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Role of Adipokines and Other Inflammatory Mediators in Gestational Diabetes Mellitus and Previous Gestational Diabetes Mellitus  [PDF]
Nikolaos Vrachnis,Panagiotis Belitsos,Stavros Sifakis,Konstantinos Dafopoulos,Charalambos Siristatidis,Kalliopi I. Pappa,Zoe Iliodromiti
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/549748
Abstract: Previous Gestational Diabetes Mellitus (pGDM) is a common condition and has been associated with future development of Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS) in women affected. The pathogenesis and risk factors implicated in the development of these conditions later in the lives of women with pGDM are not as yet fully understood. Research has recently focused on a group of substances produced mainly by adipose tissue called adipokines, this group including, among others, adiponectin, leptin, Retinol-Binding Protein-4 (RBP-4), and resistin. These substances as well as other inflammatory mediators (CRP, IL-6, PAI-1, TNF-α) seem to play an important role in glucose tolerance and insulin sensitivity dysregulation in women with pGDM. We summarize the data available on the role of these molecules. 1. Introduction Pregnancy is a progressively hyperglycemic period of life, accompanied by increasing insulin resistance as from mid-gestation, with the hyperglycemia serving a highly important role in the nutrition and development of the fetus by providing it with adequate levels of glucose [1]. Gestational Diabetes Mellitus is a common pathologic state that increases the incidence of complications in both the mother and the fetus [2]. Furthermore, GDM and gestational dysregulation of blood glucose levels expose the women affected to higher risk for subsequent development of type 2 diabetes mellitus and cardiovascular disease later in their lives [3–5], the risk being proportional to the degree of the dysregulation. Glucose tolerance and metabolism as well as insulin resistance are altered in Type II Diabetes Mellitus (T2DM), Gestational Diabetes Mellitus (GDM), and the postpartum period of a pregnancy complicated by pGDM. T2DM and pGDM have the same predisposing factors, namely, high body mass index before pregnancy, elevated levels of fasting glucose, and a degree of hyperglycemia in pregnancy, these leading to dysglycemia 1 to 4 months after delivery and recurrent gestational diabetes mellitus [6–26]. Although the pathophysiologic mechanisms responsible for these changes are not as yet completely understood, growing insight into the processes involved has been gained over the last few years. There are two main pathways leading to GDM, T2DM, and possibly pGDM: insulin resistance and chronic subclinical inflammation. Insulin resistance is caused by the inability of tissues to respond to insulin and the deficient secretion of insulin by pancreatic beta cells [27–29]. The deficient secretion cannot compensate for the pregnancy-induced insulin
F. Akhlaghi A. B. Hamedi
Acta Medica Iranica , 2005,
Abstract: Presence of maternal diabetes mellitus (DM) during pregnancy has important consequences for both mother and child. To determine maternal and fetal/neonatal complications of gestational DM and compare them with pre-gestational DM, a prospective study was performed in 100 diabetic women delivered in our hospital from January 2001 to April 2002. Pregnancy outcome in 27 women with gestational DM and 73 women with pre-gestational DM and their offspring were studied and analyzed. The mean age of women was 28 years, women with gestational DM being slightly older than women with pre-gestational DM. Mothers with gestational DM were at increased risk of presenting with pre-eclampsia and preterm labor compared to pre-gestational DM. Frequency of Cesarean section was higher in mothers with pre-gestational DM. Frequencies of abortion and hypoglycemic episodes were similar in gestational DM and pre-gestational DM. Infants born to mothers with pre-gestational DM were at increased risk of suffering from respiratory distress syndrome and congenital malformations but rates of unexplained intrauterine fetal death and large for gestational age were higher in infant of mothers with gestational DM. Gestational and pre-gestational DM are associated with increased risk of maternal and neonatal morbidity. Pregnant women with gestational and pre-gestational DM and their offsprings should be monitored and managed carefully.
N-terminal-pro-brain natriuretic peptide is decreased in insulin dependent gestational diabetes mellitus: a prospective cohort trial
Martin Andreas, Harald Zeisler, Ammon Handisurya, Maximilian B Franz, Michael Gottsauner-Wolf, Michael Wolzt, Alexandra Kautzky-Willer
Cardiovascular Diabetology , 2011, DOI: 10.1186/1475-2840-10-28
Abstract: We have measured NT-proBNP in 223 otherwise healthy women between gestational week 24 and 32 referred to the outpatient diabetes unit in a cross-sectional study.88 control subjects, 45 patients with indication for medical nutrition therapy (MNT) alone and 90 patients who required insulin therapy were included. Groups of women were comparable regarding gestational week. Body mass index before pregnancy and at blood draw was significantly higher in subjects with insulin dependent gestational diabetes mellitus compared to MNT controlled gestational diabetes mellitus. NT-proBNP was significantly lower in patients with insulin dependent gestational diabetes mellitus (35 ± 25 pg/ml) compared to controls (53 ± 43 pg/ml, p = 0.012).NT-proBNP is within the reference range of normal subjects in women with gestational diabetes mellitus. Differences in body mass index, changes in glomerular filtration rate and haemodynamics may explain lower NT-proBNP concentrations in insulin dependent gestational diabetes mellitus. A false negative interpretation needs to be considered in these women.Women with gestational diabetes mellitus (GDM) are at risk to develop preeclampsia and other complications during pregnancy[1-3]. Previously, it has been reported that NT-proBNP is elevated in gestational hypertension and preeclampsia[4], but no data exist in GDM patients.Amino-terminal pro B-type natriuretic peptide (NT-proBNP) is co-secreted with B-type natriuretic peptide (BNP) from the cardiac ventricle. It is increased in response to ventricular volume expansion and pressure overload[5,6]. The cardiovascular action of BNP includes vasodilation, diuresis, inhibition of renin and aldosterone production and reduction of cardiac and vascular growth[7,8]. Beside these direct pharmacological effects, BNP is also used as a biomarker in patients with heart failure to assess systolic ventricular dysfunction[9].Although NT-proBNP reference values are well established in a healthy population, co-morbid
Gestational Diabetes Mellitus: a review of the diagnosis, clinical implications and management  [cached]
Vincent Wing-Ming Wong
Reviews in Health Care , 2013, DOI: 10.7175/rhc.48142127-139
Abstract: Gestational diabetes mellitus (GDM) is a condition that affects the wellbeing of mother and fetus. Women with GDM are at risk of type 2 diabetes mellitus in the future, while fetal exposure to hyperglycaemia in-utero may affect their glycometabolic profile later in life. Appropriate screening and management of this problem is important in ensuring good pregnancy outcomes. In this review, the clinical implications, the various ways to screen and diagnose GDM, and management strategies during pregnancy will be discussed. For years, insulin is the mainstay of treatment if medical nutrition therapy fails to maintain adequate glycaemic control, but use of other oral pharmacotherapy may gain greater acceptance in the future. Following delivery, ongoing follow-up of these women is worthwhile as early intervention through lifestyle or pharmacotherapy may prevent the development of diabetes.
Inherited destiny? Genetics and gestational diabetes mellitus
Richard M Watanabe
Genome Medicine , 2011, DOI: 10.1186/gm232
Abstract: Gestational diabetes mellitus (GDM) refers to hyperglycemia that first presents during pregnancy and typically resolves itself post-partum. There are inadequate data on the prevalence of GDM; however, in 1988 it was estimated that about 4% of pregnancies in the United States were complicated by diabetes, with 88% of these accounted for by GDM [1]. More recent data suggest that, as with the overall increased prevalence of diabetes, rates of GDM are significantly increasing [2]. For example, Dabelea and colleagues [3] examined trends in singleton pregnancies from the Kaiser Permanente health maintenance organization of Colorado between 1994 and 2002 and noted that rates of GDM increased two-fold in all ethnic groups. Accurate data on the prevalence and incidence of GDM are likely to become available given that screening during pregnancy is almost routine and consistent diagnostic criteria are now being implemented [4].Hyperglycemia during pregnancy, whether due to GDM or other forms of diabetes, has implications for mother, developing fetus, and child. Women diagnosed with GDM have a higher risk for future type 2 diabetes mellitus (T2DM) [5]. Kjos et al. [6] were the first to demonstrate that this risk was even higher in Hispanic women with previous GDM by showing that 45% of a cohort followed for 5 years post-partum developed T2DM despite plasma glucose returning to non-diabetic levels. The observation that previous GDM increases risk for future T2DM was subsequently confirmed in other ethnic groups [7]. Women with GDM have a higher rate of caesarean section, gestational hypertension, and large for gestational age deliveries [8]. Maternal diabetes has been shown to be associated with increased risk for macrosomia [8,9], and GDM-associated macrosomia is associated with increased rates of a variety of complications, including hypoglycemia and respiratory distress syndrome [10].Pettitt et al. [11] were among the first to show the association between maternal hyperglycem
Gestational Diabetes Mellitus: A Positive Predictor of Type 2 Diabetes?  [PDF]
Gregory E. Rice,Sebastian E. Illanes,Murray D. Mitchell
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/721653
Abstract: The aim of this paper is to consider the relative benefits of screening for type two diabetes mellitus in women with a previous pregnancy complicated by gestational diabetes mellitus. Recent studies suggest that women who experience GDM are at a greater risk of developing type 2 diabetes within 10–20 years of their index pregnancy. If considered as a stand-alone indicator of the risk of developing type 2 diabetes, GDM is a poor diagnostic test. Most women do not develop GDM during pregnancy and of those that do most do not develop type 2 diabetes. There is, however, a clear need for better early detection of predisposition to disease and/or disease onset to significantly impact on this global pandemic. The putative benefits of multivariate approaches and first trimester and preconception screening to increase the sensitivity of risk assignment modalities for type 2 diabetes are proposed. 1. Introduction The keystone to improving disease management and health outcomes remains the early and accurate diagnosis of the predisposition to, or onset of, disease. Early detection of disease risk and onset is the first step in implementing efficacious treatment and improving patient outcomes. In the context of screening for prediabetic and diabetic conditions in asymptomatic individuals, early detection may allow the implementation of dietary, lifestyle, and/or pharmacologic interventions that limit or prevent the development of disease-specific pathophysiologies. The rationale for seeking to develop predictive tests for diabetes and other metabolic disorders, thus, is clearly evident. Recent studies suggest that women who experience gestational diabetes mellitus (GDM) are at a greater risk of developing type 2 diabetes mellitus (type 2 diabetes) within 10–20 years of their index pregnancy [1]. Monitoring glycemic control and intervention strategies to delay or prevent disease onset have been advocated in such women. Type 2 diabetes, however, is a disease of heterogeneous aetiology and GDM is but one risk factor. If considered as a stand-alone indicator of the risk of developing type 2 diabetes, GDM is a poor diagnostic test. Most women do not develop GDM during pregnancy and of those that do most do not develop type 2 diabetes. Postpartum monitoring of women who developed GDM during pregnancy, nevertheless, may be of clinical utility in this higher risk cohort. There is, however, a clear need for better early detection of predisposition to disease and/or disease onset to significantly impact on this global pandemic. For women (and their partners), pregnancy
Previous Gestational Diabetes Mellitus and Markers of Cardiovascular Risk  [PDF]
Nikolaos Vrachnis,Areti Augoulea,Zoe Iliodromiti,Irene Lambrinoudaki,Stavros Sifakis,George Creatsas
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/458610
Abstract: The prevalence of gestational diabetes mellitus (GDM) in the developed world has increased at an alarming rate over the last few decades. GDM has been shown to be associated with postpartum diabetes, insulin resistance, hypertension, and dyslipidemia. A history of previous GDM (pGDM), associated or not with any of these metabolic abnormalities, can increase the risk of developing not only type 2 diabetes mellitus but also cardiovascular disease (CVD) independent of a diagnosis of type 2 diabetes later in life. In this paper we discuss the relationship among inflammatory markers, metabolic abnormalities, and vascular dysfunction in women with pGDM. We also review the current knowledge on metabolic modifications occurring in normal pregnancy and the link between alterations of a normal metabolic state with the long-term maternal complications that may result in increased CVD risk. Our review of studies on pGDM prompts us to recommend that these women be considered a population at risk for later CVD events, which however could be avoided via the use of specially designed follow-up programs in the future. 1. Introduction Gestational diabetes mellitus (GDM) is any degree of glucose intolerance with onset or first recognition during pregnancy [1, 2]. In early gestation fasting blood glucose is lower and insulin sensitivity decreases slightly. This is followed by progressively increasing insulin resistance in the second and third trimesters with a borderline increase of insulin production or hyperinsulinemia. Furthermore, insulin resistance occurs as a result of placental hormones that antagonize insulin, estrogen, progesterone, human placental lactogen (HPL), human placental growth hormone, cortisol, prolactin, and tumor necrosis factor-alpha (TNF-α) [3]. The above different pathophysiologic mechanisms accompanying pregnancy result in metabolic changes that allow for higher postprandial maternal glucose. Pregnancy is a hyperinsulinemic state which may develop into impaired glucose tolerance if insulin secretion is unable to compensate for pregnancy-associated insulin resistance [3–5]. The condition of GDM is a state of chronic low-grade subclinical inflammation characterized by abnormal production of cytokine and mediators and activation of a network of inflammatory signaling pathways. Although the characteristic of GDM is insulin resistance, the exact mechanism involved in this process is still unknown. The increased insulin resistance during pregnancy has been, as just described, attributed to cortisol and gestational hormones, but more recent data have
Non classical risk factors for gestational diabetes mellitus: a systematic review of the literature
Dode, Maria Alice Souza de Oliveira;Santos, Iná S. dos;
Cadernos de Saúde Pública , 2009, DOI: 10.1590/S0102-311X2009001500002
Abstract: age, obesity and family history of diabetes are well known risk factors for gestational diabetes mellitus. others are more controversial. the objective of this review is to find evidence in the literature that justifies the inclusion of these other conditions among risk factors. the medline, cochrane, lilacs and pan american health organization databases were searched, covering articles dating from between 1992 and 2006. keywords were used in combination (and) with gestational diabetes mellitus separately and with each one of the risk factors studied. the methodological quality of the studies included was assessed, resulting in the selection of 41 papers. most studies investigating maternal history of low birth weight, low stature, and low level of physical activity have found positive associations with gestational diabetes mellitus. low socioeconomic levels, smoking during pregnancy, high parity, belonging to minority groups, and excessive weight gain during pregnancy presented conflicting results. publication bias cannot be ruled out. standardization of techniques, cutoff points for screening and diagnosis, as well as studies involving larger sample sizes would allow future meta-analyses.
Urinary incontinence and vaginal squeeze pressure two years post-cesarean delivery in primiparous women with previous gestational diabetes mellitus
Barbosa, Angélica Mércia Pascon;Dias, Adriano;Marini, Gabriela;Calderon, Iracema Mattos Paranhos;Witkin, Steven;Rudge, Marilza Vieira Cunha;
Clinics , 2011, DOI: 10.1590/S1807-59322011000800006
Abstract: objective: to assess the prevalence of urinary incontinence and associated vaginal squeeze pressure in primiparous women with and without previous gestational diabetes mellitus two years post-cesarean delivery. methods: primiparous women who delivered by cesarean two years previously were interviewed about the delivery and the occurrence of incontinence. incontinence was reported by the women and vaginal pressure evaluated by a perina perineometer. sixty-three women with gestational diabetes and 98 women without the disease were screened for incontinence and vaginal pressure. multiple logistic regression models were used to evaluate the independent effects of gestational diabetes. results: the prevalence of gestational incontinence was higher among women with gestational diabetes during their pregnancies (50.8% vs. 31.6%) and two years after a cesarean (44.8% vs. 18.4%). decreased vaginal pressure was also significantly higher among women with gestational diabetes (53.9% vs. 37.8%). maternal weight gain and newborn weight were risk factors for decreased vaginal pressure. maternal age, gestational incontinence and decreased vaginal pressure were risk factors for incontinence two years after a cesarean. in a multivariate logistic model, gestational diabetes was an independent risk factor for gestational incontinence. conclusions: the prevalence of incontinence and decreased vaginal pressure two years post-cesarean were elevated among women with gestational diabetes compared to women who were normoglycemic during pregnancy. we confirmed an association between gestational diabetes mellitus and a subsequent decrease of vaginal pressure two years post-cesarean. these results may warrant more comprehensive prospective and translational studies.
Gestational Diabetes Mellitus: New Diagnostic Criteria  [PDF]
Letícia Nascimento Medeiros Bortolon, Luciana de Paula Le?o Triz, Bruna de Souza Faustino, Larissa Bianca Cunha de Sá, Denise Rosso Tenório Wanderley Rocha, Alberto Krayyem Arbex
Open Journal of Endocrine and Metabolic Diseases (OJEMD) , 2016, DOI: 10.4236/ojemd.2016.61003
Abstract: Gestational mellitus diabetes (GDM) is a highly prevalent metabolic disorder among pregnant women nowadays. It is defined as any level of glucose intolerance, appearing or first being recognized during pregnancy. It is essential to diagnose and treat GDM early, in order to reduce or avoid complications for mother and fetus. Recently, new guidelines have changed the diagnosis criteria, and it is expected that the prevalence of GDM will increase by approximately 18%. A relevant goal of these new definitions is to provide a better care for pregnant women, in an attempt to reduce fetal and maternal complications. These new criteria will also increase the impact on costs of the health care system. Treatment must be individualized for best results, including a specific diet, physical activity and the use of medications. Metformin and Insulin use are analyzed in detail, in face of new evidences regarding their safety and efficacy during pregnancy.
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