Improved Learning and Memory in Aged Mice Deficient in Amyloid β-Degrading Neutral Endopeptidase

Background

Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-β (Aβ) degradation. The aim of our study was to explore the impact of NEP deficiency on the initial development of dementia-like symptoms in mice.

Methodology/Principal Findings

We found that while endogenous Aβ concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis using monoclonal antibodies did not detect any Aβ deposits even in old NEP knockout mice. Surprisingly, tests of learning and memory revealed that the ability to learn was not reduced in old NEP-deficient mice but instead had significantly improved, and sustained learning and memory in the aged mice was congruent with improved long-term potentiation (LTP) in brain slices of the hippocampus and lateral amygdala. Our data suggests a beneficial effect of pharmacological inhibition of cerebral NEP on learning and memory in mice due to the accumulation of peptides other than Aβ degradable by NEP. By conducting degradation studies and peptide measurements in the brain of both genotypes, we identified two neuropeptide candidates, glucagon-like peptide 1 and galanin, as first potential candidates to be involved in the improved learning in aged NEP-deficient mice.

Conclusions/Significance

Thus, the existence of peptides targeted by NEP that improve learning and memory in older individuals may represent a promising avenue for the treatment of neurodegenerative diseases.     

Serum Acylated Ghrelin Concentrations in Response to Short-Term Overfeeding in Normal Weight,Overweight, and Obese Men

Background

Ghrelin, an orexigenic gut hormone secreted primarily from the stomach, is involved in energy homeostasis. However, little data is available regarding its response to energy surplus and the development of human obesity.

Objective

The present study investigated the response of circulating acylated ghrelin to a 7-day positive energy challenge.

Design

A total of 68 healthy young men were overfed 70% more calories than required, for 1-week. Subjects were classified based on percent body fat (measured by dual-energy X-ray absorptiometry) as normal weight, overweight, and obese. Serum acylated ghrelin concentration was measured before and after the positive energy challenge. Additionally, the relationship between acylated ghrelin and obesity-related phenotypes including weight, body mass index, percent body fat, cholesterol, HDL-c, LDL-c, glucose, insulin and homeostasis model assessment of insulin resistance and β-cell function at baseline and change due to overfeeding, were assessed.

Results

Contrary to our expectations, serum acylated ghrelin was significantly increased in response to overfeeding and the increase was independent of obesity status. There was no significant difference in fasting acylated ghrelin between normal weight, overweight, and obese men at baseline. Acylated ghrelin was negatively correlated with weight and BMI for normal weight and with BMI in overweight men. Also ghrelin was correlated with change in weight and BMI in overweight (negative relationship) and obese (positive relationship) groups.

Conclusion

Our results showed that circulating acylated ghrelin was increased after a 7-day positive energy challenge regardless of adiposity status. However, acylated ghrelin was correlated with change in weight and BMI in opposing directions, in overweight and obese subjects respectively, thus dependent on obesity status.     

Vaccination against GIP for the treatment of obesity

Background

According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR^−/−) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity.

Methodology/Principal Findings

In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance.

Conclusions/Significance

This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans.     

Severe Obesity in Young Women and Reproductive Health: The Danish National Birth Cohort

Background

Little is known about reproductive health in severely obese women. In this study, we present associations between different levels of severe obesity and a wide range of health outcomes in the mother and child.

Methods

From the Danish National Birth Cohort, we obtained self-reported information about prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly selected women from the remaining cohort who served as a comparison group. Information about maternal and infant outcomes was also self-reported or came from registers. Logistic regression was used to estimate the association between different levels of severe obesity and reproductive outcomes.

Principal Findings

Subfecundity was more frequent in severely obese women, and during pregnancy, they had an excess risk of urinary tract infections, gestational diabetes, preeclampsia and other hypertensive disorders which increased with severity of obesity. They tended to have a higher risk of both pre- and post-term birth, and risk of cesarean and instrumental deliveries increased across obesity categories. After birth, severely obese women more often failed to initiate or sustain breastfeeding. Risk of weight retention 1.5 years after birth was similar to that of other women, but after adjustment for gestational weight gain, the risk was increased, especially in women in the lowest obesity category. In infants, increasing maternal obesity was associated with decreased risk of a low birth weight and increased risk of a high birth weight. Estimates for ponderal index showed the same pattern indicating an increasing risk of neonatal fatness with severity of obesity. Infant obesity measured one year after birth was also increased in children of severely obese mothers.

Conclusion

Severe obesity is correlated with a substantial disease burden in reproductive health. Although the causal mechanisms remain elusive, these findings are useful for making predictions and planning health care at the individual level.     

Physical Deconditioning as a Cause of Breathlessness among Obese Adolescents with a Diagnosis of Asthma

Background

Obese children frequently complain of breathlessness. Asthma and obesity can both contribute to the symptoms during exercise, and this symptom can contribute to a diagnosis of asthma in these children. Despite the high prevalence of obesity few studies have investigated the cardiopulmonary physiology of breathlessness in obese children with a diagnosis of asthma.

Methods

In this case-control study, thirty adolescents between age 12 and 19 were studied with baseline spirometry and a cardiopulmonary exercise test. Ten adolescents were normal controls, ten had obesity without a diagnosis of asthma, and ten had obesity with a history of physician-diagnosed asthma.

Results

Baseline characteristics including complete blood count and spirometry were comparable between obese adolescents with and without a diagnosis of asthma. During exercise, obese asthmatic and obese non-asthmatic adolescents had significantly reduced physical fitness compared to healthy controls as evidenced by decreased peak oxygen uptake after adjusting for actual body weight (21.7±4.5 vs. 21.4±5.4 vs. 35.3±5.8 ml/kg/min, respectively). However, pulmonary capacity at the peak of exercise was comparable among all three groups as evidenced by similar pulmonary reserve.

Conclusion

In this study, breathlessness was primarily due to cardiopulmonary deconditioning in the majority of obese adolescents with or without a diagnosis of asthma.     

Lifelong Obesity in a Polygenic Mouse Model Prevents Age- and Diet-Induced Glucose Intolerance– Obesity Is No Road to Late-Onset Diabetes in Mice

Aims/Hypothesis

Visceral obesity holds a central position in the concept of the metabolic syndrome characterized by glucose intolerance in humans. However, until now it is unclear if obesity by itself is responsible for the development of glucose intolerance.

Methods

We have used a novel polygenic mouse model characterized by genetically fixed obesity (DU6) and addressed age- and high fat diet-dependent glucose tolerance.

Results

Phenotype selection over 146 generations increased body weight by about 2.7-fold in male 12-week DU6 mice (P<0.0001) if compared to unselected controls (Fzt:DU). Absolute epididymal fat mass was particularly responsive to weight selection and increased by more than 5-fold (P<0.0001) in male DU6 mice. At an age of 6 weeks DU6 mice consumed about twice as much food if compared to unselected controls (P<0.001). Absolute food consumption was higher at all time points measured in DU6 mice than in Fzt:DU mice. Between 6 and 12 weeks of age, absolute food intake was reduced by 15% in DU6 mice (P<0.001) but not in Fzt:DU mice. In both mouse lines feeding of the high fat diet elevated body mass if compared to the control diet (P<0.05). In contrast to controls, DU6 mice did not display high fat diet-induced increases of epididymal and renal fat. Control mice progressively developed glucose intolerance with advancing age and even more in response to the high fat diet. In contrast, obese DU6 mice did neither develop a glucose intolerant phenotype with progressive age nor when challenged with a high fat diet.

Conclusions/Interpretation

Our results from a polygenic mouse model demonstrate that genetically pre-determined and life-long obesity is no precondition of glucose intolerance later in life.     

Prevalence of Overweight and Obesity and Weight Loss Practice among Beijing Adults, 2011

Objective

This study aims to determine the up-to-date prevalence of overweight and obesity, the distributions of body weight perception and weight loss practice in Beijing adults.

Methods

A cross-sectional study was conducted in 2011. A total of 2563 men and 4088 women aged 18–79 years from the general population were included. Data were obtained from questionnaire and physical examination.

Results

The prevalence of overweight (BMI 24–27.9 kg/m²) and obesity (BMI≥28 kg/m²) was 42.1% and 20.3% in men and 35.6% and 17.1% in women, respectively. Age was inversely associated with overweight in both sexes, and obesity in women. Education level was negatively associated with overweight and obesity in women but not in men. Only 49.1% men and 58.3% women had a correct perception of their body weight. Underestimation of body weight was more common than overestimation, especially in men, the older people, and those with low education level. The percentage of taking action to lose weight was inversely associated with men and old age, and positively associated with higher education level, higher BMI, and self-perception as “fat” (OR = 3.78 in men, OR = 2.91 in women). Only 26.1% of overweight/obese individuals took action to lose weight. The top two weight loss practices were to reduce the amount of food intake and exercise.

Conclusion

Overweight and obesity were highly prevalent with high incorrect body weight perceptions in the general adult population in Beijing. Weight loss practice was poor in overweight and obese individuals. Actions at multiple levels are needed to slow or control this overweight and obesity epidemic.     

Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model

Background

Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice.

Methodology/Principal Findings

Male TSP1-/- mice and wild type littermate controls were fed a low-fat (LF) or a high-fat (HF) diet for 16 weeks. Throughout the study, body weight and fat mass increased similarly between the TSP1-/- mice and WT mice under HF feeding conditions, suggesting that TSP1 deficiency does not affect the development of obesity. However, obese TSP1-/- mice had improved glucose tolerance and increased insulin sensitivity compared to the obese wild type mice. Macrophage accumulation and inflammatory cytokine expression in adipose tissue were reduced in obese TSP1-/- mice. Consistent with the local decrease in pro-inflammatory cytokine levels, systemic inflammation was also decreased in the obese TSP1-/- mice. Furthermore, in vitro data demonstrated that TSP1 deficient macrophages had decreased mobility and a reduced inflammatory phenotype.

Conclusion

TSP1 deficiency did not affect the development of high-fat diet induced obesity. However, TSP1 deficiency reduced macrophage accumulation in adipose tissue and protected against obesity related inflammation and insulin resistance. Our data demonstrate that TSP1 may play an important role in regulating macrophage function and mediating obesity-induced inflammation and insulin resistance. These data suggest that TSP1 may serve as a potential therapeutic target to improve the inflammatory and metabolic complications of obesity.     

Adult Type 3 Adenylyl Cyclase–Deficient Mice Are Obese

Background

A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time.

Methodology/Principal Findings

We discovered that AC3^−/− mice become obese as they age. Adult male AC3^−/− mice are about 40% heavier than wild type male mice while female AC3^−/− are 70% heavier. The additional weight of AC3^−/− mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3^−/− mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3^−/− mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis.

Conclusions/Significance

We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight.     

Weight and metabolic effects of CPAP in obstructive sleep apnea patients with obesity

Background

Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.

Methods

In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.

Results

CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.

Conclusions

Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.     

Parent-Child Resemblance in Weight Status and Its Correlates in the United States

Background

Few studies have examined parent-child resemblance in body weight status using nationally representative data for the US.

Design

We analyzed Body Mass Index (BMI), weight status, and related correlates for 4,846 boys, 4,725 girls, and their parents based on US nationally representative data from the 2006 and 2007 Medical Expenditure Panel Survey (MEPS). Pearson partial correlation coefficients, percent agreement, weighted kappa coefficients, and binary and multinomial logistic regression were used to examine parent-child resemblance, adjusted for complex sampling design.

Results

Pearson partial correlation coefficients between parent and child’s BMI measures were 0.15 for father-son pairs, 0.17 for father-daughter pairs, 0.20 for mother-son pairs, and 0.23 for mother-daughter pairs. The weighted kappa coefficients between BMI quintiles of parent and child ranged from −0.02 to 0.25. Odds ratio analyses found children were 2.1 (95% confidence interval (CI): 1.6, 2.8) times more likely to be obese if only their father was obese, 1.9 (95% CI: 1.5, 2.4) times more likely if only their mother was obese, and 3.2 (95% CI: 2.5, 4.2) times more likely if both parents were obese.

Conclusions

Parent-child resemblance in BMI appears weak and may vary across parent-child dyad types in the US population. However, parental obesity status is associated with children’s obesity status. Use of different measures of parent-child resemblance in body weight status can lead to different conclusions.     

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

Objective

Acute administration of cannabinoid CB₁ receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice.

Methods

Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally.

Results

THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice.

Conclusions

Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.     

Measured parental weight status and familial socio-economic status correlates with childhood overweight and obesity at age 9

Background

Parental obesity is a predominant risk factor for childhood obesity. Family factors including socio-economic status (SES) play a role in determining parent weight. It is essential to unpick how shared family factors impact on child weight. This study aims to investigate the association between measured parent weight status, familial socio-economic factors and the risk of childhood obesity at age 9.

Methodology/Principal Findings

Cross sectional analysis of the first wave (2008) of the Growing Up in Ireland (GUI) study. GUI is a nationally representative study of 9-year-old children (N = 8,568). Schools were selected from the national total (response rate 82%) and age eligible children (response rate 57%) were invited to participate. Children and their parents had height and weight measurements taken using standard methods. Data were reweighted to account for the sampling design. Childhood overweight and obesity prevalence were calculated using International Obesity Taskforce definitions. Multinomial logistic regression examined the association between parent weight status, indicators of SES and child weight. Overall, 25% of children were either overweight (19.3%) or obese (6.6%). Parental obesity was a significant predictor of child obesity. Of children with normal weight parents, 14.4% were overweight or obese whereas 46.2% of children with obese parents were overweight or obese. Maternal education and household class were more consistently associated with a child being in a higher body mass index category than household income. Adjusted regression indicated that female gender, one parent family type, lower maternal education, lower household class and a heavier parent weight status significantly increased the odds of childhood obesity.

Conclusions/Significance

Parental weight appears to be the most influential factor driving the childhood obesity epidemic in Ireland and is an independent predictor of child obesity across SES groups. Due to the high prevalence of obesity in parents and children, population based interventions are required.     

Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice

Background

Glucagon-like peptide-1 (GLP-1) is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a non-peptidic GLP-1 receptor (GLP-1R) agonist. While its oral bioavailability still poses significant challenges, Boc5, one of the first such compounds, has demonstrated the attainment of GLP-1R agonism in diabetic mice. The present work was to investigate whether subchronic Boc5 treatment can restore glycemic control and induce sustainable weight loss in diet-induced obese (DIO) mice, an animal model of human obesity and insulin resistance.

Methodology/Principal Findings

DIO mice were treated three times a week with Boc5 (0.3, 1 and 3 mg) for 12 weeks. Body weight, body mass index (BMI), food intake, fasting glucose, intraperitoneal glucose tolerance and insulin induced glucose clearance were monitored regularly throughout the treatment. Glucose-stimulated insulin secretion, β-cell mass, islet size, body composition, serum metabolic profiles, lipogenesis, lipolysis, adipose hypertrophy and lipid deposition in the liver and muscle were also measured after 12 weeks of dosing. Boc5 dose-dependently reduced body weight, BMI and food intake in DIO mice. These changes were associated with significant decreases in fat mass, adipocyte hypertrophy and peripheral tissue lipid accumulation. Boc5 treatment also restored glycemic control through marked improvement of insulin sensitivity and normalization of β-cell mass. Administration of Boc5 (3 mg) reduced basal but enhanced insulin-mediated glucose incorporation and noradrenaline-stimulated lipolysis in isolated adipocytes from obese mice. Furthermore, circulating leptin, adiponectin, triglyceride, total cholesterol, nonesterified fatty acid and high-density lipoprotein/low-density lipoprotein ratio were normalized to various extents by Boc5 treatment.

Conclusions/Significance

Boc5 may produce metabolic benefits via multiple synergistic mechanisms and may represent an attractive tool for therapeutic intervention of obesity and diabetes, by means of non-peptidic GLP-1R agonism.     

Sarcopenia as a Determinant of Blood Pressure in Older Koreans: Findings from the Korea National Health and Nutrition Examination Surveys (KNHANES) 2008–2010

Background

Blood pressure (BP) is directly and causally associated with body size in the general population. Whether muscle mass is an important factor that determines BP remains unclear.

Objective

To investigate whether sarcopenia is associated with hypertension in older Koreans.

Participants

We surveyed 2,099 males and 2,747 females aged 60 years or older.

Measurements

Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight (ASM/Wt) that was <1 SD below the gender-specific mean for young adults. Obesity was defined as a body mass index (BMI) ≥25 kg/m². Subjects were divided into four groups based on presence or absence of obesity or sarcopenia. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg, a diastolic BP (DBP) ≥90 mmHg, or a self-reported current use of antihypertensive medications.

Results

The overall prevalence of hypertension in the four groups was as follows 49.7% for non-obese non-sarcopenia, 60.9% for non-obese sarcopenia, 66.2% for obese non-sarcopenia and 74.7% for obese sarcopenia. After adjustment for age, gender, regular activity, current smoking and alcohol use, the odds ratio (OR) for having hypertension was 1.5 (95% confidence interval (CI) = 1.23–1.84) in subjects in the non-obese sarcopenia group, 2.08 (95% CI = 1.68–2.57) in the obese non-sarcopenia group and 3.0 (95% CI = 2.48–3.63) in the obese sarcopenia group, compared with the non-obese non-sarcopenia group (p for trend <0.001). Controlling further for body weight and waist circumference did not change the association between hypertension and sarcopenia. The association between sarcopenia and hypertension was more robust in the subjects with diabetes mellitus.

Conclusion

Body composition beyond BMI has a considerable impact on hypertension in elderly Koreans. Subjects with sarcopenic obesity appear to have a greater risk of hypertension than simply obese or sarcopenia subjects.     

Increased Hepatic Insulin Action in Diet-Induced Obese Mice Following Inhibition of Glucosylceramide Synthase

Background

Obesity is characterized by the accumulation of fat in the liver and other tissues, leading to insulin resistance. We have previously shown that a specific inhibitor of glucosylceramide synthase, which inhibits the initial step in the synthesis of glycosphingolipids (GSLs), improved glucose metabolism and decreased hepatic steatosis in both ob/ob and diet-induced obese (DIO) mice. Here we have determined in the DIO mouse model the efficacy of a related small molecule compound, Genz-112638, which is currently being evaluated clinically for the treatment of Gaucher disease, a lysosomal storage disorder.

Methodology/Principal Findings

DIO mice were treated with the Genz-112638 for 12 to 16 weeks by daily oral gavage. Genz-112638 lowered HbA1c levels and increased glucose tolerance. Whole body adiposity was not affected in normal mice, but decreased in drug-treated obese mice. Drug treatment also significantly lowered liver triglyceride levels and reduced the development of hepatic steatosis. We performed hyperinsulinemic-euglycemic clamps on the DIO mice treated with Genz-112638 and showed that insulin-mediated suppression of hepatic glucose production increased significantly compared to the placebo treated mice, indicating a marked improvement in hepatic insulin sensitivity.

Conclusions/Significance

These results indicate that GSL inhibition in obese mice primarily results in an increase in insulin action in the liver, and suggests that GSLs may have an important role in hepatic insulin resistance in conditions of obesity.     

Impact of Obesity on Pregnancy Outcome in Different Ethnic Groups: Calculating Population Attributable Fractions

Objectives

To quantify the proportion of adverse pregnancy outcome attributable to maternal obesity.

Design

Cross sectional analysis of routine obstetric dataset.

Setting

Guy’s and St Thomas’s NHS Foundation Trust (GSTFT).

Population

23,668 women who had singleton deliveries at GSTFT between 2004 and 2008.

Methods

Logistic regression was used to estimate the association between BMI and outcome in different ethnic groups. Adjusted odds ratios, and the proportions of obese women, were used to calculate population attributable risk fractions (PAFs).

Main Outcome Measures

(i) Maternal outcomes: diabetes, type of delivery, post-partum haemorrhage, and preterm delivery. (ii) Perinatal outcomes: macrosomia, low birth weight, admission to neonatal intensive care/special care baby unit, and perinatal death.

Results

The prevalence of maternal obesity was 14%. Increasing BMI was independently associated with increasing risk of adverse obstetric and neonatal outcome. At the individual level, the effect of obesity on diabetes was highest in Asian women compared to white women (p for interaction = 0.03). Calculation of population attributable risk fractions demonstrated that one third of diabetes cases and one in six Caesarean sections could be avoided in this population if all obese women were of normal BMI. At the population level, the contribution of obesity to diabetes was highest for Black women (42%), and lowest for oriental women (8%). Seven percent of neonatal macrosomia in all the population, and 13% in Black mothers, were attributable to obesity.

Conclusions

Preventing obesity prior to pregnancy will substantially reduce the burden of obstetric and neonatal morbidity in this population. This reduction will be higher in Black women.     

Increase in prevalence of overweight in Dutch children and adolescents: a comparison of nationwide growth studies in 1980, 1997 and 2009

Objective

To assess the prevalence of overweight and obesity among Dutch children and adolescents, to examine the 30-years trend, and to create new body mass index reference charts.

Design

Nationwide cross-sectional data collection by trained health care professionals.Participants: 10,129 children of Dutch origin aged 0–21 years.

Main Outcome Measures

Overweight (including obesity) and obesity prevalences for Dutch children, defined by the cut-off values on body mass index references according to the International Obesity Task Force.

Results

In 2009, 12.8% of the Dutch boys and 14.8% of the Dutch girls aged 2–21 years were overweight and 1.8% of the boys and 2.2% of the girls were classified as obese. This is a two to three fold higher prevalence in overweight and four to six fold increase in obesity since 1980. Since 1997, a substantial rise took place, especially in obesity, which increased 1.4 times in girls and doubled in boys. There was no increase in mean BMI SDS in the major cities since 1997.

Conclusions

Overweight and obesity prevalences in 2009 were substantially higher than in 1980 and 1997. However, the overweight prevalence stabilized in the major cities. This might be an indication that the rising trend in overweight in the Netherlands is starting to turn.