Impact of Systemic Inflammation on the Progression of Gestational Diabetes Mellitus

Lekva, Tove; Norwitz, Errol R.; Aukrust, Pål; Ueland, Thor

doi:10.1007/s11892-016-0715-9

Cited by 98 publications

(90 citation statements)

References 97 publications

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“…Metabolic adaptations to fail or excess the fetal nutritional demand (as for glucose in diabetic pregnancies), stress, chronic and acute inflammation are some of the aspects that are being studied [10]. The unbalanced expression of inflammatory mediators alter the maternal environment and metabolism during gestation and increase the potential for gestational systemic insulin resistance, participating in the development of DM2 and GDM [11][12]. Inflammation at the placental territory also contributes to the fetal developmental environment and therefore has been the subject of numerous studies in hyperglycemic gestations [9].…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia induces inflammatory mediators in the human chorionic villous

et al. 2018

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This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1β, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1β. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes.

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Section: Introductionmentioning

confidence: 99%

Hyperglycemia induces inflammatory mediators in the human chorionic villous

et al. 2018

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“…A tightly regulated balance between pro-and anti-inflammatory statuses may be necessary for normal implantation, invasion of the extravillous trophoblast, and placentation [13]. Exaggerated inflammation has been blamed in the pathogenesis of pregnancy complications such as pre-eclampsia and GDM [4]. Taken together, these data support a possible role for inflammation in the pathogenesis, although direct evidence of causality is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with the literature, in this study we show increased levels of HbA1c, insulin, and HOMA-IR in those pregnant with GDM compared to those without GDM. In recent years, the role of immune activation and inflammation in the pathogenesis of GDM has gained increasing attention [12]. Pregnancy itself is associated with a changed inflammatory profile compared to the non-pregnant state.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory mediators such as C-reactive protein (CRP), IL-6, and TNF-α are associated with type 2 and gestational diabetes. Although currently available data regarding inflammation in women with GDM are still conflicting, it has been hypothesized that adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation [3,4]. Systemic inflammation can be measured using a variety of hematological markers.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Inflammatory Related Markers in Gestational Diabetes Mellitus

Kırbaş¹

2016

Ann Clin Anal Med

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Anahtar Kelimelerİnflamasyon; İnsülin Rezistansı; Lenfosit; Nötrofil; C Reaktif Protein Abstract Aim: Subclinical inflammation has been suggested as an important factor in the pathophysiology of gestational diabetes mellitus (GDM). Measuring the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) may be a simple and inexpensive method for assessing inflammatory status. The aim of this study is to evaluate the NLR and LMR and other commonly used inflammatory markers in women with GDM and to determine the correlation of NLR and LMR with metabolic parameters in gestational diabetic women. Material and Method: In this controlled cross-sectional study we examined 35 singleton, consecutive pregnant women with GDM and a control group of 40 healthy women with uncomplicated pregnancies, matched for body mass index and age. Oral glucose tolerance tests (OGTT) were performed at 24-28 weeks of pregnancy to diagnose GDM. The highsensitive C-reactive protein (hs-CRP), NLR and LMR, fasting blood glucose (FBG), fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) scores of the two groups were also compared. Results: NLR levels were higher and LMR levels were lower in pregnant with GDM women compared with healthy ones. Although hs-CRP levels were found to be higher in the GDM group, this difference was not statistically significant (p=0.08). While HbA1c, insulin, and HOMA-IR scores were significantly elevated in the GDM group compared with the healthy pregnant group, FBG levels were comparable. Discussion: Systemic inflammation was associated with GDM, and the association was independent of maternal BMI and weight gain during pregnancy. The results of this study suggest that inflammation plays an important role in the pathogenesis of GDM.

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“…Given the potential for error in estimation of due date according to last menstrual period alone or by ultrasound in later pregnancy, confirmation or determination of due date by ultrasound performed at ≤ 15 weeks gestation was required for study participation (American College of Obstetricians and Gynecologists, 2014). Women were excluded if they reported tobacco, alcohol, or illicit drug use beyond the first trimester, a chronic immune-impacting condition (e.g., diabetes, rheumatoid arthritis), regular use of medications with immune implications (e.g., corticosteroids, progesterone), or experienced a complication of pregnancy with known immune implications (i.e., gestational diabetes or preeclampsia; Chaiworapongsa, Chaemsaithong, Yeo, & Romero, 2014; Lekva, Norwitz, Aukrust, & Ueland, 2016). Women diagnosed with fetal anomaly were also not eligible for enrollment.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

et al. 2017

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Background Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN) gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN SNP rs2637988 was genotyped and lipopolysaccharide-stimulated IL-1Ra and IL-1β production quantified. Medical record review determined timing of birth. Results Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = 0.21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]. Women with GG genotype demonstrated less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = 0.93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = 0.21, p = .05). Discussion Women with GG genotype may be at risk for earlier birth due to diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

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Impact of Systemic Inflammation on the Progression of Gestational Diabetes Mellitus

Cited by 98 publications

References 97 publications

Hyperglycemia induces inflammatory mediators in the human chorionic villous

Hyperglycemia induces inflammatory mediators in the human chorionic villous

Evaluation of Inflammatory Related Markers in Gestational Diabetes Mellitus

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

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