TY - JOUR
T1 - Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD
AU - CRIC Study Investigators
AU - Navaneethan, Sankar D.
AU - Kirwan, John P.
AU - Remer, Erick M.
AU - Schneider, Erika
AU - Addeman, Bryan
AU - Arrigain, Susana
AU - Horwitz, Ed
AU - Fink, Jeffrey C.
AU - Lash, James P.
AU - McKenzie, Charles A.
AU - Rahman, Mahboob
AU - Rao, Panduranga S.
AU - Schold, Jesse D.
AU - Shafi, Tariq
AU - Taliercio, Jonathan J.
AU - Townsend, Raymond R.
AU - Feldman, Harold I.
AU - Appel, Lawrence J.
AU - Go, Alan S.
AU - He, Jiang
AU - Nelson, Robert G.
AU - Shah, Vallabh O.
AU - Unruh, Mark L.
AU - Sondheimer, James H.
N1 - Funding Information:
The CRIC Study Investigators who are not already named in the author list are Lawrence J. Appel, MD, MPH (Johns Hopkins), Alan S. Go, MD (Kaiser Permanente Division of Research, Oakland, CA), Jiang He, MD, PhD (Tulane University), Robert G. Nelson, MD, PhD, MS (University of New Mexico/National Institute for Diabetes and Digestive and Kidney Diseases), Vallabh O. Shah, PhD, MS (University of New Mexico), Mark L. Unruh, MD, MS (University of New Mexico), and James H. Sondheimer, MD (Wayne State University School of Medicine). Sankar D. Navaneethan, MD, MS, MPH, John P. Kirwan, PhD, Erick M. Remer, MD, Erika Schneider, PhD, Bryan Addeman, MBA, Susana Arrigain, MS, Ed Horwitz, MD, Jeffrey C. Fink, MD, James P. Lash, MD, Charles A. McKenzie, PhD, Mahboob Rahman, MD, MS, Panduranga S. Rao, MD, Jesse D. Schold, PhD, Tariq Shafi, MD, Jonathan J. Taliercio, DO, Raymond R. Townsend, MD, and Harold I. Feldman, MD, MSCE. Research idea and study design: SDN, JPK, EMR, HIF; data acquisition: SDN, ES, EH, JCF, JPL, MR, PSR, TS, JJT, RRT, HIF; data analysis/interpretation: SDN, JPK, ES, EMR, BA, CAM; statistical analysis: SA, JDS. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-R01DK101500 (Dr Navaneethan). Funding for the CRIC Study was obtained under a cooperative agreement from NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902, and U24DK060990). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award (CTSA) National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland General Clinical Research Center M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131, Department of Internal Medicine, University of New Mexico School of Medicine Albuquerque, NM R01DK119199. Authors report no conflicts related to the contents of this manuscript. Outside the submitted work, Dr Navaneethan has served on an independent event adjudication committee for clinical trials sponsored by Bayer and Boehringer Ingelheim, served as a consultant to Tricida and Reata Pharmaceuticals, and received investigator-initiated research support from Keryx Biopharmaceuticals. The authors thank the participants, investigators, and staff of the CRIC Study for contributions to this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the position or policy of the Department of Veterans Affairs or the US government. Received November 25, 2019. Evaluated by 3 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Xueqing Yu, MD, PhD). Accepted in revised form May 5, 2020. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Funding Information:
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)- R01DK101500 (Dr Navaneethan). Funding for the CRIC Study was obtained under a cooperative agreement from NIDDK ( U01DK060990 , U01DK060984 , U01DK061022 , U01DK061021 , U01DK061028 , U01DK060980 , U01DK060963 , U01DK060902 , and U24DK060990 ). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award ( CTSA ) National Institutes of Health (NIH)/ National Center for Advancing Translational Sciences (NCATS) UL1TR000003 , Johns Hopkins University UL1 TR-000424 , University of Maryland General Clinical Research Center M01 RR-16500 , Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433 , University of Illinois at Chicago CTSA UL1RR029879 , Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036 , Kaiser Permanente NIH / National Center for Research Resources UCSF-CTSI UL1 RR-024131 , Department of Internal Medicine , University of New Mexico School of Medicine Albuquerque, NM R01DK119199 .
Publisher Copyright:
© 2020 National Kidney Foundation, Inc.
PY - 2021/1
Y1 - 2021/1
N2 - Rationale & Objectives: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD. Study Design: Prospective cohort study. Setting & Participants: Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419). Predictors: VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function). Outcomes: Markers of inflammation (interleukin 1β [IL-1β], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin). Analytical Approach: Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates. Results: Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2 ± 14.6 (SD) mL/min/1.73 m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors. Limitations: Lack of longitudinal data and dietary details. Conclusions: Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.
AB - Rationale & Objectives: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD. Study Design: Prospective cohort study. Setting & Participants: Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419). Predictors: VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function). Outcomes: Markers of inflammation (interleukin 1β [IL-1β], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin). Analytical Approach: Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates. Results: Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2 ± 14.6 (SD) mL/min/1.73 m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors. Limitations: Lack of longitudinal data and dietary details. Conclusions: Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.
KW - Obesity
KW - abdominal fat
KW - adipose tissue
KW - body mass index (BMI)
KW - cardiometabolic risk factor
KW - cardiovascular disease
KW - chronic kidney disease (CKD)
KW - fat
KW - fat distribution
KW - overweight
KW - physical function
KW - renal dysfunction
KW - subcutaneous fat
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U2 - 10.1053/j.ajkd.2020.05.028
DO - 10.1053/j.ajkd.2020.05.028
M3 - Article
C2 - 32798563
AN - SCOPUS:85092056524
SN - 0272-6386
VL - 77
SP - 44
EP - 55
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 1
ER -