52-OR: Emotional Distress and Insulin Initiation in the GRADE Trial
Authors: PRESLEY CAROLINE A. , BUTERA NICOLE M. , KRAUSE-STEINRAUF HEIDI , DESOUZA CYRUS , HOLLANDER PRISCILLA A. , HOOGENDOORN CLAIRE J. , LAGARI VIOLET , LEGOWSKI ELIZABETH , MARTIN CATHERINE , RASOULI NEDA , GONZALEZ JEFFREY S. , CHERRINGTON ANDREA 
Published: June 2024

Introduction & Objective: We evaluated if higher emotional distress (depressive symptoms [DS] or diabetes distress [DD]) were associated with lower initiation of basal or rapid-acting insulin among participants enrolled in the GRADE Emotional Distress Study (EDS).
Methods: Individuals with type 2 diabetes &lt;10 years duration on metformin only were randomized to add one of four glucose-lowering drugs. Per protocol, participants were required to start basal or rapid-acting insulin rescue therapy after reaching secondary or tertiary glycemic outcomes (HbA1c ≥7.5% confirmed). DS and DD within 6 months prior to glycemic outcome confirmation were measured by the Patient Health Questionnaire and Diabetes Distress Scale. Multinomial logistic regression models examined the associations of DS and DD with basal insulin initiation (≤6 weeks vs. &gt;6 weeks from time of outcome confirmation vs. never) adjusting for treatment group, diabetes duration, and diabetes complications. Unadjusted logistic regression models examined the association of DS and DD with rapid-acting insulin initiation (any time vs. never).
Results: We examined 473 participants expected to start basal insulin per protocol; median age 56.2; 35% female; 66% White, 18% Black, 22% Hispanic; median diabetes duration of 5.2 years. Of these, 170 participants initiated basal insulin ≤6 weeks, 154 initiated &gt;6 weeks, and 149 never initiated. We examined 274 participants expected to start rapid-acting insulin; median age 54.9; 35% female; 62% White, 24% Black, 24% Hispanic; median diabetes duration of 5.4 years. Of these, 100 never initiated rapid acting insulin. Neither DS nor DD were associated with starting basal insulin or rapid-acting insulin.
Conclusion: In the GRADE EDS, approximately one third of participants did not start protocol required basal or rapid-acting insulin. Emotional distress does not appear to play a role in insulin initiation among volunteer trial participants. Findings go against commonly held beliefs of ‘psychological insulin resistance.’

Disclosure
C.A. Presley: None. N.M. Butera: None. H. Krause-Steinrauf: None. C. Desouza: Advisory Panel; Novo Nordisk, Bayer Inc., Madrigal Pharmaceuticals, Inc. Other Relationship; ADA/ACC Diabetes by Heart Program. Advisory Panel; Asahi Kasei. P.A. Hollander: None. C.J. Hoogendoorn: None. V. Lagari: None. E. Legowski: None. C. Martin: None. N. Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk. Research Support; Novo Nordisk. J.S. Gonzalez: None. A. Cherrington: Research Support; Genentech, Inc.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (U01DK098246); The planning of GRADE was supported by a U34 planning grant from the NIDDK (U34-DK-088043). The American Diabetes Association supported the initial planning meeting for the U34 proposal. The National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention also provided funding support. The Department of Veterans Affairs provided resources and facilities. Additional support was provided by grant numbers P30 DK017047, P30 DK020541, P30 DK020572, P30 DK072476, P30 DK079626, P30 DK092926, U54 GM104940, UL1 TR000170, UL1 TR000439, UL1 TR000445, UL1 TR001102, UL1 TR001108, UL1 TR001409, 2UL1TR001425, UL1 TR001449, UL1 TR002243, UL1 TR002345, UL1 TR002378, UL1 TR002489, UL1 TR002529, UL1 TR002535, UL1 TR002537, UL1 TR002541 and UL1 TR002548. Educational materials were provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies were provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics, and Sanofi. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The GRADE Study Research Group is deeply grateful to our participants whose loyal dedication made GRADE possible.The GRADE Emotional Distress Substudy was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under Award Number R01 DK104845. Additional support was provided by grant numberP30 DK111022.