TY - JOUR
T1 - Insulin resistance and chronic kidney disease progression, cardiovascular events, and death
T2 - Findings from the chronic renal insufficiency cohort study
AU - Schrauben, Sarah J.
AU - Jepson, Christopher
AU - Hsu, Jesse Y.
AU - Wilson, F. Perry
AU - Zhang, Xiaoming
AU - Lash, James P.
AU - Robinson, Bruce M.
AU - Townsend, Raymond R.
AU - Chen, Jing
AU - Fogelfeld, Leon
AU - Kao, Patricia
AU - Landis, J. Richard
AU - Rader, Daniel J.
AU - Hamm, L. Lee
AU - Anderson, Amanda H.
AU - Feldman, Harold I.
N1 - Funding Information:
AHA was supported by NIH/NIDDK R01DK107566 and R01DK104730. FPW was supported by R01 DK113191 and K23 DK097201. BMR was supported by the Dialysis Outcomes and Practice Patterns Study (DOPPS) Program which is supported by Amgen, Kyowa Hakko Kirin, and Baxter Healthcare. Additional support for specific projects and countries is provided by AstraZeneca, the European Renal Association-European Dialysis and Transplant Association, Fresenius Medical Care Asia-Pacific Ltd., Fresenius Medical Care Canada Ltd., the German Society of Nephrology, Janssen, the Japanese Society for Peritoneal Dialysis, Keryx, Kidney Care UK, MEDICE Arzneimittel Pütter GmbH & Co KG, Proteon, and Vifor Fresenius Medical Care Renal Pharma. Public funding and support is provided for specific DOPPS projects, ancillary studies, or affiliated research projects by: Australia: the National Health and Medical Research Council; Canada: Cancer Care Ontario (CCO) through the Ontario Renal Network (ORN); France: French National Institute of Health and Medical Research (INSERM); Thailand: Thailand Research Foundation (TRF), Chulalongkorn University Matching Fund, King Chulalongkorn Memorial Hospital Matching Fund, and the National Research Council of Thailand (NRCT); the United Kingdom: National Institute for Health Research (NIHR) via the Comprehensive Clinical Research Network (CCRN); and the United States: the National Institutes of Health and the Patient-Centered Outcomes Research Institute. All support is provided without restrictions on publications. Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/NCATS UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131. The funding for the CRIC Study supported the collection of the data that was analyzed for this study. The funders had no role in the study design, analysis and interpretation of the data, writing the manuscript, or the decision to submit for publication.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/2/20
Y1 - 2019/2/20
N2 - Background: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD. Methods: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without diabetes (N = 1883). Linear regression was used to assess associations with insulin resistance, defined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The relationship of HOMA-IR, fasting glucose, hemoglobin A1c (HbA1c), and C-peptide with CKD progression, cardiovascular events, and all-cause mortality was examined with Cox proportional hazards models. Results: Novel positive associations with HOMA-IR included serum albumin, uric acid, and hemoglobin A1c. After adjustment, HOMA-IR was not associated with CKD progression, cardiovascular events, or all-cause mortality. There was a notable positive association of one standard deviation increase in HbA1c with the cardiovascular endpoint (HR 1.16, 95% CI: 1.00-1.34). Conclusion: We describe potential determinants of HOMA-IR among a cohort of non-diabetics with mild-moderate CKD. HOMA-IR was not associated with renal or cardiovascular events, or all-cause mortality, which adds to the growing literature describing an inconsistent relationship of insulin resistance with CKD-related outcomes.
AB - Background: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD. Methods: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without diabetes (N = 1883). Linear regression was used to assess associations with insulin resistance, defined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The relationship of HOMA-IR, fasting glucose, hemoglobin A1c (HbA1c), and C-peptide with CKD progression, cardiovascular events, and all-cause mortality was examined with Cox proportional hazards models. Results: Novel positive associations with HOMA-IR included serum albumin, uric acid, and hemoglobin A1c. After adjustment, HOMA-IR was not associated with CKD progression, cardiovascular events, or all-cause mortality. There was a notable positive association of one standard deviation increase in HbA1c with the cardiovascular endpoint (HR 1.16, 95% CI: 1.00-1.34). Conclusion: We describe potential determinants of HOMA-IR among a cohort of non-diabetics with mild-moderate CKD. HOMA-IR was not associated with renal or cardiovascular events, or all-cause mortality, which adds to the growing literature describing an inconsistent relationship of insulin resistance with CKD-related outcomes.
KW - Cardiovascular disease
KW - Chronic kidney disease
KW - Chronic renal insufficiency
KW - Insulin resistance
KW - Mortality
UR - http://www.scopus.com/inward/record.url?scp=85061979798&partnerID=8YFLogxK
U2 - 10.1186/s12882-019-1220-6
DO - 10.1186/s12882-019-1220-6
M3 - Article
C2 - 30786864
AN - SCOPUS:85061979798
VL - 20
JO - BMC Nephrology
JF - BMC Nephrology
SN - 1471-2369
IS - 1
M1 - 60
ER -