Nerve growth factor is closely related to glucose metabolism, insulin sensitivity and insulin secretion in the second trimester: a case–control study in Chinese

Abstract

Objective Inflammation-related factors have been shown to play a significant role throughout pregnancy. In this study, we aimed to explore the relationships between selected inflammatory cytokines and gestational diabetes (GDM) in Chinese pregnant women. Design and methods This was a 1:1 matched case–control study that included 200 pairs of subjects in the second trimester and 130 pairs of subjects in the third trimester. Serum levels of nerve growth factor (NGF), Interleukin-6 (IL-6), leptin, Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) were measured by enzyme immunoassay. The associations of these inflammatory factors with metabolic parameters were analysed. Results In the second trimester, GDM patients had higher NGF levels and lower IL-8 levels than did normal controls (P < 0.001 and P = 0.015, respectively). However, in the third trimester, only lower leptin levels were observed in the GDM group (P = 0.031). Additionally, in the second trimester, NGF levels were not only positively associated with fasting, 1-h and 2-h glucose levels and the area under curve of glucose, but also positively related to insulin sensitivity and secretion, as suggested by fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment index of β-cell secretion (HOMA-β) (all P < 0.05). Moreover, IL-6 and leptin levels were positively correlated with HOMA-IR and HOMA-β, and TNF-α levels were positively related to HOMA-IR (all P < 0.05). Except for the relationships between NGF and HOMA-β and TNF-α and HOMA-IR, the other correlations still existed even after adjusting for confounding factors (all P < 0.05). Conclusion In addition to the positive associations of IL-6 and leptin with insulin resistance and secretion, NGF was higher in the GDM patients and strongly linked to glucose metabolism, insulin resistance and pancreatic β cell function in Chinese pregnant women in the second trimester.

Oral Peroxisome Proliferator–Activated Receptor-α Agonist Enhances Corneal Nerve Regeneration in Patients With Type 2 Diabetes

“…Notably, this increment in tear SP was significantly associated with the increase in CNFD, demonstrating that tear SP may serve as a surrogate biomarker for corneal nerve regeneration in concordance with previous studies illustrating a significant correlation between tear SP and CNFD ( 42 , 43 ). Tear NGF concentrations were also found to be significantly higher in the patients with diabetes than in control subjects, which could be due to 1 ) a consequence of neuroinflammation ( 44 ), 2 ) a compensatory reaction to decreased corneal nerves ( 44 ), 3 ) an impaired uptake and transportation system of NGF in patients with diabetes ( 45 , 46 ), or 4 ) a protective response to degenerative nerves ( 47 ).…”

IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies

“…This is supported by case-control studies reporting increased circulating IL-8 levels in GDM patients, compared to healthy pregnancies [ 115 , 176 , 179 , 180 ]. However, comparable concentrations of IL-8 in the plasma of GDM patients vs. healthy pregnant women are also reported [ 167 , 184 , 185 ], as well as a lower IL-8 level in early pregnancy [ 184 ]. These inter-study inconsistencies probably emerge from the differences in the applied protocols and assays.…”

Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry

“…Intriguingly, NGF levels in rat uterus are reduced during middle and late pregnancy compared to controls, which does correlate with known myometrial nerve degeneration 45 . Similarly, NGF expression is elevated in diabetes mellitus and it was shown to be a protective factor in diabetic neuropathy and vasculopathy [50][51][52][53] , but was also elevated and implicated in insulin resistance in gestational diabetic Chinese women in the second trimester 54 . Lobos et al, also demonstrated that proNGF levels increase during gestation possibly due to impaired processing of the pro form to the mature form 44,45 .…”