Diabetes In Adult Life Research Articles

1782-P: Perinatal Hypoxia Lowers the Glucose Threshold for Insulin Secretion Causing Hypoglycemia and Hyperinsulinism

Perinatal stress-induced hyperinsulinism is a common cause of persistent hypoglycemia in at-risk neonates. The hypoxia-inducible factor-1 (HIF-1) pathway regulates cellular adaptation in hypoxic conditions through hypoxia response elements. We hypothesize that perinatal hypoxia leads to activation of the HIF1 pathway causing increased insulin secretion from neonatal β-cells. We examined glucose homeostasis and insulin secretion in NeuroD1-Cre;VhlLoxp/Loxp(VhlbetaKO) and in hypoxic wild type (WT) mouse pups in the first week of life. In VhlbetaKO pups postnatal day 8 (P8), plasma glucose was significantly lower compared to littermate controls (76 vs 129 mg/dL). Plasma insulin (0.54 vs 0.27 ng/mL) and the insulin to glucose ratio were significantly greater in VhlbetaKO pups indicating a failure to suppress insulin secretion. VhlbetaKO islet perifusion showed the lower plasma glucose level was due to a lower threshold (5 mM) for glucose stimulated insulin secretion (GSIS) compared to controls (10 mM). To assess the consequences of perinatal hypoxia, we exposed WT mouse pups to hypoxia (10% O2) between embryonic day 18 and P6. Islets from the hypoxia exposed pups had a lower GSIS threshold (3 mM) compared to islets from normoxic pups (5 mM) at P6. Hypoxic islets also had a lower insulin secretion threshold when stimulated with BCH, a glutamate dehydrogenase activator, or tolbutamide, a KATP channel inhibitor, suggesting that HIF1 pathway activation leads to a decreased stimulus threshold for secretion at or distal to the KATP channel. Patch clamps revealed that β-cells from hypoxic pups were more depolarized than normoxic controls. Our results show that the HIF1 pathway is critical for setting the GSIS threshold and a potential mediator of PSHI. We posit perinatal hypoxia and the HIF1 pathway at the core of β-cell maturational defects leading to increased risk of diabetes in adult life and the long-sought answer to the cause of perinatal stress-induced hyperinsulinism. Disclosure C.Juliana: Research Support; Crinetics Pharmaceuticals, Inc., Twist Bioscience, AmideBio. D.De leon: Consultant; Zealand Pharma A/S, Crinetics Pharmaceuticals, Inc., Eiger BioPharmaceuticals, Hanmi Pharm. Co., Ltd., Research Support; Ultragenix, Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Rezolute, Inc.

Maternal Calorie Restriction Induces a Transcriptional Cytoprotective Response in Embryonic Liver Partially Dependent on Nrf2.

Calorie restriction is known to enhance Nrf2 signaling and longevity in adult mice, partially by reducing reactive oxygen species, but calorie restriction during pregnancy leads to intrauterine growth retardation. The latter is associated with fetal reprogramming leading to increased incidence of obesity, metabolic syndrome and diabetes in adult life. Transcription factor Nrf2 is a central regulator of the antioxidant response and its crosstalk with metabolic pathways is emerging. We hypothesized that the Nrf2 pathway is induced in embryos during calorie restriction in pregnant mothers. From gestational day 10 up to day 16, 50% of the necessary mouse diet was provided to Nrf2 heterozygous pregnant females with fathers being of the same genotype. Embryos were harvested at the end of gestational day 16 and fetal liver was used for qRT-PCR and assessment of oxidative stress (OS). Intrauterine calorie restriction led to upregulation of mRNA expression of antioxidant genes (Nqo1, Gsta1, Gsta4) and of genes related to integrated stress response (Chac1, Ddit3) in WT embryos. The expression of a key gluconeogenic (G6pase) and two lipogenic genes (Acacb, Fasn) was repressed in calorie-restricted embryos. In Nrf2 knockout embryos, the induction of Nqo1 and Gsta1 genes was abrogated while that of Gsta4 was preserved, indicating an at least partially Nrf2-dependent induction of antioxidant genes after in utero calorie restriction. Measures of OS showed no difference (superoxide radical and malondialdehyde) or a small decrease (thiobarbituric reactive substances) in calorie-restricted WT embryos. Calorie restriction during pregnancy elicits the transcriptional induction of cytoprotective/antioxidant genes in the fetal liver, which is at least partially Nrf2-dependent, with a physiological significance that warrants further investigation.

Postnatal Catch-Up Growth Programs Telomere Dynamics and Glucose Intolerance in Low Birth Weight Mice.

Low birth weight and rapid postnatal weight gain are independent predictors of obesity and diabetes in adult life, yet the molecular events involved in this process remain unknown. In inbred and outbred mice, this study examines natural intrauterine growth restriction (IUGR) in relation to body weight, telomere length (TL), glucose tolerance, and growth factor gene (Igf1, Igf2, Insr, Igf1r, and Igf2r) mRNA expression levels in the brain, liver, and muscle at 2- and 10 days of age and then at 3- and 9 months of age. At birth, ~15% of the animals showed IUGR, but by 3 and 9 months, half of these animals had regained the same weight as controls without IUGR (recuperated group). At 10 days, there was no difference in TL between animals undergoing IUGR and controls. However, by 3 and 9 months of age, the recuperated animals had shorter TL than the control and IUGR-non recuperated animals and also showed glucose intolerance. Further, compared to controls, Igf1 and Igf2 growth factor mRNA expression was lower in Day 2-IUGR mice, while Igf2r and Insr mRNA expression was higher in D10-IUGR animals. Moreover, at 3 months of age, only in the recuperated group were brain and liver Igf1, Igf2, Insr, and Igf2r expression levels higher than in the control and IUGR-non-recuperated groups. These data indicate that catch-up growth but not IUGR per se affects TL and glucose tolerance, and suggest a role in this latter process of insulin/insulin-like growth signaling pathway gene expression during early development.

Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies.

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague-Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.

Transcriptome Characterization of Repressed Embryonic Myogenesis Due to Maternal Calorie Restriction.

Fetal malnutrition decreases skeletal myofiber number and muscle mass in neonatal mammals, which increases the risk of developing obesity and diabetes in adult life. However, the associated molecular mechanisms remain unclear. Here, we investigated how the nutrient (calorie) availability affects embryonic myogenesis using a porcine model. Sows were given a normal or calorie restricted diet, following which skeletal muscle was harvested from the fetuses at 35, 55, and 90 days of gestation (dg) and used for histochemical analysis and high-throughput sequencing. We observed abrupt repression of primary myofiber formation following maternal calorie restriction (MCR). Transcriptome profiling of prenatal muscles revealed that critical genes and muscle-specific miRNAs associated with increased proliferation and myoblast differentiation were downregulated during MCR-induced repression of myogenesis. Moreover, we identified several novel miRNA-mRNA interactions through an integrative analysis of their expression profiles, devising a putative molecular network involved in the regulation of myogenesis. Interestingly, NC_010454.3_1179 was identified as a novel myogenic miRNA that can base-pair with sequences in the 3′-UTR of myogenic differentiation protein 1 (MyoD1). And we found that this UTR inhibited the expression of a linked reporter gene encoding a key myogenic regulatory factor, resulting in suppression of myogenesis. Our results greatly increase our understanding of the mechanisms underlying the nutrient-modulated myogenesis, and may also serve as a valuable resource for further investigation of fundamental developmental processes or assist in rational target selection ameliorating repressed myogenesis under fetal malnutrition.

SUN-048 Maternal Caloric Restriction during Pregnancy Activates the Nrf2 Antioxidant Program in Embryonic Mouse Liver

Obesity and type 2 diabetes in adult life are influenced by the intrauterine environment. The fetus adapts to the environment to which it was exposed, leading potentially to resistance to similar exposures experienced after birth. Studies in both mice and humans suggest that exposure of pregnant females to nutrient deprivation may lead their offspring to develop obesity, insulin resistance and ultimately cardiovascular disease in their adulthood. As the cytoprotective transcription factor Nrf2 (Nfe2l2) is known to be activated upon oxidative and electrophilic stress and has an emerging role in metabolism and specifically in hepatic gluconeogenesis and lipogenesis, we hypothesized that it should be important in the adaptation of the embryos to the metabolic stress induced by maternal caloric restriction. To this end, pregnant C57BL6 mice underwent calorie restriction (CR) by providing them with 50% of the necessary calories per body weight (assessed in pilot experiments) from gestation day 10 to gestation day 16. This CR scheme guarantees the delivery of viable pups that weigh 50% less than the pups whose mothers were fed ad libitum standard chow diet. This CR experiment was performed using either wild-type (WT) or Nrf2 knockout (Nrf2KO) parents. Pregnant females of both genotypes fed ad libitum were used as control. The pregnant females were sacrificed on gestational day 16 and embryos were extracted. Embryonic liver was used for DNA extraction for sex determination by PCR and for RNA preparation to be used for quantitative real-time PCR (qPCR). Statistical significance was set at p<0.05. 10 male embryonic livers were used in qPCR per each condition (CR or control) per each genotype (WT or Nrf2KO). The prototypical Nrf2 antioxidant target gene Nqo1 was increased 2-fold in CR mice. Nrf2-regulated glutathione transferases Gsta1 and Gsta4 were also induced 7.7-fold and 2-fold respectively after CR. Deletion of Nrf2 abrogated completely Nqo1 induction after CR and reduced Gsta1 induction to just 1.4-fold while Gsta1 induction remained unchanged. De novo lipogenesis genes Fasn and Acc2 expression was ~50% and ~90% lower after CR and this change was not significantly affected by Nrf2 deletion. The expression of G6Pase, one of the key gluconeogenic enzymes was also repressed 5-fold in CR mice while expression of Pepck remained unaffected. Lack of Nrf2 impaired the repression of G6Pase to 2-fold. Our study shows for the first time induction of Nrf2 pathway in embryonic liver exposed to CR. Molecular mechanisms and physiological significance of this effect in adult life of the CR WT and Nrf2KO embryos are currently investigated.

Exposure to Adverse Childhood Experiences and Oral Health Measures in Adulthood: Findings from the 2010 Behavioral Risk Factor Surveillance System.

Adverse childhood experiences (ACEs) are negative life events occurring before the age of 18 y. ACEs are risk factors for heart disease and diabetes in adult life. Furthermore, individuals who experience ACEs are more likely to smoke and become obese-factors associated with poor oral health. This study investigated likely associations between ACEs and the oral health measures of the 2010 Behavioral Risk Factor Surveillance System (BRFSS). Data from 16,354 participants of the 2010 BRFSS were analyzed with SAS 9.4. ACE scores were calculated in 2 domains: abuse (emotional, physical, or sexual) and household challenges (parental separation or divorce, intimate partner violence, household substance abuse, household mental illness, and incarceration). ACE scores, ranging from 0 to 8, were categorized into 0, 1, 2, 3, and ≥4. The 2010 BRFSS oral health measures included >1 y since last dental visit, ≥6 teeth extracted, and ≥2 y since last dental cleaning. Survey logistic regression estimated prevalence odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, and educational attainment. The weighted mean ACE score was 1.74 (95% CI = 1.68 to 1.81), and the weighted and age-standardized percentages of study participants with ACE scores of 0, 1, 2, 3, and ≥4 were 33.1%, 24.3%, 14.9%, 9.69%, and 18.1%, respectively. There appeared to be a dose-response association between categories of ACE scores and the oral health measures. Specifically, when compared with participants with an ACE score of 0, participants with ACE scores of 1, 2, 3, and ≥4 had adjusted prevalence odds ratios (95% CIs) of 1.10 (0.82 to 1.47), 1.20 (0.90 to 1.60), 1.35 (0.98 to 1.85), and 1.72 (1.31 to 2.26), respectively, for reporting ≥2 y since last dental cleaning. Findings suggest that ACEs may be associated with poor oral health measures in adulthood, even after adjusting for important oral diseases risk factors. Longitudinal follow-up studies are needed to delineate pathways by which this relationship occurs. Our findings indicate that exposure to childhood trauma may have negative impacts on oral health in adulthood. Oral health practitioners need to be aware of the potential impacts of childhood trauma on health behaviors that ultimately affect oral health outcomes.

Timing of Exposure and Bisphenol-A: Implications for Diabetes Development.

Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDCs). It is used as the base compound in the production of polycarbonate and other plastics present in many consumer products. It is also used as a building block in epoxy can coating and the thermal paper of cash register receipts. Humans are consistently exposed to BPA and, in consequence, this compound has been detected in the majority of individuals examined. Over the last decade, an enlarging body of evidence has provided a strong support for the role of BPA in the etiology of diabetes and other metabolic disorders. Timing of exposure to EDCs results crucial since it has important implications on the resulting adverse effects. It is now well established that the developing organisms are particularly sensitive to environmental influences. Exposure to EDCs during early life may result in permanent adverse consequences, which increases the risk of developing chronic diseases like diabetes in adult life. In addition to that, developmental abnormalities can be transmitted from one generation to the next, thus affecting future generations. More recently, it has been proposed that gestational environment may also program long-term susceptibility to metabolic disorders in the mother. In the present review, we will comment and discuss the contributing role of BPA in the etiology of diabetes. We will address the metabolic consequences of BPA exposure at different stages of life and comment on the final phenotype observed in different whole-animal models of study.

Impact of age at menarche on obesity and glycemic control in Japanese patients with type 2 diabetes: Fukuoka Diabetes Registry.

Aims/IntroductionA younger age at menarche is associated with obesity and type 2 diabetes in adult life. The impact of early‐onset menarche on obesity and glycemic control in type 2 diabetes has not been investigated. The present study examined the relationship between age at menarche and obesity and glycemic control in type 2 diabetes.Materials and MethodsA total of 2,133 patients with type 2 diabetes aged ≥20 years were divided into groups according to age at menarche (≤11, 12, 13, 14 and ≥15 years). A retrospective cohort study examined the association of menarcheal age with adiposity and hemoglobin A1c.ResultsAge at menarche was inversely associated with body mass index (BMI) and abdominal circumference (P < 0.001). Each 1‐year decrease in age at menarche was associated with a 0.25‐kg/m2 and 0.6‐cm increase in BMI and abdominal circumference, respectively, using a multivariate‐adjusted model. Odds ratios for obesity and abdominal obesity significantly increased in participants with age at menarche ≤11 years after multivariable adjustments when age at menarche of 13 years was used as the reference (odds ratio 1.95, 95% CI 1.33–2.88, odds ratio 1.95, 95% CI 1.32–2.87, respectively). Younger age at menarche was significantly associated with higher hemoglobin A1c (P < 0.001); however, the association was not statistically significant after adjusting for BMI.ConclusionsAge at menarche of ≤11 years was associated with obesity after adjusting for confounding factors, and poor glycemic control associated with high BMI in type 2 diabetes. Age at menarche should be considered during clinical assessments.

Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid composition in rat offspring.

Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes. Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring. Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning. Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet. Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation. Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS-55 offspring exposed during suckling only. By 12weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS-55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring.

Malnutrition in early life and risk of type 2 diabetes: Theoretical framework and epidemiological evidence

There exist numerous experimental and epidemiological data indicating that malnutrition in early development may influence the risk of developing metabolic disorders in adult life, including type 2 diabetes mellitus (T2DM). Epidemiological evidence for such a relationship was mostly obtained in quasi-experimental studies (natural experiments) carried out on the populations of different countries. These studies revealed that exposure to famine in prenatal and/or early postnatal development is associated with increased risk of developing type 2 diabetes in adult life. Epigenetic regulation of gene activity is considered to be the main mechanism linking starvation in early life and increased risk of type 2 diabetes in adulthood. It is believed that exposure to famine during pregnancy may induce persistent epigenetic variations that are thought to have some adaptive value in the early postnatal development but that also lay grounds for metabolic disorders, including type 2 diabetes, in later life. The present review consolidates and discusses the data indicating the possibility of early developmental programming of type 2 diabetes obtained in the course of quasi-experimental studies.

Medium chain fatty acids in intrauterine growth restricted and small for gestational age pregnancies

Low birth weight is associated with an increased risk of heart disease, high blood pressure and diabetes in adult life. Fetal growth is determined by nutrient availability, which is related to placenta nutrient transport. Medium chain fatty acids (MCFAs) are a particular class of nutrients, known to be a readily available energy source. Until now no data are reported on these MCFAs in low birth weight fetus. This is a prospective study conducted in a tertiary center of prenatal diagnosis to investigate the maternal and fetal MCFAs levels in appropriate for gestational age (AGA), intrauterine growth restricted (IUGR), and small for gestational age (SGA) pregnancies. The plasmatic levels of MCFAs in AGA, IUGR and SGA mother–infant pairs were quantified by gas chromatography–mass spectrometry. The analytical method had a linearity range of 0.1–50 mg/L and a limit of quantification of 0.03 mg/L. Reduced fetal growth was defined as an estimated fetal weight below the 3rd–10th percentile for gestational age, with (IUGR) or without (SGA) fetal Doppler abnormalities. Maternal and fetal MCFAs plasma levels were significantly different among SGA, IUGR and AGA groups. Additionally, the observed MCFAs fetal to maternal ratio is >1 for IUGR group, whilst for SGA and AGA the fetal to maternal ratio is less than one. Changes in MCFAs levels in fetal and maternal plasma are not related to placental functionality or nutrients availability, suggesting the presence of a de novo biosynthesis.

The Long-Term Effects of the Periconceptional Period on Embryo Epigenetic Profile and Phenotype; The Paternal Role and His Contribution, and How Males Can Affect Offspring's Phenotype/Epigenetic Profile.

The number of adults afflicted with heart disease, obesity and diabetes, central components of metabolic disorder, has grown rapidly in recent decades, affecting up to one quarter of the world's population. Typically, these diseases are attributed to lifestyle factors such as poor diet, lack of exercise and smoking. However, studies have now identified strong associations between patterns of growth during foetal and neonatal life and an increase predisposition towards developing heart disease, obesity and diabetes in adult life. While the connection between a mother's diet and the long-term health of her offspring has been studied in great detail, our understanding of whether offspring health might be affected by a father's diet remains limited. Greater insight into the impact that paternal nutrition has on sperm quality, epigenetic status and potential offspring programming mechanisms is needed to redress this parental-programming knowledge imbalance. Disturbances in paternal reproductive epigenetic status represents one key mechanism linking paternal diet with the programing of offspring development and adult health, as many enzymatic processes involved in epigenetic regulation use metabolic intermediates to modify DNA and histones. Here, poor paternal nutrition could result in perturbed sperm and testicular epigenetic status, impacting on post-fertilisation gene transcriptional regulation and protein expression in offspring tissues, resulting in increased incidences of metabolic disorder in adult life.

Can Prevention of Low Birth Weight in Newborn may be Associated with Primordial Prevention of Cardiovascular Diseases and Type 2 Diabetes in Adult Life?

Poor nutrition during pregnancy may be a risk factor for low birth weight and for irreversible health issues including obesity, type 2 diabetes, hypertension and hypercholesterolemia in adult life. Low birth weight has also been related to greater mortality from coronary artery disease(CAD) and type 2 diabetes in adult life. One earlier study from Northern Europe proposed that poor social conditions in childhood may be risk factor for obesity, diabetes and cardiovascular diseases (CVDs) in later life. It is possible that multiple confounders related to energy and micronutrient deficiencies may be interacting in the process of adaptations in critical time periods, during fetal, postnatal and child development. A review of literature on the effects on birth size and length of babies and of multiple micronutrient supplementation during pregnancy in low-income countries indicates that incidence of low birth weight may be decreased by supplementation of about 15 micronutrients. This finding poses the possibility that for prevention of low birth weight, maternal micronutrient supplementation (15-20 nutrients) may be an important strategy. It is proposed that this strategy may lead the prevention of CVDs and type 2 diabetes in adult life. Cohort studies and long term follow up population based trials are needed to confirm this hypothesis.

Insulin sensitivity and secretory response in adults born preterm: the Helsinki Study of Very Low Birth Weight Adults.

Preterm birth is associated with an increased risk of type 2 diabetes in adult life. The mechanisms are poorly known. We studied insulin sensitivity and secretion in adults born preterm at very low birth weight (VLBW; < 1500 g). Longitudinal Birth Cohort Study (Helsinki Study of Very Low Birth Weight Adults). The study was conducted at Uusimaa, Finland. One hundred seven adults born at VLBW and 100 controls born at term not small for gestational age (SGA), group-matched for sex, age, and birth hospital. The mean age was 25.0 years. We performed a 14-sample intravenous glucose tolerance test and calculated insulin sensitivity (Si), insulin secretory response (AIR), and disposition index, by Minimal Model (Minmod Millennium®). Compared with controls, VLBW adults had lower Si (mean difference -11.9%, 95% CI -22.1 to -0.4%, adjusted for sex, age, and body mass index) and higher AIR (19.9%; 4.4-37.7%). The association with Si attenuated when further adjusted for height, parental diabetes, parental education, smoking, maternal smoking, hormonal contraception, and physical activity, but the association with AIR remained. Disposition index was similar. There was no difference between the 40 VLBW adults born SGA and the remaining VLBW adults. Adults born preterm at VLBW have lower insulin sensitivity than their term-born peers with a similar body size. In young adulthood, this remains compensated by higher insulin secretion. We suggest that this represents an early stage in the pathway leading to type 2 diabetes. Our results underline the importance of a healthy lifestyle and prompt vigilance in the screening of type 2 diabetes and impaired glucose tolerance in adults born preterm.

Maternal and child nutrition: The first 1,000 days

Maternal and child nutrition: The first 1,000 days

Application of Intima Media Thickness Measurement and Omics in Intrauterine Growth Restriction Disease

Intrauterine growth restriction is defined as a fetus with an estimated fetal weight less than 10th percentile for gestational age and cardiovascular changes, usually detected by means of Doppler ultrasonography. Noncommunicable diseases (such as cardiovascular diseases -CVD- and diabetes) still represent the main cause of mortality and morbidity in the industrialized world. Various studies support the hypothesis, formulated by Barker, that an adverse intrauterine environ-ment results in physiological adaptations of the fetus, maximizing its immediate chances for survival, but with detri-mental effects in adulthood. Low birth weight caused by IUGR was recently known to be associated with increased rates of CVD, non-insulin dependent diabetes in adult life, and neuromotor development alteration. The ultrasound-based measurement of fetal aorta intima media thickness (aIMT) represents an easy marker to investigate the pre-atherosclerotic changes. Omics research holds great promise for discoveries in nutrition research, including profiles and characteristics of dietary and body proteins; metabolism of nutrients; functions of nutrients and other dietary factors in growth, reproduction, and health. The proteome and metabolome analysis are expected to play an important role in understanding pathophysiological molecular mechanisms and in solving major nutrition-associated problems in humans, such as IUGR and cardiovascular disease. This review focuses the importance to identify a class of fetuses at risk of cardiovascular disease in utero, childhood and adult life, combining clinical and omics markers. It should be interesting to combine functional and structural information discovered to develop preventative and/or interventional therapeutic strategies.

Infant Nutrition and Later Health: A Review of Current Evidence

There is a growing recognition of the need for a lifecourse approach to understanding the aetiology of adult disease, and there is now significant evidence that links patterns of infant feeding to differences in health outcomes, both in the short and longer term. Breastfeeding is associated with lower rates of infection in infancy; in high-income populations, it is associated with reductions in blood pressure and total blood cholesterol, and lower risks of obesity and diabetes in adult life. Breastfeeding rates are suboptimal in many countries, and strategies to promote breastfeeding could therefore confer important benefits for health at a population level. However, there are particular challenges in defining nutritional exposures in infancy, including marked social gradients in initiation and duration of breastfeeding. In recent studies of low and middle-income populations of children and young adults, where the influences on infant feeding practice differ, beneficial effects of breastfeeding on blood pressure, BMI and risk of diabetes have not been confirmed, and further information is needed. Little is currently known about the long-term consequences of differences in the timing and nature of the weaning diet. Future progress will depend on new studies that provide detailed prospective data on duration and exclusivity of breastfeeding together with appropriate characterisation of the weaning diet.

Obesity in the pregnant diabetic population and delivery outcomes

IntroductionDiabetes is the most common pre-existing medical condition in pregnancy in the UK. The global obesity epidemic has led to an increase in the incidence of Type 2 Diabetes in...

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.