two meal challenges. Two minor phenotypes (n=3/group) with distinct responses were observed, one consistent with sub-clinical insulin resistance, and the other suggestive of hyperleptinemia. Conclusions: The differential responses of glucose, insulin and leptin to low and high glycemic test meals revealed three distinct phenotypes. Future efforts should evaluate whether these phenotypic sub-groups have differential susceptibility to disease and or response to nutritional interventions.