UC Davis

Abstract Background Established clinical tests are commonly used in disease diagnosis, but tools that enhance identification of metabolic dysfunctions are needed. This study was conducted 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 20-50 y, with BMI of 25-30 kg/m2 using a cross-over design. On test days, blood glucose, insulin, leptin and non-esterified fatty acids were measured after an overnight fasting, and for 8 h following test meal consumption. The data were range scaled, and multivariate statistics were used to assess the presence of distinct response groups to the meal challenge tests. Results As expected, participants showed higher circulating glucose and insulin in response to the high GI compared to the low GI meal challenge. However, 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 group (n = 18) displayed little deviation from the expected response to the two meal challenges. Two minor groups (n = 3/group) with distinct responses were observed, one suggestive of 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 response groups. Dietary intervention studies traditionally evaluate group responses, and aim to identify the overall effect in the population studied. In contrast, our study analyzed the variance in the meal challenge responses, using an integrated physiological approach, rather than a reductionist approach. This phenotyping approach may be useful for detecting subclinical metabolic dysfunctions, and it could contribute to improved personalized nutrition management. This study is registered in ClinicalTrials.gov, record #200210295