Gestational diabetes, pregnancy hypertension, and late vascular disease

The complexity of the several pathogenic pathways that cause hypertension and vascular disease and the prolonged interval that appears to predate clinical morbidity have hindered inquiry into the association between GDM and vascular disorders. As a forme fruste of later type 2 diabetes, GDM-affected gravidas are identified as at risk of diabetes-related atherosclerosis, glomerular disruption, and pathogenic retinal angio-genesis. That GDM is evidence for underlying chronic conditions such as dysregulation of innate immune response that, independent of the diabetic state, produces vascular disease is difficult state, produces vascular disease is difficult to assert with the present published literature. Cross-sectional studies of patients with established gestational hypertension or preeclampsia are ambiguous as to the possible pathogenic effect of insulin resistance. Cohort studies initiated in early and mid-pregnancy show evidence that both gestational hypertension and preeclampsia may be more prevalent in gravidas with greater insulin resistance. The association of gestational glucose intolerance with gestational hypertension appears to be independent of obesity and ambient glycemia but explained in part by insulin resistance. Late pregnancy preeclampsia is associated with elevated mid-pregnancy BMI, blood pressure, fasting glucose and insulin, urate, and C-reactive protein, suggestive of metabolic and immune dysregulation. GDM appears to be associated with overexpressed innate immune response, which, in turn, is associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an association of insulin resistance with both inflammatory dysregulation and vascular dysfunction. Cohort studies that have used population-based pregnancy databases consistently identify a clinically significant association of both gestational hypertension and preeclampsia with later hypertensive disorders. Associations with coronary artery disease or stroke are less consistent, requiring further investigation. Preventing the evolution of diabetes and lipid and immune dysregulation of the metabolic syndrome has become a silent public health issue because of the epidemic of childhood and early adulthood obesity and the opportunity at hand to treat insulin resistance by behavioral and pharmacological interventions. However, limited available literature highlights the need for long-term cohort studies of women with well-characterized metabolic and vascular profiles during pregnancy and decades later. Our present knowledge suggests that screening for GDM provides an opportunity of pregnancy outcome improvement. Limited studies of diabetes prevention in at-risk patient groups suggest that we may have the opportunity to reduce the risk of later diabetes. Additional investigation is required to determine if interventions that prevent or postpone diabetes also delay the onset of vascular disease.     

Lysosomal enzymes in preeclamptic women in northern Nigeria

BACKGROUND: The incidence of preeclampsia is high in northern Nigeria, as it is in many other developing countries, and preeclampsia is associated with significant maternal and fetal morbidity and mortality. We inquired if proteinuria or hypertension alone could account for the altered concentrations of urinary lysosomal hydrolases that have been reported in preeclamptic women and pregnant women without preeclampsia. METHODS: The activities of urinary beta-hexosaminidase and beta-galactosidase were determined fluorometrically in pregnant women assigned to one of four groups: Group I: 41 preeclamptic women; Group II: 31 hypertensive aproteinuric women; Group III: 44 normotensive proteinuric women; and Group IV: 52 healthy pregnant women (controls). RESULTS: The urinary beta-hexosaminidase concentrations were decreased in the preeclamptic women (P<0.005) and proteinuric women (P<0.001) when compared to the healthy pregnant controls. There was no significant difference in beta-hexosaminidase concentrations between the hypertensive women and the healthy pregnant controls. The urinary beta-galactosidase concentrations for preeclamptic, hypertensive, and proteinuric women did not differ significantly versus healthy pregnant controls. CONCLUSIONS: The reduced urinary excretion of beta-hexosaminidase in preeclamptic women is associated with proteinuria, but not hypertension. Measuring urinary concentrations of lysosomal hydrolases alone or in conjunction with urinary protein concentrations is not likely to be useful in predicting or monitoring the clinical course of preeclampsia; however, it might prove important in gaining a more complete understanding of the pathogenesis of renal tubular epithelial cell injury and proteinuria that occurs in preeclampsia.     

子痫前期患者子宫动脉多普勒与血清chemerin的变化及意义

目的:讨论妊娠期高血压孕妇和正常妊娠妇女妊娠早、中、晚期子宫动脉血流变化及血清chemerin变化的规律及意义。方法:选取潍坊市妇幼保健院系统产前检查的孕妇共300例作为研究对象,分别于妊娠14周、24周、34周收集和测量两组孕妇的血液样本和子宫动脉多普勒信息。比较两组孕妇血清chemerin浓度,子宫动脉舒张末期流速(S/D)、搏动指数(PI)、阻力指数(RI)。结果:1)子痫前期患者血清中chemerin浓度明显高于对照组(P<0.05),且重度子痫前期组明显高于轻度子痫前期组(P<0.05)。2)子宫动脉血流动态变化:正常妊娠组孕妇随妊娠进展,子宫动脉RI、PI、S/D 3项指标逐渐降低,妊娠早、中、晚期分别比较,均有统计学差异(P<0.01)。子痫前期组孕妇子宫动脉RI、PI、S/D 3项指标以孕晚期最高,妊娠早、中、晚期分别比较,均有统计学差异(P<0.01)。子痫前期组孕妇妊娠中、晚期子宫动脉3项指标均高于正常妊娠组,有统计学差异(P<0.01)。3)子痫前期患者血清中chemerin浓度在孕早期与子宫动脉血流无明显相关性,在妊娠中晚期呈明显正相关。结论:随着妊娠进展,子痫前期患者血清中chemerin浓度逐渐升高,正常妊娠妇女子宫动脉的血流阻力逐渐下降;而子痫前期组孕妇随妊娠进展子宫动脉的血流阻力明显升高。两者共同参与妊娠期高血压的发病。     

Obstetric and gynecologic diseases

Edema is one of symptoms frequently found during pregnancy. The incidence of edema during pregnancy is reported to be 30-35%. Edema does not deteriorate pregnancy outcome in normal pregnancy and preeclampsia. Therefore, it is suggested that edema should be excluded from diagnostic criteria of preeclampsia. However, edema developing before 28 weeks' gestation and/or anasarca occurring suddenly is a noteworthy symptom, because pregnant women who have these symptoms frequently develop gestational hypertension or preeclampsia. In conclusion, edema during pregnancy is not an important symptom, although edema developing before 28 weeks' gestation or anasarca occurring suddenly is a noteworthy symptom.     

妊娠期糖尿病与血糖正常孕妇胰岛素抵抗及胰岛β细胞功能比较

目的对比观察妊娠期糖尿病(GDM)与血糖正常孕妇胰岛素抵抗及胰岛β细胞功能。方法选择187例有GDM危险因素的产妇进行前瞻性研究,于早孕期和中孕期进行口服葡萄糖耐量试验(OGTT)检查,根据OGTT结果分为GDM组(86例)和非GDM组(对照组,101例)。检测两组胰岛素水平,采用稳态模型评估胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β),计算早期胰岛素分泌指数(ΔI30/ΔG30)、混合胰岛素敏感度(ISIcomp)并比较。结果 GDM组早孕期、中孕期的HOMA-IR显著高于对照组,ΔI30/ΔG30、ISIcomp显著低于对照组。与早孕期相比,中孕期对照组和GDM组的HOMA-IR显著高于早孕期,ΔI30/ΔG30、ISIcomp显著低于早孕期。结论 GDM患者早孕期就存在明显的胰岛素抵抗。应进行严格管理,控制血糖,保护胰岛β细胞功能,从而改善妊娠结局。     

Mildly elevated thyroid-stimulating hormone is associated with endothelial dysfunction and severe preeclampsia among pregnant women with insufficient iodine intake in Eastern Cape province,South Africa

BackgroundPreeclampsia and hypothyroidism are associated with endothelial dysfunction. Iodine deficiency is a risk factor for subclinical hypothyroidism in pregnancy. However, there is a paucity of data on the relationship between iodine nutrition state in pregnancy, the degree of endothelial dysfunction, and the risk of preeclampsia.MethodsNinety-five normotensive pregnant women, 50 women with preeclampsia with no severe features, and 50 women with severe preeclampsia were enrolled into the current study from the maternity units of Nelson Mandela Academic Hospital and Mthatha Regional Hospitals in Eastern Cape Province, South Africa. Urinary iodine concentration (UIC), serum markers of thyroid function, aortic augmentation index, and pulse wave velocity (PWV) were compared.ResultsMedian UIC was 167.5, 127.7, and 88.5 µg/L, respectively for normotensive pregnant women, those with preeclampsia and severe preeclampsia (p = .150). Participants with severe preeclampsia had significantly higher median thyroid-stimulating hormone (TSH) and oxidized LDL than normotensive and preeclamptic women without severe features (respectively 3.0, 2.3, and 2.3 IU/L; 1.2, 1.0, and 1.0 IU/L, p < .05). The median Aortic augmentation index was 7.5, 19.0, and 21.0 (p < .001), and the pulse wave velocity 5.1, 5.7, and 6.3, respectively for normotensive, preeclampsia, and severe preeclampsia participants (both p < .001). In linear regressions, TSH, age, and hypertensive disease were independent predictors of elevated PWV.ConclusionUpper normal-range TSH levels in women with severe preeclampsia were associated with markers of endothelial dysfunction. The low UIC and trend towards the elevation of thyroglobulin suggest that inadequate iodine intake may have increased TSH levels and indirectly caused endothelial dysfunction.     

5项心肌标志物联合检测对先兆子痫心肌损伤的诊断价值研究

目的探讨超敏肌钙蛋白-T(hs-cTnT)、人心型脂肪酸结合蛋白(H-FABP)、B型尿钠肽(BNP)、缺血修饰清蛋白(IMA)和肌酸激酶同工酶(CK-MB)对先兆子痫心肌损伤的诊断价值。方法正常妊娠50例纳入妊娠组,诊断为先兆子痫167例为先兆子痫组,分为心肌损伤组42例和无心肌损伤组125例。另选择50例健康非妊娠女性为对照组。采用ELISA一步法测定血清中H-FABP,微粒子化学发光免疫法检测hs-cTnT和BNP,清蛋白-钴结合试验测定IMA,以及免疫抑制法测定CK-MB。结果先兆子痫组中心肌损伤组的CK-MB、H-FABP、IMA、hs-cTnT和BNP水平明显高于对照组、妊娠组和无心肌损伤组,差异有统计学意义[(t=8.521、7.489、7.256;7.561、6.897、6.235;12.314、9.236、10.251;13.657、11.023、12.031;11.301、10.364、15.567),(P=0.008,0.030,0.035;0.027,0.031,0.033;0.002,0.005,0.003;0.002,0.004,0.003;0.003,0.004,0.001)]。先兆子痫组中无心肌损伤组的CK-MB和hs-cTnT与对照组、妊娠组比较,差异无统计学意义[(t=1.678、1.401;1.887、1.784),(P=0.339、0.401;0.289、0.398)]。无心肌损伤组和妊娠组的IMA、H-FABP和BNP明显高于对照组[(t=4.784、4.021;3.894、3.784;5.801、5.215),(P=0.024、0.032;0.037、0.041;0.021、0.029)]。无心肌损伤组的IMA、H-FABP和BNP与妊娠组比较,差异无统计学意义[(t=1.325、1.257、1.241);(P=0.451、0.329、0.378)]。5项标志物联合检测灵敏度明显高于单个标志物(χ2=3.021、3.561、4.215、4.496、5.249;P=0.027、0.024、0.019、0.015、0.009)。结论采用心肌标志物判断孕妇心肌损伤时,应考虑到妊娠这一特殊的生理周期,5项心肌标志物联合检测,有利于早期诊断先兆子痫的缺血性心肌损伤。     

妊娠期体质量、血清瘦素、脂联素水平与胰岛素抵抗的关系

目的了解妊娠妇女的体质量、血清瘦素、脂联素与胰岛素抵抗之间的关联度。方法通过检测孕妇妊娠早期、中期、晚期血清脂联素(APN),瘦素(LP)、空腹血糖(FINS),同时测量身高,体质量,计算体质指数(BMI)、孕期体质量增加值和胰岛素抵抗指数(HOMA-IR),来探讨孕前体质量、孕期体质量增长与孕妇糖代谢间的关系。结果胰岛素抵抗与孕周无显著性相关,与孕期BMI、血清瘦素以及脂联素水平呈正相关。结论糖尿病对母婴的危害较大,对孕妇的管理和围产期监护,饮食控制治疗尤为重要,要注意补充脂联素充沛的食物,减少可能导致肥胖的食物摄入,才能有效的降低糖尿病的发生率。     

早发型重度子痫前期母血中抗磷脂抗体及血栓前状态变化的研究

目的：研究重度子痫前期患者母血的抗磷脂抗体及血栓前状态等标志物变化,寻找敏感、有效的指标预测早发型重度子痫前期的发生。方法收集需住院分娩的重度子痫前期的孕妇共70例,早发型重度子痫前期患者32例;晚发型重度子痫前期患者38例。同时随机选取30例同期入院的正常孕妇为对照组。所有的孕妇均为单胎妊娠,排除慢性高血压及慢性肾病。住院时检测：血常规、血脂、肾功能、肝功能、糖耐量、24 h尿蛋白定量;凝血四项、栓溶二聚体（D-Dimer）、抗凝血酶Ⅲ（AT-Ⅲ）等血栓前状态分子标志物;抗心磷脂抗体（ACA）-IgM、IgG及抗β2-GPI抗体定量等生化指标。结果早发型重度子痫前期抗磷脂抗体阳性率及ACA-IgM的滴度值明显高于晚发型重度子痫前期及正常对照组,差异有统计学意义（P＜0.05）,晚发型重度子痫前期抗磷脂抗体阳性率高于正常对照组,差异无统计学意义（P＞0.05）;早发型和晚发型重度子痫前期的血栓前状态比正常妊娠组更为严重,差异有统计学意义（P＜0.05）,但早发型和晚发型重度子痫前期的血栓前状态比较差异无统计性意义（P＞0.05）;抗磷脂抗体定量与血栓前状态的严重程度不存在明显相关性。结论对有高危因素的孕妇可通过检测血栓前状态的变化预测重度子痫前期的发病,进一步可通过抗磷脂抗体阳性率及ACA-IgM的滴度值鉴别早发型和晚发型重度子痫前期。     

Urinary tract infection during pregnancy affects the level of leptin,ghrelin and insulin in maternal and placental blood

Abstract

Aim. We examined ghrelin, leptin and insulin in maternal blood during normal pregnancy and pregnancy complicated by urinary tract infection (UTI), as well as in cord blood at labor. Methods. A total of 36 delivering women with history of UTI during the third trimester of pregnancy were enrolled in the study; 12 healthy pregnant women served as a control. Infection markers (CRP and procalcitonin) were determined in maternal blood during the course of UTI and at labor. Ghrelin, leptin and insulin were determined during labor in venous maternal and in umbilical cord blood. Results. We found negative correlation between infection markers in maternal blood during UTI, and level of tested hormones in cord blood, indicating potential risk of placental impairment due to energetic imbalance. We noted lower level of leptin in mothers with UTI and no change in leptin from umbilical blood comparing subjects with and without UTI. Low level of ghrelin was observed in maternal and cord blood when pregnancy was complicated by UTI. Insulin concentrations were high in mothers with UTI and low in their newborn's cord blood. Increased maternal insulin level could indicate peripheral insulin resistance caused by the infection. Conclusion. UTI during pregnancy affects the concentration of hormones responsible for regulating energetic homeostasis within the placenta.     

孕早期脂代谢异常对妊娠期糖尿病发病率的影响

[目的]孕早期脂代谢异常对妊娠期糖尿病(GDM)发病率的影响.[方法]选取120例孕早期脂代谢异常的孕妇为观察组,另选120例孕早期脂代谢正常的孕妇为对照组.检测两组血清脂代谢指标:胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)以及脂肪细胞因子:瘦素、游离脂肪酸;血糖及胰岛素抵抗指标:空腹血糖(FBG)、糖化血红蛋白(HbAlc)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)水平.分析TG、瘦素与血糖及胰岛素抵抗指标的相关性,并统计两组GDM发生率、妊娠结局、胎儿及相关并发症发生情况.[结果]观察组孕妇TG、TC、LDL-C、瘦素、游离脂肪酸水平明显高于对照组,HDL-C水平明显低于对照组(P<0.05);观察组血糖指标FBG、HbAlc、HOMA-IR高于对照组,胰岛素抵抗指标FINS低于对照组(P<0.05).单因素相关分析显示TG、瘦素水平均与FBG、HbAlc、HOMA-IR呈正相关,与FINS呈负相关(P<0.05).观察组GDM发生率为35.00%,显著高于对照组16.67%(P<0.05);与对照组相比,观察组剖宫产率明显增高(P<0.05),观察组分娩后胎儿窘迫、巨大儿发生率明显增高(P<0.05).     

Pregnancy-induced hypertension and preeclampsia: levels of angiogenic factors in malaysian women

Preeclampsia (PE) is a major contributor to maternal and fetal mortality. The cause of preeclampsia remains unclear, but oxidative stress on the endothelium leading to endothelial dysfunction is said to be the root cause of the disease. The aim of this study was to measure and determine the plasma levels of key angiogenic factors in pregnancy as an indicator for the early onset of preeclampsia in pregnancy. Plasma levels of circulating a soluble fms like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), both pro-angiogenic factors were analyzed in normal pregnant Malaysian women (control group, n = 34), women with pregnant induced hypertension (PIH, n = 34) and women with preeclampsia (PE, n = 34) all at three gestational ages, 24–28 weeks (early pregnancy: EP), 32–36 weeks (late pregnancy: LP) and 6 weeks after delivery (postpartum: PN). The plasma levels of angiogenic factors were determined by ELISA. sFlt-1 levels were elevated in PIH and PE patients as compared to controls. PIGF and VEGF were significantly decreased in PIH and PE as compared to the controls. These results suggest that elevated concentration of sFlt-1 and suppressed levels of PIGF and VEGF may contribute to the development of hypertension in pregnancy which precedes preeclampsia.     

Linking preeclampsia and cardiovascular disease later in life

Preeclampsia (PE), which is defined as new onset hypertension after 20 weeks of pregnancy accompanied by proteinuria, is characterized by inadequate placentation, oxidative stress, inflammation and widespread endothelial dysfunction. A link between PE and long-term risk of cardiovascular disease (CVD) was suggested by retrospective studies, which found that PE was associated with a 2–3-fold risk of CVD later in life, with a 5–7-fold risk in the case of severe and/or early-onset PE. Recently, meta-analyses and prospective studies have confirmed the association between PE and the emergence of an unfavorable CVD risk profile, in particular a 3–5-fold increased prevalence of the metabolic syndrome only 8 years after the index pregnancy. PE and CVD share many risk factors, including obesity, hypertension, dyslipidemia, hypercoagulability, insulin resistance and both entities are characterized by endothelial dysfunction. PE and CVD are complex traits sharing common risk factors and pathophysiological processes, but the genetic link between both remains to be elucidated. However, recent evidence suggests that genetic determinants associated with the metabolic syndrome, inflammation and subsequent endothelial dysfunction are involved. As the evidence now supports that PE represents a risk factor for the emergence of the metabolic syndrome and CVD later in life, the importance of long-term follow-up assessment of CVD risk beginning early in women with a history of PE must be considered and translated into new preventive measures.     

Effect of homocysteine concentration in early pregnancy on gestational hypertensive disorders and other pregnancy outcomes

BACKGROUND: Increased total homocysteine (tHcy) may be associated with placental-mediated adverse pregnancy outcomes, but few prospective studies have measured tHcy before pregnancy outcome. This study was undertaken to determine whether increased tHcy measured in early pregnancy is associated with pregnancy loss, gestational hypertension (GH), preeclampsia, or small for gestational age (SGA) infants. METHODS: We conducted a prospective cohort study between 2002 and 2005. We measured tHcy and serum folate in blood samples from pregnant women (<20 weeks' gestation) and collected detailed pregnancy information through a questionnaire and medical record review. RESULTS: Of the 2119 women included in the study, 103 had a pregnancy loss, 115 had gestational hypertension, 65 had preeclampsia, and 129 had an SGA infant. Subjects with increased tHcy concentrations were at increased risk of pregnancy loss [relative risk (RR) 2.1, 95% CI 1.2-3.6] or preeclampsia (RR 2.7, 95% CI 1.4-5.0) than subjects with lower tHcy concentrations, but increased tHcy concentration was not associated with increased risk of developing GH or having an SGA infant. CONCLUSION: The finding of high tHcy in early pregnancy as a risk factor for pregnancy loss and preeclampsia is consistent with a hypothesis that increased tHcy results in abnormalities of the placental vasculature.     

Are nutrition-induced epigenetic changes the link between socioeconomic pathology and cardiovascular diseases?

The prevalence of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM 2) is decreasing in developed countries despite the increase in the percentage of subjects with obesity and other well-recognized cardiovascular risk factors. In contrast, the recent transition of the economic model experienced by developing countries, characterized by the adoption of a Western lifestyle, that we have named "socioeconomic pathology," has led to an increase in the burden of CVD. It has been demonstrated that conventional cardiovascular risk factors in developed and developing countries are the same. Why then does the population of developing countries currently have a higher incidence of CVD than that of developed countries if they share the same risk factors? We have proposed the existence of a higher susceptibility to the development of systemic inflammation at low levels of abdominal obesity in the population of developing countries and the consequent endothelial dysfunction, insulin resistance, DM 2, and CVD. In contrast, an important percentage of obese people living in developed countries have a healthy phenotype and low risk of developing CVD and DM 2. Human epidemiologic studies and experimental dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances early in life may later have a persistent effect on an adult's health that may even be transmitted to the next generations. Epigenetic changes dependent on nutrition could be key in this evolutionary health behavior, acting as a buffering system, permitting the adaptation to environmental conditions by silencing or increasing the expression of certain genes.     

Low-Dose Aspirin for the Prevention of Preeclampsia

Preeclampsia is a hypertensive disorder specific to pregnancy that remains a significant cause of maternal and neonatal morbidity and mortality. Identification of women who are most at risk for preeclampsia is imprecise. Because of the potential negative health consequences of preeclampsia for women and newborns and the lack of effective screening mechanisms preventing preeclampsia is an important component of prenatal care. Researchers have documented that low-dose aspirin, taken daily after the first trimester, can decrease the development of preeclampsia and reduce the incidence of preterm birth and birth of small-for-gestational-age infants. This column includes an overview of low-dose aspirin in pregnancy and a review of current recommendations from leading national organizations.     

Insulin resistance and preeclampsia in gestational diabetes mellitus

OBJECTIVE: To compare the degree of insulin resistance in women with gestational diabetes mellitus (GDM) who do and do not develop preeclampsia. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and glucose clamp studies in the early third trimester (n = 150) and 15 months postpartum (n = 89). After delivery, the women were categorized as nonpreeclamptic or preeclamptic (systolic blood pressure [SBP] > or = 140 mmHg, diastolic blood pressure [DBP] > or = 90 mmHg, and at least >1+ proteinuria or >300 mg/24 h). Metabolic parameters between the groups were compared by chi2 or Fisher's exact tests and ANOVA with P < 0.05 as significant. RESULTS: A total of 29 women (19%) developed preeclampsia, which was mild in 21 and severe in 8 women. At entry, there were no differences in age, weight indexes, and glycemic measures between the nonpreeclamptic and preeclamptic groups. Those with preeclampsia were significantly taller (61.5 +/- 2.4 vs. 60.1 +/- 2.3 in, P = 0.003), were more often nulliparous (38 vs. 16%, P = 0.01), and had higher entry SBP (112 +/- 10 vs. 103 +/- 6.9 mmHg, P < 0.0001) and DBP (64 +/- 9 vs. 59 +/- 5 mmHg, P = 0.002). No significant differences between the groups were found in any measures of the OGTT glucose levels, insulin sensitivity index, glucose effectiveness, acute response to glucose, or disposition index, nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose, insulin, free fatty acid, hepatic glucose output, peripheral glucose clearance, C-peptide, or glucagon. At 15 months postpartum, blood pressure levels remained significantly higher in the preeclamptic group (n = 19) compared with the nonpreeclamptic group (n = 70). No differences in any glycemic or insulin resistance measures were found. CONCLUSIONS: Women with GDM were uniformly insulin resistant. Those who developed preeclampsia, when compared with those who remained nonpreeclamptic, were not more insulin resistant in either the third trimester or 15 months postpartum. However, women who developed preeclampsia had blood pressure levels that were significantly higher, although still in the normal range, than those of women who remained nonpreeclamptic.     

Hepatic insulin resistance,metabolic syndrome and cardiovascular disease

BackgroundThe metabolic syndrome is a constellation of common metabolic disorders that is associated with cardiovascular disease. Insulin resistance has a central role in the pathophysiology of metabolic syndrome.Recent advancesIt is now commonly accepted that chronic inflammation associated with visceral obesity induces insulin resistance in the liver. Chronic inflammation is characterized by the production of abnormal adipokines and cytokines such as TNF-α, FFA, IL-1, IL-6, leptin and resistin. These factors inhibit insulin signalling in hepatocytes by activating SOCS proteins, several kinases such as JNK, IKK-β and PKC and protein tyrosine phosphatases such as PTP1B and PTEN, that in turn impair insulin signalling at insulin receptor and insulin receptor substrate (IRS) level. Hepatic insulin resistance in turn causes impaired suppression of glucose production by insulin in hepatocytes leading to hyperglycemia. An important and early complication of hepatic insulin resistance is the induction of hepatic VLDL production, via changes in the rate of apoB synthesis and degradation and de novo lipogenesis, or increased FFA flux from adipose tissue into the liver. Insulin resistance also stimulates the production of CRP and PAI-1, both markers of an inflammatory state. All metabolic abnormalities related to hepatic insulin resistance have been shown to directly or indirectly promote atherosclerosis. Hyperglycemia induces a series of alterations including endothelial dysfunction, cellular proliferation, changes in extracellular matrix conformation and impairment of LDL receptor-mediated uptake decreasing the in vivo clearance of LDL. Small dense LDLs associated with high circulating VLDL have higher affinity to the intimal proteoglycans leading to the penetration of more LDL particles into the arterial wall. CRP can also accelerate atherosclerosis by increasing the expression of PAI-1 and adhesion molecules in endothelial cells, inhibition of nitric oxide formation and increasing LDL uptake into macrophages.ConclusionsOverall, growing evidence suggests that hepatic insulin resistance is sufficient to induce several components of the metabolic syndrome and promote progression to cardiovascular disease. Many unresolved questions remain however on the molecular and cellular mechanisms that trigger hepatic insulin resistance and promote the development of clinical metabolic syndrome.     

Diagnosis and management of uncomplicated urinary tract infections

Most uncomplicated urinary tract infections occur in women who are sexually active, with far fewer cases occurring in older women, those who are pregnant, and in men. Although the incidence of urinary tract infection has not changed substantially over the last 10 years, the diagnostic criteria, bacterial resistance patterns, and recommended treatment have changed. Escherichia coli is the leading cause of urinary tract infections, followed by Staphylococcus saprophyticus. Trimethoprim-sulfamethoxazole has been the standard therapy for urinary tract infection; however, E. coli is becoming increasingly resistant to medications. Many experts support using ciprofloxacin as an alternative and, in some cases, as the preferred first-line agent. However, others caution that widespread use of ciprofloxacin will promote increased resistance.     

Vascular biology of preeclampsia

Summary.  Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.