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Adipokines underlie the early origins of obesity and associated metabolic comorbidities in the offspring of women with pregestational obesity.
Arroyo-Jousse, V, Jaramillo, A, Castaño-Moreno, E, Lépez, M, Carrasco-Negüe, K, Casanello, P
Biochimica et biophysica acta. Molecular basis of disease. 2020;(2):165558
Abstract
Maternal pregestational obesity is a well-known risk factor for offspring obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes. The mechanisms by which maternal obesity can induce alterations in fetal and later neonatal metabolism are not fully elucidated due to its complexity and multifactorial causes. Two adipokines, leptin and adiponectin, are involved in fetal and postnatal growth trajectories, and both are altered in women with pregestational obesity. The placenta synthesizes leptin, which goes mainly to the maternal circulation and in lesser amount to the developing fetus. Maternal pregestational obesity and hyperleptinemia are associated with placental dysfunction and changes in nutrient transporters which directly affect fetal growth and development. By the other side, the embryo can produce its own leptin from early in development, which is associated to fetal weight and adiposity. Adiponectin, an insulin-sensitizing adipokine, is downregulated in maternal obesity. High molecular weight (HMW) adiponectin is the most abundant form and with most biological actions. In maternal obesity lower total and HMW adiponectin levels have been described in the mother, paralleled with high levels in the umbilical cord. Several studies have found that cord blood adiponectin levels are related with postnatal growth trajectories, and it has been suggested that low adiponectin levels in women with pregestational obesity enhance placental insulin sensitivity and activation of placental amino acid transport systems, supporting fetal overgrowth. The possible mechanisms by which maternal pregestational obesity, focusing in the actions of leptin and adiponectin, affects the fetal development and postnatal growth trajectories in their offspring are discussed.
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Glycemic profile assessment during betamethasone administration in women with gestational diabetes mellitus.
Kakoulidis, I, Ilias, I, Linardi, A, Milionis, C, Michou, A, Koukkou, E
Diabetes & metabolic syndrome. 2019;(1):214-215
Abstract
AIM: Betamethasone's effect on glucose homeostasis in the presence of gestational diabetes has not been adequately investigated. MATERIALS-METHODS We assessed the glycemic profile of 99 women with gestational diabetes (52 on insulin, 47 on medical nutrition therapy) who were given betamethasone during hospitalization for at risk pregnancies. RESULTS In insulin-treated women the increase in total daily insulin dose significantly linked to betamethasone dose (p = 0.014). In women on diet, the need for insulin was positively related to betamethasone dose, age and gestational age >34th week (all p < 0.05). CONCLUSION Parsimonious betamethasone use might still be beneficial with a milder effect on glycemia.
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High risk of metabolic syndrome after delivery in pregnancies complicated by gestational diabetes.
Shen, Y, Li, W, Leng, J, Zhang, S, Liu, H, Li, W, Wang, L, Tian, H, Chen, J, Qi, L, et al
Diabetes research and clinical practice. 2019;:219-226
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Abstract
AIMS: To investigate the risk of postpartum metabolic syndrome in women with GDM compared with those without GDM in a Chinese population. METHODS Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM. Multivariate logistic regression was used to assess risks of postpartum metabolic syndrome between women with and without GDM. Postpartum metabolic syndrome was diagnosed by two commonly used criteria. RESULTS During a mean 3.53 years of follow up, 256 cases of metabolic syndrome were identified by using the NCEP ATPIII criteria and 244 cases by using the IDF criteria. Multivariable-adjusted odds ratios of metabolic syndrome in women with GDM compared with those without GDM were 3.66 (95% confidence interval [CI] 2.02-6.63) for NCEP ATPIII criteria and 3.90 (95% CI 2.13-7.14) for IDF criteria. Women with GDM had higher multivariable-adjusted odds ratios of central obesity, hypertriglyceridemia, and high blood pressure than women without GDM. The multivariable-adjusted odds ratios of low HDL cholesterol and hyperglycemia were not significant between women with and without GDM, however, the multivariable-adjusted odds ratio of hyperglycemia became significant when we used the modified criteria. CONCLUSIONS The present study indicated that women with prior GDM had significantly higher risks for postpartum metabolic syndrome, as well as its individual components.
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Family history of diabetes and the risk of gestational diabetes mellitus in Iran: A systematic review and meta-analysis.
Moosazadeh, M, Asemi, Z, Lankarani, KB, Tabrizi, R, Maharlouei, N, Naghibzadeh-Tahami, A, Yousefzadeh, G, Sadeghi, R, Khatibi, SR, Afshari, M, et al
Diabetes & metabolic syndrome. 2017;:S99-S104
Abstract
OBJECTIVE Gestational diabetes is the most prevalent metabolic disorder being firstly diagnosed during pregnancy. The relationship between the family history of diabetes and the gestational diabetes mellitus (GDM) has been investigated in several primary studies with a number of contradictions in the results. Hence, the purpose of the present study is to determine the relationship between the GDM and the family history of diabetes using the meta-analysis method. METHOD All published papers in main national and international databases were systematically searched with some specific keywords to find the related studies between 2000 and 2016. We calculated the odds ratio (OR) with 95% confidence interval (CI) in analysis for each study using a random-effect and Mantel-Haenzel method. We also determined heterogeneity among these 33 articles and their publication bias. RESULTS We entered 33 relevant studies of 2516 articles into the meta-analysis process including 2697 women with family history of diabetes mellitus as well as 29134 women without. Of them, 954 and 4372 subjects developed GDM respectively. Combining the results of the primary studies using the meta-analysis method, the overall odds ratio of family history for developing GDM was estimated as of 3.46 (95% CI: 2.80-4.27). CONCLUSION This meta-analysis study revealed that the family history of diabetes is an important risk factor for the gestational diabetes mellitus.
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Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus.
Phelan, S
American journal of perinatology. 2016;(13):1291-1299
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Abstract
Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early-life health complications and later disease. GDM recurrence is common, affecting 40 to 73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and prepregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify body weight. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of interpregnancy or prepregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy.
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Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.
Facchinetti, F, Bizzarri, M, Benvenga, S, D'Anna, R, Lanzone, A, Soulage, C, Di Renzo, GC, Hod, M, Cavalli, P, Chiu, TT, et al
European journal of obstetrics, gynecology, and reproductive biology. 2015;:72-76
Abstract
In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).
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[Metformin and the obstetric patient].
Pedersen, KD, Bülow, NS, Aaboe, K, Galsgaard, J, Odgaard, HS, Mathiesen, ER, Lauenborg, J
Ugeskrift for laeger. 2015;(50):V05150438
Abstract
Polycystic ovary syndrome (PCOS) is associated with insulin resistance, infertility, obesity and gestational complications. Metformin is widely used in fertility treatment of women with PCOS, due to a suggested positive effect of continued metformin treatment beyond the first trimester on pregnancy complications. Larger randomized trials have failed to confirm this. Metformin treatment has not been found to be superior to insulin treatment in women with gestational diabetes and may be associated with long-term consequences in the children in the form of overweight and disturbed glucose metabolism.
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Impact of breastfeeding on maternal metabolism: implications for women with gestational diabetes.
Gunderson, EP
Current diabetes reports. 2014;(2):460
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Lactating compared with nonlactating women display more favorable metabolic parameters, including less atherogenic blood lipids, lower fasting and postprandial blood glucose as well as insulin, and greater insulin sensitivity in the first 4 months postpartum. However, direct evidence demonstrating that these metabolic changes persist from delivery to postweaning is much less available. Studies have reported that longer lactation duration may reduce long-term risk of cardiometabolic disease, including type 2 diabetes, but findings from most studies are limited by self-report of disease outcomes, absence of longitudinal biochemical data, or no assessment of maternal lifestyle behaviors. Studies of women with a history gestational diabetes mellitus (GDM) also reported associations between lactation duration and lower the incidence of type 2 diabetes and the metabolic syndrome. The mechanisms are not understood, but hormonal regulation of pancreatic β-cell proliferation and function or other metabolic pathways may mediate the lactation association with cardiometabolic disease in women.
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Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy.
Leiva, A, Pardo, F, Ramírez, MA, Farías, M, Casanello, P, Sobrevia, L
Experimental diabetes research. 2011;:349286
Abstract
Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are pathological conditions associated with placenta vascular dysfunction coursing with metabolic changes at the fetoplacental microvascular and macrovascular endothelium. These alterations are seen as abnormal expression and activity of the cationic amino acid transporters and endothelial nitric oxide synthase isoform, that is, the "endothelial L-arginine/nitric oxide signalling pathway." Several studies suggest that the endogenous nucleoside adenosine along with insulin, and potentially arginases, are factors involved in GDM-, but much less information regards their role in OP-associated placental vascular alterations. There is convincing evidence that GDM and OP prone placental endothelium to an "altered metabolic state" leading to fetal programming evidenced at birth, a phenomenon associated with future development of chronic diseases. In this paper it is suggested that this pathological state could be considered as a metabolic marker that could predict occurrence of diseases in adulthood, such as cardiovascular disease, obesity, diabetes mellitus (including gestational diabetes), and metabolic syndrome.
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Prevention of gestational diabetes: design of a cluster-randomized controlled trial and one-year follow-up.
Luoto, RM, Kinnunen, TI, Aittasalo, M, Ojala, K, Mansikkamäki, K, Toropainen, E, Kolu, P, Vasankari, T
BMC pregnancy and childbirth. 2010;:39
Abstract
BACKGROUND Annual prevalence of gestational diabetes mellitus (GDM) is 12.5% among Finnish pregnant women. The prevalence is expected to rise with the increasing overweight among women before pregnancy. Physical activity and diet are both known to have favourable effects on insulin resistance and possibly on the risk of GDM. We aimed to investigate, whether GDM can be prevented by counseling on diet, physical activity and gestational weight gain during pregnancy. METHODS/DESIGN A cluster-randomized controlled trial was conducted in 14 municipalities in the southern part of Finland. Pairwise randomization was performed in order to take into account socioeconomic differences. Recruited women were at 8-12 weeks' gestation and fulfilled at least one of the following criteria: body mass index>or=25 kg/m2, history of earlier gestational glucose intolerance or macrosomic newborn (>4500 g), age>or=40 years, first or second degree relative with history of type 1 or 2 diabetes. Main exclusion criterion was pathological oral glucose tolerance test (OGTT) at 8-12 weeks' gestation. The trial included one counseling session on physical activity at 8-12 weeks' gestation and one for diet at 16-18 weeks' gestation, and three to four booster sessions during other routine visits. In the control clinics women received usual care. Information on height, weight gain and other gestational factors was obtained from maternity cards. Physical activity, dietary intake and quality of life were followed by questionnaires during pregnancy and at 1-year postpartum. Blood samples for lipid status, hormones, insulin and OGTT were taken at 8-12 and 26-28 weeks' gestation and 1 year postpartum. Workability and return to work were elicited by a questionnaire at 1- year postpartum. Linkage to the national birth register of years 2007-2009 will provide information on perinatal complications and GDM incidence among the non-participants of the study. Cost-effectiveness evaluation will be based on quality-adjusted life years. This study has received ethical approval from the Ethical board of Pirkanmaa Hospital District. DISCUSSION The study will provide information on the effectiveness and cost-effectiveness of gestational physical activity and dietary counseling on prevention of GDM in a risk group of women. Also information on the prevalence of GDM and postpartum metabolic syndrome will be gained. Results on maintaining the possible health behaviour changes are important in order to prevent chronic diseases such as cardiovascular disease and diabetes. TRIAL REGISTRATION The trial is registered ISRCTN 33885819.