Search

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 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 sought to determine incidence rates for micro- and macrovascular events in youth-onset type 1 (T1D) and type 2 (T2D) diabetes in the SEARCH (T1D: N=564; T2D: N=149) and TODAY (T2D: N=495) studies. At study visits, we ascertained self-reported ophthalmologic, kidney, neuropathy, cardiac, and peripheral and cerebrovascular events , obtained medical records for these events, and adjudicated each event using predetermined standardized and harmonized criteria. Data were available from more than 6,000 person-years in T1D and more than 8,000 person-years in T2D. Incidence rates (events per 10,000 person-years) were calculated. As shown in the table, despite similar mean diabetes duration of 10-13 years and mean HbA1c >9%, the incidence of reported complications was higher in the youth with T2D than those with T1D, with rates 2.5-fold higher for microvascular and 4.0-fold higher for macrovascular disease. These data support the aggressive nature of youth-onset T2D. Disclosure A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. S.Isom: None. J.B.Tryggestad: None. R.Gubitosi-klug: None. L.M.Dolan: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. K.Drews: None. Funding National Institutes of Health DK061230; R01DK127208 Center for Disease Control

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 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.

With the high prevalence of pediatric obesity, it is challenging to accurately classify diabetes (DM) type, especially in a diverse population of youth. Maintained fasting C-peptide ≥ 0.75ng/ml (250pmol/L) , a level associated with type 2 diabetes and successful insulin withdrawal in adult cohorts, may have implications for treatment and risks of acute complications. We developed clinical prediction models to identify individuals with youth onset DM who will retain endogenous insulin secretion. We studied 2991 youth in the SEARCH study (DM diagnosed ≤ age years) to develop logistic regression based prediction models using clinical measures (race/ethnicity, BMI Z-score, age at diagnosis, triglycerides and HDL-C) with or without islet autoantibodies (Aab) (GADA, IA-2A, ZnT8A) , to identify those with fasting C-peptide ≥ 0.75ng/ml at 3-yr (median 75 months) DM duration. Model covariates (measured median 9 months duration) were chosen based on previous literature and availability. A prediction model using clinical measures was highly accurate in identifying participants with C-peptide ≥75 ng/ml (17% of participants, 3% and 59% of those with and without positive Aab) : area under receiver operator curve (AUC ROC) 0.950 (95%CI 0.938-0.962) , model pseudo-R2 0.69. Adding Aab improved discrimination to AUC ROC 0.976 (0.968,0.983) , pseudo-R2 0.81. In internal validation, optimism was very low, with excellent calibration (slope 0.995-0.999) . Performance remained high in difficult to classify groups: AUC ROC was 0.947 (0.927, 0.966) in those with negative Aab and 0.923 (0.960, 0.984) (model with Aab) in youth with high BMI (Z-score >2) . Discrimination was lower in non-Hispanic white participants (AUC ROC 0.94) compared to participants of other race and ethnic groups (AUC ROC 0.97-0.99) (model with Aab) . In conclusion, prediction models combining routine clinical measures can accurately identify youth with DM who maintain endogenous insulin secretion. Disclosure A.Jones: None. A.H.Williams: None. S.M.Marcovina: None. C.Pihoker: None. J.Divers: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. B.Shields: None. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. D.Dabelea: None. W.Hagopian: Research Support; Janssen Research & Development, LLC. E.Lustigova: None. A.S.Shah: None. A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. Funding Centers for Disease Control and Prevention (PA numbers 00097, DP-05-069, and DP-10-001) and the National Institute of Diabetes and Digestive and Kidney Diseases. This work is also supported by NIH RO1 awards DK124395 and DK121843-01.

Arterial stiffness and echocardiograms were assessed in participants with youth-onset DM (N=399, 22.8 ± 5.1 years, duration 10.8 ± 3.2 years, 63% female, 45% non-Hispanic White; 33% non-Hispanic Black, 13.5% Hispanic, 8% Other, 44% type 2 DM (T2D)) . Cardiovascular risk factors (CVRF) , arterial stiffness and cardiac measures were compared between those with or without elevated arterial stiffness (stiff = Pulse Wave Velocity [PWV] ≥ 90th% for lean controls) . Association between PWV and cardiac parameters after adjusting for CVRF was assessed. Participants with high PWV were 4.6 yrs older, had 0.6 yrs longer diabetes duration, were more likely to be female (71.5 vs. 54.9%) , non-Hispanic White (68.8 v 42.3) , have T2D (72.0 v 20.2%) , higher BMI (35.6 v 26.3 kg/m2) , BP (122/79 v 109/72 mmHg) , LDL-C (113 v 100 mg/dl) , CRP (0.6 v 0.1mg/dL) , and HbA1c (9.6 v 8.9%; all p≤0.04) . Those with high PWV had higher left ventricular mass index (LVMI) and lower systolic and diastolic function. PWV remained a significant predictor of LVMI (R2 0.37) , systolic (EF, R2 0.235) and diastolic (e’/a’, R2 0.461) function after adjustment for CVRF, all p≤0.0002. Higher arterial stiffness is associated with adverse changes in cardiac structure and function and was more prevalent in persons with T2D compared to type 1 DM. Disclosure E.M. Urbina: Advisory Panel; Astellas Pharma Inc. D. Dabelea: None. R. Dagostino Jr: None. S.R. Daniels: None. L.M. Dolan: None. G. Imperatore: None. E. Lustigova: None. S.M. Marcovina: None. A.K. Mottl: Advisory Panel; Bayer AG. Board Member; Bayer AG. Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. C. Pihoker: None. A.S. Shah: None. Funding Grant Support (SEARCH 4) : 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. The Population Based Registry of Diabetes in Youth Study (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, and U18DP006139) is funded by the Centers for Disease Control and Prevention (DP-15-002) and supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Grant Support (SEARCH 1, 2, 3) : SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA numbers 00097, DP-05-069, and DP-10-001) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Kaiser Permanente Southern California (U48/CCU919219, UDP000246, and U18DP002714) , University of Colorado Denver (U48/CCU819241-3, UDP000247, and U18DP000247-06A1) , Cincinnati's Children's Hospital Medical Center (U48/CCU519239, UDP000248, and 1U18DP002709) , University of North Carolina at Chapel Hill (U48/CCU419249, UDP000254, and U18DP002708) , Seattle Children's Hospital (U58/CCU019235-4, UDP000244, and U18DP002710-01] and Wake Forest University School of Medicine (U48/CCU919219, UDP000250, and 200-2010-35171) .

To examine CRF trends that may impact future CVD risk, the SEARCH study assessed CRF for diabetes-related complications in incident cohorts established from 2002 - 2016. Linear regression was used to assess trends over each incident year for non-HDL-c, LDL-c, VLDL-c, TG, BMI z-score, systolic and diastolic blood pressure (BP) z-scores, albumin/creatinine ratio (ACR) and eGFR. Models were stratified by diabetes type (Type 1, N=4600; Type 2, N=932) , adjusted for age at diagnosis, sex, DM duration and race/ethnicity. An interaction analysis was conducted to assess differential time trends by type. For youth with type 1, non-HDL-c, BP, BMI and ACR >30 decreased while HDL-c increased over time. For youth with type 2, non-HDL-c, and eGFR decreased, and BMI increased over time (table) . Significant time change interactions by type were seen for HDL-c and for BMI z-score and BP measures (table) .We observed small but significant changes in several CRFs over time in youth with incident DM, especially lipids, with greater improvements seen in youth with type 1. Youth with type 2 had worsening trends over time in BMI, BP, and kidney function. Further research is needed to better understand these trends and their implications for long term CVD risk. Disclosure R.A.Bell: None. A.D.Liese: None. E.Lustigova: None. S.M.Marcovina: None. L.Merjaneh: None. D.J.Pettitt: n/a. C.Pihoker: None. A.S.Shah: None. A.M.South: None. L.E.Wagenknecht: None. J.Rigdon: None. A.Bellatorre: None. D.Dabelea: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. J.Divers: None. L.M.Dolan: None. G.Imperatore: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. Funding Centers for Disease Control and Prevention U18DP006131

Limited data exist examining arterial stiffness and heart rate variability (HRV) over time in young adults with youth-onset type 1 (T1D) and type 2 diabetes (T2D) . We compared arterial stiffness and HRV over time and by diabetes type and determined the risk factors associated with worsening arterial stiffness and HRV. Arterial stiffness (pulse wave velocity, augmentation index) and HRV (SDNN and PNN50) were measured twice (∼ 5 years apart) in the SEARCH for Diabetes in Youth Study. Linear regression models assessed risk factors overtime and with arterial stiffness and HRV at follow-up. Of 1159 participants studied, 949 had T1D (mean age 17.1 ± 4.7 years, 60.3% non-Hispanic White, 55% female) and 2had T2D (mean age 22.1 ± 3.5 years, 23.8% non-Hispanic White, 71% female) at initial assessment when diabetes duration was 7.9 years (both groups) . Participants with T2D vs. T1D had greater arterial stiffness and more abnormalities in HRV at initial and follow-up assessments (Figure) .For AIx and PNN50 T2D compared to T1D had a greater change over time (p Disclosure A.S. Shah: None. R. Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. L.M. Dolan: None. D. Dabelea: None. G. Imperatore: None. A.K. Mottl: Advisory Panel; Bayer AG. Board Member; Bayer AG. Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. E. Lustigova: None. C. Pihoker: None. S.M. Marcovina: None. E.M. Urbina: Advisory Panel; Astellas Pharma Inc. Funding NIH and CDC

We studied arterial stiffness in youth and young adults with T1D and potential longitudinal mediators of racial and ethnic disparities. SEARCH for Diabetes in Youth Study participants (n=2317; 14% Hispanic, 12% non-Hispanic Black, 74% non-Hispanic White) had CV risk factors (body size, lipid profile, blood pressure, A1c, urinary creatinine, pulse) measured 2-6 times from ∼9 months up to ˜years after T1D diagnosis. Arterial stiffness was measured with pulse wave velocity (PWV) at ˜years T1D duration (˜18 years of age) . For each risk factor, we summarized the longitudinal data as mean, max, slope, and area-under-the-curve (AUC) . Using split test/replication datasets, we a) identified the summary statistic for each risk factor most associated with PWV using flipped multivariate general linear models, and b) used the resulting statistics to construct a risk score predicting PWV with a stepwise general linear model. The final score included AUC for BMI, triglycerides and creatinine; heart rate slope; max mean arterial pressure; and age and T1D duration at PWV measurement, explaining 35% of variability in PWV at 18 years. PWV varied by race and ethnicity (Figure - left) . Adjustment for the risk score partially attenuated this disparity (Figure - right) . These data suggest CV risk factors from T1D diagnosis onward are related to racial and ethnic disparities in arterial stiffness, but other factors are likely involved. Disclosure K.A.Sauder: None. S.M.Marcovina: None. E.J.Mayer-davis: None. A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. C.Pihoker: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. A.S.Shah: None. E.M.Urbina: Advisory Panel; Astellas Pharma Inc. L.E.Wagenknecht: None. S.R.Daniels: None. D.Dabelea: None. D.H.Glueck: None. K.K.Harrall: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. L.M.Dolan: None. A.Lane-cordova: None. A.D.Liese: None. E.Lustigova: None. F.Malik: n/a. Funding National Institutes of Health

Hemoglobin A1c (HbA1c) monitoring over time is thought to facilitate care and support diabetes management goals, but only half of youth and young adults with diabetes report ≥3 HbA1c tests/year despite poor glycemic control. We explored disparities in HbA1c testing over time and association with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) in the SEARCH for Diabetes in Youth study. Individuals diagnosed with diabetes at In conclusion, we report that mainly healthcare-related factors are associated with disparities in HbA1c testing frequency over time in youth-onset type 1 and type 2 diabetes, and these disparities are associated with HbA1c levels in type 1 diabetes. Disclosure K. A. Sauder: None. R. Dagostino: Consultant; Self; AstraZeneca, Biogen, Daiichi Sankyo. D. Dabelea: None. J. M. Stafford: None. S. R. Ehrlich: None. A. D. Liese: None. S. M. Marcovina: None. A. K. Mottl: Advisory Panel; Self; Bayer U. S. C. Pihoker: None. S. Saydah: None. A. S. Shah: None. Funding National Institutes of Health; Centers for Disease Control and Prevention

The objective was to assess changes in diabetes autoantibodies (DA) in children and adolescents with diabetes and explore whether observed changes were associated with participants’ characteristics, clinical parameters and diabetes complications. Participants with diabetes had DA (GAD, IA2 and ZnT8) measured at baseline (within 10.3± 7.1 months of diagnosis) and at 1, 2 and/or ≥ 5 years after baseline. At the > 5 year follow-up, the following measures were obtained: HbA1c, insulin dose, c-peptide, frequency of diabetes ketoacidosis (DKA) and severe hypoglycemia in the past 6 months, presence of microalbuminuria, hypertension, arterial stiffness, retinopathy and neuropathy. In those with positive baseline DAs, we examined the association between the change in the number of positive DA and change in each DA status with participants’ characteristics and clinical parameters. At baseline, 3,183 participants had positive DAs. At a mean diabetes duration of 7.3±2.3 years, 1,749 participants had longitudinal DA data, with 83.4% remaining positive (35.0% had 1 DA, 48.4% had 2 or more DAs). There was less DA persistence associated with longer diabetes duration (p=0.003 for those with baseline 1 DA and p Conclusions: DA status remained relatively stable at 7 years after diabetes diagnosis in those with baseline positive DA. Younger age at diagnosis and longer duration were associated with less DA persistence. Measuring DAs after initial presentation may aid in diabetes classification but not in prediction of clinical course. Disclosure L. Merjaneh: None. D. Dabelea: None. C. Pihoker: None. L. M. Dolan: None. C. Suerken: None. R. Dagostino: Consultant; Self; AstraZeneca, Biogen, Daiichi Sankyo. G. Imperatore: None. S. Saydah: None. A. J. Roberts: None. S. M. Marcovina: None. E. J. Mayer-davis: None. Funding Centers for Disease Control and Prevention (00097, DP-05-069, DP-10-001); National Institute of Diabetes and Digestive and Kidney Diseases (1UC4DK108173, 1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); Kaiser Permanente Southern California (U18DP006133, U48/CCU919219, U01DP000246, U18DP002714); University of Colorado Denver (U18DP006139, U48/CCU819241-3, U01DP000247, U18DP000247-06A1); Cincinnati’s Children’s Hospital Medical Center (U18DP006134, U48/CCU519239, U01DP000248, 1U18DP002709); University of North Carolina at Chapel Hill (U18DP006138, U48/CCU419249, U01DP000254, U18DP002708); Seattle Children’s Hospital (U18DP006136, U58/CCU019235-4, U01DP000244, U18DP002710-01); Wake Forest University School of Medicine (U18DP006131, U48/CCU919219, U01DP000250, 200-2010-35171)

Poor cognition has been observed in children and adolescents with type 1 (T1D) and type 2 (T2D) diabetes. Differences in cognition between young adults with youth-onset T1D and T2D, however, have not been explored, nor is the effect of shared etiologic processes, e.g., poor glycemic control, on cognition fully understood. Using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we compared cognition between young adults with youth-onset T1D and T2D, testing whether glycemic control modified the relationship between diabetes type and cognition. Cognition was assessed via the NIH Toolbox Cognition Battery and age-corrected composite Fluid Cognition scores used. Glycemic control was estimated from repeated measures of HbA1c. Linear regression modeling was used to test the interaction effect of diabetes type and glycemic control on Fluid Cognition score while controlling for sex, race/ethnicity, waist-height ratio, duration of diabetes, depression, alcohol and drug use, any hypoglycemic episode in the past year, parental highest level of education, household income, and clinic site. The T2D group (n = 254) had significantly lower Fluid Cognition scores, compared to the T1D group (n = 953) (mean [SD] 84.7 [17.3] vs. 95.4 [16.8], p Disclosure A. Shapiro: None. D. Dabelea: None. J.M. Stafford: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. C. Pihoker: None. A.D. Liese: None. A.S. Shah: None. A. Bellatorre: None. J.M. Lawrence: None. L. Henkin: None. G. Wilkening: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1UC4DK108173-01)

Medical nutrition therapy (MNT) is integral to diabetes (DM) management, but little is known about MNT use in youth and young adults. The SEARCH for Diabetes in Youth study assessed MNT use among 1476 participants with type 1 DM (T1D) and 245 with type 2 DM (T2D) who had up to 3 research visits over 5.2 years (range 1.7-11.5). Participants reported often, sometimes, or never using each of 10 MNT strategies, which we categorized with 5 mutually exclusive groups: often using across visits; start using at later visits; sometimes using across visits; stop using at later visits; or never using at every visit. We used general linear models to examine A1c levels at the most recent visit (mean 11.0 [range 6.3-17.0] years after DM diagnosis) for each MNT strategy, adjusting for sociodemographic and DM-related variables. Most participants with T1D reported often counting carbs (n=1080, 75%), while half (n=107, 47%) of those with T2D reported often limiting sweets. Table presents significant associations of A1c levels with MNT use by DM type. In T1D, mean A1c differed significantly across MNT use of 7 strategies, but only for 2 strategies in T2DM. For both T1D and T2D, A1c did not differ by use of dietary exchanges, drinking more milk, or eating more fruits/vegetables. Our data suggest that often using most MNT strategies is related to relatively better glycemic control in T1D, but this applies to fewer MNT strategies for T2DM. Disclosure K.A. Sauder: None. J.M. Stafford: None. N.S. The: None. E.J. Mayer-Davis: None. J. Thomas: None. J.M. Lawrence: None. G. Kim: None. K.R. Siegel: None. E.T. Jensen: None. A.S. Shah: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. D. Dabelea: None. Funding National Institutes of Health

Individuals with diabetes are at high risk for heart failure with preserved ejection fraction due to diabetic cardiomyopathy (DCM), defined as abnormal myocardial structure and function in the absence of overt coronary artery disease. DCM leads to myocardial fibrosis and remodeling with one of the first signs being left ventricular (LV) diastolic dysfunction. The objective was to compare the prevalence of diastolic dysfunction among young adults with type 1 diabetes (T1D) vs. type 2 diabetes (T2D) with diabetes diagnosed in childhood. Participants had T1D or T2D and were enrolled in the SEARCH for Diabetes in Youth Study. Cardiovascular risk factors and diastolic function via echocardiography were measured at an in-person visit, after an average disease duration of 10.9 years (both groups). Unadjusted means were compared between those with T1D and T2D, p Disclosure A.S. Shah: None. D. Dabelea: None. L.M. Dolan: None. S. Isom: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. L.E. Wagenknecht: None. G. Imperatore: None. S. Saydah: None. A.D. Liese: None. J.M. Lawrence: None. C. Pihoker: None. E.M. Urbina: None. Funding Centers for Disease Control and Prevention (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); National Institutes of Health (1UC4DK108173)

Limited information exists regarding the evolution of dyslipidemia in youth with type 2 diabetes (T2D). Understanding dyslipidemia risk factors may influence treatment. We studied 212 youth with T2D not on lipid lowering therapy (68% female, 43% non-Hispanic black, mean age 14.9±2.7y at baseline, mean follow-up 7.0±2.0y). Dyslipidemia was defined as HDL-C100mg/dL, or triglycerides (TG)>150mg/dL. Progression was defined as normal lipids at baseline, dyslipidemia at follow-up; regression as dyslipidemia at baseline, normal at follow-up; stable abnormal as dyslipidemia at both; stable normal as normal at both. Associations of A1c and abdominal adiposity (waist to height ratio, WHtR) over time (area under the curve, AUC) with progression and stable abnormal were examined and relative risks estimated. HDL-C progressed, regressed, was stable normal and stable abnormal in 12%, 11%, 62%, and 14%, respectively. Corresponding LDL-C values were 16%, 13%, 43% and 29%; TG were 17%, 11%, 56% and 16%. Each 1% increase in A1c AUC was associated with 13% higher risk of TG>150mg/dL and 22% higher risk of LDL-C>100mg/dL, after adjusting for WHtR (Table). There were no significant associations with WHtR. In youth with T2D, 33% and 45% had progression or stable dyslipidemia of TG and LDL-C, respectively. Higher A1c over time is associated with worse TG and LDL-C, highlighting the importance of glycemic control. Disclosure R.P. Brady: None. A.S. Shah: None. E.T. Jensen: None. J.M. Stafford: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. L.M. Dolan: None. L.M. Knight: None. G. Imperatore: None. C.B. Turley: None. A.D. Liese: None. E.M. Urbina: None. J.M. Lawrence: None. C. Pihoker: None. S.M. Marcovina: None. D. Dabelea: None. Funding Centers for Disease Control and Prevention (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); National Institutes of Health (1UC4DK108173)

Accurate classification of diabetes type guides correct treatment. We recently showed a type 1 diabetes (T1D) genetic risk score (GRS-1), combined with clinical features and biomarkers discriminates between T1D and type 2 (T2D) and MODY in European adults. We aimed to test the ability of an improved 67 SNP T1D score (GRS-2) to discriminate T1D in an ethnically diverse U.S. pediatric population. We included 1818 SEARCH Study participants who had a C-peptide at a median (IQR) of 8 (6-9) years post diagnosis. T1D was defined based on severe insulin deficiency (fasting C-peptide The T1D GRS-2 was discriminative of T1D across all three ethnic groups AUC (95% CI) for GRS-1 vs. GRS-2 was 0.88 (0.84, 0.93) vs. 0.88 (0.83, 0.92) in white, 0.82 (0.77, 0.87) vs. 0.87 (0.83, 0.92) in blacks, and 0.87 (0.82, 0.92) vs. 0.9 (0.86, 0.95) in Hispanics). Combined risk scores were most accurate at classifying T1D. AUC for different scores were: 0.93 (0.91, 0.95) for type assigned by provider at diagnosis, 0.95 (0.93, 0.96) for age and BMI, 0.95 (0.94, 0.97) for GAD/IA-2/ZNT8 autoantibodies, and 0.99 (0.99, 1.00) for a combined approach using autoantibodies, GRS-2 and clinical features. These results were similar across all race/ethnic groups. A new T1D GRS-2 is discriminative of T1D in a racial/ethnically diverse pediatric population. Using GRS2 in a combined model of clinical features, autoantibodies and genetics offers near perfect classification of T1D and could be used to accurately classify diabetes type. Disclosure R.A. Oram: Other Relationship; Self; Randox Laboratories Ltd. S.A. Sharp: None. C. Pihoker: None. L.A. Ferrat: None. G. Imperatore: None. S. Saydah: None. A.H. Williams: None. L.E. Wagenknecht: None. J.M. Lawrence: None. M.N. Weedon: None. R. Dagostino: Consultant; Self; Acelity, Amgen Inc. W. Hagopian: Research Support; Self; Novo Nordisk A/S. J. Divers: None. D. Dabelea: None. Funding National Institutes of Health (UC4DK108173)

Urinary (U) neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are markers of renal tubular injury. Whether NGAL and KIM-1 are elevated in early diabetic kidney disease (DKD) is not known. We performed a pilot study to compare the U concentrations (C) of NGAL and KIM-1 in YA with T1D or T2D from the SEARCH registry and healthy controls (n 45 in each group). The YA with diabetes were selected based on age at dx > 10 years and duration >8 years and were randomly selected across the quartiles of eGFR with similar age, gender and ethnicity. T1D (age 21 ± 2 years; duration 9.6 ± 1.0 years; HbA1c 9.3 ± 2.1% eGFR 126 ± 19 mL/min/1.73m2, UACR 11 ± 16 µg/mg), T2D (age 24 ± 3 years, duration 9.8 ± 1.2 years, HbA1c 8.5 ± 3.0%, eGFR 128 ± 21 mL/min/1.73m2, UACR 38 ± 71 µg/mg), controls (age 23 ± 3 years). In each group 50% were female, 41% white, 43% AA, and 16% Hisp. NGAL and KIM-1 were significantly elevated in T1D and T2D compared with controls (p < 0.001, p< 0.007). Although there was a trend for a greater UC of NGAL in T2D than T1D and a greater UC of KIM-1 in T1D than T2D, these differences were not statistically significant. Elevated UC of NGAL and KIM-1 are present in YA with T1D and T2D suggesting the presence of tubular damage early in the course of diabetes. Further investigation will determine if these markers can be used to assess the natural history of tubular injury or monitor therapeutic intervention in DKD. Disclosure N.M. Sheanon: None. A.K. Mottl: None. R. Dagostino: Consultant; Self; Teva Pharmaceutical Industries Ltd., Acelity, RedHill Biopharma, Edwards Lifesciences. C. Suerken: None. M. Afkarian: None. D. Dabelea: None. G. Imperatore: None. S.M. Marcovina: None. D.J. Pettitt: None. S. Saydah: None. L.M. Dolan: None.

INTRODUCTION: Although recognition of insulin sensitivity as a risk factor for cardiovascular disease is growing, a deeper understanding of its role is impeded by the cost and complexity of currently available measures. This report evaluates previously described alternative indices of insulin sensitivity with the goal of identifying a reliable, but logistically simpler, alternative. METHODS: Data from 1460 participants in the Insulin Resistance Atherosclerosis Study (IRAS) were used to assess the proportion of the relationship between a recognized measure of insulin sensitivity (Bergman’s S I ) and cardiovascular risk factors that is contained in each of nine alternative measures. RESULTS: A number of the alternative indices contained a substantial proportion of the information available in Bergman’s S I . The Galvin’s index and the homeostasis model were most promising. However, there remained a significant amount of the information in Bergman’s S I that was not contained in any of the alternative indices. DISCUSSION: There are simpler alternative indices of insulin sensitivity for use in epidemiological studies, but each alternative is associated with some loss of information. It may be possible that this loss can be overcome with an increased sample size; however, using the alternative indices may also confound the assessment of insulin sensitivity with other underlying factors (i.e., hyperinsulinemia). The alternative indices are not recommended for the clinical assessment of insulin sensitivity for an individual patient or subject.

This study evaluated the effects of vitamin E (alpha-tocopherol) on oxidative DNA damage in a randomized double-blind Phase II chemoprevention trial. Oxidative DNA damage was measured by the level of auto-antibody (Ab) against 5-hydroxymethyl-2'-deoxyuridine (HMdU) in plasma. After the baseline screening, eligible subjects (n = 31; plasma samples from 28 subjects were available for this study) were randomized to receive 15, 60, or 200 mg of alpha-tocopherol per day for 28 days. Biomarkers were measured twice at baseline--on day 1 (visit 1) and day 3 (visit 2)--and twice after intervention--on day 17 (visit 3) and day 31 (visit 4). At baseline, there was a highly significant inverse correlation between anti-HMdU Ab titer and plasma vitamin E level (r = -0.53; P = 0.004; n = 28). Smoking did not affect baseline anti-HMdU Ab titer; however, anti-HMdU Ab titer levels at baseline were significantly lower in subjects with above-median (0.75 ounce/day) alcohol consumption (P = 0.008). No significant change in anti-HMdU Ab level occurred at either visit 3 or visit 4 for subjects on the lowest dose, 15 mg alpha-tocopherol per day. Subjects receiving 60 mg of alpha-tocopherol per day had a significant decrease in anti-HMdU Ab level at visits 3 and 4 compared with baseline (P = 0.049 and P = 0.02, respectively). However, subjects receiving the highest dose, 200 mg/day, had less consistent results: a significant decrease in anti-HMdU Ab level was seen at visit 4 (P = 0.04) but not at visit 3. Our results demonstrate an inverse relationship between alpha-tocopherol and anti-HMdU Abs in plasma; oxidative DNA damage can be modulated by short-term dietary supplementation of alpha-tocopherol in some subjects.

The FoCaS (Forsyth County Cancer Screening) Project was one of six projects funded by the National Cancer Institute "Public Health Approaches to Breast and Cervical Cancer" initiative. The goal of this project was to improve the use of breast and cervical cancer screening among low-income, predominately African-American, women age 40 and older. Strategies implemented in the intervention city included public health clinic in-reach strategies (chart reminders, exam room prompts, in-service meetings, and patient-directed literature) and community outreach strategies (educational sessions, literature distribution, community events, media, and church programs). Baseline and follow-up data from independent cross-sectional samples in both the intervention and comparison cities were used to evaluate the effects of the intervention program. A total of 248 women were surveyed at baseline, and 302 women were surveyed 3 years later at follow-up. The proportion of women reporting regular use of mammography increased (31 to 56%; P0.001) in the intervention city. In the comparison city, a nonsignificant (ns) increase in mammography utilization was observed (33 to 40%; P = ns). Pap smear screening rates also improved in the intervention city (73 to 87%; P = 0.003) but declined in the comparison city (67 to 60%; P = ns). These relationships hold in multivariate models. The results suggest that a multifaceted intervention can improve screening rates in low-income populations. These results have important implications for community-based research and efforts in underserved populations.

The frequency of oxidative base damage along the human p53 and PGK1 genes was determined at nucleotide resolution by cleaving DNA at oxidized bases with endonuclease III and formamidopyrimidine DNA glycosylase and then using the ligation-mediated PCR technique to map induced break frequency. Damage was induced either in vivo by exposing cultured human male fibroblasts to H2O2 or in vitro by exposing purified genomic DNA to H2O2 plus ascorbate in the presence of Cu(II), Fe(III), or Cr(VI) metal ions. All four base damage patterns from either in vivo or in vitro treatments were nearly identical in both regions of the genome. The frequency of base damage varied along the DNA, with guanine being the most commonly damaged base. In the Fe(III)-mediated in vitro reactions, single-stranded breaks were almost completely suppressed by addition of sucrose, which facilitated mapping of base damage. The in vitro base damage pattern generated by Cr(VI), ascorbate, and H2O2 was similar to that of the other metal ions, with the exception of several unique positions; these were heavily damaged only in the presence of Cr(VI). Isolated nuclei suffered little oxidative base damage in the presence of ascorbate and H2O2, and we conclude that during H2O2 in vivo treatment of cells, metal ions (or metal-like ligands) are freed from the cytoplasm to migrate into the nucleus and supply the redox cycling ligands necessary for oxidative base damage. These data simplify the complexity of H2O2-induced oxidative damage and mutagenesis studies by demonstrating the commonality of damage catalyzed by different transition metal ions and by showing that the pattern of H2O2-mediated oxidative base damage is determined almost entirely by the primary DNA sequence, with chromatin structure having a limited effect. Our data suggest a model for base damage in which DNA-metal ion binding domains can equally accommodate a variety of different metal ions and thus are a key factor in determining the local probability of DNA damage.