Changes of serum selenium in pregnant women with gestational diabetes mellitus

Gestational diabetes is one of the most common diseases in pregnancy. In the present work, the possible relationship between serum selenium concentration and gestational diabetes was investigated. Blood samples of 234 pregnant women were collected, including 98 subjects with impaired glucose tolerance (IGT), 46 subjects with gestational diabetes mellitus (GDM), and 90 normal pregnant women (NPW). An additional 17 samples of normal women of fertile age (NW) were collected for comparison. The hydride generation atomic fluorescence spectrometry was used for selenium determination. The mean serum selenium levels obtained for each group were 0.0741±0.0167 mg/L for NPW, 0.0631±0.0132 mg/L for IGT, 0.0635±0.0120 mg/L for GDM, and 0.108±0.0170 mg/L for NW. Serum selenium levels were significantly lower in pregnant woman with IGT (p<0.001) and GDM (p<0.001) than in NPW. Furthermore, an inverse correlation between the serum selenium concentration and the gestational period was also observed. Selenium supplementation during gestation for pregnant women, especially with IGT and GDM, should be considered.     

Serum levels of irisin in gestational diabetes mellitus during pregnancy and after delivery

ObjectiveIrisin has recently been introduced as a novel an exercise-inducible myokine which improves glucose metabolism in mice. However, regulation of circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal period has not been assessed so far.MethodsCirculating irisin was quantified in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls. In a subset of these patients (44 GDM, 41 controls), postpartum follow-up data were also available. In a second study population of 40 healthy women with singleton pregnancies undergoing elective Cesarean section, irisin was assessed in maternal serum before and within 24 h after delivery, as well as in umbilical cord blood and in placental tissue.ResultsIn the first study population, median [interquartile range] irisin levels were significantly higher in GDM patients as compared to controls after delivery (previous GDM: 446.3 [146.9] μg/l; controls: 378.0 [111.4] μg/l) but not during pregnancy (GDM: 482.1 [132.1] μg/l; controls: 466.6 [178.0] μg/l). Interestingly, fasting insulin (FI) was independently and positively associated with serum irisin in multivariate analysis during pregnancy. In agreement with these findings, relative changes (ratio) of FI independently and positively predicted relative changes of irisin (ratio) in the second study population.ConclusionsThe myokine irisin is independently associated with FI in pregnancy. The physiological significance of these findings needs to be assessed in future experiments.     

The oral microbiome of pregnant women facilitates gestational diabetes discrimination

The oral microbiota plays an important role in the development of various diseases,whereas its association with gestational diabetes mellitus (GDM) remains largely unclear.The aim of this study is to identify biomarkers from the oral microbiota of GDM patients by analyzing the microbiome of the saliva and dental plaque samples of 111 pregnant women.We find that the microbiota of both types of oral samples in GDM patients exhibits differences and significantly varies from that of patients with periodontitis or dental caries.Using bacterial biomarkers from the oral microbiota,GDM classification models based on support vector machine and random forest algorithms are constructed.The area under curve (AUC) value of the classification model constructed by combination of Lautropia and Neisseria in dental plaque and Streptococcus in saliva reaches 0.83,and the value achieves a maximum value of 0.89 by adding clinical features.These findings suggest that certain bacteria in either saliva or dental plaque can effectively distinguish women with GDM from healthy pregnant women,which provides evidence of oral microbiome as an informative source for developing noninvasive biomarkers of GDM.     

Concentrations of preptin,salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.     

妊娠期糖尿病对母亲及子代肠道菌群的影响研究

妊娠期糖尿病(gestational diabetes mellitus,GDM)被定义为“妊娠期间首次被诊断为糖耐量异常”,可导致不良妊娠结局,对母亲及新生儿产生不同程度的影响。近些年随着肥胖人群的不断扩增,GDM呈现上升趋势。因此预防或治疗GDM成为当务之急。近几年的研究发现GDM患者及其子代的肠道菌群发生了改变,提示GDM的发生与肠道菌群紊乱可能存在某种联系。本文分析和总结了GDM母亲及其子代肠道菌群的变化和GDM母亲对子代的影响,探讨GDM对母亲及子代肠道菌群的影响,以期为预防或治疗GDM提供一个新的方向。     

妊娠期糖尿病母亲哺乳期母乳N-聚糖的岩藻糖基化水平差异及其对新生儿肠道菌群的影响

目的 比较中国妊娠期糖尿病母亲与正常母亲母乳中N-聚糖的岩藻糖基化水平差异,分析这些差异对其子代肠道微生态的影响。方法 收集妊娠期糖尿病母亲和健康母亲在哺乳期第6天和第42天母乳样本各15例,及其纯母乳喂养的新生儿在同一天的粪便样本;以凝集素AAL分析母乳中N-聚糖的岩藻糖基化水平;以变性梯度凝胶电泳（DGGE）检测两组新生儿肠道菌群差异。结果 妊娠期糖尿病母亲母乳N-聚糖岩藻糖基化水平显著高于健康母亲(t=4.438,P<0.01;t=3.238,P<0.001);两组新生儿肠道菌群存在明显差异,其中主要的微生物群如长双歧杆菌属、肠球菌属、泛菌属等的相对丰度有所不同。结论 母乳中N-聚糖岩藻糖基化水平在妊娠期糖尿病母亲母乳中显著升高,这一变化可能影响其子代的肠道菌群结构。     

Implication of SH2B1 gene polymorphism studies in gestational diabetes mellitus in Saudi pregnant women

Genome-wide association studies have identified loci that are firmly associated with obesity. The Src-homology-2 B adaptor protein 1 (SH2B1) loci is abundantly expressed in the brain, liver, heart, muscle, and fat tissues. Gestational diabetes mellitus (GDM) is a growing health concern that usually appears during the latter half of pregnancy, and it is characterized by carbohydrate intolerance of variable severity. The SH2B1 gene polymorphism has been linked with an increased risk of weight gain in several but not all population studies. This study aimed to investigate the genetic association of rs4788102 variants in the SH2B1 gene with GDM in Saudi pregnant women. Genomic DNA samples from 200 women with GDM and 300 women without GDM were genotyped using the TaqMan method. The distribution of the GG, GA, and AA genotypes was significantly different between GDM and non-GDM women (p < 0.05). Thus, we identified rs4788102 variants as additional risk factors for GDM in Saudi women, and we suggest that these variants may have a prognostic value.     

Copeptin,adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus

Copeptin, adropin and irisin are polypeptide hormones implicated in energy homostasis and diabetes. The purposes of this study were (1) to compare the copeptin, adropin and irisin concentrations between colostrum, transitional and mature milk and plasma in lactating women with and without GDM and (2) to compare these values with those from non-lactating women. Venous blood samples were obtained before suckling from 15 healthy lactating women aged 26–30 years, 15 lactating women with GDM aged 26–32 years, and 14 age-matched controls aged 25–31 years. Colostrum, transitional milk and mature milk samples were collected just before suckling. The concentration of copeptin was determined by EIA while the concentrations of adropin and irisin were determined by ELISA. The levels of copeptin, adropin and irisin in the colostrum were significantly higher than those in transitional and mature milk samples from healthy women; also, transitional milk had higher copeptin, adropin and irisin concentrations than mature milk. The amounts of copeptin in the colostrum and transitional milk were significantly higher than in mature milk samples from women with GDM, while the amounts of adropin and irisin were significantly lower. The relative concentrations of copeptin, adropin and irisin in the plasma samples from these groups of women were similar to those in the colostrum, transitional and mature milk samples, but the latter concentrations were higher than those in the plasma. These peptides could influence the regulation of metabolic pathways and the postnatal growth and development of different organs in the newborn.     

Global DNA methylation profiling in peripheral blood cells of South African women with gestational diabetes mellitus

Background/Objective: Recently, several studies have reported that DNA methylation changes in tissue are reflected in blood, sparking interest in the potential use of global DNA methylation as a biomarker for gestational diabetes mellitus (GDM). This study investigated whether global DNA methylation is associated with GDM in South African women.

Methods: Global DNA methylation was quantified in peripheral blood cells of women with (n?=?63) or without (n?=?138) GDM using the MDQ1 Imprint® DNA Quantification Kit.

Results: Global DNA methylation levels were not different between women with or without GDM and were not associated with fasting glucose or insulin concentrations. However, levels were 18% (p?=?0.012) higher in obese compared to non-obese pregnant women and inversely correlated with serum adiponectin concentrations (p?=?0.005).

Discussion: Contrary to our hypothesis, global DNA methylation was not associated with GDM in our population. These preliminary findings suggest that despite being a robust marker of overall genomic methylation that offers opportunities as a biomarker, global DNA methylation profiling may not offer the resolution required to detect methylation differences in the peripheral blood cells of women with GDM. Moreover, global DNA methylation in peripheral blood cells may not reflect changes in placental tissue. Further studies in a larger sample are required to explore the candidacy of a more targeted approach using gene-specific methylation as a biomarker for GDM in our population.     

Insulin receptor binding from mid-term and full-term placentas of patients with gestational diabetes mellitus and normal pregnant women

Insulin receptor binding was examined in the microvillous membranes of mid-term (20–22 weeks of gestation, MT) and full-term (FT) placentas from patients with gestational diabetes mellitus (GDM) and in normal pregnant control (N). Mid-term placentas were obtained from patients who have had spontaneous abortion. The maximum per cent specific binding (%SB) in MT placenta for GDM was significantly lower (4.8%) compared with the FT placenta (22%, p<0.001), while in the N group the maximum per cent specific binding for MT placenta was 14.1% compared with 26% for the FT placneta (p<0.001). Binding data from FT placenta of well-controlled GDM patients were similar with the FT placenta from N group (22%SB for GDM VS 26% SB for N). Even as there were similarities in the binding characteristics of FT placentas from both groups the placental membrane protein content in the GDM group was lower by 50% compared with the N control (2.5±0.11 VS 4.8±0.15 mg protein/g placenta respectively, p<0.001) suggesting that in the GDM group achieving a tight glycemic control could improve receptor affinities. Data from the competitive binding assay of GDM patients showed that the insulin necessary to achieve 50% inhibition (ID₅₀) was significantly lower in MT compared with the FT placenta (0.9×10^–9 M VS 3.8×10^–9 M, p<0.001) but in the N placenta there was no alteration in the ID₅₀ of MT and FT placentas (3.1×10^–9 M VS 4×10^–9 M, p<0.01, respectively). The present study demonstrated that in GDM the placental insulin receptor binding was significantly lower in spontaneously aborted placenta compared with placentas collected at full-term. Furthermore, these data suggest that the objective to achieve a tight glycemic control in GDM patients could optimize insulin receptor function similar to that of a normal pregnancy. Thus a full term placenta from GDM patients under a well managed glycemic control throughout the entire duration of pregnancy would result in an optimum insulin receptor function.     

妊娠期糖尿病产妇妊娠晚期阴道微生态改变与围产结局的相关性分析

目的 探讨妊娠期糖尿病(GDM)产妇妊娠晚期阴道微生态的改变与围产结局的关系.方法 选择2017年1月至2019年6月期间在我院门诊进行产检并于我院产科分娩的150例GDM孕妇组成GDM组,并选择同期于我院产检及分娩的150例健康孕妇作为对照组(NC组),孕检时所有研究对象进行阴道分泌物标本采集,并行白带常规检查.检查...     

Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N?=?63) and those without (N?=?54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R?=?0.18; p?=?.08) and HOMA β (R?=??0.19; p?=?.09) as well as significant positive associations with total cholesterol (R?=?0.25; p?=?.02), LDL-cholesterol (R?=?0.25; p?=?.02), 25(OH)D (R?=?0.22; p?=?.04), albumin (R?=?0.30; p?<?.01) and IL1β (R?=?0.41; p?<?.01). Stepwise regression analysis also suggested that IL1β, leptin and albumin were the significant predictors of SPX. In summary, SPX levels modestly affect glucose and insulin sensitivity in pregnant women but is not associated with GDM and obesity. The significant association of SPX to ILβ warrants further investigation as to the role of SPX in immune modulation.     

Plasma levels of trace element status in early pregnancy and the risk of gestational diabetes mellitus: A nested case-control study

PurposeWe investigated the impacts of plasma levels of magnesium (Mg), zinc (Zn), calcium (Ca), iron (Fe), copper (Cu), selenium (Se), and chromium (Cr) on GDM risk and the potential mediation effect of blood glucose levels on the relationship between trace elements and GDM risk.MethodsThis nested case-control study was based on data from a birth cohort study conducted in Wuhan, China in 2013−2016. A total of 305 GDM cases and 305 individually-matched controls were included in the study. Conditional logistic regression models were used to estimate the associations between plasma trace element concentrations and GDM risk. A mediation analysis was conducted to explore whether blood glucose levels act as a mediator between trace element levels and GDM risk.ResultsAn IQR increment in plasma levels of Fe and Cu was associated with a significant increase in GDM risk [OR = 2.04 (95 % CI 1.62, 2.57) and OR = 1.52 (95 % CI 1.25, 1.82)], respectively. On the other hand, an IQR increment in plasma levels of Zn and Ca was associated with a significant decrease in GDM risk [OR = 0.55 (95 % CI 0.43, 0.71) and OR = 0.72 (95 % CI 0.56, 0.92)], respectively. The mediation analysis showed significant mediation of the association between Cu and GDM risk via the FBG (%mediated: 19.27 %), 1 h-PBG (12.64 %), 2h-PBG (28.44 %) pathways.ConclusionsPlasma levels of Zn and Ca were negatively associated with GDM risk, while Fe and Cu were positively associated. Blood glucose levels act as a mediator between plasma trace element exposures and GDM risk.     

妊娠期糖尿病患者肠道微生态失衡与炎症因子的相关性

目的探讨妊娠期糖尿病(GDM)妊娠妇女肠道微生态失衡与炎症因子的相关性。方法选择2017年3月至2018年8月于我院产科门诊建立产检完整档案的妊娠妇女,其中确诊为GDM妊娠妇女78例作为研究组,正常妊娠妇女99例作为对照组;定性、定量分析2组妊娠妇女肠道肠杆菌、肠球菌、双歧杆菌、乳杆菌、拟杆菌和梭杆菌数量,分析肠道微生态失衡情况并比较肠道失衡组、非肠道失衡组临床资料,分析肠道失衡发生危险因素;Spearman相关分析明确肠道微生态失衡与炎性因子白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)水平相关性。结果研究组SBP(收缩压)、DBP(舒张压)、FBG(空腹血糖)、HbA_(1c)(糖化血红蛋白)、IL-2、CRP、TNF-α水平高于对照组(均P0.05),肠杆菌、肠球菌、拟杆菌、梭杆菌数量大于对照组,而双歧杆菌、乳杆菌数量小于对照组(均P0.05)。研究组发生肠道微生态失衡例数23例(29.49%),对照组发生肠道微生态失衡例数10例(10.10%),研究组肠道微生态失衡发生率高于对照组(P0.05)。IL-2≥34.10 pg/mL、CRP≥19.33 mg/L、TNF-α≥89.96 ng/L、肠杆菌≥8.42 logN/g、肠球菌≥7.46 logN/g、双歧杆菌8.49 logN/g、乳杆菌6.32 logN/g、拟杆菌≥8.87 logN/g、梭杆菌≥3.13 logN/g是GDM妊娠妇女妊娠期发生肠道微生态失衡危险因素(均P0.05)。GDM妊娠妇女IL-2、CRP、TNF-α水平均与双歧杆菌、乳杆菌数量呈负相关(均P0.05),与肠杆菌、肠球菌、拟杆菌和梭杆菌数量呈正相关(均P0.05)。结论高炎性应激状态下的GDM患者表现出更明显的肠道微生态失调,可导致或加剧GDM发生或发展;妊娠期注意益生菌补充对防治GDM有重要价值。     

The association between serum selenium and gestational diabetes mellitus: A systematic review and meta-analysis

BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women.     

Increased tissue kallikrein amidase activity in urine of patients with type 1 diabetes under insulin therapy, and in those with gestational diabetes mellitus not under insulin therapy

Human tissue kallikrein (hK1) is reduced in hypertension, cardiovascular and renal diseases. There is little information on the participation of hK1 in type 1 diabetes mellitus (DM), type 2 DM, and gestational diabetes mellitus (GDM), respectively. The aim of this study was to evaluate the roles of insulin and hyperglycemia on urinary hK1 activity in type 1 DM and in GDM. Forty-three type 1 DM patients (5–35 years, disease duration ?5 years, receiving insulin, HbA_1c > 7.6%) were selected. Forty-three healthy individuals, paired according to gender and age, were used as controls. Thirty GDM patients (18–42 years, between the 24th and 37th week of pregnancy, recently diagnosed, not under insulin therapy) were also selected. Thirty healthy pregnant (18–42 years, between the 24th and 37th week of pregnancy) and 30 healthy non-pregnant women (18–42 years) were selected as controls. Random midstream urine was used. hK1 amidase activity was estimated with D-Val-Leu-Arg-Nan substrate. Creatinine was determined by Jaffe’s method. hK1 specific amidase activity was expressed as μM/(min mg creatinine) to correct for differences in urine flow rate. hK1 specific amidase activity was significantly higher in the urine of type 1 DM than in controls, and in the urine of GDM patients than in healthy pregnant women and healthy non-pregnant women, respectively. The data suggest that hyperglycemia, rather than insulin, is involved in the mechanism of increased hK1 specific amidase activity in both type 1 DM and GDM patients, respectively.     

Elemental contents in serum of pregnant women with gestational diabetes mellitus

Diabetes mellitus is characterized by hyperglycemia and is closely related to trace elements. Quite a few pregnant women suffer from impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM). Investigation of the changes of elemental contents in serum of the pregnant women with IGT and GDM is significant in the etiological research and cure of the diseases. In the present work, the elements Cu, Zn, Ca, Sr, Mg, P, Fe, and Al in the serum of pregnant women were determined. The elemental contents in different experimental groups were compared. Also, the correlation between elemental contents and gestational period was observed. The results showed that compared with normal pregnant women, the Cu contents in serum of pregnant women with GDM increased, but Zn contents had a decreasing trend. In addition, for all pregnant women, the Ca contents in serum had an obvious inverse correlation with gestational period.     

高通量测序分析妊娠期糖尿病对早产儿肠道菌群的影响

目的 通过高通量测序技术探究妊娠期糖尿病对早产儿肠道菌群的影响,并对相关功能及代谢通路进行预测。 方法 选取符合入组条件的早产儿40例,依据孕母是否患有妊娠期糖尿病分为妊娠期糖尿病组(GDM组)和对照组,各20例,于出生后24 h内收集早产儿胎便进行16S rRNA基因测序,对测序结果进行物种分类学分析及生物信息学分析。 结果 GDM组显示出更低的物种丰富度及多样性(P=0.048)。两组物种组成存在显著差异(P=0.048),GDM组厚壁菌门与拟杆菌门比值明显升高,机会致病菌相对丰度增加,同时革兰阴性杆菌比例上升。PICRUSt功能预测分析表明,GDM组在碳水化合物转运及代谢、细胞外结构、环境信息处理代谢通路和免疫性疾病代谢通路的功能丰度增高。 结论 妊娠期糖尿病可导致早产儿肠道微生态平衡被破坏,肠道菌群失调或为母亲患有GDM的早产儿多种疾病发病率增高的原因之一。     

The association of plasma peroxiredoxin 3 with insulin in pregnant women

Peroxiredoxin 3 (PRX3) is predominantly located in mitochondria and plays a major role in scavenging hydrogen peroxide of mitochondria. In the present study, we detected plasma PRX3 in pregnant women receiving oral glucose tolerance test at 24–28 gestational weeks. Plasma PRX3 was significantly increased about 1?h later than insulin secretion. In vitro detection of PRX3 in mouse islet cells showed up-regulation by more than 2-fold at 1?h and reached its top at 2?h of glucose stimulation, and the PRX3 level in cultured mediums was concomitantly elevated in a glucose concentration-dependent manner. In addition, both fasting plasma insulin and PRX3 were significantly higher in the subjects of term pregnancy as compared to that at 24–28 gestational weeks, and there was a positive correlation between plasma PRX3 and insulin. Our results indicate that PRX3 plays an active role in the response to insulin release. The positive association of plasma PRX3 and insulin suggest PRX3 to be a potential indicator of high insulin resistance.     

Metabolomics-based identification of apoptosis-inducing metabolites in recombinant fed-batch CHO culture media

A liquid chromatography-mass spectrometry (LC-MS) based metabolomics platform was previously established to identify and profile extracellular metabolites in culture media of mammalian cells. This presented an opportunity to isolate novel apoptosis-inducing metabolites accumulating in the media of antibody-producing Chinese hamster ovary (CHO mAb) fed-batch bioreactor cultures. Media from triplicate cultures were collected daily for the metabolomics analysis. Concurrently, cell pellets were obtained for determination of intracellular caspase activity. Metabolite profiles from the LC-MS data were subsequently examined for their degree of correlation with the caspase activity. A panel of extracellular metabolites, the majority of which were nucleotides/nucleosides and amino acid derivatives, exhibited good (R² > 0.8) and reproducible correlation. Some of these metabolites, such as oxidized glutathione, AMP and GMP, were later shown to induce apoptosis when introduced to fresh CHO mAb cultures. Finally, metabolic engineering targets were proposed to potentially counter the harmful effects of these metabolites.