Pregnant type 1 diabetes women with rises in C-peptide display higher levels of regulatory T cells: A pilot study - 11/09/20

Doi : 10.1016/j.diabet.2020.04.005

C. Amouyal ^a,^b,⁎ , D. Klatzmann ^c,^d, E. Tibi ^c, J.-E. Salem ^e,^f, M. Halbron ^a, M. Popelier ^a, S. Jacqueminet ^a, C. Ciangura ^a, O. Bourron ^a,^g, F. Andreelli ^a,^b, A. Hartemann ^a,^g, M. Rosenzwajg ^c,^d
^a AP-HP, Pitié-Salpêtrière Hospital, Diabetology Department, F-75013 Paris, France
^b Sorbonne Université, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, UMRS U1269, Paris, France
^c AP-HP, Pitié-Salpêtrière Hospital, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (I2B), Sorbonne Université, Paris, France
^d Sorbonne Université, INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France
^e Clinical Investigation Centre Paris-Est, CIC-1421, UNICO-GRECO Cardio-oncology Program, INSERM, Department of Pharmacology, Sorbonne Université, Paris, France
^f Department of Medicine and Pharmacology, Cardio-oncology Program, Vanderbilt University Medical Center, Nashville, TN, USA
^g Sorbonne Université, INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Institute of Cardiometabolism and Nutrition, Paris, France

^⁎Corresponding author at: Service de Diabétologie, Pôle Cardio Métabolisme, Hôpitaux Universitaires Pitié Salpêtrière — Charles Foix, 47/83 Boulevard de l’Hôpital, 75013 Paris, France.Service de DiabétologiePôle Cardio MétabolismeHôpitaux Universitaires Pitié Salpêtrière — Charles Foix47/83 Boulevard de l’HôpitalParis75013France

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Abstract

Aim

During pregnancy of type 1 diabetes (T1D) women, a C peptide rise has been described, which mechanism is unclear. In T1D, a defect of regulatory T cells (Tregs) and its major controlling cytokine, interleukin-2 (IL2), is observed.

Methods

Evolution of clinical, immunological (Treg (CD4+CD25hiCD127-/loFoxp3+ measured by flow cytometry and IL2 measured by luminex xMAP technology) and diabetes parameters (insulin dose per day, HbA1C, glycaemia, C peptide) was evaluated in 13 T1D women during the three trimesters of pregnancy and post-partum (PP, within 6 months) in a monocentric pilot study. Immunological parameters were compared with those of a healthy pregnant cohort (QuTe).

Results

An improvement of beta cell function (C peptide rise and/or a decrease of insulin dose-adjusted A1c index that estimate individual exogenous insulin need) was observed in seven women (group 1) whereas the six others (group 2) did not display any positive response to pregnancy. A higher level of Tregs and IL2 was observed in group 1 compared to group 2 during pregnancy and at PP for Tregs level. However, compared to the healthy cohort, T1D women displayed a Treg deficiency

Conclusion

This pilot study highlights that higher level of Tregs and IL2 seem to allow improvement of endogenous insulin secretion of T1D women during pregnancy.

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Keywords : Type 1 diabetes, Pregnancy, C peptide, Regulatory T cells, Interleukine 2