Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10(-5), Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10(-06)/Pfemales: 3.45 × 10(-07)/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.

Intermittent Fasting Induces Hypothalamic Modifications Resulting In Low Feeding Efficiency, Low Body Mass And Overeating.

Intermittent fasting (IF) is an often-used intervention to decrease body mass. In male Sprague-Dawley rats, 24 hour cycles of IF result in light caloric restriction, reduced body mass gain, and significant decreases in the efficiency of energy conversion. Here, we study the metabolic effects of IF in order to uncover mechanisms involved in this lower energy conversion efficiency. After 3 weeks, IF animals displayed overeating during fed periods and lower body mass, accompanied by alterations in energy-related tissue mass. The lower efficiency of energy use was not due to uncoupling of muscle mitochondria. Enhanced lipid oxidation was observed during fasting days, whereas fed days were accompanied by higher metabolic rates. Furthermore, an increased expression of orexigenic neurotransmitters AGRP and NPY in the hypothalamus of IF animals was found, even on feeding days, which could explain the overeating pattern. Together, these effects provide a mechanistic explanation for the lower efficiency of energy conversion observed. Overall, we find that IF promotes changes in hypothalamic function that explain differences in body mass and caloric intake.

Association Between Parity, Pre-pregnancy Body Mass Index And Gestational Weight Gain.

To analyze the relationship between parity, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG). This observational controlled study was conducted from November 2013 to April 2014, with postpartum women who started antenatal care up to 14 weeks and had full-term births. Data were collected from medical records and antenatal cards. Descriptive and bivariate analyses were performed. The significance level was 5%. Data were collected from 130 primiparous and 160 multiparous women. At the beginning of prenatal care, 54.62% of the primiparous were eutrophic, while the majority of multiparous were overweight or obese (62.51%). Multiparas are two times more likely to be obese at the beginning of their pregnancies, when compared to primiparas. The average pre-pregnancy weight and final pregnancy weight was significantly higher in multiparous, however, the mean GWG was higher among primiparous. We found an inverse correlation between parity and the total GWG, but initial BMI was significantly higher in multiparas. Nevertheless, monitoring of the GWG through actions that promote a healthier lifestyle is needed, regardless of parity and nutritional status, in order to prevent excessive GWG and postpartum weight retention and consequently inadequate pre-pregnancy nutritional status in future pregnancies.

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry

Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 ± 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.

Body trunk fat and insulin resistance in post-pubertal obese adolescents

CONTEXT AND OBJECTIVE: Insulin resistance is a metabolic disorder commonly associated with excess body fat accumulation that may increase chronic disease risk. The present study was undertaken to evaluate the relationship between body composition and insulin resistance among obese adolescents. DESIGN AND SETTING: Cross-sectional study, at the Adolescence Center, Pediatric Department, Universidade Federal de São Paulo. METHODS: Body composition was assessed using dual-energy X-ray absorptiometry. Dietary intake was evaluated using a three-day dietary record. The biochemical evaluation comprised glucose, insulin, serum lipid, leptin and ghrelin measurements. Insulin resistance was calculated by means of the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Forty-nine post-pubertal obese adolescents participated in the study: 12 boys and 37 girls of mean age 16.6 (1.4) years and mean body mass index (BMI) of 35.0 (3.9) kg/m². The mean glucose, insulin and HOMA values were 90.3 (6.4) mg/dl, 16.6 (8.1) µIU/ml and 3.7 (1.9), respectively. Hyperinsulinemia and insulin resistance were observed in 40.2% and 57.1% of the subjects, respectively. Adolescents with insulin resistance had higher BMI and body trunk fat. There was a trend towards higher leptin concentration in obese individuals with insulin resistance. Insulin resistance was positively correlated with body trunk fat, BMI, body fat mass (kg), leptin and body fat percentage. Furthermore, there was a negative correlation between HOMA-IR and lean body mass. The body composition predicted 30% of the HOMA-IR levels, according to linear regression models. CONCLUSION: Body trunk fat was significantly associated with insulin resistance, demonstrating the clinical importance of abdominal obesity during adolescence.

Body Mass Index, Cigarette Smoking, and Alcohol Consumption and Cancers of the Oral Cavity, Pharynx, and Larynx: Modeling Odds Ratios in Pooled Case-Control Data

study-specific results, their findings should be interpreted with caution

Short-term nutritional counseling reduces body mass index, waist circumference, triceps skinfold and triglycerides in women with metabolic syndrome

Background: It is recognized that the growing epidemic of metabolic syndrome is related to dietary and lifestyle changes. Objective: The purpose of this study was to evaluate short-term application of nutritional counseling in women with metabolic syndrome. Methods: This follow-up study was conducted from September to November 2008 with thirty three women >= 35 years old screened clinically for nutritional counseling. Dietary intake was reported, and biochemical and body composition measures were taken at baseline and after three months of follow-up. Results: Of the 33 women evaluated, 29 patients completed the study. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity was high at 38%, 72.4%, 55.2%, and 75.8%, respectively. At the end of three-months of follow-up, a significant decline in body mass index, waist circumference, triceps skinfold, and triglycerides was observed, as was an increase in calcium and vitamin D intake. The multiple regression analysis showed that changes in body mass index, triceps skinfold, waist circumference and triglyceride levels after nutritional intervention were positively associated with changes in anthropometric (loss of body weight) and biochemical (decrease of TG/HDL-c ratio) parameters. Moreover, waist circumference changes were negatively associated with changes in calcium and vitamin D intake. Conclusion: Short-term nutritional counseling improved some factors of metabolic syndrome. Moreover, the increases in calcium and vitamin D consumption can be associated with the improvement in markers of metabolic syndrome.

Performance of body fat and body mass index cutoffs in elevated blood pressure screening among male children and adolescents

For percentage of body fat (%BF), there are no internationally accepted cutoffs. The primary function of body fat cutoffs should be to identify not only excessive body fatness, but also the increased risk of unhealthy outcomes, such as hypertension. The purpose of this study was to analyze the accuracy of different %BF and body mass index (BMI) cutoffs as screening measures for EBP in pediatric populations. It was a cross-sectional study with a sample of 358 male subjects from 8 to 18 years old. BP was measured by the oscilometric method, and body composition was measured by dual-energy X-ray absorptiometry (DXA). The accuracy of three reference tables used for body fat cutoffs was assessed. The three body fat reference tables were highly specific, but insensitive, for elevated BP screening. For elevated BP screening, all body fat cutoffs presented similar sensitivity (range=48.3-53.7%) and specificity (range=79.2-84.1%). The body fat cutoffs performed no better than BMI in screening of children and adolescents at risk of elevated BP (EBP). BMI seems a more attractive tool for this function, as it performed similarly and can be applied in large surveys and with lower costs. Hypertension Research (2011) 34, 963-967; doi:10.1038/hr.2011.61; published online 26 May 2011

Increased MMA concentration and body mass index are associated with spontaneous abortion in Brazilian women A pilot study

Background: The pathophysiology of spontaneous abortion is complex and may involve the interaction of genetic and environmental factors. We evaluated the predictors of spontaneous abortion in Brazilian pregnant women. The effects of age, gestational age. body mass index (BMI), cigarette smoking, alcohol ingestion, use of multivitamins and concentrations of vitamins (folate, cobalamin and vitamin 136) and vitamin-dependent metabolites were analyzed. Methods: Study population included 100 healthy women that attended pre-natal care in 2 health centers of Sao Paulo, Brazil, and in whom pregnancy outcome was known. Folate and cobalamin status was measured in blood specimens collected between 4 and 16 weeks. The genotypes for 8 gene polymorphisms were evaluated by PCR-RFLP. Results: Eighty-eight women had normal pregnancy outcome (Group 1), while 12 experienced a miscarriage after blood collection (Group 2). Increased methylmalonic acid (MMA) concentrations were found in Group 2 (median [25th-75th percentile]=274 [149-425] nmol/l) relative to Group 1 (138 [98-185]) (P<0.01). No differences between the groups were observed for serum cobalamin, serum or red cell folate, and serum total homocysteine or allele frequencies for 8 polymorphisms. In a conditional logistic regression analysis including age, gestational age, serum creatinine, MMA, cystathionine, body mass index (BMI), cigarette smoking, alcohol ingestion and use of multivitamins the risk of abortion was significantly associated with MMA (OR [95% CI] = 3.80 [1.36, 10.62] per quartile increase in MMA), BMI (OR [95% CI] = 5.49 [1.29,23.39] per quartile) and gestational age (OR [95% CI] = 0.10 [0.01, 0.77] per increase of interval in gestational age). Conclusions: Increased serum MMA and BMI concentrations are associated with spontaneous abortion in Brazilian women. (C) 2009 Elsevier B.V. All rights reserved.

Bioimpedance spectrometry in the determination of body water compartments: Accuracy and clinical significance

Bioelectrical impedance analysis (BIA) offers the potential for a simple, portable and relatively inexpensive technique for the in vivo measurement of total body water (TBW). The potential of BIA as a technique of body composition analysis is even greater when one considers that body water can be used as a surrogate measure of lean body mass. However, BIA has not found universal acceptance even with the introduction of multi-frequency BIA (MFBIA) which, potentially, may improve the predictive accuracy of the measurement. There are a number of reasons for this lack of acceptance, although perhaps the major reason is that no single algorithm has been developed which can be applied to all subject groups. This may be due, in part, to the commonly used wrist-to-ankle protocol which is not indicated by the basic theory of bioimpedance, where the body is considered as five interconnecting cylinders. Several workers have suggested the use of segmental BIA measurements to provide a protocol more in keeping with basic theory. However, there are other difficulties associated with the application of BIA, such as effects of hydration and ion status, posture and fluid distribution. A further putative advantage of MFBIA is the independent assessment not only of TBW but also of the extracellular fluid volume (ECW), hence heralding the possibility of,being able to assess the fluid distribution between these compartments. Results of studies in this area have been, to date, mixed. Whereas strong relationships of impedance values at low frequencies with ECW, and at high frequencies with TBW, have been reported, changes in impedance are not always well correlated with changes in the size of the fluid compartments (assessed by alternative and more direct means) in pathological conditions. Furthermore, the theoretical advantages of Cole-Cole modelling over selected frequency prediction have not always been apparent. This review will consider the principles, methodology and applications of BIA. The principles and methodology will,be considered in relation to the basic theory of BIA and difficulties experienced in its application. The relative merits of single and multiple frequency BIA will be addressed, with particular attention to the latter's role in the assessment of compartmental fluid volumes. (C) 1998 Elsevier Science Ltd. All rights reserved.

Relationships between body mass index and well-being in young Australian women

OBJECTIVE: To explore relationships between body mass index (BMI, kg/m(2)) and indicators of health and well-being in young Australian women. DESIGN: Population based cohort study-baseline cross sectional data. SUBJECTS: 14,779 women aged 18-23 who participated in the baseline survey of the Australian Longitudinal Study on Women's Health in 1996. MEASUREMENTS: Self-reported height, weight, medical conditions, symptoms and SF-36. RESULTS: The majority of women (68%) had a BMI in the range 18.5-

(Review) Body mass index and risk of diabetes mellitus in the Asia-Pacific region

Few prospective data from the Asia Pacific region are available relating body mass index to the risk of diabetes. Our objective was to provide reliable age, sex and region specific estimates of the associations between body mass index and diabetes. Twenty-seven cohort studies from Asia, New Zealand and Australia, including 154,989 participants, contributed 1,244,793 person-years of follow-up. Outcome data included a combination of incidence of diabetes (based on blood glucose measurements) and fatal diabetes events. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. During follow-up (mean = 8 years), 75 fatal diabetes events and 242 new cases of diabetes were documented. There were continuous positive associations between baseline body mass index and risk of diabetes with each 2 kg/m(2) lower body mass index associated with a 27% (23-30%) lower risk of diabetes. The associations were stronger in younger age groups, and regional comparisons demonstrated slightly stronger associations in Asian than in Australasian cohorts (P = 0.04). This overview provides evidence of a strong continuous association between body mass index and diabetes in the Asia Pacific region. The results indicate considerable potential for reduction in incidence of diabetes with population-wide lowering of body mass index in this region.

Laparoscopic treatment of type 2 diabetes mellitus for patients with a body mass index less than 35

Background Type 2 diabetes mellitus (T2DM) is a common disease with numerous complications. Bariatric surgery is an efficient procedure for controlling T2DM in morbidly obese patients. In T2DM, the incretin effect is either greatly impaired or absent. This study aimed to evaluate the preliminary results from interposing a segment of ileum into the proximal jejunum associated with a sleeve or diverted sleeve gastrectomy to control T2DM in patients with a body mass index (BMI) less than 35 kg/m(2). Methods For this study, 39 patients (16 women and 23 men) underwent two laparoscopic procedures comprising different combinations of ileal interposition into the proximal jejunum via a sleeve or diverted sleeve gastrectomy. The mean age of these patients was 50.3 years (range, 36-66 years). The mean BMI was 30.1 kg/m(2) (range, 23.4-34.9 kg/m(2)). All the patients had a diagnosis of T2DM that had persisted for at least 3 years and evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months. The mean duration of T2DM was 9.3 years (range, 3-22 years). Results The mean operative time was 185 min, and the median hospital stay was 4.3 days. Four major complications occurred in the short term (30-days), and the mortality rate was 2.6%. The mean postoperative follow-up period was 7 months (range, 4-16 months), and the mean percentage of weight loss was 22%. The mean postoperative BMI was 24.9 kg/m(2) (range, 18.9-31.7 kg/m2). An adequate glycemic control was achieved for 86.9% of the patients, and 13.1% had important improvement. The patients whose glycemia was not normalized were using a single oral hypoglycemic agent. No patient needed insulin therapy postoperatively. All the patients except experienced normalization of their cholesterol levels. Targeted triglycerides levels were achieved by 71% of the patients, and hypertension was controlled for 95.8%. Conclusions The laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome. A longer follow-up period is needed.

Correlation between the Body Mass Index (BMI) of Pregnant Women and the Development of Hypotension after Spinal Anesthesia for Cesarean Section

Nani FS, Torres MLA - Correlation between the Body Mass Index (BMI) of Pregnant Women and the Development of Hypotension after Spinal Anesthesia for Cesarean Section. Background and objectives: Very few publications correlate hypotension in obese pregnant women, and especially morbidly obese, after spinal anesthesia for cesarean section. The objective of the present study was to evaluate the incidence of hypotension according to the BMI. Methods: Forty-nine patients with pregestational BMI below 25 kg.m(-2) were included in the Eutrophia group, and 51 patients with BMI >= 25 kg.m(-2) were included in the Overweight group. After spinal anesthesia, blood pressure, volume of crystalloid infused, and dose of vasopressors used until delivery were recorded. A fall in systolic blood pressure below 100 mmHg or 10% reduction of the initial systolic blood pressure (SBP) was considered as hypotension and it was corrected by the administration of vasopressors. Results: Episodes of hypotension were fewer in the Eutrophia group (5.89 +/- 0.53 vs. 7.80 +/- 0.66, p = 0.027), as well as the amount of crystalloid administered (1,298 +/- 413.6 mL vs. 1,539 +/- 460.0 mL; p = 0.007), and use of vasopressors (5.87 +/- 3.45 bolus vs. 7.70 +/- 4.46 bolus; p = 0.023). As for associated diseases, we observed higher incidence of diabetes among obese pregnant women (29.41% vs. 9.76%, RR 1.60, 95%CI: 1.15-2.22, p = 0.036), however, differences in the incidence of pregnancy-induced hypertension (PIN) were not observe between both groups (overweight: 21.57%, normal weight: 12.20%, RR 1.30, 95%CI: 0.88-1.94, p = 0.28). Conclusions: In the study sample, pregestational BMI >= 25 kg.m(-2) was a risk factor for hypotension after spinal anesthesia in patients undergoing cesarean section. The same group of patients required higher doses of vasopressors. Those results indicate that the anesthetic techniques in those patients should be improved to reduce the consequences of post-spinal anesthesia hypotension, both in pregnant women and fetuses.