Circulating differentiated and senescent lymphocyte subsets and incident diabetes risk in older adults: The Cardiovascular Health Study

Nels C Olson; Margaret F Doyle; Petra Buzkova; Sally A Huber; Ian H de Boer; Colleen M Sitlani; Russell P Tracy; Bruce M Psaty; Kenneth J Mukamal; Joseph A Delaney

doi:10.1002/edm2.384

Circulating differentiated and senescent lymphocyte subsets and incident diabetes risk in older adults: The Cardiovascular Health Study

Endocrinol Diabetes Metab. 2023 Jan;6(1):e384. doi: 10.1002/edm2.384. Epub 2022 Nov 5.

Authors

Nels C Olson¹, Margaret F Doyle¹, Petra Buzkova², Sally A Huber¹, Ian H de Boer^{3

4}, Colleen M Sitlani⁵, Russell P Tracy^{1

6}, Bruce M Psaty^{5

7}, Kenneth J Mukamal⁸, Joseph A Delaney⁹

Affiliations

¹ Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
² Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington, USA.
³ Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁴ Kidney Research Institute, University of Washington, Seattle, Washington, USA.
⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁶ Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
⁷ Departments of Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, Washington, USA.
⁸ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
⁹ College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

Introduction: Cellular senescence is a feature of aging implicated in the pathophysiology of diabetes mellitus (DM). Whether senescent lymphocytes are associated with the future occurrence of DM is uncertain.

Methods: We used cryopreserved peripheral blood mononuclear cells collected from 1860 Cardiovascular Health Study participants (average age 80.2 years) and flow cytometry immunophenotyping to evaluate the longitudinal relationships of naive (CD45RA⁺ ), memory (CD45RO⁺ ), senescent (CD28^- ), and T effector memory RA⁺ (TEMRA) (CD28^- CD57⁺ CD45RA⁺ ) CD4⁺ and CD8⁺ T cells, and memory B cells (CD19⁺ CD27⁺ ), with the risk of incident DM. In exploratory analyses we evaluated the relationships of 13 additional innate lymphocyte and CD4⁺ and CD8⁺ subsets with incident DM risk.

Results: Over a median follow-up time of 8.9 years, 155 cases of incident DM occurred. In Cox models adjusted for demographic variables (age, sex, race, study site and flow cytometry analytical batch) or diabetes risk factors (demographic variables plus education, body mass index, smoking status, alcohol use, systolic blood pressure, hypertension medication use and physical activity), no significant associations were observed for any CD4⁺ , CD8⁺ or CD19⁺ cell phenotypes with incident DM.

Conclusions: These results suggest the frequencies of naive, memory and senescent T cells and memory B cells are not strongly associated with incident DM risk in older adults.

Keywords: cellular senescence; diabetes mellitus; epidemiology; lymphocyte subsets.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

CD28 Antigens
CD8-Positive T-Lymphocytes*
Cellular Senescence
Diabetes Mellitus* / epidemiology
Diabetes Mellitus* / etiology
Leukocytes, Mononuclear
Lymphocyte Subsets

Substances

CD28 Antigens

Abstract

Publication types

MeSH terms

Substances

Grants and funding