Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy

Pere Domingo, María Gracia Mateo, Joan Villarroya, Rubén Cereijo, Ferran Torres, Joan C. Domingo, Laura Campderrós, José M. Gallego-Escuredo, María del Mar Gutierrez, Isabel Mur, Noemí Corbacho, Francesc Vidal, Francesc Villarroya, Marta Giralt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: People living with HIV (PLWH) have an increased cardiovascular risk (CVR) owing to dyslipidemia, insulin resistance, metabolic syndrome, and HIV/combination antiretroviral therapy (cART)-associated lipodystrophy (HALS). Atherosclerosis and inflammation are related to growth differentiation factor-15 (GDF15). The relationship between metabolic disturbances, HALS, and CVR with GDF15 in PLWH is not known. Research design and methods: Circulating GDF15 levels in 152 PLWH (with HALS = 60, without HALS = 43, cART-naive = 49) and 34 healthy controls were assessed in a cross-sectional study. Correlations with lipids, glucose homeostasis, fat distribution, and CVR were explored. Results: PLWH had increased circulating GDF15 levels relative to controls. The increase was the largest in cART-treated PLWH. Age, homeostatic model assessment of insulin resistance 1 (HOMA1-IR), HALS, dyslipidemia, C-reactive protein, and CVR estimated with the Framingham score correlated with GDF15 levels. The GDF15-Framingham correlation was lost after age adjustment. No correlation was found between GDF15 and the D:A:D Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) score estimated CVR. CVR independent predictors were patient group (naive, HALS-, and HALS+) and cumulated protease inhibitor or nucleoside reverse transcriptase inhibitor exposure. Conclusions: PLWH, especially when cART-treated, has increased GDF15 levels-this increase is associated with dyslipidemia, insulin resistance, metabolic syndrome, HALS, and inflammation-related parameters. GDF15 is unassociated with CVR when age-adjusted.

Original languageEnglish
Article number549
Number of pages13
JournalJournal of Clinical Medicine
Volume11
Issue number3
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • Cardiovascular risk
  • D:A:D
  • Framingham
  • GDF15
  • HALS
  • Insulin resistance
  • Metabolic syndrome

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