Cumulative insulin resistance and hyperglycaemia with arterial stiffness and carotid IMT progression in 1779 adolescents: A 9-Year Longitudinal Cohort Study

Abstract

In pediatric population with diabetes and obesity, insulin resistance (HOMA-IR) has been associated with worsening vascular outcomes, however, the cumulative role of HOMA-IR, hyperglycemia, and hyperinsulinemia on repeatedly measured vascular outcomes in asymptomatic youth is unknown. We examined the longitudinal associations of fasting glucose, insulin, and HOMA-IR with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT). From the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, UK 1,779, 15-yr-old participants were followed up for 9 yr. Glucose, insulin, and HOMA-IR assessed at 15, 17, and 24 yr and sex-specifically dichotomized as ≥75th percentile, indicating high category and <75th percentile as reference. cfPWV and cIMT were measured at ages 17 and 24 yr. Associations were examined using linear mixed-effect models adjusted for cardiometabolic and lifestyle covariates. Among 1,779 participants [49.9% female], glucose, insulin, and HOMA-IR had a J- or U-shaped increase from ages 15 through 24 yr. The cumulative exposures to hyperinsulinemia effect estimate −0.019 mU/L; [95% CI −0.019 to −0.002; P = 0.033] and high HOMA-IR: −0.021; [−0.039 to −0.004; P = 0.019] from 15 to 24 yr of age were negatively associated with the 7-yr cfPWV progression. Only cumulative hyperinsulinemia and high HOMA-IR from ages 15 to 17 yr but not from ages 17 to 24 yr was associated with decreased cfPWV progression. There were no associations between cumulative hyperglycemia and cfPWV or cIMT progression. Hyperinsulinemia and HOMA-IR were not associated with cIMT progression. In conclusion, late adolescence may be an optimal timing for intervention targeted at sustaining the protective effect of the decline of insulin and insulin resistance on arterial stiffness progression.