Methods and compositions for identifying and treating obesity and obesity-induced metabolic disorders are provided. One aspect provides a method for the evaluation of risk and progression of glucose tolerance, insulin resistance and Type 2 diabetes in mammalian subjects. The method includes measuring the concentration of circulating lipocalin-2 in a subject and comparing the measured level to lipocalin-2 to a reference level. Another aspect provides methods of treating insulin resistance, type 2 diabetes and other related complications by administering to a patient a composition that can reduce the circulating levels of lipocalin-2, for example a lipocalin-2 antagonist.