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Diabetologia
Published in: Diabetologia 7/2018

01-07-2018 | Article

A proinflammatory CD4+ T cell phenotype in gestational diabetes mellitus

Authors: Angela Sheu, Yixian Chan, Angela Ferguson, Mohammad B. Bakhtyari, Wendy Hawke, Chris White, Yuk Fun Chan, Patrick J. Bertolino, Heng G. Woon, Umaimainthan Palendira, Frederic Sierro, Sue Mei Lau

Published in: Diabetologia | Issue 7/2018

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Abstract

Aims/hypothesis

Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition. We aimed to characterise pro- and anti-inflammatory CD4+ (T helper [Th]) T cell subsets in women with GDM vs women without GDM (of similar BMI), during and after pregnancy, and examine the relationship between CD4+ subsets and severity of GDM.

Methods

This is a prospective longitudinal case–control study of 55 women with GDM (cases) and 65 women without GDM (controls) at a tertiary maternity hospital. Quantification of proinflammatory (Th17, Th17.1, Th1) and anti-inflammatory (regulatory T cell [Treg]) CD4+ T cell subsets was performed on peripheral blood at 37 weeks gestation and 7 weeks postpartum, and correlated with clinical characteristics and measures of blood glucose.

Results

Women with GDM had a significantly greater percentage of Th17 (median 2.49% [interquartile range 1.62–4.60] vs 1.85% [1.13–2.98], p = 0.012) and Th17.1 (3.06% [1.30–4.33] vs 1.55% [0.65–3.13], p = 0.006) cells compared with the control group of women without GDM. Women with GDM also had higher proinflammatory cell ratios (Th17:Treg, Th17.1:Treg and Th1:Treg) in pregnancy compared with the control group of women without GDM. In the control group, there was a statistically significant independent association between 1 h glucose levels in the GTT and Th17 cell percentages, and also between 2 h glucose levels and percentage of Th17 cells. The percentage of Th17 cells and the Th17:Treg ratio declined significantly after delivery in women with GDM, whereas this was not the case with the control group of women. Nevertheless, a milder inflammatory phenotype persisted after delivery (higher Th17:Treg ratio) in women with GDM vs women without.

Conclusions/interpretation

Dysregulation of adaptive immunity supports a novel paradigm of GDM that extends beyond hyperglycaemia and altered innate immunity.
Appendix
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Metadata
Title
A proinflammatory CD4+ T cell phenotype in gestational diabetes mellitus
Authors
Angela Sheu
Yixian Chan
Angela Ferguson
Mohammad B. Bakhtyari
Wendy Hawke
Chris White
Yuk Fun Chan
Patrick J. Bertolino
Heng G. Woon
Umaimainthan Palendira
Frederic Sierro
Sue Mei Lau
Publication date
01-07-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4615-1

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