Metabolic Syndrome In Adult Life Research Articles

Scientific Analysis of Garbhini Ahar as Epigenetics Modifier of Offspring Genetics - A Critical Review

Reproduction is a bliss that aids in transferring genes from one generation to another. Every prospective parent desire procreation of progeny endowed with supreme health throughout whole life. But, in today’ s era due to faulty dietary and lifestyle habits people are not paying attention to their health resulting in rising incidence of chronic health related hazards like, NCD, DM, HTN, Dyslipidemia, allergies in later life. In last few decades, growing number of epidemiological studies provide evidence for association between nutrition during intrauterine life and major risk factors for CVS disorders and metabolic syndrome in adult life known as fetal origin of adult disease. The notion that intrauterine environmental factors can reset physiological parameters and the resetting can endure into adulthood and can even affect the following generation is known as fetal programming Ayurveda is far advanced as the concept of Garbhini paricharya particularly concept of month wise dietary regime is highly scientific and practical in terms of modern scientific knowledge. On screening the dietary articles mentioned for pregnant lady, it was found that every single fact pertaining to maternal diet mentioned in Ayurvedic text is scientific and has potential to modify the genome/phenotypic expression. Although these ancient dietary approaches have been successfully practiced from millennia but in present era elucidation of these approaches will improve the fidelity of Ayurvedic antenatal care as well as pave the way for future disease prevention. By focusing on Garbhini swasthavritta (pregnancy diet and lifestyle regimens) mentioned in Ayurveda we can reprogram the epigenetic modifications associated with increased disease risk in later life. Ghrita, milk and honey are very essential component of diet during pregnancy and should be consumed regularly. These dietary guidelines should be inoculated into general public for future imprinting of our next generation.

Risk Factors for Intrauterine Growth Restriction: 9 Years Analysis in Tertiary Care Hospital

Background: Intrauterine growth restricted (IUGR) fetuses are at higher risk of developing neonatal complications and also known to develop metabolic syndrome in adult life. So, an early antenatal detection, choosing the optimal time and method of delivery and intervention when required could minimize the risk significantly.
 Objective: To find out the prenatal outcome and the maternal and placental risk factors.
 Methods: A prospective study was conducted from January 2010 to January 2019, at a Teaching Hospital. A singleton pregnancy, above 28 weeks of gestation with clinical diagnosis of IUGR and confirmed by ultrasonography were included in the study. The statistical analysis was performed by Statistical Package of Social Sciences (SPSS) 23.0 software.
 Results: Maternal risk factors like low pregnancy body mass index, preeclampsia, anaemia, hypothyroidism and placental factors like retro placental hemorrhage were mainly responsible for intrauterine growth restriction.
 Conclusions: The early identification of risk factors and management of the same antenatal is an important issue to prevent adverse prenatal outcomes associated with IUGR.

Adverse organogenesis and predisposed long-term metabolic syndrome from prenatal exposure to fine particulate matter.

Exposure to fine particulate matter (PM) during pregnancy is associated with high risks of birth defects/fatality and adverse long-term postnatal health. However, limited mechanistic data are available to assess the detailed impacts of prenatal PM exposure. Here we evaluate fine PM exposure during pregnancy on prenatal/postnatal organogenesis in offspring and in predisposing metabolic syndrome for adult life. Between days 0 and 18 of gestation, two groups of adult female rats (n = 10 for each) were placed in a dual-exposure chamber device, one with clean ambient air (∼3 µg·m-3) and the other with ambient air in the presence of 100 to 200 µg·m-3 of ultrafine aerosols of ammonium sulfate. At birth (postnatal day 0, PND0), four males and four females were selected randomly from each litter to be nursed by dams, whereas tissues were collected from the remaining pups. At PND21, tissues were collected from two males and two females, whereas the remaining pups were fed either a high- or low-fat diet until PND105, when tissues were obtained for biochemical and physiological analyses. Maternal exposure to fine PM increased stillbirths; reduced gestation length and birth weight; increased concentrations of glucose and free fatty acids in plasma; enhanced lipid accumulation in the liver; and decreased endothelium-dependent relaxation of aorta. This lead to altered organogenesis and predisposed progeny to long-term metabolic defects in an age-, organ-, and sex-specific manner. Our results highlight the necessity to develop therapeutic strategies to remedy adverse health effects of maternal PM exposure on conceptus/postnatal growth and development.

Preterm Birth as a Risk Factor for Metabolic Syndrome and Cardiovascular Disease in Adult Life: A Systematic Review and Meta-Analysis

To determine if preterm birth is associated with components of the metabolic syndrome in adult life. A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18years of age) born preterm (<37weeks of gestation) compared with adults born at term (37-42weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data. Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P=.03), SBP (P<.0001), DBP (P<.0001), 24-hour SBP (P<.001), and 24-hour DBP (P<.001). Furthermore, preterm-born adults presented higher values of fasting glucose (P=.01), insulin (P=.002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P=.05), and total cholesterol levels (P=.05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied. Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.

Fetal and childhood malnutrition during the Korean War and metabolic syndrome in adulthood.

Koreans experienced unexpected shortages of food and refugee life during the Korean War (1950-1953). In the present study, we used the Korean War as a natural experiment for early life malnutrition with the aim of evaluating the risk for metabolic syndrome in adulthood according to participant exposure status during the Korean War. We used data from 25 708 participants from the fourth through seventh Korean National Health and Nutrition Examination Survey, a nationally representative database of Korea. By years of birth, we divided the study participants into non-exposed (1959-1963 and 1954-1958), fetal-exposed (1951-1953), early childhood-exposed (1946-1950), late-childhood-exposed (1941-1945), and adolescent-exposed (1936-1940) groups according to participants' ages during the Korean War. We calculated the risk for metabolic syndrome in adult life using logistic regression analysis. Compared with the non-exposed group, women exposed to the Korean War while in utero and during early childhood were associated with increased risk for abdominal obesity and elevated triacylglycerol levels, whereas men showed low high-density lipoprotein cholesterol levels. Fetal and early childhood exposure increased the risk for metabolic syndrome in adults compared with the non-exposed group (fetal-exposed men: odds ratio [OR], 1.28; 95% confidence interval [CI], 0.93-1.76; fetal-exposed women: OR, 1.35; 95% CI, 1.01-1.80; early-childhood-exposed men OR, 1.25; 95% CI, 0.82-1.90; and early-childhood-exposed women OR, 1.41; 95% CI, 0.97-2.06). Fetal and early childhood experiences during the Korean War were associated with increased risk for some components of metabolic syndrome. The present study suggested that early life malnutrition due to the Korean War may be associated with metabolic syndrome in later life.

Alterations in the liver of intrauterine growth retarded piglets may predispose to development of insulin resistance and obesity in later life.

Intrauterine growth retardation (IUGR) leads to increased predisposition to metabolic syndrome in adult life but the mechanisms remain obscure. Considering a significant number of functional similarities, IUGR piglets appear to be a good model to study the development of this syndrome in humans. The aim of the present study was to investigate the ultrastructure and proteomic profile of the liver in IUGR pig neonates to discover early markers of predisposition to obesity and insulin resistance. In our study intestine and liver tissue samples were investigated in 7 day old IUGR and normal body weight (NBW) littermate piglets using histometry, mass spectrometry, in-tissue cytometry analysis and confocal microscopy. Compared to NBW, the liver in IUGR neonates was characterized by a significantly enhanced ratio of Kupffer cells to hepatocytes and insulin receptor abundance as well as higher percentages of cells expressing receptors for adipokines (resistin and adiponectin), increased expression of TNF-α (as marker of inflammation), and increased expression of insulin receptor and uncoupling protein 3 (UCP3). Moreover, NBW and IUGR differed in proteomic profile, including protein metabolism (proteasomes, cathepsin D, phermitin, phosphoglucomutase), carbohydrate metabolism (hexokinase 1, phosphoglucokinase, galactokinase, aldolase B, glucose-6-phosphate isomerase), oxidative stress and chromatin organization and DNA uptake (histones, lamin a/c). Reduction of hepatocyte numbers concomitant with significant modifications of expression of key hormones and enzymes for protein and carbohydrate metabolism in IUGR neonates may predispose to insulin resistance and obesity in adult life.

Analysis of frequency and risk factors for intrauterine growth restriction

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Intrauterine growth restricted (IUGR) fetuses are at greater risk of developing fetal hypoxia, neonatal complications, impaired neurodevelopment, and also neonatal intensive care unit stay and neonatal mortality. They are also known to develop metabolic syndrome in adult life. So, the main objective of this study was to find out the frequency of intrauterine growth restriction, to identify the maternal and placental risk factors associated with intrauterine growth restriction and its perinatal outcome amongst pregnant women attending the Obstetric Outpatient Department in Dhulikhel Hospital, Kathmandu University Hospital&lt;/span&gt;.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;A prospective study was conducted from June 2011 to June 2017, at Dhulikhel Hospital, Kathmandu University Hospital, Kavre, Nepal. A singleton pregnancy, above 28 weeks of gestation with clinical diagnosis of IUGR and confirmed by ultrasonography were included in the study. The statistical analysis was performed by Statistical Package of Social Sciences (SPSS) 20.0 software. &lt;/span&gt;&lt;span lang="EN-IN"&gt; &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Maternal risk factors like preeclampsia, anaemia, low pregnancy body mass index and placental factors like retroplacental hemorrhage were mainly responsible for intrauterine growth restriction&lt;/span&gt;.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Antenatal risk factors responsible for IUGR are important for the management of IUGR pregnancies and to prevent adverse perinatal outcome. &lt;/span&gt;&lt;/p&gt;

Preterm Birth and the Metabolic Syndrome in Adult Life: A Systematic Review and Meta-analysis

Preterm birth is associated with features of the metabolic syndrome in later life. We performed a systematic review and meta-analysis of studies reporting markers of the metabolic syndrome in adults born preterm. Reports of metabolic syndrome-associated features in adults (≥18 years of age) born at <37-week gestational age and at term (37- to 42-week gestational age) were included. Outcomes assessed were BMI, waist-hip ratio, percentage fat mass, systolic (SBP) and diastolic (DBP) blood pressure, 24-hour ambulatory SBP and DBP, flow-mediated dilatation, intima-media thickness, and fasting glucose, insulin, and lipid profiles. Twenty-seven studies, comprising a combined total of 17,030 preterm and 295,261 term-born adults, were included. In adults, preterm birth was associated with significantly higher SBP (mean difference, 4.2 mm Hg; 95% confidence interval [CI], 2.8 to 5.7; P < .001), DBP (mean difference, 2.6 mm Hg; 95% CI, 1.2 to 4.0; P < .001), 24-hour ambulatory SBP (mean difference, 3.1 mm Hg; 95% CI, 0.3 to 6.0; P = .03), and low-density lipoprotein (mean difference, 0.14 mmol/L; 95% CI, 0.05 to 0.21; P = .01). The preterm-term differences for women was greater than the preterm-term difference in men by 2.9 mm Hg for SBP (95% CI [1.1 to 4.6], P = .004) and 1.6 mm Hg for DBP (95% CI [0.3 to 2.9], P = .02). For the majority of outcome measures associated with the metabolic syndrome, we found no difference between preterm and term-born adults. Increased plasma low-density lipoprotein in young adults born preterm may represent a greater risk for atherosclerosis and cardiovascular disease in later life. Preterm birth is associated with higher blood pressure in adult life, with women appearing to be at greater risk than men.

Fish Oil Supplementation During Late Pregnancy Does Not Influence Plasma Lipids or Lipoprotein Levels in Young Adult Offspring

Nutritional influences on cardiovascular disease operate throughout life. Studies in both experimental animals and humans have suggested that changes in the peri- and early post-natal nutrition can affect the development of the various components of the metabolic syndrome in adult life. This has lead to the hypothesis that n-3 fatty acid supplementation in pregnancy may have a beneficial effect on lipid profile in the offspring. The aim of the present study was to investigate the effect of supplementation with n-3 fatty acids during the third trimester of pregnancy on lipids and lipoproteins in the 19-year-old offspring. The study was based on the follow-up of a randomized controlled trial from 1990 where 533 pregnant women were randomized to fish oil (n = 266), olive oil (n = 136) or no oil (n = 131). In 2009, the offspring were invited to a physical examination including blood sampling. A total of 243 of the offspring participated. Lipid values did not differ between the fish oil and olive oil groups. The relative adjusted difference (95% confidence intervals) in lipid concentrations was −3% (−11; 7) for LDL cholesterol, 3% (−3; 10) for HDL cholesterol, −1% (−6; 5) for total cholesterol,−4% (−16; 10) for TAG concentrations, 2%(−2; 7) for apolipoprotein A1, −1% (−9; 7) for apolipoprotein B and 3% (−7; 15) in relative abundance of small dense LDL. In conclusion, there was no effect of fish oil supplementation during the third trimester of pregnancy on offspring plasma lipids and lipoproteins in adolescence.

In Utero Origins of Adult Insulin Resistance and Vascular Dysfunction

The metabolic syndrome (or syndrome X) is a constellation of risk factors including insulin resistance, hypertension, dyslipidemia, and central obesity that predispose to the development of cardiovascular disease and type 2 diabetes in adult life. Insulin resistance is believed to be a critical pathophysiological event early in the disease process, impacting both skeletal muscle metabolic function and vascular responses. Adverse changes in insulin sensitivity have been found to originate in utero; for instance, prenatal events such as placental insufficiency/oxidative stress leading to altered fetal growth trajectories are associated with increased rates of metabolic syndrome in adult life. Such intrauterine insults result in reduced skeletal muscle mass in conjunction with altered insulin signaling, decreased oxidative fibers, and impaired mitochondrial function. These developmental disturbances set the stage for development of muscle triglyceride accumulation and depressed insulin sensitivity in childhood. Abnormalities of vascular structure and function arising from deprived intrauterine conditions that are exacerbated by insulin resistance account for the progression of hypertension from childhood to adulthood. Arterial changes initiated in utero include reduced endothelial nitric oxide (NO) bioavailability, vascular smooth muscle cell proliferation and inflammation, events leading to endothelial dysfunction, and atherosclerosis that are present in those destined for metabolic syndrome. In addition, the hypertensive phenotype that is a hallmark of metabolic syndrome may also be traced to blunted kidney development and renin-angiotensin system activation in growth-restricted offspring. The summative impact of these intrauterine programmed changes in terms of influencing adult health and disease encompasses dietary and lifestyle factors introduced postnatally. Establishing novel therapeutic interventions aimed at preventing and/or reducing in utero-induced insulin resistance and vascular dysfunction warrants investigation because the numbers of low birthweight babies continue to increase.

A maternal low protein diet programs glucose and fatty acid metabolism differentially in adult male and female mouse offspring

Nutritional conditions during fetal life can influence the risk to develop the metabolic syndrome in adult life (‘metabolic programming’). We aimed to establish a mouse model of metabolic programming focusing on the effects of a maternal low protein diet during gestation on glucose and lipid metabolism in the adult offspring. Pregnant C57BL/6J mice received a control or a low protein diet throughout gestation. Offspring received a low fat diet or a high fat diet from 6–22 weeks of age. Glucose metabolism was studied with a whole‐body‐glucose test using [6,6‐2H]‐glucose. Hepatic gene expression was characterized by microarray. Maternal low‐protein‐diet did not affect glucose metabolism in male offspring. Female offspring from normal‐protein fed dams was relatively resistant to diet‐induced metabolic dysregulation. Maternal low‐protein‐diet during gestation led to deteriorated insulin sensitivity upon high‐fat feeding in female offspring. Microarray analyses showed a sex‐specific effect of the maternal diet. We conclude that, in mice, maternal protein restriction during gestation does not change the glucose response to a high fat diet in male offspring. However, it changes fatty acid and glucose metabolism in female offspring in such a way that it resembles male metabolism. Supported by the Netherlands Heart Foundation, grant 2004T048.

Fetal origins of adult diabetes

According to the fetal origin of adult diseases hypothesis, the intrauterine environment through developmental plasticity may permanently influence long-term health and disease. Therefore, intrauterine growth restriction (IUGR), due either to maternal, placental, or genetic factors, may permanently alter the endocrine-metabolic status of the fetus, driving an insulin resistance state that can promote survival at the short term but that facilitates the development of type 2 diabetes mellitus and metabolic syndrome in adult life, especially when the intrauterine nutrient restriction is followed by a postnatal obesogenic environment. Furthermore, an energy-rich environment during fetal programming may also drive the development of excess abdominal fat and type 2 diabetes in later life, demonstrating that both intrauterine nutrient restriction as well as intrauterine nutrient excessive supply may predispose for the development of adult diabetes.

Reply

We read with great interest the comments by Dr. Maitra regarding our article1 published in HEPATOLOGY. We thank the author for his kind interest in our work and welcome the opportunity to clarify the points raised by him. First, there is a difference between a field study and a clinic-based study. Despite its fallacies, the measurement of alanine aminotransferase remains the most cost-effective screening tool for significant underlying liver disease, even nonalcoholic fatty liver (NAFL) disease.2 Moreover, an elevated alanine aminotransferase level is one of the components of the various noninvasive scoring systems used for identifying NAFL subjects with advanced liver disease.3 Unfortunately, despite attempts to develop multiple noninvasive (but not necessarily cheap) scoring systems or tests for identifying subjects with nonalcoholic steatohepatitis, liver biopsy remains the ultimate gold standard for diagnosing nonalcoholic steatohepatitis.3 Second, despite the concerns regarding the unconventional forms of ethanol consumption by tribals in India, there were only 35 tribals (1.8%) among the 1911 subjects, and we rigorously excluded alcohol consumption in our study population (see the supporting information for our article1). Finally, we also speculated about the role of malnutrition in the genesis of NAFL in our population.1 However, in a case-control substudy of subsets of subjects with a body mass index < 18.5 kg/m2, we found that those with NAFL had higher indices of adiposity and a higher prevalence of markers of metabolic syndrome versus those without NAFL (see the supporting tables for our article1). We agree with Maitra that the thrifty phenotype hypothesis,4 introduced approximately 20 years ago to explain the associations between poor fetal and infant growth and the increased risk of developing impaired glucose tolerance and metabolic syndrome in adult life, can play a pathophysiological role in the development of the third-world NAFL phenotype, as highlighted by us.1 Kshaunish Das*, Abhijit Chowdhury , * Divisions of Gastroenterology, Institute of Postgraduate Medical Education and Research, Kolkata, India, Hepatology, School of Digestive and Liver Diseases, Institute of Postgraduate Medical Education and Research, Kolkata, India.

Investigation into peroxisome proliferator activated receptor α and γ hepatic mRNA levels in diet induced obesity: a potential mechanism for fetal programming

IntroductionFetal programming is a potentially maladaptive response to the nutritional environment during gestation, and may be responsive for the development of the metabolic syndrome in adult life. Changes in maternal...

INVESTIGATION INTO PPAR ALPHA AND GAMMA HEPATIC MESSENGER-RNA LEVELS IN DIET INDUCED OBESITY: A POTENTIAL MECHANISM FOR FETAL PROGRAMMING OF THE METABOLIC SYNDROME: PP.21.341

Introduction: Fetal programming is a potentially maladaptive response to the nutritional environment during gestation, and may be responsive for the development of the metabolic syndrome in adult life. Children of obese, non-diabetic mothers are at increased risk of developing metabolic syndrome in adult life. The putative mechanism behind this association involves the interaction of the metabolic environment of obese mothers with fetal genes, influencing fetal growth and development. Peroxisome proliferator activated receptor (PPAR)-α and PPAR-γ are transcription factors that are involved in the regulation of a wide range of genes including those affecting lipid and glucose metabolism and been implicated in fetal programming of the metabolic syndrome. Methods: Virgin female C57BL/6J mice were fed either an obesogenic diet or control diet (standard mouse chow) for 8 weeks prior to liver collection and RNA extraction. Hepatic PPAR-α and PPAR-γ mRNA copy numbers were quantified for the two groups using reverse transcription and real-time PCR techniques. Results: Hepatic mRNA levels of PPAR-α was significantly decreased in mice fed the obesogenic diet compared with the control diet (P = 0.018). PPAR-γ expression also decreased (P = 0.089). Conclusion: This study aimed to assess the effects of an obesogenic diet similar to that prevalent in the developed world on the gene expression of PPAR-α and PPAR-γ in a mouse model of obesity. The motivation for this work was to incorporate the results into an improved understanding of the mechanism by which over-nutrition affects maternal and fetal metabolic pathways to program the fetus for chronic disease in later life. We found the obesogenic diet significantly decreased PPAR-α expression. This may be caused by raised plasma glucose and insulin levels, which can down-regulate PPAR-α expression. Changes in PPAR-α expression in obesity alter the maternal hormonal and nutritional environment prior to pregnancy. At the time of conception and fetal development decreased maternal PPAR-α expression may mediate fetal programming for the development of adult metabolic syndrome.

Mechanisms involved in the developmental programming of adulthood disease.

There are many instances in life when the environment plays a critical role in the health outcomes of an individual, yet none more so than those experienced in fetal and neonatal life. One of the most detrimental environmental problems encountered during this critical growth period are changes in nutrition to the growing fetus and newborn. Disturbances in the supply of nutrients and oxygen to the fetus can not only lead to adverse fetal growth patterns, but they have also been associated with the development of features of metabolic syndrome in adult life. This fetal response has been termed developmental programming or the developmental origins of health and disease. The present review focuses on the epidemiological studies that identified this association and the importance that animal models have played in studying this concept. We also address the potential mechanisms that may underpin the developmental programming of future disease. It also highlights (i) how developmental plasticity, although beneficial for short-term survival, can subsequently programme glucose intolerance and insulin resistance in adult life by eliciting changes in key organ structures and the epigenome, and (ii) how aberrant mitochondrial function can potentially lead to the development of Type 2 diabetes and other features of metabolic syndrome.

Leptin and adiponectin concentrations in intrauterine growth restricted and appropriate for gestational age fetuses, neonates, and their mothers

Leptin and adiponectin are two adipocytokines that play a critical role in the control of energy balance and metabolism as well as in conditions, such as insulin resistance, inflammation, and the development of the metabolic syndrome in adult life. Leptin has been associated with asymmetric intrauterine growth restriction (IUGR). The aim of this study was to investigate the perinatal implication of leptin and adiponectin in IUGR. Design Leptin and adiponectin were measured in the plasma of 40 mothers, in the umbilical cord (UC) blood of their 20 appropriate for gestational age (AGA) and 20 IUGR singleton, full-term fetuses, and neonates on day 1 (d1) and day 4 (d4) of life postnatally. Serum leptin and adiponectin levels were measured by RIA. Serum cortisol levels were measured with an electrochemiluminescence immunoassay. Leptin and adiponectin serum levels were higher and lower respectively in IUGR (mean+/-s.e.m., 32.5+/-3.8 and 5.4+/-0.9 mug/l respectively) compared with AGA (20.4+/-2.1 and 11.8+/-1.3 mug/l respectively) mothers (P<0.05), although body mass index did not differ between these two groups. Leptin levels positively correlated with adiponectin levels in the AGA (r=0.547, P<0.05) but not in the IUGR mothers. UC, d1, and d4 leptin and adiponectin levels did not differ between IUGR and AGA groups. UC were significantly higher than d1 leptin levels (P<0.05) in the IUGR group but not in the AGA group. The increased UC leptin levels compared with d1 in IUGR fetuses might be directly and/or indirectly related to the subsequent development of insulin resistance in these neonates. This pathologic situation seems to be related to a specific profile of increased leptin and decreased adiponectin levels in IUGR mothers indicating a genetic predisposition for the development of insulin resistance.

Developmental Origins of Adult Health and Disease: The Role of Periconceptional and Foetal Nutrition

The 'developmental origins of adult health and disease' hypothesis stated that environmental factors, particularly maternal undernutrition, act in early life to programme the risks for adverse health outcomes, such as cardiovascular disease, obesity and the metabolic syndrome in adult life. Early physiological tradeoffs, including activation of the foetal hypothalamo-pituitary-adrenal (HPA) axis, confer an early fitness advantage such as foetal survival, while incurring delayed health costs. We review the evidence that such tradeoffs are anticipated from conception and that the periconceptional nutritional environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure. There is also evidence that restriction of placental growth and function, results in an increased dependence of the maintenance of arterial blood pressure on the sequential recruitment of the sympathetic nervous system and HPA axis. While the 'early origins of adult disease' hypothesis has focussed on the impact of maternal undernutrition, an increase in maternal nutritional intake and in maternal body mass intake has become more prevalent in developed countries. Exposure to overnutrition in foetal life results in a series of central and peripheral neuroendocrine responses that in turn programme development of the fat cell and of the central appetite regulatory system. While the physiological responses to foetal undernutrition result in the physiological trade off between foetal survival and poor health outcomes that emerge after reproductive senescence, exposure to early overnutrition results in poor health outcomes that emerge in childhood and adolescence. Thus, the effects of early overnutrition can directly impact on reproductive fitness and on the health of the next generation. In this context, the physiological responses to relative overnutrition in early life may directly contribute to an intergenerational cycle of obesity.

Serum fetuin-A/alpha2-HS-glycoprotein in human pregnancies with normal and restricted fetal growth

Objective. To investigate circulating concentrations of human fetuin-A (important fetal glycoprotein, involved in vascular pathology and bone metabolism) in mothers, fetuses and neonates from intrauterine-growth-restricted (IUGR, associated with low bone mass at birth and metabolic syndrome in adult life) and appropriate-for-gestational-age (AGA) pregnancies.Methods. Serum fetuin-A concentrations were prospectively measured in 40 mothers, the doubly-clamped umbilical cords (representing fetal state) and their 20 IUGR and 20 AGA full-term neonates on postnatal day 1 (N1) and 4 (N4).Results. No significant differences in fetuin-A concentrations were observed between groups, or between maternal, fetal and neonatal samples in both groups. In the AGA group, maternal fetuin-A concentrations positively correlated with fetal and N1 ones (r = 0.599, p = 0.005 and r = 0.469, p = 0.037, respectively). In the IUGR group, maternal fetuin-A concentrations positively correlated with N4 ones (r = 0.541, p = 0.014).Conclusion. Serum fetuin-A concentrations do not differ between IUGR cases and AGA controls. Maternal and fetal fetuin-A concentrations are similar and positively correlated, indicating the likelihood of passive transplacental transfer of this substance.

Perinatal Changes of Plasma Resistin Concentrations in Pregnancies with Normal and Restricted Fetal Growth

Background:The adipocytokine resistin inhibits adipogenesis and induces insulin resistance. Intrauterine growth-restricted (IUGR) neonates have reduced fat mass and changes of endocrine/metabolic mechanisms, predisposing to insulin resistance and metabolic syndrome in adult life. Objectives: To investigate plasma resistin concentrations in maternal, fetal and neonatal samples from IUGR and appropriate-for-gestational-age (AGA) pregnancies and correlate them with respective insulin concentrations. Methods: Plasma resistin and insulin concentrations were determined in 40 mothers and their 20 IUGR and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and day 4 (N4). Results: No significant differences in resistin concentrations were observed between AGA and IUGR groups. In the AGA group, maternal resistin concentrations were significantly lower compared to fetal, N1 and N4 ones (p = 0.003, p = 0.017 and p = 0.039, respectively). Maternal resistin concentrations positively correlated with fetal ones (r = 0.527, p = 0.02). In the IUGR group, maternal resistin concentrations were significantly lower compared to N1 (p < 0.001) and positively correlated with N4 concentrations (r = 0.626, p = 0.007). In both groups, the effect of gender, mode of delivery, parity and adjusted birth weight (customized centiles) on resistin concentrations was not significant. No correlation between resistin and insulin concentrations was documented. Conclusions: Lack of difference in resistin concentrations between IUGR and AGA groups, and lack of correlation between resistin and insulin concentrations as well as customized centiles, possibly suggests that resistin may not be directly involved in the regulation of insulin sensitivity and adipogenesis in the perinatal period. Mode of delivery and parity are not associated with circulating resistin concentrations.