Subclinical Inflammation and Adipose Tissue Lymphocytes in Pregnant Females with Gestational Diabetes Mellitus

Abstract

The Journal of Clinical Endocrinology & Metabolism, 2020, Vol. 105, No. 11, 1–11 doi:10.1210/clinem/dgaa528 Clinical Research Article Clinical Research Article Subclinical Inflammation and Adipose Tissue Lymphocytes in Pregnant Females With Gestational Diabetes Mellitus Anna Cinkajzlová,1,2 Kateřina Anderlová,3,4 Patrik Šimják,4 Zdeňka Lacinová,1,2 Jana Kloučková,1,2 Helena Kratochvílová,1,2 Hana Krejčí,3,4 Antonín Pařízek,4 Miloš Mráz,2,5 Michal Kršek,3 and Martin Haluzík1,2,51Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, 140 21, Czech Republic; 2Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, 120 08, Czech Republic; 33rd Department of Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, 120 08, Czech Republic; 4Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, 120 08, Czech Republic; and 5Department of Diabetes, Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, 140 21, Czech Republic ORCiD numbers: 0000-0001-5322-4612 (M. Mráz); 0000-0002-0201-6888 (M. Haluzík). Abbreviations: ALT, alanine aminotransferase; ANOVA, analysis of variance; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval; GDM, gestational diabetes mellitus; HbA1c, glycated hemoglobin A1c; hsCRP, high-sensitivity C-reactive protein; IFN-γ, interferon-γ; IL, interleukin; NK, natural killer; SAT, subcutaneous adipose tissue; Th, T helper; TNF-α, tumor necrosis factor-α; VAT, visceral adipose tissue. Received: 26 January 2020; Accepted: 9 August 2020; First Published Online: 14 August 2020; Corrected and Typeset: 10 September 2020. Abstract Context: Gestational diabetes mellitus (GDM) is accompanied by subclinical inflammation; however, little is known about local inflammation in adipose tissue and placenta. Objective: To analyze systemic and local subclinical inflammation and adipose tissue lymphocyte content and phenotype in pregnant women with and without GDM. Design: Observational study. Settings: Academic hospital. Patients: Twenty-one pregnant women with GDM (GDM group), 16 pregnant women without GDM (non-GDM group) and 15 nonpregnant control women (N group). Interventions: Serum samples taken at 28 to 32 (visit 1 [V1]) and 36 to 38 (V2) gestational weeks and 6 to 12 months after delivery (V3) in the GDM and non-GDM group and before elective gynecological surgery in the N group. Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained during cesarean delivery or surgery. Main Outcome Measures: Serum levels and adipose tissue expression of proinflammatory cytokines, adipose tissue lymphocyte content and phenotype (for a subset of GDM and non-GDM subjects). Results: Accented proinflammatory state in GDM was documented by increased circulating tumor necrosis factor-α (TNF-α) levels. In both groups of pregnant females total lymphocytes were higher in VAT compared to SAT. In GDM subjects B cells and NKT cells were higher in SAT compared to VAT and T helper cells were increased relative to SAT of non-GDM group, while no intercompartmental adipose tissue differences were seen in non-GDM women. Conclusions: Pregnant females had higher total lymphocyte count in VAT relative to SAT regardless of GDM. In addition to increased systemic subclinical inflammation, GDM was associated with significant differences in lymphocyte composition between subcutaneous and visceral adipose tissue depots.