Abstract
To explore high sensitivity C-reactive protein (hsCRP) as a moderator and homeostatic model assessment of insulin resistance (HOMAIR) as a mediator for endothelin-1 (ET-1)-glycemic progression association in African Americans. 1692 participants free of dysglycemia (prediabetes and diabetes) at baseline were assessed for: 1) risk ratios (RR) and 95% confidence intervals (CI) for dysglycemia by Zou's modified Poisson multivariable models; 2) moderation effect of hsCRP in a multivariable adjusted model; and 3) mediation effect of HOMAIR on dysglycemia through ET-1 by Valeri and VanderWeele's mediation approach. Compared to quartile 1 (<0.9 pg/mL) of ET-1, quartile 2 (0.9–1.2 pg/mL) was associated with higher risk of diabetes (RR = 1.19 [95% CI 1.02, 1.40]). Plasma ET-1 level and hsCRP level had a synergistic effect on risk of diabetes (RR = 1.06 [95% CI 1.02, 1.09]). The association between plasma ET-1 and dysglycemia was mediated by HOMAIR with a proportion of 47%. African Americans with higher ET-1 levels have an increased risk of glycemic progression. When hsCRP elevates, increased ET-1 facilitates diabetes. HOMAIR involved in glucose imbalance leads to dysglycemia.
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