Abstract P437: Cumulative Effect of Early-Onset Type 2 Diabetes on Left Ventricular Geometry - The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Yoshida Yilin , Zu Yuanhao , Fan Bingbing , Li Shengxu , Yoshida Tadashi , Harville Emily , Zhang Tao , Fonseca Vivian A 
Published: May 2024

Background:
Type 2 diabetes (T2D) is increasingly common in young adults. Increases in left ventricular (LV) mass and wall thickness are early manifestations of myocardial involvement in T2D. The association between the cumulative burden of risk factors (RFs) and LV structural abnormalities in patients with early-onset T2D has not been well characterized.

Objective:
Investigate how metabolic RFs accumulated in a 25-year period among patients with early-onset T2D relate to LV mass index (LVMI) and relative wall thickness (RWT).

Methods:
We used data from the Coronary Artery Risk Development in Young Adults study (CARDIA, baseline to year 25). We defined early-onset T2D by self-reported T2D or anti-diabetic medication use, fasting glucose (FG) ≥126 mg/dL, or oral glucose ≥200 mg/dL at or before follow-up year 10 (age<40). LV outcomes were measured by Doppler echocardiography (LVMI by Devereux formula indexed to body surface area; RWT = LV posterior wall thickness at end diastole x 2/LV internal dimension at end-diastole). Hypertrophy was defined by LVMI ≥115 g/m
2
in men or ≥95 g/m
2
in women. We used the area under the growth curve (AUC) that was derived from quadratic random-effects models of ≥4 repeated measures of RFs (BMI, SBP, DBP, LDL-c, HDL-c, triglycerides, fasting glucose, and fasting insulin) to estimate the cumulative burden of T2D through adulthood. We performed linear regressions to examine the associations of the total AUC of each RF with LVMI or RWT, accounting for sex, race, mid-life age, education, smoking, and control for hypertension, lipids, and diabetes. We assessed the associations by sex and race.

Results:
Among 227 patients with early-onset T2D, 39% had hypertrophy, and 13% had RWT>0.42 at midlife. Each standard deviation (SD) increase in total AUCs of BMI, SBP, DBP, triglycerides, FG, and fasting insulin was significantly associated with increased LVMI (β coefficients =5.9, 11.5, 10, 7, 4.1, and 6.7, respectively), while high total AUC of HDL-c was inversely associated with LVMI (β = -5.1). Increased total AUC of triglycerides was associated with increased RWT (β = 0.2). Significant sex and race differences were shown in the cumulative effect of RFs on outcomes. The positive associations between AUC of RFs and LVMI were significant in both sexes, but the associations were stronger in male patients than in women. The inverse association between AUC of HDL-c and LVMI was only significant in male patients (P-interaction <0.05). Women with early-onset T2D but not men exhibited significantly increased RWT related to the increase in AUCs of SBP, DBP, triglycerides, FG, and insulin (P-interaction <0.05). The positive association between AUC of BMI and LVMI was significant in Whites but not Blacks (P-interaction <0.05).

Conclusion:
Cumulative RFs alter mid-adulthood LV geometry in patients with early-onset T2D. This cumulative impact of early-onset T2D on LV geometry varies by sex and race.