Risk Of Adult Metabolic Syndrome Research Articles

Body Mass Index and Its Change from Adolescence to Adulthood Are Closely Related to the Risk of Adult Metabolic Syndrome in China.

Aims To investigate the influence of body mass index (BMI) and its change from adolescence to adulthood (ΔBMI) on the risk of metabolic syndrome (MetS) in early adulthood. Methods We selected 931 students from 12 to 16 years of age in Liaoyang City, China. Ninety-three participants from 18 to 22 years of age with complete baseline data were available for follow-up after 5 years. Statistical analysis determined the relationship of MetS at follow-up with baseline BMI (BMIb), ΔBMI, and follow-up BMI (BMIf). Results ΔBMI was positively correlated with the change of waist circumference (ΔWC), systolic blood pressure (ΔSBP), triglycerides (ΔTG), uric acid, and glycosylated hemoglobin (ΔHbA1c) in follow-up (p < 0.05). For every 1 kg/m2 increase in BMIb, ΔBMI, and BMIf, the risk of MetS at follow-up increased 1.201-fold, 1.406-fold, and 1.579-fold, respectively. Both BMIb and ΔBMI were predictive of MetS at follow-up, with prediction thresholds of 23.47 kg/m2 and 1.95 kg/m2. The participants were divided by the predicted BMIb and ΔBMI threshold values into four study groups. Interestingly, the group with lower BMI but a higher increase in BMI presented the same metabolic derangements and Mets% of the group with higher BMI but lower Δ BMI. Conclusion Both BMI of adolescence and ΔBMI were predictive of MetS and cardiovascular risk factors in adulthood. Control of both variables in adolescents would be more effective in decreasing the risk of MetS in young adults than control of BMI alone.

Overweight or obesity in children aged 0 to 6 and the risk of adult metabolic syndrome: A systematic review and meta-analysis.

To identify an association between overweight or obesity in early childhood and metabolic syndrome in adults. Early childhood overweight or obesity is important because it can predict metabolic syndrome in adulthood. A longer period of overweight or obesity leads to the accumulation of more risk factors. However, there are insufficient and inconsistent studies on this issue. A systematic review and meta-analysis. We followed the Meta-Analysis of Observational Studies in Epidemiology guideline, MEDLINE, EMBASE, Cochrane library and CINAHL electronic databases as well as reference lists of included studies were searched, without published date restriction. We used the Newcastle-Ottawa Scale to assess the quality of the observational studies in the systematic review, and the meta-analysis was performed using random-effects models. All of the included studies were published from 2008-2014, and the participants of this study were only Asians or Europeans. A total of 12 results from five studies were included in the meta-analysis. Overweight or obesity in early childhood was associated with a higher risk of adult metabolic syndrome compared with the controls. When confirmed in each age group (at birth, 0-2 and 2-6years), there was a statistically significant difference before and after the age of 2years. As a result of the meta-regression, when the age of the children increased, the effect size of adult metabolic syndrome for overweight or obesity also increased. The results confirm that the aetiology of metabolic syndrome includes long-term impacts from the early stage of life and indicate that early intervention for overweight or obesity is needed. these findings could help community and clinical health nurses recognize the risk of overweight or obesity in early life, and provide evidence to develop and implement the preventive intervention for early childhood.

The structural alteration of gut microbiota in low-birth-weight mice undergoing accelerated postnatal growth.

The transient disruption of gut microbiota in infancy by antibiotics causes adult adiposity in mice. Accelerated postnatal growth (A) leads to a higher risk of adult metabolic syndrome in low birth-weight (LB) humans than in normal birth-weight (NB) individuals, but the underlying mechanism remains unclear. Here, we set up an experiment using LB + A mice, NB + A mice, and control mice with NB and normal postnatal growth. At 24 weeks of age (adulthood), while NB + A animals had a normal body fat content and glucose tolerance compared with controls, LB + A mice exhibited excessive adiposity and glucose intolerance. In infancy, more fecal bacteria implicated in obesity were increased in LB + A pups than in NB + A pups, including Desulfovibrionaceae, Enterorhabdus, and Barnesiella. One bacterium from the Lactobacillus genus, which has been implicated in prevention of adult adiposity, was enhanced only in NB + A pups. Besides, LB + A pups, but not NB + A pups, showed disrupted gut microbiota fermentation activity. After weaning, the fecal microbiota composition of LB + A mice, but not that of NB + A animals, became similar to that of controls by 24 weeks. In infancy, LB + A mice have a more dysbiotic gut microbiome compared to NB + A mice, which might increase their risk of adult metabolic syndrome.

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats.

Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P < 0.0001) and obese by adulthood (p160: 613 vs. 510 g; P < 0.0001). Dual energy X-ray absorptiometry studies revealed increased central fat mass (Δ+40 g), accompanied by dyslipidemic (>30% elevated, P < 0.05) serum triglycerides (139 mg/dl), very-LDLs (27.8 mg/dl), and fatty acids (632 µM). Hyperglycemic-euglycemic clamp studies and glucose tolerance testing revealed insulin resistance. Conversely, IUGR lineage ENS-fed rats did not manifest MetS, with significantly lower body weight (p160: 410 g), >5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and very-LDLs compared with IUGR control-fed F2 offspring (P < 0.01). Moreover, increased methylation of the IGF-1 P2 transcriptional start site among IUGR lineage F2 offspring was reversed in ENS (P < 0.04). This is an initial demonstration that supplementation along the one-carbon pathway abrogates adult morbidity and associated epigenomic modifications of IGF-1 in a rodent model of multigenerational MetS.

Early onset of fatty liver in growth‐restricted rat fetuses and newborns

Intrauterine growth-restricted (IUGR) newborns have increased risk of adult metabolic syndrome, including fatty liver. However, it is unclear whether the fatty liver development is "programmed" or secondary to the accompanying obesity. In this study, we examined hepatic lipid accumulation and lipid-regulatory factors (sterol regulatory element-binding protein-1c and fatty acid synthase) in IUGR and Control fetal (embryonic day 20; e20) and newborn (postnatal day 1; p1) rat pups. Notably, despite of in utero undernutrition state, IUGR fetuses demonstrated "fatty liver" with upregulation of these lipogenic indices at as early as e20. Both IUGR and Control newborns exhibited the same extent of massive increase in hepatic lipid content, whereas IUGR newborns continued to exhibit upregulated lipogenic indices. The persistent upregulation of the lipogenic indices in fetal and newborn IUGR suggests that fatty liver is gestationally programmed. Our study suggested that IUGR offspring were born with an altered metabolic life strategy of increased fuel/lipid storage which could be a distinct metabolic pathway of the thrifty phenotype.

Childhood Fitness Reduces the Long-term Cardio-metabolic Risks Associated with Childhood Obesity

PURPOSE: To examine whether childhood fitness attenuates or modifies the long-term cardio-metabolic risks associated with childhood obesity.FigureMETHODS: The study consisted of a 20-year follow-up of 1792 adults who participated in the 1985 Australian Schools Health and Fitness Survey when they were between 7 and 15 years of age. Baseline measures included a 1.6km run to assess cardiorespiratory fitness (CRF) and waist circumference (WC) measurement to assess abdominal adiposity. At follow-up, participants attended study clinics where component indicators of the Metabolic Syndrome (MetS) (WC, blood pressure, fasting blood glucose and lipids) were measured. RESULTS: Both high WC and low CRF in childhood were significant independent predictors of subsequent MetS in early adulthood. For example, the mutually adjusted relative risk of adult MetS was 3.1 (95% Confidence Interval (CI): 1.9-5.1) for children in the highest (vs. lowest) third of WC and 0.6 (95% CI: 0.4-0.9) for children with high (vs. low) CRF. Higher levels of CRF in childhood were associated with lower risks of adult MetS among those with either low or high childhood WC values, with similar risks being observed for those who were abdominally lean but unfit in childhood and those who had high levels of abdominal adiposity but were fit in childhood (see figure). Participants who had both high WC and low CRF in childhood were 8.5 times more likely to have MetS in adulthood than those who had low WC and high CRF in childhood. CONCLUSION: Childhood WC and CRF are both strongly associated with cardio-metabolic health in later life. Higher levels of CRF substantially reduce the risk of adult metabolic syndrome, even among those with abdominal obesity in childhood.

Neonatal Leptin Administration Alters Regional Brain Volumes and Blocks Neonatal Growth Restriction-Induced Behavioral and Cardiovascular Dysfunction in Male Mice

Premature delivery is often complicated by neonatal growth restriction (GR) and neurodevelopmental impairment. Because global overnutrition increases the risk of adult metabolic syndrome, we sought a targeted intervention. Premature delivery and perinatal GR decrease circulating levels of the neurotrophic hormone leptin. We hypothesized that leptin supplementation would normalize the outcomes of mice with incipient neonatal GR. Pups were fostered into litters of 6 or 12 to elicit divergent growth patterns. Pups in each litter received injections of saline or leptin from d 4 to 14. At 4 mo, mice underwent tail cuff blood pressure measurement, behavioral testing, and MRI. Mice fostered in litters of 12 had decreased weanling weights and leptin levels. Neonatal leptin administration normalized plasma leptin levels without influencing neonatal growth. Leptin replacement also normalized the hypertension, stress-linked immobility, conditioned fear, and amygdala enlargement seen in neonatal growth restricted male mice. In control males, neonatal leptin administration led to hypothalamic enlargement, without overt neurocardiovascular alterations. Female mice were less susceptible to the effects of neonatal GR or leptin supplementation. In conclusion, the effects of neonatal leptin administration are modulated by concurrent growth and gender. In growth restricted male mice, physiologic leptin replacement improves adult neurocardiovascular outcomes.

Altered placental development in undernourished rats: role of maternal glucocorticoids

Maternal undernutrition (MUN) during pregnancy may lead to fetal intrauterine growth restriction (IUGR), which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs) has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1), 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1) predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC) to corticosterone, although can sometimes drive the opposing (inactivating reaction), and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents) in control and MUN rats at embryonic day 20 (E20). Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3) and amino acids (SLC38A1, 2, and 4). Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC38A1, and SLC38A2 expression, and by increased SLC38A4 expression, in labyrinth zones from the mid- and proximal-horns. In marked contrast to the labyrinth zone, the basal zone, which is the site of hormone production, did not show significant changes in any of these enzymes or transporters. These results suggest that dysregulation of the labyrinth zone GC "barrier", and more importantly decreased nutrient supply resulting from downregulation of some of the amino acid system A transporters, may contribute to suboptimal fetal growth under MUN.

64: Pathogenesis of hepatic lipid dysregulation and inflammation in IUGR offspring: Downregulation of transcription factor PPAR

Intrauterine growth restricted newborns (IUGR) have increased risk of adult metabolic syndrome. In addition to obesity, hypertension and lipid abnormalities, human and animal studies also indicate associated pathology of “fatty liver” and hepatic inflammation. We have shown that maternal nutrient restriction in pregnancy results in IUGR pups which develop metabolic syndrome, as evidenced by increased body fat and elevated plasma triglyceride and the inflammatory marker C-reactive protein (CRP). Liver plays a central role in lipid homeostasis and is the source of CRP.

Metabolic Syndrome in Childhood Predicts Adult Metabolic Syndrome and Type 2 Diabetes Mellitus 25 to 30 Years Later

To prospectively assess the association of the metabolic syndrome in childhood with adult metabolic syndrome and type 2 diabetes mellitus (T2DM) 25 to 30 years later. Data from the National Heart Lung and Blood Institute Lipid Research Clinics (LRC) Princeton Prevalence Study (1973-1976) and the Princeton Follow-up Study (PFS, 2000-2004) were used. Body mass index (BMI = kg/m(2)) was used as the obesity measure in childhood because waist circumference was not measured at the LRC. The adult T2DM status of participants and their parents was obtained by participant report or fasting blood glucose >/=126 mg/dL. A logistic analysis for clustered samples was used to predict adult metabolic syndrome and T2DM, taking into account sibling correlations in the cohort. Pediatric metabolic syndrome, age at PFS, sex, race, change in BMI percentile, parental history of diabetes, and the interaction of pediatric metabolic syndrome and parental diabetes were explanatory variables. Ages ranged from 5 to 19 years in the LRC and from 30 to 48 years in the PFS. Pediatric metabolic syndrome, parental diabetes, age at follow-up, and change in age-specific BMI percentile were significant predictors of metabolic syndrome in adulthood, and pediatric metabolic syndrome, age at follow-up, black race, and parental diabetes were significant predictors of T2DM. Evaluating 5- to 19-year-old children for metabolic syndrome and family history of diabetes could identify children at increased risk of adult metabolic syndrome and T2DM, allowing prospective primary prevention of these outcomes.

Gender-specific programmed hepatic lipid dysregulation in intrauterine growth-restricted offspring

Intrauterine growth restriction demonstrates increased risk of adult metabolic syndrome. The associated hyperlipidemia results from obesity or programmed metabolic abnormalities. Because lipid homeostasis is regulated by the liver, we hypothesized that hepatic structure and lipid content in intrauterine growth restriction would reflect a primary lipid dysfunction. From 10 days to term gestation, control pregnant rats received ad libitum diet; study rats were 25% food-restricted (FR). All dams received ad libitum diet throughout lactation. At 3 weeks of age, hepatic lobule size and lipid profile of the pups were determined. At 3 weeks of age, body and liver weights of the pups were comparable with controls, although with reduced hepatic lobule size. FR males had increased hepatic triglyceride and cholesterol content with elevated sterol regulatory element-binding protein-1c, fatty acid synthase, and lipoprotein lipase expression; FR females exhibited decreased hepatic cholesterol levels. Plasma lipid levels were unchanged in FR males and females. Developmental programming results in sex-dependent altered lipid metabolism with increased risk in males.

Programmed hepatic lipid dysregulation is independent of obesity

Epidemiologic studies demonstrate that IUGR newborns are at increased risk of adult metabolic syndrome. It is unknown whether the associated hyperlipidemia is a direct result of obesity or is secondary to programmed metabolic abnormalities. As lipid homeostasis is regulated primarily by the liver, we hypothesized that hepatic structure and lipid content of IUGR offspring would reflect a primary lipid dysfunction.