Adult Obese Subjects Research Articles

Not performing an OGTT results in significant underdiagnosis of (pre)diabetes in a high risk adult Caucasian population.

Type 2 diabetes (T2DM) is known to be underdiagnosed. Tests for diagnosis include fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) and HbA1c. HbA1c can be tested in non-fasting conditions. Therefore, general practitioners almost no longer execute OGTT's. We evaluated the performance of OGTT versus HbA1c in a population consisting of overweight and obese subjects, which can be considered a 'high risk' population. A total of, 1241 overweight and obese subjects without a history of diabetes (male/female: 375/866, age 44±13 years, body mass index 38.0±6.1 kg m-2) were tested for glucose tolerance status using FPG, OGTT and HbA1c. Exactly, 46.8% were found to have prediabetes and 11.9% were newly diagnosed with T2DM (male/female=18.9/8.9%) using ADA criteria. Testing only HbA1c would have resulted in 78 subjects being diagnosed with T2DM, but 47.3% of newly diagnosed patients would have been missed if OGTT would not have been done. Exactly 581 subjects were diagnosed with prediabetes, 1.4% subjects had impaired fasting glucose (IFG) 30.5% had impaired glucose tolerance (IGT), 5.1% subjects had a combined IFG+IGT, and 9.8% had an isolated elevated HbA1c (5.7-6.4%). Of the 581 subjects with prediabetes, 257 had an HbA1c <5.7%. Therefore, 44.2% subjects would have been missed when OGTT would not have been done. In a population with only overweight and obese adult subjects, 46.8% were diagnosed with prediabetes and 11.9% were newly diagnosed with diabetes. Exactly, 5.6 and 20.7% of total population met the diagnostic criteria of the OGTT for diabetes and prediabetes, respectively, but did not meet the diagnostic criteria of the HbA1c. These data suggest that not performing an OGTT results in significant underdiagnose of T2DM in an overweight and obese adult population.

Decreased serum glicentin concentration in patients with severe and morbid obesity.

Background Proglucagon-derived hormones represent a family of peptides mainly produced in the pancreas and the intestine. While several proglucagon-derived peptides play key roles in metabolic diseases, little is known about glicentin. The aim of the present study was to investigate serum glicentin concentrations in individuals with adult obesity and to study its potential link with various metabolic parameters. Methods Fifty-two individuals with normal body mass index (BMI < 25 kg/m2) and 39 patients with severe or morbid obesity (BMI > 35 kg/m2) were prospectively included at the University Hospital of Nice between January 2014 and April 2016. Clinical data were recorded, and a fasting blood sample was collected to measure glicentin, glucose, insulin, C-peptide, total cholesterol, triglyceride, LDL and HDL-cholesterol. In addition, a homeostasis model assessment for insulin resistance (HOMA2-IR) was also calculated. Results Patients with severe and morbid obesity had significantly higher plasma glucose, together with higher serum concentrations of insulin, C-peptide, HOMA2-IR, triglyceride, LDL-cholesterol and lower serum concentrations of HDL-cholesterol compared with individuals with a normal body mass index. The obese patients displayed significantly lower fasting serum concentrations of glicentin compared with subjects with a normal body mass index (12 pmol/L vs. 24 pmol/L, P < 0.0001). In the total population, fasting glicentin concentrations did not correlate with BMI, glycaemic parameters (glucose, insulin, C-peptide, HOMA-IR) or lipid parameters (total cholesterol, triglyceride, LDL and HDL-cholesterol). Conclusion To the best of our knowledge, this is the first study reporting serum glicentin concentrations in healthy lean and obese adult subjects. We found that fasting serum glicentin concentrations are decreased in patients with severe or morbid obesity suggesting the potential interest of this peptide in obesity and metabolic-related disorders.

P164 Nocturnal breathing in adult obese subjects with and without Prader-Willi syndrome

P164 Nocturnal breathing in adult obese subjects with and without Prader-Willi syndrome

1022 ANALYSIS OF SLEEP DISORDERED BREATHING AND ALVEOLAR HYPOVENTILATION AMONG OBESE HYPOTHYROID PATIENTS UNDERGOING NOCTURNAL POLYSOMNOGRAPHY

Hypothyroidism is associated with depression of hypoxic and hypercapnic ventilatory drives, resulting in alveolar hypoventilation (pCO2>45 torr). There is dearth of studies describing prevalence of hypoventilation in obese hypothyroid patients undergoing nocturnal polysomnography (NPSG). This is a retrospective study of consecutive obese (BMI ≥ 30 kg/m2) adult hypothyroid subjects who underwent NPSG between November 2015 and October 2016. Data collection included demographics, NPSG variables, end-tidal pCO2 (PetCO2), peak CO2, % of total sleep time with PetCO2 >50 torr (pCO2>50), oxygen saturation (SpO2) nadir, average sleep SpO2, comorbidities, and thyroid stimulating hormone (TSH). We used Chi-square test and Wilcoxon’s rank order test for statistical analysis. We identified 53 subjects: 18 with and 35 without alveolar hypoventilation. The demographic variables reported as median (quartile1, quartile3) were: age 58 (47, 68) years, BMI 37.8 (34.1, 44.3), female 66%. The variables which were significantly associated with hypothyroid subjects with alveolar hypoventilation compared to hypothyroid subjects without alveolar hypoventilation were: AHI 40 (19.5,69.7) vs 18.6 (7.7,30) [p=0.038], SpO2 nadir: 79% (73%,83%) vs 86% (80.5%,88.5%) [p=0.018], average sleep SpO2: 92% (90%,94%) vs 95% (94%,96%) [p=0.0076], TSH: 2.7 (1.5,7.9) vs 1.28 (0.04,2.36) [p=0.03], peak CO2: 59.5 (57,62) vs 50 (45,52.5) [p<0.0001] and pCO2>50: 57% (24%,84%) vs 0% (0%,1%) [p<0.0001]. Uncontrolled hypothyroidism was present in 36.4% of the subjects with hypoventilation as compared to 9% of those without hypoventilation, along with a higher percentage of the following comorbidities: hypertension (78% vs 71%), heart failure (39% vs 11%), depression (27% vs 22%) and diabetes (72% vs 31%), with only diabetes being statistically significant [p=0.004]. Adult obese hypothyroid subjects with alveolar hypoventilation have lower average sleep oxygen saturation, lower oxygen saturation nadir, and higher AHI compared to those without hypoventilation. None.

Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects

Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals. The study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers. In this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r 2 = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r 2 = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r 2 = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r 2 = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r 2 = 0.03) and femoral site (p < 0.04, r 2 = 0.03). In conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.

Changes in Gait over a 30-min Walking Session in Obese Females.

This study assessed the biomechanical gait changes in obese and normal-weight female adult subjects after a commonly recommended 30-min walking session. Hip and knee adduction and extensor moments, which are the primary modulators of frontal and sagittal plane load distribution, were hypothesized to increase in obese females after a 30-min walking period, resulting in more stress across the hip and knee joint. Ten obese (37.7 ± 4.8 yr of age, body mass index [BMI] = 36.1 ± 4.2 kg·m) and 10 normal-weight control female subjects (38.1 ± 4.5 yr of age, BMI = 22.6 ± 2.3 kg·m) walked 30 min continuously on the treadmill at their self-selected speed. V˙O2max was estimated using Ebbeling protocol. A three-dimensional pre- and posttreadmill gait analysis was conducted using infrared markers and force plates to calculate hip and knee moments. Knee extensor moments increased in both obese, pretreadmill (0.54 ± 0.28 N·m·kg) to posttreadmill (0.78 ± 0.43 N·m·kg) (P = 0.01), and control subjects, pretreadmill (0.57 ± 0.34 N·m·kg) to posttreadmill (0.80 ± 0.49 N·m·kg) (P = 0.02). Hip extensor moments decreased for both obese and control subjects. Knee adduction moments did not change in either obese or control subjects. Knee extensor and adductor moments showed good to moderate relationships with V˙O2max, but not BMI or waist circumference. Obese and normal-weight subjects experienced an increase in knee extensor moments after 30 min of walking similarly; therefore, clinicians do not need special consideration for obese individuals when recommending 30-min walking sessions. Fitness may be the important factor in judging the implications of exercise on joint mechanics and parameters of a walking program.

Rs1501299 Polymorphism in the Adiponectin Gene and Their Association with Total Adiponectin Levels, Insulin Resistance and Metabolic Syndrome in Obese Subjects

Background and Aims: The aim of this study was to determine the association of single nucleotide polymorphism rs1501299 in the ADIPOQ gene with body weight, insulin resistance, serum adipokine levels and metabolic syndrome (MetS). Methods: The study involved a population of 1,007 adult obese subjects. Parameters like body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, C-reactive protein, insulin concentration, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile and adipocytokines levels (leptin, adiponectin and resistin) were all measured. The genotype of ADIPOQ gene polymorphism (rs1501299) was evaluated. Results: Insulin levels (GG: 13.6 ± 5.1 mUI/l vs. GT: 14.1 ± 5.2 mUI/l vs. TT: 16.6 ± 5.2 mUI/l; p < 0.05) and HOMA-IR (GG: 3.3 ± 1.5 units vs. GT: 4.1 ± 1.1 units vs. TT: 4.5 ± 1.3 units; p < 0.05) were higher in T-allele carriers than they were in non-T-allele carriers. Total adiponectin levels (GG: 20.2 ± 2.4 ng/dl vs. GT: 15.8 ± 3.4 ng/dl vs. TT: 13.7 ± 1.4 ng/dl; p < 0.05) were lower in T-allele carriers than they were in non-T-allele carriers. Logistic regression analysis indicated that subjects with T allele were associated with an increased risk of MetS (OR 1.15, 95% CI 1.08-1.25, p = 0.033) and an increased risk of hyperglycemia (OR 1.99, 95% CI 1.37-2.55, p = 0.028) after adjusting by age and gender. Conclusions: These data suggest an important role of this ADIPOQ variant at position +276 on insulin resistance, total adiponectin levels and MetS.

Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults.

Neuregulin 4 (Nrg4) has been identified as a new secreted adipokine that may protect against development of obesity and metabolic disorders. However, information is not available regarding the association between circulating Nrg4 and subclinical atherosclerosis in humans. We measured serum Nrg4 in 485 obese adult subjects (aged 40 years or older) who had the measurement of carotid intima-media thickness (CIMT) recruited from the community. Individuals with increased CIMT and carotid plaque had lower levels of circulating Nrg4 than controls (p < 0.05). The risks of increased CIMT and atherosclerotic plaque were significantly decreased by 28% and 31% [OR (95% CI): 0.72 (0.53–0.98) and 0.69 (0.50–0.96), respectively], adjusting for age, sex, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, HOMA-IR, and body fat. Importantly, individuals in the lowest quartile of serum Nrg4 were 3.70 times (p < 0.001) more likely to have increased CIMT and 2.06 times (p < 0.05) more likely to have atherosclerotic plaque than those in the highest quartile in multivariable logistic regression analyses. These findings suggest that circulating Nrg4 concentrations are inversely associated with subclinical atherosclerosis in obese adults, and indicating that circulating Nrg4 might play a role in identifying patients at high risk for CVD.

Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study.

BackgroundNeuregulin 4 (Nrg4) is a secreted adipokine recently identified as playing an important role in modulating systemic energy metabolism and the development of obesity-associated disorders. However, information is not available regarding the association between circulating Nrg4 and risk of metabolic syndrome (MetS) in humans.MethodsWe measured serum Nrg4 in 1212 obese adult subjects (aged 40 years or older), with a waist circumference greater than 90 cm for men or 80 cm for women, recruited from the community.ResultsMetS subjects had lower levels of circulating Nrg4 than healthy controls (P < 0.01). The prevalence of MetS was higher in subjects with lower levels of circulating Nrg4 compared to those with higher values (67.3 % vs. 57.4 %, P < 0.05). Likewise, subjects with low levels of circulating Nrg4 had high prevalence of raised fasting glucose and blood pressure, but there was no association with raised triglycerides and reduced HDL-c. In multivariable logistic regression analyses, increased serum Nrg4 was significantly associated with reduced risk of MetS (OR: 0.603; 95 % CI, 0.439–0.828; P = 0.002), adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic blood pressure, fasting glucose, triglyceride, HDL-c, HOMA-IR, and body fat mass; however, such associations with serum Nrg4 were not noted for each component of MetS.ConclusionsThese findings indicate that circulating Nrg4 concentrations are inversely associated with risk of MetS in obese Chinese adults, suggesting that circulating Nrg4 concentrations may be a protective factor in the development of MetS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0703-6) contains supplementary material, which is available to authorized users.

Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype

Epidemiologic and clinical evidence supports the existence of an obesity-related asthma phenotype. No distinct pathophysiologic elements or specific biomarkers have been identified thus far, but increased oxidative stress has been reported. We aimed at verifying whether metabolomics of exhaled breath condensate from obese asthmatic (OA) patients, lean asthmatic (LA) patients, and obese nonasthmatic (ONA) subjects could recognize specific and statistically validated biomarkers for a separate "asthma-obesity" respiratory metabolic phenotype, here defined as "metabotype." Twenty-five OA patients, 30 ONA subjects, and 30 mild-to-moderate LA age-matched patients participated in a cross-sectional study. Nuclear magnetic resonance (NMR) profiles were analyzed by using partial least-squares discriminant analysis, and the results were validated with an independent patient set. From NMR profiles, we obtained strong regression models that distinguished OA patients from ONA subjects (quality parameters: goodness-of-fit parameter [R2]=0.81 and goodness-of-prediction parameter [Q2]=0.79), as well as OA patients from LA patients (R2=0.91 and Q2=0.89). The all-classes comparison (R2=0.86 and Q2=0.83) indicated that OA patients possess a respiratory metabolic profile fully divergent from those obtained in the other patient groups. We also identified specific biomarkers for between-class separation, which are independent from clinical bias. They are involved in the methane, pyruvate, and glyoxylate and dicarboxylate metabolic pathways. NMR-based metabolomics indicates that OA patients are characterized by a respiratory metabolic fingerprint fully different from that of patients independently affected by asthma or obesity. Such a phenotypic difference strongly suggests unique pathophysiologic pathways involved in the pathogenesis of asthma in adult obese subjects. Furthermore, the OA metabotype could define a strategy for patient stratification based on unbiased biomarkers, with important diagnostic and therapeutic implications.

Sarcopenic Obesity and Metabolic Syndrome in Adult Caucasian Subjects.

Recently metabolic aspects linked to sarcopenic obesity (SO) were investigated. Extant studies involved especially older people from Asian or White-mixed American cohorts. to explore the prevalence of sarcopenia in Caucasian adult obese subjects using two different indices of sarcopenia, and to investigate the relationship among SO, metabolic syndrome (MS), inflammation, and serum albumin concentrations. Cross- sectional study. The study was performed from 2011 to 2014 in a hospitalized care setting. Inclusion criteria were: age>18 and <65 years, BMI≥30 Kg/m2. Fat mass (FM) and fat-free mass (FFM) were assessed by DXA. Appendicular skeletal muscle mass (ASMM) was calculated. Sarcopenia was defined as ASMM/height2 or ASMM/weight <2SD than the sex-specific mean of a young population. The cutoffs were ASMM/h2<6.54 Kg/m2 for men and 4.82 Kg/m2 for women, and ASMM/weight<0.2827 for men and 0.2347 for women. ISI-Matsuda was calculated. MS was diagnosed (NCEP-ATPIII). 727 subjects (age: 45.72±13.56 years, BMI: 37.74±5.82 kg/m2) were enrolled. The prevalence of SO was 1.0% or 34.8% in men and 0.6% or 50.1% in women, using ASMM/height2 ratio or ASMM/weight. Subjects with SO based on ASMM/height2 were scarce, only data relying on ASMM/weight were considered. Subjects with SO had higher BMI, waist circumference, FM, and lower FFM and ASMM than nonsarcopenic obese individuals (all p<0.05). ISI-Matsuda was lower and hs-CRP levels were higher in subjects with SO (all p<0.05). MS was more prevalent in subjects with SO than nonsarcopenic obese subjects (47.6% vs 34.3%, p<0.001). ASMM/weight was decreased in subjects with MS (0.2522±0.0410 vs 0.2423±0.0352, p=0.001). SO is associated with MS and low- grade inflammation in adult Caucasian subjects. Metabolic profile evaluation should be recommended in subjects with SO.

Intra- and inter-examination repeatability of magnetic resonance spectroscopy, magnitude-based MRI, and complex-based MRI for estimation of hepatic proton density fat fraction in overweight and obese children and adults.

Determine intra- and inter-examination repeatability of magnitude-based magnetic resonance imaging (MRI-M), complex-based magnetic resonance imaging (MRI-C), and magnetic resonance spectroscopy (MRS) at 3T for estimating hepatic proton density fat fraction (PDFF), and using MRS as a reference, confirm MRI-M and MRI-C accuracy. Twenty-nine overweight and obese pediatric (n = 20) and adult (n = 9) subjects (23 male, 6 female) underwent three same-day 3T MR examinations. In each examination MRI-M, MRI-C, and single-voxel MRS were acquired three times. For each MRI acquisition, hepatic PDFF was estimated at the MRS voxel location. Intra- and inter-examination repeatability were assessed by computing standard deviations (SDs) and intra-class correlation coefficients (ICCs). Aggregate SD was computed for each method as the square root of the average of first repeat variances. MRI-M and MRI-C PDFF estimation accuracy was assessed using linear regression with MRS as a reference. For MRI-M, MRI-C, and MRS acquisitions, respectively, mean intra-examination SDs were 0.25%, 0.42%, and 0.49%; mean intra-examination ICCs were 0.999, 0.997, and 0.995; mean inter-examination SDs were 0.42%, 0.45%, and 0.46%; and inter-examination ICCs were 0.995, 0.992, and 0.990. Aggregate SD for each method was <0.9%. Using MRS as a reference, regression slope, intercept, average bias, and R (2), respectively, for MRI-M were 0.99%, 1.73%, 1.61%, and 0.986, and for MRI-C were 0.96%, 0.43%, 0.40%, and 0.991. MRI-M, MRI-C, and MRS showed high intra- and inter-examination hepatic PDFF estimation repeatability in overweight and obese subjects. Longitudinal hepatic PDFF change >1.8% (twice the maximum aggregate SD) may represent real change rather than measurement imprecision. Further research is needed to assess whether examinations performed on different days or with different MR technologists affect repeatability of MRS voxel placement and MRS-based PDFF measurements.

Effects Of Aerobic Exercise Based Upon Gas Exchange Aerobic Threshold In Obese Sarcopenic Subjects.

It is well known that in sarcopenic obese subjects a correct life style, including diet and physical activity, is part of a correct intervention protocol to reduce weight and increase physical fitness. In order to reach these positive effects, the exercise program should be tailored according to the individual’s physical function, health status, exercise responses, and stated goals. PURPOSE: Aim of this study was to evaluate the effects of aerobic training intervention, basedupongait speed corresponding to aerobic gas exchange threshold (AerTge), on physical and physiological parameters in sarcopenic obese adult subjects(OBS). METHODS: Twenty-two sedentary Caucasian sarcopenic obese women (age 46.5±15.4 yrs; BMI 36.1 ± 9.5) were included in the study. Subjects’ height, weight, VO2peak and AerTgewere assessedbefore starting aerobic training. Moreover 6 minute walking test (6MWT), sit and reach test, short physical performance battery test (4 meter gait speed, balance, chair stand test) were performed. Subjects were required to walk or run 30 min/day for at least 5 day/week for 2 months at the speed corresponding to the individual AerTge. After two month all variables were assessed to verify the effects of aerobic training on body composition, physical and physiological parameters. RESULTS: Significant differences (p<0.05) were found between PRE and POST aerobic training in weight (95.2±26.1 vs 93.0±23.4 kg), BMI (36.1±9.5 vs 34.8±9.2 kg/m2), FM%(47.8±11.1 vs 45.3±11.2 %), VO2 peak(19.7±5.4 vs 21.8±6.1 ml/kg/min) and MET (5.6±1.5 vs 6.2±1.8)at maximal exercise capacity.Significant differences were also found in chair stand test (8.6±3.1vs 7.7±2.8 sec),four meters walking tests(3.9±1.1 vs 3.6±1.0 sec),sit and reach (9.6±6.6 vs 11.5±7.4 cm) and six minutes walking tests (550.4±144.9 vs 681.9 ±141.8 m) whileno differences were found for the other considered parameters. CONCLUSION: Our results showed that a 2 months aerobic exercise training based on gait speed corresponding to subjects’ AerTge, had a positive effect on body composition and improved physical fitness and maximal exercise capacity. Thus, the prescription of physical activity intensity based onAerTge, should become more frequent in sarcopenic obese subjects.

Urinary proteomic profiling in severe obesity and obstructive sleep apnoea with CPAP treatment

IntroductionObstructive sleep apnoea (OSA) is common in obesity and is associated with cardiovascular and metabolic complications. Continuous positive airway pressure (CPAP) in OSA may lead to physiological changes reflected in the urinary proteome. The aim of this study was to characterise the urinary proteome in severely obese adult subjects with OSA who were receiving CPAP compared with severely obese subjects without OSA. MethodsSeverely obese subjects with and without OSA were recruited. Subjects with OSA were receiving CPAP. Body composition and blood pressure measurements were recorded. Urinary samples were analysed by Capillary Electrophoresis–Mass Spectrometry (CE–MS). ResultsTwenty-seven subjects with OSA-on-CPAP (age 49±7years, BMI 43±7kg/m2) and 25 controls without OSA (age 52±9years, BMI 39±4kg/m2) were studied. Age and BMI were not significantly different between groups. Mean CPAP use for OSA patients was 14.5±1.0 months. Metabolic syndrome was present in 14(52%) of those with OSA compared with 6(24%) of controls (p=0.039). A urinary proteome comprising 15 peptides was identified showing differential expression between the groups (p<0.01). Although correction for multiple testing did not reach significance, sequences were determined for 8 peptides demonstrating origins from collagens, fibrinogen beta chain and T-cadherin that may be associated with underlying cardiovascular disease mechanisms in OSA. ConclusionsThe urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA.

Supplementation of a Standardized Extract fromPhyllanthus emblicaImproves Cardiovascular Risk Factors and Platelet Aggregation in Overweight/Class-1 Obese Adults

The objective of this study (clinicaltrials.gov NCT01858376) was to determine the effect of oral supplementation of a standardized extract of Phyllanthus emblica (CAPROS®) on cardiovascular disease (CVD) risk factors in overweight adult human subjects from the US population. Overweight/Class-1 obese (body–mass index: 25–35) adult subjects received 500 mg of CAPROS supplement b.i.d for 12 weeks. The study design included two baseline visits followed by 12 weeks of supplementation and then 2 weeks of washout. At all visits, peripheral venous blood was collected in sodium citrate tubes. Lipid profile measurements demonstrated a significant decrease in calculated low-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein following 12 weeks of CAPROS supplementation when compared to averaged baseline visits. Circulatory high-sensitivity C reactive protein (hs-CRP) levels were significantly decreased after 12 weeks of supplementation. In addition, both ADP- and collagen-induced platelet aggregation was significantly downregulated following 12 weeks of supplementation. Overall, the study suggests that oral CAPROS supplementation may provide beneficial effects in overweight/Class-1 obese adults by lowering multiple global CVD risk factors.

Exome sequencing followed by genotyping suggests SYPL2 as a susceptibility gene for morbid obesity

Recently developed high-throughput sequencing technology shows power to detect low-frequency disease-causing variants by deep sequencing of all known exons. We used exome sequencing to identify variants associated with morbid obesity. DNA from 100 morbidly obese adult subjects and 100 controls were pooled (n=10/pool), subjected to exome capture, and subsequent sequencing. At least 100 million sequencing reads were obtained from each pool. After several filtering steps and comparisons of observed frequencies of variants between obese and non-obese control pools, we systematically selected 144 obesity-enriched non-synonymous, splicing site or 5′ upstream single-nucleotide variants for validation. We first genotyped 494 adult subjects with morbid obesity and 496 controls. Five obesity-associated variants (nominal P-value<0.05) were subsequently genotyped in 1425 morbidly obese and 782 controls. Out of the five variants, only rs62623713:A>G (NM_001040709:c.A296G:p.E99G) was confirmed. rs62623713 showed strong association with body mass index (beta=2.13 (1.09, 3.18), P=6.28 × 10−5) in a joint analysis of all 3197 genotyped subjects and had an odds ratio of 1.32 for obesity association. rs62623713 is a low-frequency (2.9% minor allele frequency) non-synonymous variant (E99G) in exon 4 of the synaptophysin-like 2 (SYPL2) gene. rs62623713 was not covered by Illumina or Affymetrix genotyping arrays used in previous genome-wide association studies. Mice lacking Sypl2 has been reported to display reduced body weight. In conclusion, using exome sequencing we identified a low-frequency coding variant in the SYPL2 gene that was associated with morbid obesity. This gene may be involved in the development of excess body fat.

Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation.

Several chronic metabolic alterations are present in obese subjects. While it is well known about the detrimental effect of abdominal adipose tissue on chronic metabolic clinical condition, less is known on the role of lean mass in obese subjects. Thus, the aim of our study was to evaluate the potential correlation of muscle mass, metabolic condition and inflammation status in obese individuals. The study included 426 obese subjects (86 men and 340 female; mean age 44.8 ± 14 years; BMI: 34.9 ± 6.1 kg/m(2)). Exclusion criteria were chronic medical conditions or use of medications affecting bone metabolism, alterations of hormonal and nutritional status, vitamin D supplementation, recent weight loss and prior bariatric surgery. Patients underwent measurements of bone mineral density (lumbar and hip) and body composition (lean mass, total and trunk fat mass) by dual X-ray absorptiometry and were evaluated for hormonal and metabolic profile and inflammatory markers. Higher lean body mass (LM%) was inversely correlated with homeostasis model assessment of insulin resistance (p < 0.0091; r(2) 0.03938) and associated with lower fibrinogen levels (p < 0.0001; r(2) 0.1263). Interestingly, in obese subjects, LM% was associated with higher levels of vitamin D (p < 0.0001, r(2) 0.1140), osteocalcin (p < 0.0001, r(2) 0.2401) and insulin-like growth factor-1 (IGF-1) (p < 0.0002, r(2) 0.1367). Our results show for the first time that in obese patients, higher amounts of lean mass are directly linked to a lower inflammatory profile and to better insulin sensitivity, but also to the presence of higher level of vitamin D and IGF-1. Moreover, these data suggest that higher levels of lean mass in obese people correlate with a better metabolic profile and, thus, strongly suggest the need to develop programs to facilitate an increase in physical activity in obese people.

Obstructive sleep apnea is associated with increased arterial stiffness in severe obesity.

Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non-invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy-two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42±7kgm(-2) ), without obstructive sleep apnea (non-OSA) 25 (body mass index 40±5kgm(-2) )] were characterised using anthropometric, respiratory and cardio-metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non-OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P<0.001), with significantly higher systolic (P=0.003), diastolic (P=0.04) and mean arterial pressures (P=0.004) than patients without obstructive sleep apnea (non-OSA). Arterial stiffness correlated with mean arterial blood pressure (P=0.003) and obstructive sleep apnea severity (apnea-hypopnea index; P<0.001). apnea-hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.

Effect of licorice flavonoid oil on visceral fat in obese subjects in the United States

Abdominal obesity, or accumulation of visceral fat, is mainly associated with the onset of metabolic syndrome. Licorice flavonoid oil (LFO) consisting of licorice hydrophobic polyphenols in mediumchain triglycerides (MCT) is a new functional food ingredient effective in preventing metabolic syndrome. We have demonstrated significant effects of LFO on reduction of total body fat and visceral fat together with body weight in overweight Japanese subjects. Obesity is a more serious problem in Western countries such as Europe and the United States compared to Japan. We hypothesized that LFO could also work for abdominally obese people in Western countries. We therefore tested the effects of 300 mg LFO concentrate solution taken once daily with evening meals for up to 12 weeks in obese adult male and female subjects in the United States. Results showed that visceral fat, as measured by an abdominal CT scan, waist circumference measurements and waist-to-hip ratio significantly decreased in subjects in the LFO group compared to the placebo group at Week 12. The side-effect profile of LFO was indistinguishable from placebo. Moreover, no adverse trends or toxicologically meaningful differences in haematology and chemistry test results, vital signs or physical examinations were observed that were attributable to LFO. These results indicate that LFO is a safe food ingredient for preventing metabolic syndrome not only in Japan but also in Western countries such as Europe and the United States.

Obesity indices and inflammatory markers in obese non-diabetic normo- and hypertensive patients: a comparative pilot study

BackgroundThe aim of this study was to estimate associations between inflammatory markers and obesity indices in normo- and hypertensive subjects.Methods65 obese adult subjects were divided into two groups: (A) of hypertensives (n = 54) and (B) of normotensives (n = 11). Waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and high sensitivity C-reactive protein (hsCRP) serum concentrations were estimated.ResultsIn group A WHtR was higher (0.69 ± 0.07 vs 0.63 ± 0.06; p < 0.01), hsCRP correlated with BMI and WHtR (r = 0.343; p = 0.011 and r = 0.363; p < 0.01, respectively). BAI correlated with hsCRP in group A and B (r = 0.329; p < 0.05 and r = 0.642; p < 0.05; respectively) and in females and males (r = 0.305; p = 0.05 and r = 0.44; p < 0.05, respectively). In females hsCRP was higher (3.2 ± 2.2 mg/l vs 2.1 ± 1.5 mg/l; p < 0.05). In patients without lipid lowering treatment hsCRP and IL-6 were higher (3.2 ± 1.7 mg/l vs 2.4 ±2.2 mg/l; p = 0.01 and 15.9 ± 7.2 pg/ml vs 13.6 ± 9.9 pg/ml; p < 0.01, respectively).ConclusionsWHtR is a sensitive index associated with chronic inflammation in obese hypertensive subjects. BAI correlates with hsCRP independently of hypertension and sex. hsCRP is more sensitive marker associated with obesity than IL-6 and TNF-α. Lipid lowering treatment influence chronic inflammation.