The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study

Abstract Background Rheumatoid arthritis (RA) is associated with increased cardiometabolic risk due to inflammation and traditional risk factors, both of which can be mitigated by lifestyle modifications. This study examines metabolic pathways influenced by lifestyle changes and related to improved...

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Main Authors: Grace Kim, Leanna M. Ross, Alyssa M. Sudnick, Johanna L. Johnson, Carl F. Pieper, Margery A. Connelly, Olga Ilkayeva, Michael J. Muehlbauer, Connie W. Bales, Kathryn N. Porter Starr, William E. Kraus, Brian J. Andonian, Kim M. Huffman
Format: Article
Language:English
Published: BMC 2025-06-01
Series:BMC Rheumatology
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Online Access:https://doi.org/10.1186/s41927-025-00525-8
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author Grace Kim
Leanna M. Ross
Alyssa M. Sudnick
Johanna L. Johnson
Carl F. Pieper
Margery A. Connelly
Olga Ilkayeva
Michael J. Muehlbauer
Connie W. Bales
Kathryn N. Porter Starr
William E. Kraus
Brian J. Andonian
Kim M. Huffman
author_facet Grace Kim
Leanna M. Ross
Alyssa M. Sudnick
Johanna L. Johnson
Carl F. Pieper
Margery A. Connelly
Olga Ilkayeva
Michael J. Muehlbauer
Connie W. Bales
Kathryn N. Porter Starr
William E. Kraus
Brian J. Andonian
Kim M. Huffman
author_sort Grace Kim
collection DOAJ
description Abstract Background Rheumatoid arthritis (RA) is associated with increased cardiometabolic risk due to inflammation and traditional risk factors, both of which can be mitigated by lifestyle modifications. This study examines metabolic pathways influenced by lifestyle changes and related to improved cardiometabolic risk. Methods This is a secondary exploratory analysis of the Supervised Weight loss and Exercise Training (SWET) study, in which twenty older adults with RA and overweight/obesity were randomized to 16 weeks of SWET or a counseling program. Baseline and post-intervention measures included mass spectrometry (MS) and nuclear magnetic resonance (NMR) metabolites and lipoproteins; cardiometabolic risk parameters; and RA clinical outcomes. Principal components analysis (PCA) reduced MS change scores into change factors. Between-group differences were assessed with t-tests and linear regression. Within-group differences were assessed with Wilcoxon-signed rank tests. Spearman’s rank correlated MS change factors and NMR change scores with clinical outcomes. Results Group differences were minimal. In all participants, improvements in metabolic syndrome score were associated with increases in PCA Factor 1 (short- and medium-chain acylcarnitines) and ketone bodies (ρ=-0.57, unadjusted p = 0.009, adjusted p = 0.04; ρ=-0.45, unadjusted p = 0.049, adjusted p = 1.00) and decreases in large low-density lipoprotein particles (LDLp) and large high-density lipoprotein particles (HDLp) (ρ = 0.48, unadjusted p = 0.03, adjusted p = 1.00; ρ = 0.48, unadjusted p = 0.03, adjusted p = 1.00). Improvements in RA disease activity (DAS-28ESR) were associated with reductions in very large triglyceride-rich lipoprotein particles (TRLp) (ρ = 0.60, unadjusted p = 0.01, adjusted p = 0.48). Improvements in patient-reported physical health were associated with reductions in HDL-c, ApoA1 concentrations, and medium HDLp (ρ=-0.50, unadjusted p = 0.03, adjusted p = 1.00; ρ=-0.47, unadjusted p = 0.04, adjusted p = 1.00; ρ=-0.45, unadjusted p = 0.047, adjusted p = 1.00). Improvements in patient-reported mental health were associated with decreases in high-density lipoprotein 6 (H6) particles (ρ=-0.60, unadjusted p = 0.03, adjusted p = 1.00), medium HDLp (ρ=-0.54, unadjusted p = 0.01, adjusted p = 0.48), and LDL size (ρ=-0.52, unadjusted p = 0.02, adjusted p = 0.96). Conclusion In older adults with RA and overweight/obesity, both intensive supervised weight loss and exercise and lifestyle-based counseling influenced metabolic pathways, enhancing lipid metabolism (e.g., reductions in large LDLp) and metabolic flexibility (e.g., increases in fasting ketones and short- and medium-chain acylcarnitines). However, reductions in HDL-related measures should be interpreted cautiously as they may not reflect improved cardiometabolic risk. Trial registration ClinicalTrials.gov, NCT04356183, 04/17/2020.
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spelling doaj-art-2a47bde42fc84a26ad82b0be16adcbb52025-08-20T02:39:44ZengBMCBMC Rheumatology2520-10262025-06-019111510.1186/s41927-025-00525-8The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA studyGrace Kim0Leanna M. Ross1Alyssa M. Sudnick2Johanna L. Johnson3Carl F. Pieper4Margery A. Connelly5Olga Ilkayeva6Michael J. Muehlbauer7Connie W. Bales8Kathryn N. Porter Starr9William E. Kraus10Brian J. Andonian11Kim M. Huffman12Duke Molecular Physiology Institute, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineDepartment of Biostatistics & Bioinformatics, Division of Bioinformatics, Duke University School of MedicineDiagnostics R&D, LabcorpDuke Molecular Physiology Institute, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineDepartment of Medicine, Division of Geriatrics, Duke University School of MedicineDepartment of Medicine, Division of Geriatrics, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineDuke Molecular Physiology Institute, Duke University School of MedicineAbstract Background Rheumatoid arthritis (RA) is associated with increased cardiometabolic risk due to inflammation and traditional risk factors, both of which can be mitigated by lifestyle modifications. This study examines metabolic pathways influenced by lifestyle changes and related to improved cardiometabolic risk. Methods This is a secondary exploratory analysis of the Supervised Weight loss and Exercise Training (SWET) study, in which twenty older adults with RA and overweight/obesity were randomized to 16 weeks of SWET or a counseling program. Baseline and post-intervention measures included mass spectrometry (MS) and nuclear magnetic resonance (NMR) metabolites and lipoproteins; cardiometabolic risk parameters; and RA clinical outcomes. Principal components analysis (PCA) reduced MS change scores into change factors. Between-group differences were assessed with t-tests and linear regression. Within-group differences were assessed with Wilcoxon-signed rank tests. Spearman’s rank correlated MS change factors and NMR change scores with clinical outcomes. Results Group differences were minimal. In all participants, improvements in metabolic syndrome score were associated with increases in PCA Factor 1 (short- and medium-chain acylcarnitines) and ketone bodies (ρ=-0.57, unadjusted p = 0.009, adjusted p = 0.04; ρ=-0.45, unadjusted p = 0.049, adjusted p = 1.00) and decreases in large low-density lipoprotein particles (LDLp) and large high-density lipoprotein particles (HDLp) (ρ = 0.48, unadjusted p = 0.03, adjusted p = 1.00; ρ = 0.48, unadjusted p = 0.03, adjusted p = 1.00). Improvements in RA disease activity (DAS-28ESR) were associated with reductions in very large triglyceride-rich lipoprotein particles (TRLp) (ρ = 0.60, unadjusted p = 0.01, adjusted p = 0.48). Improvements in patient-reported physical health were associated with reductions in HDL-c, ApoA1 concentrations, and medium HDLp (ρ=-0.50, unadjusted p = 0.03, adjusted p = 1.00; ρ=-0.47, unadjusted p = 0.04, adjusted p = 1.00; ρ=-0.45, unadjusted p = 0.047, adjusted p = 1.00). Improvements in patient-reported mental health were associated with decreases in high-density lipoprotein 6 (H6) particles (ρ=-0.60, unadjusted p = 0.03, adjusted p = 1.00), medium HDLp (ρ=-0.54, unadjusted p = 0.01, adjusted p = 0.48), and LDL size (ρ=-0.52, unadjusted p = 0.02, adjusted p = 0.96). Conclusion In older adults with RA and overweight/obesity, both intensive supervised weight loss and exercise and lifestyle-based counseling influenced metabolic pathways, enhancing lipid metabolism (e.g., reductions in large LDLp) and metabolic flexibility (e.g., increases in fasting ketones and short- and medium-chain acylcarnitines). However, reductions in HDL-related measures should be interpreted cautiously as they may not reflect improved cardiometabolic risk. Trial registration ClinicalTrials.gov, NCT04356183, 04/17/2020.https://doi.org/10.1186/s41927-025-00525-8Rheumatic diseaseDisease managementMetabolismMetabolic flexibilityCardiometabolic diseaseLifestyle intervention
spellingShingle Grace Kim
Leanna M. Ross
Alyssa M. Sudnick
Johanna L. Johnson
Carl F. Pieper
Margery A. Connelly
Olga Ilkayeva
Michael J. Muehlbauer
Connie W. Bales
Kathryn N. Porter Starr
William E. Kraus
Brian J. Andonian
Kim M. Huffman
The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study
BMC Rheumatology
Rheumatic disease
Disease management
Metabolism
Metabolic flexibility
Cardiometabolic disease
Lifestyle intervention
title The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study
title_full The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study
title_fullStr The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study
title_full_unstemmed The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study
title_short The impact of lifestyle modification on metabolic pathways in older adults with overweight/obesity and rheumatoid arthritis: a secondary exploratory analysis of the SWET-RA study
title_sort impact of lifestyle modification on metabolic pathways in older adults with overweight obesity and rheumatoid arthritis a secondary exploratory analysis of the swet ra study
topic Rheumatic disease
Disease management
Metabolism
Metabolic flexibility
Cardiometabolic disease
Lifestyle intervention
url https://doi.org/10.1186/s41927-025-00525-8
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