Cumulative hyperinsulinemia, hyperglycaemia, and insulin resistance from mid-adolescence through young adulthood with carotid intima-media thickness progression: a 9-year longitudinal study
Authors: Agbaje A O , Zachariah J P , Bamsa O , Odili A N , Tuomainen T P 
Published: October 2022

Abstract

Background
In a recent meta-analysis of randomized clinical trials conducted among adults, carotid intima-media thickness (cIMT) progression was established as a predictor of cardiovascular morbidity and mortality. However, due to the paucity of hard outcomes among adolescents and young adults, a single cIMT measure has largely been used as a marker of preclinical atherosclerotic changes. The repeated measure of cIMT in the young population is scarce thus a knowledge gap exists on the associations of metabolic indices with cIMT progression.

Purpose
To investigate the associations of cumulative fasting plasma glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) with cIMT progression in adolescence.

Methods
We studied 1779 British 15-year-olds (50% females) followed up for 9 years. Fasting insulin and glucose were measured in line with standard protocols at ages 15, 17, and 24 years, respectively. HOMA-IR was computed for each time point. Metabolic indices were age and sex-specifically dichotomized as ≥75%, indicating high category and &lt;75% indicating moderate or reference category. cIMT from the right and left common carotid arteries at 17 years was assessed by ultrasound using a linear 12-MHz transducer (Vivid7, GE Medical, Chicago, Illinois) and cIMT from the right and left common carotid arteries at 24 years was measured using an ultrasound machine (CardioHealth Panasonic and a 13.5 MHz linear array broadband transducer (probe; centre frequency 9.0 MHz). We conducted linear mixed-effect model analyses and adjusted for statistically significant determinants of cIMT progression, viz: sex, age, high sensitivity C-reactive protein, insulin or glucose, dual-energy Xray absorptiometry measured total fat mass and lean mass, systolic blood pressure, diastolic blood pressure, smoking status, and ActiGraph measured sedentary time and light physical activity. Covariates were repeatedly measured.

Results
Participants mean (SD) age in years at different time points were 15.43 (0.29), 17.69 (0.31), and 24.53 (0.72). Cumulative high exposures to glucose: effect estimate 0.009 mm [95% CI −0.003 to 0.021; p=0.130], insulin: 0.002 mm [−0.030 to 0.013; p=0.704], and HOMA-IR: 0.003 mm [−0.009 to 0.016; p=0.608] from 15 to 24 years of age were not associated with the 7-year cIMT progression after full covariate adjustments. Sex-based analyses were consistent with the group analyses in both males and females.

Conclusion
These findings suggest that hyperinsulinemia, hyperglycaemia, and elevated insulin resistance from mid-adolescence through young adulthood may not be associated with progressive carotid wall thickening during late adolescence through young adulthood. Future studies investigating the role of other metabolic indices such as cumulative elevated lipid exposures on cIMT progression in the young population are warranted.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Cultural Foundation