脂肪因子Chemerin与妊娠相关疾病的关系展望

<正>1 Introduction Recurrent pregnant loss,gestational diabetes,premature delivery,intrauterine growth restriction,preeclampsia and other pregnancy-related complications have severe impact on the fetus development and the health and life quality of the mother.These diseases are also causes of unstability and huge economic burden for the family as well as the     

Fetomaternal adrenomedullin levels in diabetic pregnancy.

We investigated whether maternal and fetoplacental adrenomedullin, a newly discovered hypotensive peptide involved in the insulin regulatory system, is modified in diabetic pregnancy. We studied its correlation with pregnancy complications associated with this disease. Thirty-six pregnant women with diabetes (13 with type I and 23 with gestational diabetes mellitus) and in 40 uncomplicated pregnancies were included. 10 out of 36 diabetic pregnancies were complicated by gestational hypertension. In each woman, adrenomedullin concentration in maternal and fetal plasma and in amniotic fluid was assessed by specific radioimmunoassay. We found that overall mean amniotic fluid adrenomedullin concentration was higher (p < 0.05) in diabetic (14.7 +/- 1.6 fmol/ml) than in uncomplicated pregnancies (10.8 +/- 0.9 fmol/ml), whereas no differences were present in maternal and fetal plasma adrenomedullin levels between diabetic and uncomplicated pregnant women. High levels of amniotic fluid adrenomedullin were found in both type I and gestational diabetes mellitus pregnancies (13.7 +/- 1.4 and 15.6 +/- 2.2 fmol/ml, respectively). Diabetic pregnancies complicated by gestational hypertension showed lower (p < 0.05) amniotic fluid adrenomedullin concentrations than normotensive diabetic patients. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy, and it may be important to prevent excessive vasoconstriction of placental vessels.     

Metabolic syndrome in type 1 diabetes mellitus. Does it have any impact on the course of pregnancy?

To determine whether the symptoms of metabolic syndrome (MS), if accompanied by oxidative stress (OS), in type 1 diabetes mellitus (DM) patients could affect the course of pregnancy and the perinatal outcome. Oxidized low density lipoproteins (ox-LDL) and total lipid peroxides (TLP) were studied in 98 pregnant women with type 1 DM in the I(st) and III(rd) trimesters. 24% of the participants met the criteria of MS. Vascular complications were significantly more frequent in the MS-group (41.9% vs. 17.4% in the non-MS group, p<0.05). No differences in the markers of OS between the MS and the non-MS groups were noted in either the I(st) or the III(rd) trimester. A significant gestational rise in Per-Ox was found in both groups. Chronic hypertension was associated with significant differences in ox-LDL levels in both the I(st) and III(rd) trimester. No differences in perinatal outcome, as measured by abnormal birth weight or poor neonatal status (Apgar score<6, umbilical venous and/or arterial pH<7.20), were found. Conclusions: 1) MS in type 1 DM is associated with some changes in markers of oxidative stress, but it poses no additional risk to the course of pregnancy and perinatal outcome in properly controlled and treated pregnant women with type 1 DM. 2) Maternal hypertension is the only component of MS in diabetic pregnancy that is associated with significant changes in markers of oxidative stress. 3) MS is significantly more frequent in diabetic pregnant women with co-existing vascular complications and obesity.     

Neonatal complications in infants born to mothers with diabetes mellitus

Health status of 53 babies delivered by diabetic mothers are discussed. Neonatal period was uncomplicated only in 12 cases. The remaining babies suffered from respiratory disorders, edema, neurological disturbances, prolonged jaundice, infections etc. Metabolic disorders in diabetic female are unfavourable for the development of pregnancy and neonate health. it may be improved by the proper diagnostico-therapeutical management prior to and during pregnancy and by intensive care of neonates after delivery. It requires, however, the establishment of health institution with highly qualified teams well equipped which will be able to carry out diagnosis and therapy of diabetes mellitus in females in the reproductive age, during pregnancy as well as proper care of the neonates.     

Advanced glycation end-products and the progress of diabetic vascular complications

Epidemiological studies have confirmed that hyperglycemia is the most important factor in the onset and progress of vascular complications, both in Type 1 and 2 diabetes mellitus. The formation of advanced glycation end-products (AGEs) correlates with glycemic control. The AGE hypothesis proposes that accelerated chemical modification of proteins by glucose during hyperglycemia contributes to the pathogenesis of diabetic complications including nephropathy, retinopathy, neuropathy and atherosclerosis. Recent studies have shown that increased formation of serum AGEs exists in diabetic children and adolescents with or without vascular complications. Furthermore, the presence of diabetic complications in children correlates with elevated serum AGEs. The level of serum AGEs could be considered as a marker of later developments of vascular complications in children with Type 1 and 2 diabetes mellitus. The careful metabolic monitoring of young diabetics together with monitoring of serum AGEs can provide useful information about impending AGE-related diabetic complications. It is becoming clear that anti-AGE strategies may play an important role in the treatment of young and older diabetic patients. Several potential drug candidates such as AGE inhibitors have been reported recently.     

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。     

The Case for Control in Diabetes Mellitus

In all diabetic animal models studied to date, microangiopathic complications develop which can be prevented by tight control and reversed by either islet cell transplantation or transplanting the diabetic kidney into a nondiabetic environment. In humans the prevalence of these complications in secondary diabetes mellitus is similar to the prevalence in genetic diabetes. Furthermore, mesangial basement membrane thickness is normal at the onset of the disease and increases shortly thereafter. These two facts strongly suggest that the microangiopathic complications are not an independent genetic component but rather are secondary to the metabolic derangements of uncontrolled diabetes. Normal kidneys transplanted into diabetic recipients developed the vascular lesions of diabetes. Conversely, two diabetic kidneys inadvertently transplanted into nondiabetic recipients showed clearing of the vascular lesions.Most retrospective studies support the conclusion that control is associated with lessened complications. The three prospective studies published to date also support this hypothesis. Because glucose concentrations cannot be brought to normal levels by present methods, the critical question is whether a major emphasis on restoring metabolism to as nearly normal as possible will help ameliorate the microangiopathic complications in our patients. The accumulated evidence would strongly favor an affirmative answer. Two daily injections of intermediate-acting insulin supplemented with small amounts of short-acting insulin as needed is one method to approach this goal.     

Macroangiopathy in adults and children with diabetes: from molecular mechanisms to vascular damage (part 1).

Type 2 diabetes mellitus (T2DM) is an increasing problem in childhood; however type 1 diabetes mellitus (T1DM) remains by far the most common type of diabetes in this age group. In this review we will focus on T1DM, because this will have the greatest implication for patients diagnosed in childhood. During the atherosclerotic process, several molecular, receptorial and cellular factors provide a continous mechanism of vascular damage. In diabetic children this state seems to be enhanced and facilitated so that accelerated atherosclerosis is associated with an increased risk of cardiovascular events in respect to the non diabetic population. Hyperglycemia PER SE and associated with diabetes is an important risk factor for atherosclerosis. At present a substantial part of children with diabetes do not reach satisfactory glycemic control. Other risk factors for the development and progression of atherosclerosis may be inherited or develop in the course of the disease: hypertension, dyslipidemia, insulin resistance, obesity, cigarette smoking, physical inactivity, disturbance of platelet function, coagulation and fibrinolysis. The development and progression of atherosclerosis should be blocked at an early age, if possible. Primary prevention to all risk factors for cardiovascular disease is important and intervention is indicated if necessary. At the moment the best therapeutic strategy is to maintain metabolic control at a physiologic level and perform screening and early intervention for vascular complications.     

Insulin-like growth factor-1 and its binding proteins, IGFBP-1 and IGFBP-3, in adolescents with type-1 diabetes mellitus and microalbuminuria

BACKGROUND/AIMS: Numerous clinical and experimental studies suggest that growth factors may contribute to the development of diabetic microvascular complications. The aim of the study was to test the hypothesis that in adolescents with type-1 diabetes mellitus and microalbuminuria (MA) there are specific disorders of serum insulin-like growth factor-1 (IGF-1) and concentrations of its binding proteins, IGFBP-1 and IGFBP-3, that could be of importance in the pathogenesis of microvascular diabetic complications. METHODS: 25 adolescents with MA, 24 adolescents with diabetes without complications, and 17 controls were examined. There were no differences with regard to age, puberty stage, HbA1c and body mass index between the groups examined. Two of the patients in the first group also had diabetic retinopathy. Serum fasting concentrations of IGF-1 and overnight urine albumin concentrations were measured by radioimmunoassay, IGFBP-1 and IGFBP-3 concentrations by immunoradiometric assay and HbA1c by high-performance liquid chromatography methods. Diabetic patients were examined by an experienced ophthalmologist and neurologist. The data were analyzed using Kruskal-Wallis ANOVA and multiple regression analysis. RESULTS: Significantly lower IGF-1 concentrations were found in adolescents with diabetes and MA compared to diabetic patients without complications and healthy contemporaries. IGFBP-1 concentrations were significantly higher and IGFBP-3 concentrations were statistically lower in diabetic patients with MA than in patients without complications. CONCLUSIONS: The IGF-IGFBP system is deranged in adolescents with type-1 diabetes mellitus and MA. Our results suggest the participation of circulating IGFBP-1 in the origin of diabetic complications. It could be also possible that IGFBP-3 takes part in the protection from them.     

Insulin release from the pancreas and fuel metabolism during late gestation in chemically diabetic rats

The effects of chemical diabetes and fasting on fuel metabolism and insulin secretory activity in late pregnancy were investigated. Female Wistar rats were made chemically diabetic (CD) by intravenous injection of streptozotocine (30 mg/kg) 2 weeks before conception. When CD pregnant rats were fed, plasma glucose and insulin levels were not significantly different from those of normal pregnant rats. Ketone body levels, however, were higher in CD pregnant rats than in normal pregnant rats, indicating insulin resistance in CD rats. Insulin secretion from the perfused pancreas caused by arginine or glucose was markedly decreased in CD pregnant rats. The pregnant rats were fasted for 2 days, from day 19 to 21 of gestation. Plasma glucose and insulin concentrations decreased similarly in the two groups, whereas ketone body concentrations in CD pregnant rats were significantly higher than those in normal pregnant rats. Glucose-induced insulin secretion by the perfused pancreas was markedly attenuated by fasting and was not significantly different in normal and CD pregnant rats. These observations suggest that diabetes mellitus accelerates starvation in late gestation, due to increased insulin resistance and poor insulin secretion, and that fasting in diabetic pregnancy amplifies ketogenesis.     

妊娠合并甲状腺功能减退症26例妊娠结局分析

目的：对妊娠合并甲状腺功能减退症进行分析,探讨其对母儿的影响,及孕期筛查甲状腺功能有无意义。方法：对我院26例妊娠合并甲减的临床资料进行回顾性统计分析。结果：26例妊娠合并甲减病例中有1例早产（孕33周）,其余25例患者维持至足月妊娠,其中剖宫产17例（65.38%）,合并妊娠期高血压疾病5例（19.23%）,妊娠期糖尿病3例（11.53%）,羊水胎粪污染3例（11.54%）,新生儿无先天性甲减。经过治疗后甲状腺功能减退孕妇的剖宫产率,糖尿病发生率、高血压疾病发生率、羊水粪染的发生率较对照组增加;但两组妊娠结局差异无统计学意义（P〉0.05）。结论：妊娠合并甲状腺功能减退症孕妇多种妊娠并发症的发病率高于正常孕妇,应加强对妊娠甲减的早期筛查及治疗,可有效降低不良妊娠结局,减少先天性甲低的出生。     

GDM患者综合性干预的应用研究

本研究旨在探讨综合性干预对妊娠期糖尿病(gestational diabetes mellitus, GDM)孕妇妊娠结局及新生儿并发症的影响。本研究选取130例妊娠晚期糖尿病患者随机分组,对照组患者给予常规护理,试验组患者实施综合性干预,观察两组患者血糖指标、妊娠结局、新生儿健康状况、血脂水平差异。实验结果显示,试验组空腹血糖(fasting blood glucose, FBG)、糖化血清蛋白(glycosylated serum pritein, GSP)、血管细胞黏附分子-1(CD106)明显低于对照组(p<0.05);试验组早产、剖宫产、羊水过多、产后出血、胎儿窘迫现象明显低于对照组(p<0.05);试验组患者新生儿窒息、巨大儿、新生儿低血糖、新生儿高胆红素血症显著低于对照组(p<0.05);治疗后实验组患者TC (5.63±1.52) mmol/L,TG (3.18±0.45) mmol/L,LDL-C (3.15±0.64) mmol/L显著低于对照组(p<0.05)。研究表明,针对妊娠晚期糖尿病患者应用综合性干预可改善患者血糖水平、血脂水平、妊娠结局,降低巨大儿发生率,具有临床应用推广价值。     

Antioxidative treatment reverses imbalances of nitric oxide synthase isoform expression and attenuates tissue-cGMP activation in diabetic rats

Oxidative stress and impaired bioactivity of vascular nitric oxide (NO) play an important role in the pathogenesis of macro- as well as microangiopathic complications in diabetes mellitus. To determine the cause of this impaired bioactivity, we tested the effect of long-term hyperglycemia and antioxidative treatment on tissue-specific endothelial (e)NOS- and inducible (i)NOS-expression and the main target of NO action, cGMP, in diabetic rats. After 4 weeks of hyperglycemia, eNOS-mRNA expression was significantly down-regulated in all tissues tested. In contrast, iNOS-mRNA was significantly up-regulated and tissue generation of cGMP significantly increased. Treatment with alpha-lipoicacid reversed changes of NOS-isoform expression as well as cGMP-concentration without changing blood glucose levels. In addition, oxidative stress significantly decreased in diabetic rats treated with alpha-lipoicacid. Together, diabetes regulates NOS-isoforms differentially by down-regulating eNOS and up-regulating iNOS. In addition, our data suggest that the cause of impaired endothelial vasodilatation in experimental diabetes is not degradation or inactivation of NO. On the contrary, these results support the concept of decreased reactivity of the vascular smooth muscle to NO or increased NO activity as a possible vascular damaging agent, e.g., by inducing apoptosis in vascular cells. Furthermore, our data show that antioxidative treatment is capable of reversing changes in the NO-cGMP system and may therefore be an important therapeutic option for preventing vascular damage in diabetes mellitus.     

妊娠期糖尿病患者妊娠中期体质指数水平对分娩结局的影响

目的:研究妊娠期糖尿病患者妊娠中期体质指数(BMI)水平对妊娠结局的影响。方法:选取2012年1月到2014年11月我院产检诊断为妊娠期糖尿病患者390例,根据患者的妊娠中期BMI水平由低到高依次将患者分为三组:I组119例,II组165例,III组106例,随访所有入选者至分娩,观察其分娩结局。结果:III组妊娠晚期出现巨大胎儿者24例,占22.64%,羊水过多者为26例,占24.53%,显著高于I组和II组,比较差异具有统计学意义(P0.05);III组出现妊娠期高血压者8例,占7.55%,新生儿窒息者4例,占3.77%,与I组和II组比较差异无统计学意义(P0.05)。结论:妊娠期糖尿病患者妊娠中期BMI较高者发生巨大儿和羊水过多的比率显著增加,应该适当控制妊娠期糖尿病患者的BMI水平。     

Low prevalence of glucokinase gene mutations in gestational diabetic patients with good glycemic control

Glucokinase (GCK) plays a key role in glucose homeostasis. Gestational diabetes mellitus increases the risk of gestational complications in pregnant women and fetuses. We screened for mutations in coding and flanking regions of the GCK gene in pregnant women with or without gestational diabetes in a Brazilian population. A sample of 200 pregnant women classified as healthy (control, N = 100) or with gestational diabetes (N = 100) was analyzed for mutations in the GCK gene. All gestational diabetes mellitus patients had good glycemic control maintained by diet alone and no complications during pregnancy. Mutations were detected by single-strand conformation polymorphism and DNA sequencing. Thirteen of the 200 subjects had GCK gene mutations. The mutations detected were in intron 3 (c.43331A>G, new), intron 6 (c.47702T>C, rs2268574), intron 9 (c.48935C>T, rs2908274), and exon 10 (c.49620G>A, rs13306388). None of these GCK mutations were found to be significantly associated with gestational diabetes mellitus. In summary, we report a low frequency of GCK mutations in a pregnant Brazilian population and describe a new intronic variation (c.43331A>G, intron 3). We conclude that mutations in GCK introns and in non-translatable regions of the GCK gene do not affect glycemic control and are not correlated with gestational diabetes mellitus.     

The diabetic vasculature: Physiological mechanisms of dysfunction and influence of aerobic exercise training in animal models

Diabetes mellitus (DM) is associated with a number of complications of which chronic vascular complications are undoubtedly the most complex and significant consequence. With a significant impact on health care, 50–80% of people with diabetes die of cardiovascular disease (including coronary artery disease, stroke, peripheral vascular disease and other vascular disease), making it the major cause of morbidity and mortality in diabetic patients. A healthy lifestyle is essential in the management of DM, especially the inclusion of aerobic exercise, which has been shown effective in reducing the deleterious effects in vasculature. Interest in exercise studies has increased significantly with promising results that demonstrate a future for investigation. Considering the importance of this emerging field, the aim of this mini-review is to summarize and integrate animal studies investigating physiological mechanisms of vascular dysfunction and remodeling in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and how these are influenced by chronic aerobic exercise training.     

2 型糖尿病血管并发症发生机制及中药干预作用的研究进展

糖尿病血管并发症是导致糖尿病患者死亡的主要原因之一。许多糖尿病患者非常重视血糖的控制,而对于糖尿病血管并发症并未予 以足够的关注。随着中药研究领域的开展,人们发现中药在糖尿病慢性血管并发症的治疗中具有明显的优势。从糖脂代谢异常、胰岛素抵抗、 氧化应激以及肾素-血管紧张素-醛固酮系统异常等方面,综述2 型糖尿病血管并发症的发生机制,并简介中药针对各发病机制过程的干预 作用。     

妊娠期糖尿病与妊娠结局的临床分析

目的:探讨妊娠期糖尿病(GDM)对孕妇妊娠结局和胎儿健康的影响。方法:回顾性分析2009年8月~2012年12月在我院分娩的184例GDM患者及200例健康孕妇的临床资料,并对两组孕妇的妊娠结局进行比较。结果:GDM组妊高症35例(19.0%)、羊水过多17例(9.2%)、早产21例(11.4%)、产后出血14例(7.6%)、产褥感染12例(6.5%),发生率均显著高于对照组(P0.05);GDM组中发生巨大儿48例(26.1%)、新生儿低血糖31例(16.8%),与对照组比较均显著增高(P0.05),而胎儿宫内窘迫的发生率(3.3%)也较对照组升高,但差异无统计学意义(P0.05);GDM组剖宫产141例(76.6%),阴道产43例(23.4%),剖宫产比例较对照组显著升高(P0.05)。结论:GDM对孕妇的妊娠结局有不利影响,孕妇应加强孕期保健,规范治疗妊娠期糖尿病,减少各种并发症的发生。     

Clinical significance of cardiovascular dysmetabolic syndrome

Although diabetes mellitus is predominantly a metabolic disorder, recent data suggest that it is as much a vascular disorder. Cardiovascular complications are the leading cause of death and disability in patients with diabetes mellitus. A number of recent reports have emphasized that many patients already have atherosclerosis in progression by the time they are diagnosed with clinical evidence of diabetes mellitus. The increased risk of atherosclerosis and cardiovascular complications in diabetic patients is related to the frequently associated dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, and endothelial dysfunction. The evolving knowledge regarding the variety of metabolic, hormonal, and hemodynamic abnormalities in patients with diabetes mellitus has led to efforts designed for early identification of individuals at risk of subsequent disease. It has been suggested that insulin resistance, the key abnormality in type II diabetes, often precedes clinical features of diabetes by 5–6 years. Careful attention to the criteria described for the cardiovascular dysmetabolic syndrome should help identify those at risk at an early stage. The application of nonpharmacologic as well as newer emerging pharmacologic therapies can have beneficial effects in individuals with cardiovascular dysmetabolic syndrome and/or diabetes mellitus by improving insulin sensitivity and related abnormalities. Early identification and implementation of appropriate therapeutic strategies would be necessary to contain the emerging new epidemic of cardiovascular disease related to diabetes.     

Predictive parameters of gestational diabetes mellitus

Gestational diabetes mellitus is a carbohydrate intolerance recognized in pregnancy. The objective of this study was to determine the prevalence of gestational diabetes mellitus (GDM) of all deliveries at the University Hospital Rijeka, Croatia (34 997 deliveries over 10-year period) using 2-hour 75 g oral glucose tolerant test and to evaluate the impact of GDM on neonatal outcomes and mother's health. Gestational diabetes was diagnosed in 55 of 128 pregnant women with suspected glucose intolerance. Logistic regression analysis was used to examine the relationship between fasting plasma glucose, age, family history, body mass index, maternal weight gain, neonatal weight, neonatal head diameter and Apgar score in the gestational diabetes group and in the non-diabetes group. The results indicate that fasting plasma glucose greater than 7.0 mmol/L and maternal overweight are strong predictors for GDM and macrosomia. There was no difference in the mode of delivery, and vitality and metabolic complications among the infants of all analyzed mothers. We concluded that to prevent GDM as well as to reduce the rate of macrosomic infants good glycemic control should be initiated as soon as possible. The 2-hour 75 g OGTT is worth enough to evaluate GDM. Women should be counseled and encouraged to lose weight before or at the beginning of the conception period.