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), UK cohort, 1595 adolescents, mean (SD) age 17.7 (0.4) years, who had fasting plasma glucose, insulin, and echocardiography left ventricular mass indexed for height2.7 (LVMI2.7) and repeatedly measured at age 24-year clinic visit were included. Homeostatic model assessment for IR (HOMA-IR) was computed, while hyperglycemia was defined as glucose concentration of ≥5.6mmol/L and ≥6.1mmol/L and LV hypertrophy 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 = 0.37g/m2.7 [95% CI, 0.23 – 0.52], p<0.001) and HOMA-IR (1.10g/m2.7 [0.63 – 1.57], p<0.001) were independently associated with increased LVMI2.7 over 7 years. Persistent hyperglycemia of 5.6mmol/L and 6.1mmol/L were respectively associated with (Odds ratio 1.46 [1.35 – 1.47], p<0.001) and (3.10 [1.19 – 8.08], p=0.021) higher odds 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 insulin resistance were associated with the risk of worsening structural and functional cardiac damage, largely explained by increased fat mass.