Abstract Body (Do not enter title and authors here): Background: Early-onset adult type 2 diabetes (T2D) is a more severe phenotype than later-onset T2D. We evaluated the extent to which Life’s Essential 8 (LE8) attenuates the risk of premature mortality in early-onset versus later-onset T2D.

Methods: We used data from the Coronary Artery Risk Development in Young Adults study (CARDIA; Year 0-30) to identify those with early-onset T2D (a self-reported diagnosis or elevated HbA1c, fasting glucose, or oral glucose, wherever available, before 45 years) and later-onset T2D. We compared age, sex, and race-adjusted LE8 total and component mean scores between the two T2D groups. We performed adjusted Cox regressions for the association between LE8 scores and all-cause mortality and estimated the absolute risk reduction (ARR) of the outcome associated with ideal or moderate LE8 in the two groups separately. The analysis was replicated in NHANES 2005-2006 to 2017-2018 cycles with linked mortality data.

Results:
In both cohorts, the LE8 total score did not significantly differ between the two T2D groups, but the glucose score was significantly poorer in early-onset than later-onset T2D (both cohorts p<0.005, Table 1). The diet score was lower, but the lipid and blood pressure scores were higher in the early-onset than later-onset T2D (NHANES p<0.05, CARDIA not statistically significant, Table 1). Ideal or moderate LE8 (vs. poor) was associated with a reduced mortality risk in the early-onset T2D group (CARDIA Hazard Ratio 0.45, 95% CI 0.26-0.78, mean 21-year follow-up; 0.54, 0.34-0.85, mean 7-year follow-up). ARR indicates that maintaining LE8 ideal/moderate (vs. poor) would prevent two to eight deaths in 1000 young adults with T2D annually (Table 2). The association between LE8 and mortality risk was less significant in the later-onset T2D group (0.74, 0.36-1.5 CARDIA; 0.72, 0.56-0.91 NHANES; ARR not significant, Table 2).

Conclusion:
Maintaining optimal cardiovascular health may significantly attenuate the risk of premature death in adults with early-onset T2D.