Persistent Hyperglycemia and Insulin Resistance With the Risk of Worsening Cardiac Damage in Adolescents: A 7-Year Longitudinal Study of the ALSPAC Birth Cohort

OBJECTIVE Insulin resistance (IR) and dysglycemia can induce cardiac remodeling in adulthood, but little evidence exists with respect to cardiac remodeling in youth with and without evidence of new-onset glucose metabolic alterations. This study investigated whether changes in metabolic status from adolescence to young adulthood are associated with the risk of progressive cardiac remodeling and examined potential mechanistic pathways. RESEARCH DESIGN AND METHODS From the Avon Longitudinal Study of Parents and Children (ALSPAC), U.K. cohort, 1,595 adolescents, mean (SD) age 17.7 (0.4) years, who had data on fasting plasma glucose and insulin levels, and echocardiography left ventricular (LV) mass indexed for height raised to the power of 2.7 (LVMI2.7) and in whom these factors repeatedly were measured at a clinic visit when they were aged 24 years were included. HOMA-IR was computed, hyperglycemia was defined as glucose concentration of ≥5.6 mmol/L and ≥6.1 mmol/L, and LV hypertrophy was defined as LVMI2.7 ≥51g/m2.7. RESULTS The prevalence of LV hypertrophy increased from 2.4% at baseline to 7.1% at follow-up. Each unit increase of glucose (β = 0.37 g/m2.7 [95% CI 0.23–0.52]; P < 0.001) and HOMA-IR (1.10 g/m2.7 [0.63–1.57]; P < 0.001) was independently associated with increased LVMI2.7 over 7 years. Persistent hyperglycemia of 5.6 mmol/L and 6.1 mmol/L was associated with higher odds (odds ratio [OR] 1.46 [95% CI 1.35–1.47], P < 0.001; and 3.10 [95% CI 1.19–8.08], P = 0.021, respectively) of worsening LV hypertrophy over 7 years. Increased fat mass (62% mediation) significantly mediated the association of increased HOMA-IR with increased LVMI2.7. CONCLUSIONS Persistent adolescent hyperglycemia and worsening IR were associated with the risk of worsening structural and functional cardiac damage, and these were largely explained by increased fat mass.