DESCRIPTION (provided by applicant): Emotional distress, including depression and diabetes-specific distress (e.g., feeling overwhelmed by living with diabetes, feelings of failure related to diabetes self-care), is a significant and prevalent problem for patients with type 2 diabetes. Both depression and diabetes distress have been associated with metabolic/glycemic control, diabetes complications, mortality, and quality of life. Recent findings further suggest tht risk for emotional distress is influenced by diabetes treatment. The GRADE study (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is generating prospective data that will provide a unique opportunity to examine the relationships between emotional distress, diabetes treatment, and outcomes in an experimental design. The GRADE study is a randomized clinical trial that will compare the metabolic effects of four common anti-diabetic drugs when combined with metformin. This sub- study will recruit a total of 2,500 patients who are within 10 years of diagnosis and are being treated with metformin monotherapy at the time of enrollment. The study will examine patient-level variation in baseline emotional distress as a predictor of glycemic control and other health outcomes, independent of treatment effects. The study will also provide a rigorous experimental examination of treatment regimen effects on emotional distress over time as part of the

PUBLIC HEALTH RELEVANCE: Emotional distress, including depression and diabetes-related distress, is a significant and prevalent problem for patients with type 2 diabetes. Distress is associated with poor glycemic control, increased risk for complications and mortality, and reduced quality of life. Risk for emotional distress is associated with diabetes treatment initiatin and intensity. This sub-study leverages the ongoing the GRADE study (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) to assess the impact of emotional distress on outcomes for 2500 participants randomly assigned to 4 diabetes treatment combinations. Findings will inform practice decisions regarding screening and treatment for emotional distress as part of diabetes care.