Sex-Based Differences in BMI and LDL-C Trajectories Following Type 1 Diabetes Diagnosis in Youth

Abstract

Introduction: Cardiovascular disease (CVD) disproportionately affects females with type 1 diabetes (T1D), yet the emergence of sex-specific metabolic risk during early disease remains unclear. We evaluated whether sex differences in BMI percentile (BMIp) and LDL-cholesterol (LDL-C) trajectories appear within the first 2 years following T1D diagnosis. Methods: We conducted a retrospective cohort study of 542 youth with new-onset T1D (mean age 10.4 ± 3.9 years; 54.1% male) and assessed sex differences in BMIp and LDL-C trajectories using linear mixed-effects models, adjusting for age, HBA1c and diabetic ketoacidosis (DKA) status at diagnosis, and baseline weight category (LDL-C model only). Results: At diagnosis, median BMIp did not differ by sex (females: 50.9 [IQR: 19.2–84.1] vs. males: 63.0 [17.8–93.0]; p = 0.15). Over 2 years, females experienced significantly greater BMIp increases (median change: 27.4 [5.1, 49.7] vs. 13.1 [–4.3, 30.5] percentage points; p = 0.002). Adjusted models confirmed steeper increases in BMIp for females compared to males (sex × time interaction: 7.54 [3.13, 11.94]; p < 0.001). LDL-C was higher in females at diagnosis (2.51 ± 0.80 vs. 2.30 ± 0.70 mmol/L [97 ± 31 vs. 89 ± 27 mg/dL]; p = 0.003) and follow-up (2.25 ± 0.59 vs. 2.12 ± 0.65 mmol/L [87 ± 23 vs., 82 ± 25 mg/dL]; p = 0.02), with adjusted models confirming a persistent difference (0.17 [0.06, 0.27] mmol/L [6.39 [2.39, 10.40] mg/dL]; p = 0.002). Discussion: Females with T1D exhibit steeper early increases in adiposity and persistently higher LDL-C levels compared to males, independent of age, glycemic control, and DKA status at diagnosis. These findings underscore the importance of sex-specific metabolic monitoring and early intervention beginning at diagnosis to mitigate long-term cardiovascular risk.