1269-P: Cumulative Effect of Early-Onset Type 2 Diabetes on Cardiac Dysfunction—The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Objective: Adults with early-onset type 2 diabetes (T2D, diagnosed age 40)="" experience="" premature="" and="" more="" severe="" cardiovascular="" complications.="" we="" investigated="" cumulative="" hyperglycemia="" insulin="" resistance="" (ir)="" over="" 25="" years="" in="" patients="" with="" early-onset="" t2d="" related="" to="" cardiac="" dysfunction="" midlife.="" Methods: We used Coronary Artery Risk Development in Young Adults study (CARDIA, Year 0 to 25) data. Early-onset T2D was self-reported or by fasting glucose (FG)≥126 or oral glucose≥200 mg/dL at/before Year 10. Left ventricular systolic function was estimated by ejection fraction and global longitudinal strain (GLS); diastolic function by early peak diastolic mitral annular velocity, e’, and mitral E/e′. We used the area under the growth curve (AUC) derived from quadratic random-effects models of≥4 repeated measures of FG and HOMA-IR to estimate the cumulative burden of T2D. We performed linear regressions to examine the associations of the total AUC of FG or HOMA-IR with echocardiographic outcomes, accounting for sex, race, education, mid-life age, smoking, alcohol drinking, hypertension, hyperlipidemia, diabetic medication, and heart rate. Results: We included 271 CVD-free patients with early-onset T2D and 514 sociodemographic-matched individuals with euglycemia. In adjusted models, an SD higher AUC of FG was significantly associated with the worsening of diastolic function (β coefficients for e’= - 0.18 and E/e’=0.27) and marginally associated with the worsening of GLS (β=0.13). However, these associations were not significant in the euglycemia group. One SD higher AUC of HOMA-IR was associated with the worsening of e’ and GLS irrespective of T2D status (e’ β= -0.2 and -0.16, and GLS β=0.13 and 0.19 in T2D and euglycemia, respectively). Conclusion: Cumulative hyperglycemia alters midlife diastolic function in patients with early-onset T2D. Sustained IR negatively affects both systolic and diastolic function regardless of T2D status. Disclosure Y. Yoshida: None. K.C. Ferdinand: Consultant; Amgen Inc., Novartis Pharmaceuticals Corporation, Lilly Diabetes, Janssen Pharmaceuticals, Inc., Medtronic, Boehringer-Ingelheim. D. Aguilar: None. V. Fonseca: Consultant; Abbott, Bayer Inc. Stock/Shareholder; BRAVO4HEALTH, LLC. Consultant; Corcept Therapeutics. Speaker's Bureau; Eli Lilly and Company. Research Support; Fractyl Health, Inc. Consultant; Sun Pharmaceutical Industries Ltd. Stock/Shareholder; Amgen Inc. Funding American Diabetes Association (7-23-JDFWH-10)