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

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<0.05) . Risk factors associated with worse arterial stiffness and HRV at follow-up in both T1D and T2D included higher BP, HbA1c, waist circumference, and triglycerides overtime, and longer diabetes duration. Arterial stiffness and HRV worsened over time with greater changes among those with T2D and features of the metabolic syndrome regardless of diabetes type. 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

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) .