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Diabetologia. 2015 Nov;58(11):2596-605. doi: 10.1007/s00125-015-3731-4. Epub 2015 Aug 20.

Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

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School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
CUNY School of Public Health, New York, NY, USA.
CUNY Institute for Demographic Research, New York, NY, USA.
Cancer Research UK Centre, University of Birmingham, Birmingham, UK.
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Department of Psychology, University of Amsterdam, Weesperplein 4, 1018 XA, Amsterdam, The Netherlands.



Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(-)CD45RA(+/-); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV(+) and CMV(-) individuals.


A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27(-)CD45RA(-)) and CD45RA re-expressing effector memory (EMRA; CD27(-)CD45RA(+)) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors.


Among CMV(+) individuals (n = 400), elevated HbA(1c) was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV(-) individuals.


The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV(+) individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence.


CMV; Cholesterol; Cytomegalovirus; Diabetes; Glucose; Haemoglobin A1c; HbA1c; Immune ageing; Metabolic syndrome; T cell

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