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Delineating and diagnosing depression and anxiety in the presence of a medical condition, such as diabetes, is complicated by the presence of overlapping symptoms that, therefore, are etiologically ambiguous. These overlapping symptoms include feelings of fatigue, concentration difficulties, restlessness, changes in appetite, irritability and autonomic arousal. The difficulty in understanding these overlapping symptoms has been proposed to lead to an underdiagnosis of depression and anxiety disorders among adults with diabetes, which is problematic given that such disorders are associated with poorer health outcomes. The goal of the current study is to test whether or not these overlapping symptoms are affected by the presence of diabetes by comparing structural models of these symptoms in adults with diabetes versus those free of major medical conditions. Participants include 226 adults with diabetes and 379 adults free of diabetes who completed a series of questionnaires assessing symptoms of depression, anxiety and health status. In addition, for adults with diabetes, the most recent hemoglobin A1c lab result was collected from patient medical records. Results indicate that overlapping symptoms were strongly related to mood for adults with and without diabetes. In conclusion, it is recommended that when these overlapping symptoms are present in adults with diabetes, depression and anxiety should be considered as possible contributors to their presence.