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Epidemiology/Health Services Research

Soluble CD14 and CD14 Variants, Other Inflammatory Markers, and Glucose Dysregulation in Older Adults: The Cardiovascular Health Study

  1. Sanyog G. Shitole1,2,
  2. Mary L. Biggs3,
  3. Alexander P. Reiner2,
  4. Kenneth J. Mukamal4,5,
  5. Luc Djoussé5,6,7,
  6. Joachim H. Ix8,9,
  7. Joshua I. Barzilay10,11,
  8. Russell P. Tracy12,
  9. David Siscovick13 and
  10. Jorge R. Kizer1,2⇑
  1. 1San Francisco VA Health Care System, San Francisco, CA
  2. 2University of California, San Francisco, San Francisco, CA
  3. 3University of Washington, Seattle, WA
  4. 4Beth Israel Deaconess Medical Center, Boston, MA
  5. 5Harvard Medical School, Boston, MA
  6. 6Brigham and Women’s Hospital, Boston, MA
  7. 7VA Boston Healthcare System, Boston, MA
  8. 8University of California San Diego School of Medicine, La Jolla, CA
  9. 9VA San Diego Healthcare System, San Diego, CA
  10. 10Kaiser Permanente Georgia Region, Atlanta, GA
  11. 11Emory University School of Medicine, Atlanta, GA
  12. 12University of Vermont, Burlington, VT
  13. 13New York Academy of Medicine, New York, NY
  1. Corresponding author: Jorge R. Kizer, jorge.kizer{at}ucsf.edu
Diabetes Care 2019 Nov; 42(11): 2075-2082. https://doi.org/10.2337/dc19-0723
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Abstract

OBJECTIVE Experimental studies have implicated soluble (s)CD14, an effector of lipopolysaccharide-induced inflammation, in insulin resistance, but its role in human metabolic endotoxemia has not been studied. We evaluated sCD14 in relation to dysglycemia in older adults and how this compares to other markers of inflammation.

RESEARCH DESIGN AND METHODS We investigated associations of sCD14, interleukin-6 (IL-6), CRP, and white blood cell (WBC) count with insulin resistance (quantitative insulin-sensitivity check index and HOMA 2 of insulin resistance) and incident type 2 diabetes in a population-based cohort of older adults. We also assessed the causal role of sCD14 in insulin resistance using an instrumental variable approach by Mendelian randomization.

RESULTS After adjustment for conventional risk factors, each of the four biomarkers showed positive cross-sectional associations with both insulin resistance measures. These associations persisted after mutual adjustment for all markers except sCD14. Over a median follow-up of 11.6 years, 466 cases of diabetes occurred. All biomarkers except sCD14 were positively associated with diabetes, although only WBC count remained associated (hazard ratio 1.43 per doubling [95% CI 1.07, 1.90]) after mutual adjustment. Instrumental variable analysis did not support a causal role for sCD14 in insulin resistance.

CONCLUSIONS Among older adults, sCD14 was associated with insulin resistance, but this disappeared after adjustment for other biomarkers, showed no evidence of a causal basis, and was not accompanied by a similar association with diabetes. IL-6, CRP, and WBC count were each associated with insulin resistance and diabetes, WBC count most robustly. These findings do not support a central role for sCD14, but they highlight the preeminence of WBC count as an inflammatory measure of diabetes risk in this population.

Footnotes

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc19-0723/-/DC1.

  • Received April 10, 2019.
  • Accepted August 6, 2019.
  • © 2019 by the American Diabetes Association.
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Diabetes Care: 42 (11)

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November 2019, 42(11)
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Soluble CD14 and CD14 Variants, Other Inflammatory Markers, and Glucose Dysregulation in Older Adults: The Cardiovascular Health Study
Sanyog G. Shitole, Mary L. Biggs, Alexander P. Reiner, Kenneth J. Mukamal, Luc Djoussé, Joachim H. Ix, Joshua I. Barzilay, Russell P. Tracy, David Siscovick, Jorge R. Kizer
Diabetes Care Nov 2019, 42 (11) 2075-2082; DOI: 10.2337/dc19-0723

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Soluble CD14 and CD14 Variants, Other Inflammatory Markers, and Glucose Dysregulation in Older Adults: The Cardiovascular Health Study
Sanyog G. Shitole, Mary L. Biggs, Alexander P. Reiner, Kenneth J. Mukamal, Luc Djoussé, Joachim H. Ix, Joshua I. Barzilay, Russell P. Tracy, David Siscovick, Jorge R. Kizer
Diabetes Care Nov 2019, 42 (11) 2075-2082; DOI: 10.2337/dc19-0723
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