Adipokines and Transitions in Metabolic Health Over Time: The Atherosclerosis Risk In Communities (ARIC) Study

Bige Ozkan; Sui Zhang; Justin B Echouffo-Tcheugui; Roberta Florido; Vijay Nambi; Erin D Michos; Layla A Abushamat; Kunihiro Matsushita; Gary Gerstenblith; Roger S Blumenthal; Ron Hoogeveen; Christie M Ballantyne; Josef Coresh; Elizabeth Selvin; Chiadi E Ndumele

doi:10.1210/clinem/dgae916

Adipokines and Transitions in Metabolic Health Over Time: The Atherosclerosis Risk In Communities (ARIC) Study

J Clin Endocrinol Metab. 2025 Jan 7:dgae916. doi: 10.1210/clinem/dgae916. Online ahead of print.

Authors

Bige Ozkan^{1

2}, Sui Zhang², Justin B Echouffo-Tcheugui³, Roberta Florido¹, Vijay Nambi⁴, Erin D Michos¹, Layla A Abushamat⁵, Kunihiro Matsushita², Gary Gerstenblith¹, Roger S Blumenthal¹, Ron Hoogeveen⁵, Christie M Ballantyne⁴, Josef Coresh², Elizabeth Selvin², Chiadi E Ndumele^{1

2}

Affiliations

¹ Division of Cardiology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
² Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³ Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁴ Division of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
⁵ Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

PMID: 39761818
DOI: 10.1210/clinem/dgae916

Abstract

Context: Transitions in metabolic health status over time are strongly linked to risk for cardiovascular events, particularly among individuals with obesity. Adipokines are proteins with metabolic effects, but their role in transitions in metabolic health status over time is unknown.

Objective: To evaluate the associations of adiponectin and leptin with metabolic risk transitions over time.

Methods: Among 8,423 individuals who attended ARIC Visits 2 (1990-92) and 4 (1996-98), we evaluated prospective associations of Visit 2 levels of the adipokines adiponectin and leptin (per 1-SD higher) with 6-year transitions in metabolic health. Metabolic health was categorized as metabolically "healthy" (no metabolic syndrome [MetS] or diabetes), unhealthy (MetS present) without diabetes, or unhealthy with diabetes. Analyses were performed overall and stratified by obesity (body mass index [BMI] ≥30 kg/m2).

Results: At Visit 2, the mean age was 58, with 56% female and 21% Black adults. Adults with 1-SD higher adiponectin were less likely to progress from metabolically healthy to unhealthy status over 6 years (OR 0.53, 95%CI: 0.48-0.57), while those with higher leptin were more likely to progress (OR 2.22, 95%CI: 2.01-2.47). Conversely, those with 1-SD higher adiponectin were more likely to regress from metabolically unhealthy to healthy status (OR 1.58, 95% CI: 1.42-1.76), while those with higher leptin were less likely to regress (OR 0.68, 95% CI: 0.60-0.78). Similar patterns were seen across obesity strata. After adjustment for BMI, associations of adiponectin with metabolic transitions were similar, whereas associations for leptin were significantly attenuated.

Conclusion: Leptin and adiponectin are differentially linked to the likelihood of worsening and improving metabolic health over time. Adipokines should be explored as targets to improve metabolic health and decrease the risk of future cardiovascular events.

Keywords: adipokines; adiponectin; diabetes; leptin; metabolic syndrome; regression.