Sex-Dependent and Asymmetric Associations of Bodyweight History in the Twenties with Later HbA1c Trajectories in a Japanese Occupational Cohort

Background: Underweight status is common among young women in Japan and has been linked to impaired glucose tolerance, but its long-term association with HbA1c trajectories remains unclear. This study examined whether body size history in the twenties is associated with subsequent HbA1c trajectories across adulthood. Methods: We analyzed health check-up data from Fujita Health University, collected between 2003 and 2025. Participants were classified as normal weight in the twenties (NW20s), underweight at least once in the twenties (UW20s_ever), or overweight at least once in the twenties (OW20s_ever), excluding mixed underweight/overweight histories. Eligible individuals had at least 5 years of follow-up, at least five BMI and HbA1c measurements, and at least one BMI record between ages 20 and 29 years. HbA1c trajectories were evaluated using sex-stratified linear mixed-effects models. Kaplan–Meier and Cox regression analyses were used to assess the risk of first reaching HbA1c ≥ 5.6%. Results: A total of 2923 participants were included in the trajectory analysis. For the time-to-event analysis, 2753 participants were included after exclusion of 170 participants with HbA1c ≥ 5.6% at study entry. Body size history in the twenties was associated with distinct, sex-specific HbA1c trajectories. OW20s_ever showed persistently higher HbA1c levels in both women and men, but the local slope of HbA1c was greater at ages 35 and 45 years in women and at age 25 years in men. In contrast, UW20s_ever showed lower HbA1c levels than NW20s at ages 25 and 35 years only in women. In complementary time-to-event analyses, OW20s_ever was associated with a higher risk of HbA1c ≥ 5.6% in both women and men (women: HR 1.37, 95% CI 1.06–1.76, p = 0.016; men: HR 1.81, 95% CI 1.41–2.32, p < 0.001), whereas UW20s_ever was associated with a lower risk only in women (HR 0.81, 95% CI 0.67–0.98, p = 0.028). Conclusions: Underweight and overweight history in the twenties are not simply mirror-image exposures but rather have sex-dependent and asymmetric associations with later HbA1c regulation.