Insulin Sensitivity is Inversely Associated with Cardiovascular Disease Risk Factors in Adolescents with and without Type 1 Diabetes Brian J. Specht 1, B.A.; R. Paul Wadwa 2, M.D.; Janet K. Snell-Bergeon 2, Ph.D.; Franziska K. Bishop 2, M.S.; David M. Maahs 2, M.D. Ph.D. 1 University of Colorado School of Medicine, Aurora, CO; 2 Barbara Davis Center for Childhood Diabetes, Aurora, CO Objective  The ISS for adolescents ages years with T1D (n=292; age 15.4 ± 2.1 years; duration 8.8 ± 3.0 years) and non-DM controls (n=89; age 15.4 ± 2.1 years) was determined using the SEARCH ISS model: log e IS = – (waist, cm) – (HbA 1c, %) – (TG, mg/dl).  The ISS for the T1D adolescents was then divided into tertiles (ISS ≤ 6.83, ISS 6.83 – 8.59, and ISS ≥ 8.59) ; CVD risk factors were compared between all non-DM controls and by ISS tertile in T1D subjects. Comparisons were then stratified by sex and adjusted for race- ethnicity and Tanner Stage of puberty, both known to influence insulin sensitivity.  To compare the relationship between insulin sensitivity and CVD risk factors in adolescents. We tested two hypotheses: 1) Adolescents with T1D have increased CVD risk factors as compared to non-DM controls and 2) CVD risk factors are inversely associated with ISS in adolescents with T1D. Conclusions  T1D adolescents have increased CVD risk factors as compared to non-DM controls, including decreased estimated insulin sensitivity score indicating reduced insulin sensitivity.  Additionally, CVD risk factors are inversely associated with estimated insulin sensitivity in T1D adolescents.  Adolescence is a crucial period in the understanding and prevention of CVD risk factors in T1D and insulin sensitivity may be an important therapeutic target. Background Methods  Cardiovascular disease (CVD) is the primary cause of death in type 1 diabetes (T1D) with many risk factors beginning in early adolescence.  Insulin sensitivity is decreased in T1D as compared to non-diabetic (non-DM) controls and is already present in adolescents. An insulin sensitivity score (ISS) developed in the SEARCH for Diabetes in Youth Study can be used to estimate insulin sensitivity (lower ISS = less insulin sensitive). This project was supported by the following:  NIDDK Medical Student Research Program, Grant 3T32DK S1  NIDDK DK for Dr. Maahs  JDRF Early Career Award ( ) for Dr. Wadwa  NIH/NCRR Colorado CTSI Grant Number UL1 RR Its contents are the authors’ sole responsibility and do not necessarily represent official NIH views.  CVD risk factors were more atherogenic for T1D adolescents as compared to non-DM controls (p<0.05) for body-mass index (BMI), total cholesterol, HDL-cholesterol, LDL-cholesterol, systolic blood pressure (SBP), diastolic blood pressure (DBP) and C-reactive protein (CRP). The ISS was also significantly different between the two groups (non-DM ISS 11.5  2.9, T1D ISS 7.8  2.4; p<0.0001), and hemoglobin A1c (HbA 1c ) was significantly different by diabetes status, as expected.  When ISS was divided into tertiles in T1D subjects, CVD risk factors were progressively more atherogenic as insulin sensitivity decreased and as compared to non-DM controls. When the data were adjusted for race-ethnicity and Tanner Stage and stratified by sex, similar differences were seen in both males and females. Results Acknowledgments