e64b5e35e41048a4c8b4dad319e3b1bd pmc_35160008.pdf 8be3a4738e4c229163a09e477913f3b75f574c5e pmc_35160008.pdf 450029cef86b5c02864d535b6944e04f65adea421db591f9842160c21cd91a41 pmc_35160008.pdf Title: Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy Subject: 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: GDF15; cardiovascular risk; Framingham; D:A:D; insulin resistance; metabolic syndrome; HALS Author: 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 and Marta Giralt Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Jan 22 11:41:32 2022 CET ModDate: Sat Jan 22 11:46:13 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 609815 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 TYUELJ+VnURWPalladioL Type 1 Custom yes yes no 15 0 SWSCPX+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 LAJPTE+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 FGTVAR+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 GQWIGS+CMSY10 Type 1 Builtin yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 48 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 60 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 63 0 ZXDKIP+EURM10 Type 1 Builtin yes yes no 88 0 LYGTIE+URWPalladioL-BoldItal Type 1 Custom yes yes no 95 0 HYYHEA+CMBSY10 Type 1 Builtin yes yes no 108 0 NFBLMK+TimesNewRoman,Bold CID TrueType Identity-H yes yes yes 115 0 NFBMHP+TimesNewRoman,Italic TrueType WinAnsi yes yes no 121 0 NFBMPO+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 124 0 NFBLPK+TimesNewRoman CID TrueType Identity-H yes yes yes 127 0 NFBMAL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 133 0 NFBMAM+PalatinoLinotype CID TrueType Identity-H yes yes yes 136 0 NFBMAN+PalatinoLinotype TrueType WinAnsi yes yes no 142 0 NFBMAO+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 145 0 NFBMAP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 151 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-15 02:32:57 CET RepresentationInformation: pmc_35160008.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-02-27 18:43:26 CET Size: 609815 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 358 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Patients and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Subjects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Biochemistry Laboratory Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Body Composition Measurements, the Definition of HALS, Metabolic Syndrome, and Cardiovascular Risk Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: GDF15, Cytokine, and Fatty Acid Circulating Levels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Population Studied Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Antiretroviral Drug Exposure and Immuno-Virological Status Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: GDF15 Circulating Levels in Controls and PLWH Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: GDF15 Circulating Levels, Fat Mass, HALS, and Metabolic Syndrome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: GDF15 Circulating Levels, Lipids, Glucose Homeostasis, and Inflammation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: GDF15 Circulating Levels and Cardiovascular Risk Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Subgroup Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Independent Predictors of Cardiovascular Risk Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy Author: 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 and Marta Giralt Subject: 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. 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