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。     

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.     

Three new players in energy regulation: Preptin,adropin and irisin

Homeostasis of energy is regulated by genetic factors, food intake, and energy expenditure. When energy input is greater than expenditure, the balance is positive, which can lead to weight gain and obesity. When the balance is negative, weight is lost. Regulation of this homeostasis is multi-factorial, involving many orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) peptide hormones. Peripheral tissues are now known to be involved in weight regulation and research on its endocrine characteristics proceeds apace. Preptin with 34 amino acids (MW 3948 Da), adropin with 43 amino acids and a molecular weight of (4999 Da), and irisin with 112 amino acids (12587 Da), are three newly discovered peptides critical for regulating energy metabolism. Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in the liver and brain, and many peripheral tissues. Irisin, however, is synthesized principally in the heart muscle, along with peripheral tissues, including salivary glands, kidney and liver. The prime functions of preptin and adropin include regulating carbohydrate, lipid and protein metabolisms by moderating glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic hormone regulating adipose tissue metabolism and glucose homeostasis by converting white to brown adipose tissue. This review offers a historical account of these discovery and function of these peptides, including their structure, and physiological and biochemical properties. Their roles in energy regulation will be discussed. Their measurement in biological fluids will be considered, which will lead to further discussion of their possible clinical value.     

Is oxidative stress induced by iron status associated with gestational diabetes mellitus?

Gestational diabetes mellitus (GDM) is a common pregnancy complication in high risk populations, and is associated with increased perinatal and long term outcomes for both mothers and newborns. Both its prevention and early management can be reinforced by identifying risks factors, particularly those factors influencing glucose metabolism. On the other hand, several epidemiological studies have shown an increased oxidative stress (OS) in pregnant women with GDM. Elevated OS was also reported in pregnant women supplemented with iron, which can generate OS and may also influence insulin resistance. This review summarizes the current state of knowledge, highlighting the potential relationship between OS induced by iron status and the development of GDM.     

200例妊娠期糖尿病临床分析

目的:回顾性研究妊娠期糖尿病产妇孕中晚期及新生儿并发症情况,以加深对妊娠期糖尿病的认识,完善孕期管理,避免或减少并发症的发生,保证母婴安全。方法:随机抽取2011年1月至2012年12月在我院住院生产的200名妊娠期糖尿病产妇,其中在我院产检并接受管理的产妇138例为观察组,没有经过我院糖尿病管理的62例产妇为对照组,分析两组并发症发生情况。结果:观察组中51例产妇发生并发症(37.0%),新生儿21例(占15.2%);对照组中产妇发生并发症50例(占80.6%),新生儿23例(占37.1%),经糖尿病管理和治疗的观察组孕产妇出现的并发症明显比没有经过管理的对照组孕产妇出现的并发症少(如妊娠期高血压疾病、产后感染、酮症酸中毒、羊水过多、早产、巨大儿、低出生体重儿、死胎、畸形、呼吸窘迫综合征等),结果具有统计学意义。结论:需要重视妊娠期糖尿病,加强妊娠期糖尿病孕期管理是减少妊娠期糖尿病并发症的有效措施。     

妊娠期糖尿病孕妇血糖水平与新生儿体质量的相关性

目的:探究妊娠期糖尿病(GDM)孕妇产前血糖水平与新生儿质量的关系。方法:选取2012年6月至2014年6月我院分娩的GDM孕妇97例为研究对象,按照随机数字表法将患者随机分为严格组(50例)和宽松组(47例),选择同期血糖正常孕妇50例作为对照组;分析孕妇血糖水平与新生儿出生质量的关系。结果:对照组血糖水平、新生儿质量以及巨大儿的发生率均明显低于宽松组和严格组(P0.05);严格组的血糖水平、新生儿质量以及巨大儿的发生率均明显低于宽松组(P0.05);孕妇血糖水平与新生儿质量存在显著的正相关(r=0.72,P0.05)。结论:产前孕妇血糖水平与新生儿质量存在显著的正相关,对GDM患者产前进行严格的血糖控制有助于降低巨大儿的发生率,有利于母体和新生儿的健康。     

孕妇肠道微生物组成与孕妇及新生儿糖脂代谢相关性研究

目的研究孕妇肠道微生物组成与孕妇以及新生儿糖脂代谢的相关性。方法选择2017年6月至2018年9月在大连市妇幼保健院定期产检的诊断为妊娠期糖尿病(GDM)的孕妇89例为GDM组,血糖正常孕妇96例为对照组。收集孕妇一般资料,孕妇和新生儿糖脂代谢物、孕妇粪便进行微生物检测。结果 GDM组孕妇空腹血糖、甘油三酯明显高于对照组,高密度脂蛋白水平明显低于对照组(均P<0.05)。GDM新生儿脂联素和血糖明显低于对照组,胰岛素和糖化血红蛋白明显高于对照组(均P<0.05)。对照组孕妇肠道微生物中拟杆菌(Bacteroides)丰富度最高(36.6%),其次是普雷沃菌(Prevotella)(15.3%)、柔嫩梭菌(Faecalibacterium)(10.2%)、考拉杆菌(Phascolarctobacterium)(7.2%)。GDM组孕妇肠道微生物中拟杆菌(Bacteroides)丰富度最高(29.4%),其次是柔嫩梭菌(Faecalibacterium)(19.7%)、普雷沃菌(Prevotella)(11.1%)、考拉杆菌(Phascolarctobacterium)(9.3%)。柔嫩梭菌(Faecalibacterium)与孕妇空腹血糖呈正相关(r=0.377 6,P=0.027 6),拟杆菌(Bacteroides)、埃希菌(Escherichia)与孕妇甘油三酯呈负相关(r=-0.027 5,-0.585 8,P=0.023 7,0.041 3)。柔嫩梭菌(Faecalibacterium)与新生儿空腹血糖呈负相关(r=-0.397 6,P=0.027 6)。结论 GDM孕妇肠道微生物构成与血糖正常孕妇不同,菌群丰富度和多样性较低,并且孕妇肠道菌群与其及新生儿的糖脂代谢相关,调节孕妇肠道菌群或有利于改善其与新生儿的糖脂代谢功能。     

妊娠早期血清Hcy、铁蛋白水平对妊娠期糖尿病的预测价值研究

摘要 目的：探讨妊娠早期血清同型半胱氨酸（Hcy）、血清铁蛋白（SF）水平对妊娠期糖尿病（GDM）的预测价值。方法：按妊娠24~28周75 g口服葡萄糖耐量试验（75 g OGTT）结果,将412例孕妇分为GDM组（n=96）与糖耐量正常（NGT）组（n=316）。收集孕妇一般资料,于妊娠6~14周行血清Hcy、铁蛋白水平检测,比较两组临床资料差异,使用Logistic筛选GDM的危险因素,并使用受试者工作特征（ROC）评价相关指标对GDM的预测能力。结果：较于NGT组,GDM组孕妇年龄较大,妊娠前BMI、空腹血糖、糖化血红蛋白、三酰甘油水平和血清Hcy、铁蛋白水平更高（P<0.05）。Logistic回归分析得出,年龄较大、妊娠前BMI较高、HbA1c水平较高及血清Hcy水平较高、铁蛋白水平较高均是GDM的危险因素（P<0.05）。ROC曲线分析得出,血清Hcy、铁蛋白对GDM均有一定预测能力,其AUC分别为0.753、0.746。联合预测模型的预测效能更大,其AUC高达0.917。结论：妊娠早期血清Hcy、铁蛋白水平增高与GDM发病相关,可作为GDM的预测生物标志物。     

2型糖尿病视网膜病变患者血清和肽素、脂质运载蛋白2水平的表达及其临床意义

摘要 目的：探讨2型糖尿病（T2DM）视网膜病变（DR）患者血清和肽素（copeptin）、脂质运载蛋白2（LCN2）的表达及其临床意义。方法：选取2021年1月~2023年1月期间江南大学附属医院接收的2型糖尿病（T2DM）患者141例,将所有患者分为不合并糖尿病视网膜病变（DR）组（NDR组,n=49）、非增生期DR组（NPDR组,n=45）和增生期DR组（PDR组,n=47）,另选取同期行健康体检的志愿者50例作为对照组。比较各组临床指标、生化指标及血清copeptin、LCN2水平,采用Pearson相关性分析血清copeptin、LCN2水平与临床指标及生化指标的相关性,采用多因素Logistic回归分析DR的危险因素。结果：对照组、NDR组、NPDR组、PDR组的血清copeptin、LCN2水平呈逐渐升高趋势（P<0.05）。NDR组、NPDR组、PDR组的体重指数（BMI）、收缩压（SBP）、舒张压（DBP）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FPG）均高于对照组（P<0.05）;对照组、NDR组、NPDR组、PDR组的糖化血红蛋白（HbAlc）、胰岛素抵抗指数（HOMA-IR）呈逐渐升高趋势（P<0.05）;NDR组、NPDR组、PDR组糖尿病病程呈逐渐递增趋势（P<0.05）。Pearson相关性分析显示,copeptin、LCN2水平与HbAlc、HOMA-IR、糖尿病病程呈正相关（P<0.05）,与血压、血脂、FPG、BMI无明显相关性（P>0.05）。多因素Logistic回归分析结果显示：糖尿病病程、HbAlc、HOMA-IR、copeptin、LCN2均为DR发生发展的独立危险因素（P<0.05）。结论：高水平copeptin、LCN2可能与DR的发生、发展有关,且与患者糖尿病病程、HbAlc、HOMA-IR关系密切,可用于DR患者的早期诊断及判断其病情的严重程度。     

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.     

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。     

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.     

胰岛素对不同孕期妊娠糖尿病患者血糖水平及妊娠结局的影响

目的:探讨胰岛素对不同孕期妊娠合并糖尿病孕产妇血糖水平及妊娠结局的影响。方法:选择2011年7月-2015年4月在我院接受治疗的妊娠期糖尿病患者200例,均采用胰岛素治疗。检测患者血糖变化、妊娠期并发症的发生情况,并分析孕期对胰岛素治疗效果的影响。结果:治疗后产妇空腹血糖及餐后2 h血糖均低于治疗前,差异具有统计学意义(P0.05);孕期32周的产妇治疗后空腹血糖及餐后2 h血糖均低于孕期≥32周的产妇,差异具有统计学意义(P0.05)。孕期32周的产妇妊娠高血压及产后出血的发生率均低于孕期≥32周的产妇,但早产及剖宫产的发生率高于孕期≥32周的产妇,差异具有统计学意义(P0.05)。结论:胰岛素治疗能够有效控制妊娠期糖尿病产妇的血糖水平,改善妊娠结局,早期干预效果较好。     

Glucose homeostasis during canine pregnancy: Insulin resistance, ketosis, and hypoglycemia

Through a variety of mechanisms, pregnancy causes insulin resistance, which suppresses the intracellular transport of glucose and increases blood glucose concentrations. In the extreme, gestational diabetes (GDM) mellitus may develop. In addition to insulin resistance, pregnant bitches have decreased ability to produce glucose via gluconeogenesis, glycogenolysis and lipolysis, because the normal multi-factorial responses to hypoglycemia are blunted late in pregnancy. Simply fasting late-pregnant bitches is sufficient to cause blood glucose and insulin concentrations to decrease and ketones to increase. The purpose of this paper is to review the clinical implications of pregnancy-associated changes in glucose homeostasis in bitches.     

妊娠期糖耐量标准与妊娠结局的关系

目的:探讨不同的诊断标准的妊娠期糖尿病的妊娠结局。方法:回顾性分析我院2001-2004年产前检查并分娩,无显性糖尿病及其他内分泌疾病的单胎孕妇共337例,按糖尿痛不同的诊断标准分成三组进行比较:干预组78例(OGTT(oral glucose toler- ante test)血糖值达到妊娠期糖尿病诊断标准,予饮食调整、运动指导,和或胰岛素治疗);未干预组91例(OGTT值小于妊娠期糖尿病诊断标准,但第2小时血糖≥7.8mmol/L,一般产科检查,无相应血糖的检测与治疗);对照组168例(OGTT正常,且第2小时血糖<7.8mmol/L一般产科检查)。结果:未干预组在巨大胎与干预组及对照组间有显著差异。干预组在妊娠周数与对照组及未干预组之间有差异。三组在年龄、分娩前体重指数、分娩方式等方面无显著差异。结论:未干预糖尿病组与巨大胎有关。建议诊断妊娠期糖尿病标准采用空腹血糖≥5.8mmol/L和或75克糖耐量试验2小时血糖≥7.8mmol/L。