A common haplotype in NAPEPLD is associated with severe obesity in a Norwegian population-based cohort (the HUNT study)

Obesity has a strong genetic etiology involving numerous identified metabolic pathways and others not yet examined. We investigated the association between severe obesity and genetic variation in selected candidate genes, including three drug-related genes: cannabinoid receptor 1 (CNR1), N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), and gastric lipase (LIPF); and three genes related to inflammation: nicotinamide phosphoribosyltransferase, six-transmembrane epithelial antigen of the prostate 4 (STEAP4) and interleukin 18 (IL-18). Subjects were 1,632 individuals with severe obesity (BMI ≥ 35 kg/m2) and 3,379 controls (BMI 20-24.9 kg/m2) that took part in a Norwegian population based cohort study. Tagging single-nucleotide polymorphisms (SNPs) of the coding region of these genes were analyzed. SNP-haplotypes for each gene were constructed in order to analyze allelic, genotypic, and haplotypic association to obesity. A single SNPs rs17605251 in NAPEPLD was nominally associated with BMI ≥ 35 kg/m2 (P = 0.035). A common haplotype in NAPEPLD was associated with BMI ≥ 35 kg/m2 after correction for multiple testing. The allele frequency was 56.8% in cases and 60.3% in controls, giving an odds ratio (OR) of 0.87 (95% confidence interval (CI) 0.79, 0.95; P = 0.0016). Homozygosity for this haplotype was protective against obesity (OR 0.79 (CI 0.70-0.91); P = 0.00059). The SNP rs7913071 in LIPF was associated with obesity, but the association lost statistical significance after correction for multiple testing. The CNR1, IL-18, STEAP4, and nicotinamide phosphoribosyltransferase genes were not associated with obesity. In conclusion a common haplotype in NAPEPLD, an enzyme involved in endocannabinoid synthesis, was protective against obesity.     

Race, childhood insulin, childhood caloric intake, and class 3 obesity at age 24: 14-year prospective study of schoolgirls

The prevalence of Class 3 obesity (BMI ≥40 kg/m²) has more than doubled in the past 25 years. In a 14‐year prospective study from age 10 to 24 of a biracial schoolgirl cohort (293 black, 256 white), we assessed childhood correlates of Class 3 BMI at age 24. Of 42 girls with Class 3 BMI at age 24, 36 (86%) were black. By logistic regression, significant explanatory variables of Class 3 BMI at age 24 included top decile waist circumference at age 11 (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.3–13.9, P = 0.0002), age 10 BMI ≥ the Center for Disease Control (CDC) 2000 top 15% (OR 7.0, 95% CI 2.5–19.3, P = 0.0002), and a three‐way interaction between race, childhood insulin, and average caloric intake from age 10 to age 19 (for each unit increase, OR 1.7 95% CI 1.3–2.2, P = 0.0003). Age 10 BMI, age 11 waist circumference, and interaction of race, childhood insulin, and childhood caloric intake predict Class 3 obesity in young adulthood, facilitating childhood identification of girls at high risk for developing Class 3 obesity.     

Higher prevalence of obesity among children with asthma

The aim of this study is to investigate the association between childhood obesity and asthma, and whether this relationship varies by race/ethnicity. For this population-based, cross-sectional study, measured weight and height, and asthma diagnoses were extracted from electronic medical records of 681,122 patients aged 6-19 years who were enrolled in an integrated health plan 2007-2009. Weight class was assigned based on BMI-for-age. Overall, 18.4% of youth had a history of asthma and 10.9% had current asthma. Adjusted odds of current asthma for overweight, moderately obese, and extremely obese youth relative to those of normal weight were 1.22 (95% confidence interval (CI): 1.20, 1.24), 1.37 (95% CI: 1.34, 1.40), and 1.68 (95% CI: 1.64, 1.73), respectively (P trend < 0.001). Black youth are nearly twice as likely (adjusted odds ratio (OR) = 1.93, 95% CI: 1.89, 1.99), and Hispanic youth are 25% less likely (adjusted OR = 0.75, 95% CI: 0.74, 0.77), to have current asthma than to non-Hispanic white youth. However, the relationship between BMI and asthma was strongest in Hispanic and weakest in black youth. Among youth with asthma, increasing body mass was associated with more frequent ambulatory and emergency department visits, as well as increased inhaled and oral corticosteroid use. In conclusion, overweight, moderate, and extreme obesity are associated with higher odds of asthma in children and adolescents, although the association varies widely with race/ethnicity. Increasing BMI among youth with asthma is associated with higher consumption of corticosteroids and emergency department visits.     

Breastfeeding and subsequent maternal visceral adiposity

Women gain visceral fat during pregnancy. Studies examining the impact of breastfeeding on maternal body composition are inconclusive. We examined the extent to which breastfeeding was associated with visceral adiposity in a sample of US women. This was a cross-sectional analysis of 351 women aged 45-58 years, who were free of clinical cardiovascular disease and had not used oral contraceptives or hormone replacement therapy in the 3 months prior to enrollment in the Study of Women's Health Across the Nation (SWAN)-Heart Study (2001-2003). History of breastfeeding was self-reported. Computed tomography was used to assess abdominal adiposity. Among premenopausal/early-peri-menopausal mothers, those who never breastfed had 28% greater visceral adiposity (95% confidence interval (CI): 11-49, P = 0.001), 4.7% greater waist-hip ratio (95% CI: 1.9-7.4, P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71-9.26, P < 0.001) than mothers who breastfed all of their children for ≥3 months in models adjusting for study site; age; parity; years since last birth; socioeconomic, lifestyle, and family history variables; early adult BMI; and current BMI. In comparison to women who were nulliparous, mothers who breastfed all of their children for ≥3 months had similar amounts of visceral fat (P > 0.05). In contrast, premenopausal/early-peri-menopausal mothers who had never breastfed had significantly greater visceral adiposity (42% (95% CI: 17-70), P < 0.001), waist circumference (6.15 cm (95% CI: 2.75-9.56), P < 0.001), and waist-hip ratio (3.7% (95% CI: 0.69-6.8), P = 0.02) than nulliparous women. No significant relationships were observed among late peri-menopausal/postmenopausal women. In conclusion, until menopause, mothers who did not breastfeed all of their children for ≥3 months exhibit significantly greater amounts of metabolically active visceral fat than mothers who had breastfed all of their children for ≥3 months.     

Obesity paradox in amputation risk among nonelderly diabetic men

The association between BMI and amputation risk is not currently well known. We used data for a cohort of diabetic patients treated in the US Department of Veterans Affairs Healthcare System in 2003. Men aged <65 years at the end of follow-up were examined for their amputation risk and amputation-free survival during the next 5 years (2004-2008). Compared to overweight individuals (BMI 25-29.9 kg/m(2)), the risks of amputation and treatment failure (amputation or death) were higher for patients with BMI <25 kg/m(2) and were lower for those with BMI ≥30 kg/m(2). Individuals with BMI ≥40 kg/m(2) were only half as likely to experience any (hazard ratios (HR) = 0.49; 95% confidence interval (CI), 0.30-0.80) and major amputations (HR = 0.53; 95% CI, 0.39-0.73) during follow-up as overweight individuals. While the amputation risk continued to decrease for higher BMI, amputation-free survival showed a slight upturn at BMI >40 kg/m(2). The association between obesity and amputation risk in our data shows a pattern consistent with "obesity paradox" observed in many health conditions. More research is needed to better understand pathophysiological mechanisms that may explain the paradoxical association between obesity and lower-extremity amputation (LEA) risk.     

Obesity and physical activity among Aboriginal Canadians

Objective: To investigate ethnic differences in obesity and physical activity among Aboriginal and non‐Aboriginal Canadians. Methods and Procedures: The sample included 24,279 Canadians (1,176 Aboriginals, 23,103 non‐Aboriginals) aged 2–64 years from the 2004 Canadian Community Health Survey (CCHS). Adult participants were classified as underweight/normal weight, overweight (BMI 25–29.9 kg/m²) or obese (BMI ≥ 30 kg/m²). Children and youth 2–17 years of age were classified as normal weight, overweight or obese based on the International Obesity Task Force criteria. Leisure‐time physical activity levels over the previous 3 months were obtained by questionnaire in those aged 12–64 years. Results: The prevalence of obesity in adults was 22.9% (men: 22.9%; women: 22.9%), and the prevalence was higher among Aboriginals (37.8%) compared to non‐Aboriginals (22.6%). The prevalence of obesity in children and youth was 8.2% (boys: 9.2%; girls: 7.2%), and the prevalence was higher among Aboriginals (15.8%) compared to non‐Aboriginals (8.0%). In both youth and adults, the odds for obesity were higher among Aboriginals (youth: OR = 2.3 (95% CI: 1.4–3.8); adults: OR = 2.4 (95% CI: 1.6–3.6)) after adjustment for a number of covariates. There were no ethnic differences in the prevalence of physical inactivity; however, physical inactivity was a predictor of obesity in both the Aboriginal and non‐Aboriginal samples. Discussion: The prevalence of obesity is higher among Canadian Aboriginals compared to the rest of the population. Further research is required to better delineate the determinants of obesity and the associated health consequences in this population.     

Prospective associations between measures of adiposity and periodontal disease

Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for ≤20 years (1986-2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m(2)), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI ≥30 kg/m(2) compared to BMI 18.5-24.9 kg/m(2) was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17-1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11-1.46; WHR = 1.34, 95% CI: 1.17-1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance.     

Associations among Lipids, Leptin, and Leptin Receptor Gene Gin223Arg Polymorphisms and Breast Cancer in China

We evaluated the relationship among the leptin receptor (LEPR) gene Gln223Arg polymorphism, body mass index (BMI), waist and hip circumference ratio (WHR), dietary structure, lifestyle, and other biomarkers with breast cancer and determined whether they could be effective for the prevention and treatment of breast cancer. The Gln223Arg polymorphisms in the LEPR gene were investigated in blood deoxyribonucleic acid (DNA) available for 240 breast cancer cases and 500 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Leptin, insulin were determined by enzyme-linked immunosorbent assays. We found that the serum levels of leptin, insulin, triglyceride (TG), free cholesterol (FCH), apolipoprotain (APO) A1, and BMI were significantly higher in breast cancer cases than the controls, while physical activity was clearly less in breast cancer cases (P < 0.02 approximately P < 0.001, respectively). Moreover, there were significant association between the Gln223Arg genotype and breast cancer risk; homozygotes for AA and heterozygotes for AG,AG + GG genotypes had been proved to increase the risk of breast cancer, and their corresponding odds ratio were 7.14 (95% confidence interval [CI] = 1.92-25.64), 1.33(95% CI = 1.03-2.70), and 2.04 (95% CI = 1.09-3.82). Interestingly, logistic regression analysis showed that LEPR gene Gln223Arg polymorphism and elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB increased the risk of developing breast cancer, respectively. And, it also suggested that LEPR gene Gln223Arg polymorphisms, elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB should play a major role in the development of breast cancer.     

Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation

In order to understand the role of the insulin receptor substrate-2 (IRS2) gene (chromosome region: 13q34) in obesity, a complex disorder associated with insulin resistance and glucose intolerance, we determined single nucleotide polymorphims (SNPs) and complex haplotypes in women with morbid obesity and a body mass index (BMI) of 41+/-0.8 kg/m2 ( n=99) compared with controls having a BMI of 23.8+/-0.1 kg/m2 ( n=92). Sequencing of unphased DNA or digestion of polymerase chain reaction fragments revealed seven SNPs, including a new C/T(-769) replacement at the 5' untranslated region. Considering four or seven SNPs, we reconstructed with the PHASE program nine or 24 haplotypes, respectively, that were well correlated into the cladogram. Logistic regression analysis with nine haplotypes in the whole sample revealed that obesity was associated with haplotype H3, with P<0.025, an odds ratio (OR) of 1.9 and a 95% confidence interval (CI) of 1.1-3.4, or pairs 3/3 ( P<0.005, OR=8.7, CI=1.9-40.1) and 3/4 ( P<0.023, OR=2.5, CI=1.1-5.6), all containing the the Gly1057Asp allelic variant of IRS2, whereas controls were associated with H5 and H6 ( P<0.02, OR=0.2, CI=0.01-0.81). Although obese H5 carriers (also containing Gly1057Asp mutation) were the most insulin resistant, haplotypes of IRS2 were poorly correlated (analysis of variance) with insulin resistance. By contrast, haplotypes H3, H4 and pairs 3/3 were consistently associated with increased 2-h glucose levels during an oral glucose tolerance test in obese individuals ( P<0.0005, 0.025 and 0.027, respectively). These data indicate that IRS2 is an influential gene in severe obesity and glucose intolerance in this population, whereas gene-based haplotypes of IRS2 have revealed heterogeneity in the behaviour of the Gly1057Asp mutation in relation to insulin resistance.     

Discordant risk: Overweight and cardiometabolic risk in Chinese adults

Objective:

Recent US work identified “metabolically healthy overweight” and “metabolically at risk normal weight” individuals. Less is known for modernizing countries with recent increased obesity.

Design and Methods:

Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18‐98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI ≥23 kg/m²) and five risk factors (prediabetes/diabetes (hemoglobin A1c ≥5.7%) inflammation (high‐sensitivity C‐reactive protein (hsCRP) ≥3 mg/l), prehypertension/hypertension (Systolic blood pressure/diastolic blood pressure≥130/85 mm Hg), high triglycerides (≥150 mg/dl), low high‐density lipoprotein cholesterol (<40 (men)/ <50 mg/dl (women)). Sex‐stratified, logistic, and multinomial logistic regression models estimated concurrent obesity and cardiometabolic risk, with and without abdominal obesity, adjusting for age, smoking, alcohol consumption, physical activity, urbanicity, and income.

Results:

Irrespective of urbanicity, 78.3% of the sample had ≥1 elevated cardiometabolic risk factor (normal weight: 33.2% had ≥1 elevated risk factor; overweight: 5.7% had none). At the age of 18‐30 years, 47.4% had no elevated risk factors, which dropped to 6% by the age 70, largely due to age‐related increase in hypertension risk (18‐30 years: 11%; >70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., “metabolically at risk overweight” relative to “metabolically healthy normal weight” (men: relative risk ratio (RRR) = 39.06; 95% confidence interval (CI): 23.47, 65.00; women: RRR = 22.26; 95% CI: 17.49, 28.33)).

Conclusion:

A large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic‐related outcomes dependent upon overweight will likely miss a large portion of the Chinese at risk population.     

Maternal obesity is associated with younger age at obesity onset in U.S. adolescent offspring followed into adulthood

Objective: The objective was to test the hypothesis that maternal obesity is associated with younger age of offspring's obesity onset. Research Methods and Procedures: We used prospective, nationally representative, longitudinal data collected across Waves I (1995; 12 to 20 years), II (1996; 13 to 20 years), and III (2001; 18 to 28 years) of the National Longitudinal Study of Adolescent Health (N = 14,654; 49% female). Interval regression analysis was used to assess the association between maternal obesity and age at offspring's obesity onset (International Obesity Task Force BMI ≥30 equivalent age‐ and sex‐specific cut‐off points for adolescents and BMI ≥30 for young adults) using self‐reported heights and weights, adjusting for race/ethnicity, sex, parental education, and family income, accounting for complex sampling design. Results: The net effect of having an obese mother varied by race/ethnicity and was associated with a significantly earlier age at obesity onset (p = 0.0001) for whites [β= ?8.1 year, 95% confidence interval (CI), ?9.3; ?6.9)], blacks (β = ?10.8 years, 95% CI, ?12.4; ?9.2), Hispanics (β = ?7.0 years, 95% CI, ?9.2; ?4.8), and Asians (β = ?8.6 years, 95% CI, ?13.3; ?3.9). Earlier obesity onset (<18 years) was associated with increased severity at young adulthood (mean BMI, 36.0 ± 0.3 kg/m²) vs. onset after age 18 (mean BMI, 34.4 ± 0.2 kg/m²; p = 0.0001). There were no sex differences in the association of maternal obesity to age at obesity onset. Conclusions: Having an obese mother was associated with earlier age at obesity onset across all race/ethnic groups, particularly non‐Hispanic blacks. Early obesity onset has important health consequences because of its association with more severe adult obesity.     

Sex-specific associations of adiposity with cardiometabolic traits in the UK: A multi–life stage cohort study with repeat metabolomics

BackgroundSex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages.Methods and findingsData were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B–containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m²) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m²) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required.ConclusionsThe results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.

Linda O’Keeffe and colleagues investigate sex-specific associations between cardiometabolomic traits and BMI, fat mass, and waist circumference across childhood, adolescence, early adulthood, and mid life in two generations of a UK population-based birth cohort.     

Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico

Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.     

Anthropometric risk factors for colorectal polyps in African-American women

Objective: Colorectal adenomas are thought to be precursor lesions to colorectal cancer, a leading cause of cancer incidence and mortality in African‐American women. Studies suggest that obesity is associated with risk of adenomas in white women, but little is known about the relation in African‐American women. We prospectively examined the association between selected anthropometric factors and colorectal polyps in African‐American women. Methods and Procedures: Data were obtained from the Black Women's Health Study (BWHS), a prospective cohort study of African‐American women. From 1997 to 2003, we followed 33,403 women aged ≥30 years with no prior diagnosis of cancer or polyps. Cox regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for risk of polyps, with adjustment for potential confounders. Results: After 211,797 person‐years of follow‐up, 1,189 cases of colorectal polyps were reported. The IRR comparing women with a current BMI ≥35 to <25 kg/m² was 1.35 (95% CI = 1.12–1.62), after adjustment for covariates including waist‐to‐hip ratio (WHR). Women who gained ≥30 kg since age 18 were 1.76 times as likely as those who gained <5 kg to report polyps (95% CI = 1.33–2.33). The IRR comparing the highest (≥0.87) to lowest (<0.71) quintiles of WHR was 1.26 (95% CI = 1.04–1.54), after adjustment for covariates including BMI. BMI at age 18, adult height, and waist circumference (BMI‐adjusted) were not materially associated with risk. Results were similar among women with a recent endoscopy. Discussion: Weight gain and obesity in adulthood may increase the risk of colorectal polyps in African‐American women.     

Body size phenotypes and inflammation in the Women's Health Initiative Observational Study

Individuals with "metabolically benign" obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10-year risk of cardiovascular disease (CVD) compared to normal weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute-phase reactants (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count), adhesion molecules (E-selectin, vascular cell adhesion molecule-1), and coagulation products (fibrinogen, plasminogen activator inhibitor-1 (PAI-1)) among four body size phenotypes (normal weight with 0/1 vs. ≥2 metabolic syndrome components/diabetes and overweight/obesity with 0/1 vs. ≥2 metabolic syndrome components/diabetes) in cross-sectional analyses of 1,889 postmenopausal women from the Women's Health Initiative Observational Study (WHI-OS) nested case-control stroke study. Higher levels of all three inflammatory marker categories were found among women with overweight/obesity or ≥2 metabolic syndrome components or diabetes. Compared to normal weight women with 0 or 1 metabolic syndrome components, normal weight women with ≥2 metabolic syndrome components or diabetes were more likely to have ≥3 inflammatory markers in the top quartile (multivariate odds ratio (OR) 2.0, 95% confidence interval (CI): 1.3-3.0), as were overweight/obese women with 0 or 1 metabolic syndrome components (OR 2.3; 95% CI: 1.5-3.5). Overweight/obese women with ≥2 metabolic syndrome components or diabetes had the highest OR (OR 4.2; 95% CI: 2.9-5.9). Despite findings that metabolically benign obese individuals are not at increased 10-year risk of CVD compared to normal weight individuals, the current results suggest that overweight/obese women without clustering of cardiometabolic risk factors still possess abnormal levels of inflammatory markers.     

Circulating oxidized LDL and inflammation in extreme pediatric obesity

Oxidative stress and inflammation have not been well-characterized in extreme pediatric obesity. We compared levels of circulating oxidized low-density lipoprotein (oxLDL), C-reactive protein (CRP), and interleukin-6 (IL-6) in extremely obese (EO) children to normal weight (NW) and overweight/obese (OW/OB) children. OxLDL, CRP, IL-6, BMI, blood pressure, and fasting glucose, insulin, and lipids were obtained in 225 children and adolescents (age 13.5 ± 2.5 years; boys 55%). Participants were classified into three groups based on gender- and age-specific BMI percentile: NW (<85th, n = 127), OW/OB (85th- <1.2 times the 95th percentile, n = 64) and EO (≥1.2 times the 95th percentile or BMI ≥35 kg/m(2), n = 34). Measures were compared across groups using analysis of covariance, adjusted for gender, age, and race. Blood pressure, insulin, and lipids worsened across BMI groups (all P < 0.0001). OxLDL (NW: 40.8 ± 9.0 U/l, OW/OB: 45.7 ± 12.1 U/l, EO: 63.5 ± 13.8 U/l) and CRP (NW: 0.5 ± 1.0 mg/l, OW/OB: 1.4 ± 2.9 mg/l, EO: 5.6 ± 4.9 mg/l) increased significantly across BMI groups (all groups differed with P < 0.01). IL-6 was significantly higher in EO (2.0 ± 0.9 pg/ml) compared to OW/OB (1.3 ± 1.2 pg/ml, P < 0.001) and NW (1.1 ± 1.0 pg/ml, P < 0.0001) but was not different between NW and OW/OB. Extreme pediatric obesity, compared to milder forms of adiposity and NW, is associated with higher levels of oxidative stress and inflammation, suggesting that markers of early cardiovascular disease and type 2 diabetes mellitus are already present in this young population.     

新诊断标准下妊娠期糖尿病高危因素研究

目的:调查新诊断标准下国内妊娠期糖尿病(Gestational diabetes mellitus GDM)的发病情况,分析影响GDM发生的高危因素,为新标准下国内GDM孕妇临床早期管理、诊断和干预提供理论依据。方法:对2011年1月至2011年9月我院接受产前建卡检查的所有孕妇1152例进行临床资料的收集及回顾性研究,排除孕前糖尿病患者16例,采用GDM诊断新标准进行"一步法"诊断,收集包括年龄、孕产次、体质指数(body mass index BMI)、糖尿病家族史、多囊卵巢综合征等13种影响GDM发生的危险因素,并综合分析。结果:新标准下GDM检出率为10.39%(118/1136)2)单因素分析结果发现年龄≥35岁(X2=10.2814,P=0.0013)、肥胖(孕前BMI≥28kg/m2()X2=36.2384,P<0.0001)、多囊卵巢综合征(X2=20.6725,P<0.0001)、糖尿病家族史(X2=7.8783,P=0.0050)在GDM组与非GDM组有统计学差异,多因素逐步Logistic回归分析肥胖(OR=7.546 95%CI=2.356~20.129 P=0.0002)、多囊卵巢综合征(OR=6.342 95%CI=1.783~16.329,P=0.0019)、年龄(OR=3.021 95%CI=0.983~6.459 P=0.0108)、糖尿病家族史(OR=2.43895%CI=0.612~5.231 P=0.0256)为GDM的高危因素。结论:新标准下报告GDM检出率为10.39%。肥胖、多囊卵巢综合征、年龄、糖尿病家族史为影响GDM发生的高危因素。加强GDM筛查并对具有高危因素的妊娠期妇女早期诊断,早期干预、早期管理可改善妊娠结局,提高人口素质。     

Sleep duration and BMI in a sample of young adults

We examined the association between sleep duration and BMI in young adults, and, specifically, in possible gender differences. The population-based sample included 955 young men and 1051 young women (mean age = 25.3 years, s.d. = 1.7) who participated in Project EAT-III (Eating and Activity in Teens and Young Adults)-III. In 2008-2009, study participants completed a survey, on which they reported their weight, height, and typical bed and awakening times. Gender-specific regression models estimated cross-sectional associations between sleep duration and weight status, adjusting for age, race, SES, family structure, depressive symptoms, physical activity, and sedentary and dietary behaviors. In multivariable-adjusted linear regression models, an hour increase in sleep was associated with a -0.38 (-0.70, -0.048) BMI in men. Men who slept <7 h had a 1.4 unit higher mean BMI (27.9; 95% confidence interval (CI): 26.9, 28.9) than men who slept 7-9 h/day (26.5; 95% CI: 26.1, 27.0). Prevalence estimates of overweight (BMI ≥ 25) and obesity (BMI ≥ 30) were also inversely associated with sleep duration among men. Sleep duration was not associated with BMI, overweight, or obesity in women. Among women, but not men, there was a statistically significant positive association between trouble falling or staying asleep and mean BMI. Sleep may be an important modifiable risk factor for obesity, particularly in young adult men.     

Further evidence for the role of ENPP1 in obesity: association with morbid obesity in Finns

The aim of this study was to investigate a series of single-nucleotide polymorphisms (SNPs) in the genes MC2R, MC3R, MC4R, MC5R, POMC, and ENPP1 for association with obesity. Twenty-five SNPs (2-7 SNPs/gene) were genotyped in 246 Finns with extreme obesity (BMI > or = 40 kg/m2) and in 481 lean subjects (BMI 20-25 kg/m2). Of the obese subjects, 23% had concomitant type 2 diabetes. SNPs and SNP haplotypes were tested for association with obesity and type 2 diabetes. Allele frequencies differed between obese and lean subjects for two SNPs in the ENPP1 gene, rs1800949 (P = 0.006) and rs943003 (P = 0.0009). These SNPs are part of a haplotype (rs1800949 C-rs943003 A), which was observed more frequently in lean subjects compared to obese subjects (P = 0.0007). Weaker associations were detected between the SNPs rs1541276 in the MC5R, rs1926065 in the MC3R genes and obesity (P = 0.04 and P = 0.03, respectively), and between SNPs rs2236700 in the MC5R, rs2118404 in the POMC, rs943003 in the ENPP1 genes and type 2 diabetes (P = 0.03, P = 0.02 and P = 0.02, respectively); these associations did not, however, remain significant after correction for multiple testing. In conclusion, a previously unexplored ENPP1 haplotype composed of SNPs rs1800949 and rs943003 showed suggestive evidence for association with adult-onset morbid obesity in Finns. In this study, we did not find association between the frequently studied ENPP1 K121Q variant, nor SNPs in the MCR or POMC genes and obesity or type 2 diabetes.