In youth-onset type 2 diabetes (YO-T2D; diabetes diagnosed <20 years-old) loss of glycemic control is more rapid than in adults, partly attributed to accelerated beta cell decline. However, no studies have investigated the potential heterogeneity in the longitudinal trajectories of beta cell function and whether genetic factors might contribute to heterogeneity. We derived longitudinal trajectories of fasting C-peptide (FCP) levels, a surrogate measure of beta cell function, via discrete mixture modeling of repeated measures collected over 15 years of follow-up in youth with YO-T2D (antibody negative and insulin resistant; n=266) from the SEARCH for Diabetes in Youth cohort study. We tested the association between the derived trajectories and T2D genetic risk score (GRS) using a multinomial logistic regression model with adjustment for relevant covariates. A four-trajectory model best fit the data, classifying youth with YO-T2D as having either “initial low FCP and stable over time” (32%), “initial high FCP and slow incline” (8%), “initial high FCP and slow decline” (53%), or “initial very high FCP and rapid decline” (7%) (Figure). T2D GRS was not associated with FCP trajectory membership. These data demonstrate substantial heterogeneity in trajectories of FCP in YO-T2D and suggest that genetic predisposition to T2D is not a significant determinant of this heterogeneity. Disclosure A.Shapiro: None. A.Bellatorre: None. J.M.Stafford: None. A.S.Shah: None. C.Pihoker: None. F.Malik: None. A.D.Liese: None. D.J.Pettitt: None. D.Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK127208-01, 1UC4DK108173); Centers for Disease Control and Prevention (U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139)

We examined the association between diabetes stigma, sociodemographic and psychosocial variables in AYAs with type 1 (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth study, 2016-2019. A 5-question survey assessed frequency of perceived stigma experience, from which we created a total stigma score. We used multivariable modeling to examine these associations adjusting for sex, race/ethnicity, age, clinic site, diabetes duration, education level, health insurance type, treatment regimen, and HbA1c levels. Analyses were stratified by diabetes type. Of the 1,6AYAs who completed the stigma survey, 78% had T1D, 56% were female, and 48% were non-Hispanic White. Mean (SD) age at study visit was 21.7 (5.1) years (range - 24.9 years) . Mean (SD) HbA1c level was 9.2% (2.3) . Participants with T1D with lower household income had higher stigma scores compared to those with higher household income (p=0.03) . Among AYAs with T1D or T2D, higher stigma score was associated with food insecurity (p< 0.01) , disordered eating behaviors (p < 0.01) , depressive symptoms (p < 0.01) , and decreased AYA (p<0.01) and diabetes quality of life (p < 0.01) scores. Diabetes stigma is associated with food insecurity and decreased psychosocial functioning and therefore is important to address in providing comprehensive diabetes care. Disclosure K.B.Eitel: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. A.D.Liese: None. S.M.Marcovina: None. E.J.Mayer-davis: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.J.Roberts: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. R.A.Bell: None. A.Bellatorre: None. C.E.Barrett: None. A.Cristello: None. D.Dabelea: None. L.M.Dolan: None. Funding The SEARCH for Diabetes in Youth Cohort Study (1R01DK127208-01, 1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention.

We examined the association between diabetes stigma and glycemic control, treatment regimen, and acute and chronic complications in adolescents and young adults (AYAs) with type 1 (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth Study, 2016-2019. A 5-question survey assessed frequency of perceived stigma experience, from which we created a total stigma score. We used multivariable linear modeling, stratified by T1D and T2D, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic, clinic site, duration of diabetes, health insurance type, treatment regimen, and HbA1c. Of 16respondents, 78% had T1D, 56% were female, and 48% were non-Hispanic White. Mean (SD) age at study visit was 21.7 (5.1) years (range - 24.9 years) . Mean (SD) HbA1c was 9.2% (2.3) . Higher stigma scores were associated with female sex and higher HbA1c (both p <0.01, table) . No statistically significant association between stigma score and insulin pump or continuous glucose monitor use was observed. In participants with T2D, higher stigma scores were associated with insulin use (p = 0.04) . Independent of HbA1c, higher stigma scores were associated with acute complications for AYAs with T1D and chronic complications for AYAs with T1D and T2D (table) . Diabetes stigma in AYAs is associated with worse diabetes outcomes and therefore is important to address in diabetes care. Disclosure K.B.Eitel: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. A.D.Liese: None. S.M.Marcovina: None. E.J.Mayer-davis: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.J.Roberts: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. R.A.Bell: None. A.Bellatorre: None. C.E.Barrett: None. A.Cristello: None. D.Dabelea: None. L.M.Dolan: None. Funding The SEARCH for Diabetes in Youth Cohort Study (1R01DK127208-01, 1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention.