C-reactive protein as a moderator and insulin resistance as a mediator for the association between Endothelin-1 and dysglycemia among African Americans: Jackson Heart Study. (August 2022)

• Record Type: Journal Article
• Authors: Gao, Xiang; Horbal, Steven R.; Kaze, Arnaud D.; Fan, Hao; Su, Le; Fox, Ervin R.; Musani, Solomon K.; Zoh, Roger; Echouffo-Tcheugui, Justin B.; Bidulescu, Aurelian
• Is Part Of: Obesity medicine. Volume 33(2022)
• Publication Date: 2022-08
• Subjects: African Americans -- Jackson heart study -- Endothelin-1 -- Dysglycemia -- Insulin resistance -- Inflammation; Obesity -- Periodicals; Obesity; Obesity; Periodicals; Periodicals; 616.398005
• DOI: 10.1016/j.obmed.2022.100435
• Languages: English
• ISSNs: 2451-8476

Abstract

Abstract: Aims: 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. Methods: 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. Results: 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%. Conclusions: 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. Highlights: African Americans with higher ET-1 level have an increased risk of dysglycemia. When hsCRP exceed a certain level, increased ET-1 level facilitates dysglycemia. Insulin resistance changes are involved in glucose metabolism imbalances leading to dysglycemia. Screening of ET-1 coupled with insulin resistance and inflammatory measurements would early detect dysglycemia.