Acta Diabetologica

, Volume 55, Issue 7, pp 723–731 | Cite as

Characterization of circulating leukocytes and correlation of leukocyte subsets with metabolic parameters 1 and 5 years after diabetes diagnosis

  • Maria Apostolopoulou
  • Barbara Menart-Houtermans
  • Ruth Ruetter
  • Bettina Nowotny
  • Ulrich Gehrmann
  • Daniel Markgraf
  • Julia Szendroedi
  • Nanette C. Schloot
  • Michael Roden
Original Article



Infiltration of pancreatic islets with different leukocyte subtypes likely contributes to deterioration of glycemia in diabetes mellitus. Different subsets of leukocytes have been previously associated with type 1 or type 2 diabetes. This study aimed at examining these subsets at different stages of diabetes progression and possible relationships with metabolic parameters.


A total of 206 patients, 76 with type 1 and 130 with type 2 diabetes, were studied within the first year of diabetes diagnosis. In addition, 31 patients with type 1 and 73 with type 2 diabetes were examined at 5 years after diagnosis. Whole body insulin sensitivity was assessed by hyperinsulinemic–euglycemic clamps; insulin secretion by glucagon stimulation tests and white blood cells were analyzed by flow cytometry.


The percentage of peripheral CD8+ cells was 15% lower in patients with type 1 diabetes at 5 years than in patients at diabetes onset and correlated positively with fasting glycemia, total cholesterol and high-sensitive C-reactive protein (hsCRP) (all r > 0.37, p < 0.05), but not with insulin secretion. Patients with type 2 diabetes had 7% higher percentages of CD4+ cells after 5 years than those at diagnosis. CD4+ cells correlated with hsCRP (r = 0.36, p < 0.05), whereas CD8+ cytotoxic T-cells did not correlate with any metabolic parameter.


CD8+ T-cells associate with worse glycemia, lipidemia and inflammation after 5 years of type 1 diabetes, whereas CD4+ T-cells associate with increased inflammation after 5 years upon onset of type 2 diabetes.


Leukocytes Diabetes progression Insulin secretion Insulin sensitivity 


Author contributions

MA researched data, calculated statistics and wrote the manuscript, BM-H and RR researched data, performed statistical calculations and reviewed the manuscript, BN and JS performed the clinical characterization of volunteers and reviewed the manuscript, UG provided advice for statistics and reviewed the manuscript, NCS and MR designed the study, contributed to data analysis and discussion and wrote, edited and reviewed the manuscript. NCS is currently employed by Lilly Germany. MR is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of data and the accuracy of the data analysis.


This work was supported by the Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW) and the German Federal Ministry of Health (BMG). This study was supported in part by a grant of the Federal Ministry for Research (BMBF) to the German Center for Diabetes Research (DZD e.V.), by grants of the Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases (ICEMED), the German Research Foundation (DFG, SFB1116, project B05) and by the Schmutzler-Stiftung. The funding sources had no input in the design and conduct of this study, in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the article.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest for this work.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Supplementary material

592_2018_1143_MOESM1_ESM.docx (144 kb)
Supplementary material 1 (DOCX 144 kb)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Maria Apostolopoulou
    • 1
    • 2
    • 3
  • Barbara Menart-Houtermans
    • 2
    • 3
  • Ruth Ruetter
    • 2
    • 3
  • Bettina Nowotny
    • 2
    • 3
  • Ulrich Gehrmann
    • 3
    • 4
  • Daniel Markgraf
    • 2
    • 3
  • Julia Szendroedi
    • 1
    • 2
    • 3
  • Nanette C. Schloot
    • 2
  • Michael Roden
    • 1
    • 2
    • 3
  1. 1.Division of Endocrinology and Diabetology, Medical Faculty, c/o German Diabetes CenterHeinrich-Heine University, DüsseldorfDüsseldorfGermany
  2. 2.Institute for Clinical Diabetology, German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich-Heine University DüsseldorfDüsseldorfGermany
  3. 3.German Center for Diabetes ResearchDüsseldorfGermany
  4. 4.Institute for Biometrics and Epidemiology, German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich-Heine UniversityDüsseldorfGermany

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