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Diabetes Care. 2019 Nov;42(11):2075-2082. doi: 10.2337/dc19-0723. Epub 2019 Aug 30.

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

Author information

1
San Francisco VA Health Care System, San Francisco, CA.
2
University of California, San Francisco, San Francisco, CA.
3
University of Washington, Seattle, WA.
4
Beth Israel Deaconess Medical Center, Boston, MA.
5
Harvard Medical School, Boston, MA.
6
Brigham and Women's Hospital, Boston, MA.
7
VA Boston Healthcare System, Boston, MA.
8
University of California San Diego School of Medicine, La Jolla, CA.
9
VA San Diego Healthcare System, San Diego, CA.
10
Kaiser Permanente Georgia Region, Atlanta, GA.
11
Emory University School of Medicine, Atlanta, GA.
12
University of Vermont, Burlington, VT.
13
New York Academy of Medicine, New York, NY.
14
San Francisco VA Health Care System, San Francisco, CA jorge.kizer@ucsf.edu.

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.

PMID:
31471378
PMCID:
PMC6804612
[Available on 2020-11-01]
DOI:
10.2337/dc19-0723

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