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. 2022 Jan 22;11(3):549.
doi: 10.3390/jcm11030549.

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

Pere Domingo  1 , María Gracia Mateo  1 , Joan Villarroya  1   2 , Rubén Cereijo  1   2 , Ferran Torres  3   4 , Joan C Domingo  2 , Laura Campderrós  2 , José M Gallego-Escuredo  1   2 , María Del Mar Gutierrez  1 , Isabel Mur  1 , Noemí Corbacho  1 , Francesc Vidal  5 , Francesc Villarroya  2 , Marta Giralt  2
Affiliations

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

Pere Domingo et al. J Clin Med. .

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-naïve = 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 (naïve, 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.

Keywords: D:A:D; Framingham; GDF15; HALS; cardiovascular risk; insulin resistance; metabolic syndrome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Circulating levels of GDF15 in controls and PLWH with or without HIV/cART-associated lipodystrophy (HALS) GDF15 = Growth differentiation factor 15; C = controls N = Naive HIV-infected patients HALS− = HIV-infected patients without HIV/cART-associated lipodystrophy HALS+ = HIV-infected patients with HIV/cART-associated lipodystrophy.
See this image and copyright information in PMC

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