Obese individuals are at high risk of developing life-threatening co-morbidities. However, 10-25 % of obese people stay healthy. These individuals remain glucose tolerant and insulin sensitive, with normal blood pressure and a favorable lipid profile. Gerlini, Berti, and colleagues analyzed primary subcutaneous adipocytes from morbidly obese individuals discordant for metabolic health. They discovered that instead of insulin resistance, impaired glucose homeostasis is a major determinant of adipocyte transcriptional response. Furthermore, they identified 19 genetic associations with phenotypes of glucose homeostasis and/or body weight and composition.