Soluble CD14 andCD14Variants, Other Inflammatory Markers, and Glucose Dysregulation in Older Adults: The Cardiovascular Health Study
Year: 2019
Type: article
Study design: Observational Study
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.
Source: Diabetes Care
DOI: 10.2337/dc19-0723
Institutions: University of California, San Francisco, San Francisco VA Health Care System, University of Washington, Beth Israel Deaconess Medical Center, Harvard University, Brigham and Women's Hospital, VA Boston Healthcare System, University of California San Diego, VA San Diego Healthcare System, Kaiser Permanente, Emory University, University of Vermont, New York Academy of Medicine
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1220223050, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE AND STROKE, G2194386449, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2391884931, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G3045517347, G3220743633, G3256118428, CHS research resources for the cardiovascular health of older adults, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Advanced Glycation Endproducts and Cardio-Renal Disease, Thrombosis Genetics, MI and Stroke in Older Adults, G5479317095, G581887176, CHS Events Follow-up Study, G6226795708, CHS-Transition Phase, G7176672723, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), New York Regional Center for Diabetes Translation Research
OpenAlex ID: W2970528307