Increased Circulating IL-32 Is Associated With Placenta Macrophage-derived IL-32 and Gestational Diabetes Mellitus.

OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.

Decreased Monocyte Count Is Associated With Gestational Diabetes Mellitus Development, Macrosomia, and Inflammation.

CONTEXT: The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. OBJECTIVE: Here, we investigated the potential effect of monocytes in GDM. METHODS: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages, and their products were measured. RESULTS: Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and was closely associated with glucose level, insulin resistance, and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia both in the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level, and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 109/L. Notably, CD206 and interleukin 10 (IL-10) were significantly lower, whereas CD80, CD86, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) were higher both in GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α, and IL-6. CONCLUSION: Decreased monocyte count throughout pregnancy was closely associated with the development of GDM, macrosomia, and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.

GESTATIONAL WEIGHT GAIN AS AN INDEPENDENT RISK FACTOR FOR MACROSOMIA IN WOMEN WITH INTERMEDIATE STATE GESTATIONAL BLOOD GLUCOSE.

Objective: Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose [BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG. Methods: A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured. Results: The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight (r = 0.183, P<.01), prepregnancy BMI (r = 0.135, P<.01), and GWG (r = 0.255, P<.01), and negatively correlated with high-density lipoprotein cholesterol (r = -0.172, P<.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, P<.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m2 or BMI ≥25 kg/m2 and eGWG was 3.39 and 3.27 times, respectively. Conclusion: The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation. Abbreviations: AUC = area under the curve; BG = blood glucose; 1 hour BG = 1 hour blood glucose after OGTT; 2 hour BG = 2 hour blood glucose after OGTT; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; FBG = fasting blood glucose; FINS = fasting insulin; GDM = gestational diabetes mellitus; HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance index; ISGBG = intermediate state gestation blood glucose; LDL-C = low-density lipoprotein cholesterol; Ln = natural logarithm; MLBW = mature low birth weight; NGTG = normal glucose tolerance gestation; OGTT = oral glucose tolerance test; OR = odds ratio; SD = standard deviation.