Insulin Sensitivity from Preschool to School Age in Patients with Severe Obesity

Background

Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age.

Research design and methods

Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI) ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI), Insulinogenic Index (IGI); β-cell demand index (BCDI) and Insulin Secretion-Sensitivity Index 2 (ISSI-2) were longitudinally estimated during the oral glucose tolerance test.

Results

After a median follow-up of 2.23 (1–4.52) y, obese patients showed significant decrease in WBISI (p<0.0001), and increase in fasting (p = 0.005) and 2 h glucose (2HG, p = 0.001). One child in preschool age and 4 school age children presented with 2HG between 7.8–11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R² = 0.309; p = 0.002; β = −0.556), ISSI-2 (R² = 0.465; p<0.0001; β = −0.682), and BMI z-score (R² = 0.246; p = 0.008; 0.496), respectively.

Conclusions

In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

The Expansion of the Pulmonary Rib Cage during Breath Stacking Is Influenced by Age in Obese Women

Objective

To analyze in obese women the acute effects of the breath stacking technique on thoraco-abdominal expansion.

Design and Methods

Nineteen obese women (BMI≥30 kg/m²) were evaluated by anthropometry, spirometry and maximal respiratory muscle pressures and successively analyzed by Opto-Electronic Plethysmography and a Wright respirometer during quiet breathing and breath stacking maneuvers and compared with a group of 15 normal-weighted healthy women. The acute effects of the maneuvers were assessed in terms of total and compartmental chest wall volumes at baseline, end of the breath stacking maneuver and after the maneuver. Obese subjects were successively classified into two groups, accordingly to the response during the maneuver, group 1 = prevalent rib cage or group 2 = abdominal expansion.

Results

Age was significantly lower in group 1 than group 2. When considering the two obese groups, FEV₁ was lower and minute ventilation was higher only in group 2 compared to controls group. During breath stacking, inspiratory capacity was significant differences in obese subjects with a smaller expansion of the pulmonary rib cage and a greater expansion of the abdomen compared to controls and also between groups 1 and 2. A significant inverse linear relationship was found between age and inspiratory capacity of the pulmonary rib cage but not of the abdomen.

Conclusions

In obese women the maximal expansion of the rib cage and abdomen is influenced by age and breath stacking maneuver could be a possible therapy for preventing respiratory complications.     

The Relationship between Endogenous Androgens and Body Fat Distribution in Early and Late Postmenopausal Women

Objectives

To investigate the relationship between endogenous androgens and body fat distribution in early and late postmenopausal women.

Materials and Methods

We enrolled postmenopausal women consisting of an early group (≤5 years since menopause, n = 105) and a late group (≥10 years since menopause, n = 107). Each group was subdivided into normal weight (BMI <24 kg/m²) group, overweight and obese (BMI ≥24 kg/m²) group. Fasting total testosterone (T), dehydroepiandrosterone-sulfate (DHEA-S) and sex hormone-binding globulin (SHBG) levels were measured. Body fat distribution was evaluated by dual-energy X-ray absorptiometry (DEXA).

Results

Late postmenopausal women had a higher proportion of body fat than early postmenopausal women. The body fat of the overweight and obese women had a greater tendency to accumulate in the abdomen compared with the normal weight women both in early and late postmenopausal groups. The overweight and obese women had a higher free testosterone (FT) than the normal weight women in early postmenopausal women (P<0.05). In late postmenopausal women, the overweight and obese women had higher DHEA-S levels than normal weight women (P<0.05). No direct relationship was observed between the T levels and body fat distribution both in early and late postmenopausal groups (P>0.05).The FT in early postmenopausal women and the DHEA-S levels in late postmenopausal women correlated positively with the trunk/leg fat ratio (T/L) and the proportion of android fat whereas correlated negatively with the proportion of gynoid fat in the partial correlation and multiple linear regression analyses (all P<0.05).

Conclusions

Serum T levels do not correlate directly with body fat distribution, the FT in early postmenopausal women and DHEA-S levels in late postmenopausal women correlate positively with abdominal fat accumulation.     

Influence of Body Mass Index (BMI) on Functional Improvements at 3 Years Following Total Knee Replacement: A Retrospective Cohort Study

Background

The number of patients presenting for total knee replacement who are classified as obese is increasing. The functional benefits of performing TKR in these patients are unclear.

Aim

To assess the influence pre-operative body mass index has upon knee specific function, general health status and patient satisfaction at 3 years following total knee replacement.

Design

Retrospective comparative cohort study using prospectively collected data from an institutional arthroplasty register.

Methods

1367 patients were assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Medical Outcomes Trust Short Form-36 (SF-36) scores supplemented by a validated measure of satisfaction pre-operatively and subsequently at 1,2 and 3 year post-operatively. Comparisons were made by dividing the cohort into 4 groups based on body mass index (BMI) 18.5–25.0 kg/m² (n = 253);>25.0–30.0 kg/m² (n = 559);>30.0−35.0 kg/m² (n = 373);>35.0 kg/m² (n = 182).

Results

Despite lower pre-operative, 1 and 3 year WOMAC and SF-36 scores patients with the highest BMIs >35.0 kg/m² experienced similar improvements to patients with a ‘normal‘ BMI (18.5–25.0 kg/m²) at 1 year (Difference in WOMAC improvement = 0.0 (95%CI −5.2 to 5.2), p = 1.00) and this improvement was sustained at up to 3 years (Difference in 1 year to 3 year improvement = 2.2 (95%CI: −2.1 to 6.5), p = 1.00). This effect was also observed for the SF-36 mental and physical component scores. Despite equivalent functional improvements levels of satisfaction in the >35.0 kg/m² group were lower than for any other BMI group (>35.0 kg/m² = 84.6% satisfied versus 18.5–5.0 kg/m² = 93.3% satisfied,p = 0.01) as was the proportion of patients who stated they would have the operation again (>35.0 kg/m² = 69.6% versus 18.5–25.0 kg/m² = 82.2%,p = 0.01).

Conclusion

Obese and morbidly obese patients gain as much functional benefit from total knee replacement as patients with lesser body mass indexes. This benefit is maintained for up to 3 years following surgery. However, these patients are less satisfied with their knee replacement and almost a third would not have the operation again.     

Activating Brown Adipose Tissue for Weight Loss and Lowering of Blood Glucose Levels: A MicroPET Study Using Obese and Diabetic Model Mice

Purpose

This study aims at using ¹⁸F-FDG microPET to monitor the brown adipose tissue (BAT) glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models.

Methods

Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. ¹⁸F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β₃-adrenergic receptor agonist) or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels.

Results

Compared with the controls, the obese mice and DM mice showed successively lower ¹⁸F-FDG uptake in the interscapular BAT (P = 0.036 and <0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = −0.71, P = 0.003) and DM mice (r = −0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45).

Conclusion

The inhibited BAT function in obese and DM mice can be re-activated by β₃-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM.     

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

Objective

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

Methods

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

Results

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

Conclusion

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

Women’s Satisfaction with Body Image before Pregnancy and Body Mass Index 4 Years after Delivery in the Mothers of Generation XXI

Background

Body image satisfaction (BIS) influences body weight regulation and may contribute to long-term healthier lifestyle after pregnancy. Thus, we aimed to assess the association between BIS before pregnancy and body mass index (BMI) 4 years after the index pregnancy.

Methods

As part of the follow-up of a birth cohort, 3612 women with prepregnancy BMI >18.5 kg/m² were reevaluated 4 years after the birth of a child. BIS was defined as the difference between perceived and ideal body size before pregnancy, assessed by Stunkard Silhouettes after birth. The associations of BIS with BMI change (continuous) and BMI classes at 4 years, based on measured weight and height, were estimated using linear and multinomial regression, respectively.

Results

Among women with normal prepregnancy BMI, those who felt too small, regarding their ideal, had a 0.25 kg/m² smaller increase in BMI within 4 years and a lower likelihood of becoming overweight or obese [multivariate-adjusted odds ratio (OR) = 0.63; 95% confidence interval (95%CI): 0.44–0.91 and OR = 0.21; 95%CI: 0.05–0.91, respectively) than those satisfied with body image. Feeling too large was associated with a 0.41 kg/m² larger increase in BMI and a higher risk of becoming overweight or obese (OR = 2.12; 95%CI:1.73–2.59 and OR = 3.42; 95%CI:2.02–5.79, respectively). A similar, non-significant, trend was observed for overweight women. Obese women who felt too large had a non-significant decrease in BMI.

Conclusions

BIS plays a role in maternal body weight after delivery. Realistic body size goals may promote the motivation to lose weight and contribute to higher success in attaining them.     

Metabolite Profiling Identifies Candidate Markers Reflecting the Clinical Adaptations Associated with Roux-en-Y Gastric Bypass Surgery

Background

Roux-en-Y gastric bypass (RYGB) surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data.

Methodology and Principal Findings

Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2±1.7). Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172) of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05), including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9) and obese/diabetic (n = 5) groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2), nervonic (C24:1) acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI) and estimates for insulin resistance (HOMA-IR). Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = −0.55).

Conclusions

Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.     

Association between Milk and Milk Product Consumption and Anthropometric Measures in Adult Men and Women in India: A Cross-Sectional Study

Background

The nutritional aetiology of obesity remains unclear, especially with regard to the role of dairy products in developing countries.

Objective

To examine whether milk/milk product consumption is associated with obesity and high waist circumference among adult Indians.

Methods

Information on plain milk, tea, curd and buttermilk/lassi consumption assessed using a Food Frequency Questionnaire was obtained from the cross-sectional sib-pair designed Indian Migration Study (3698 men and 2659 women), conducted at four factory locations across north, central and south India. The anthropometric measures included were Body Mass Index (BMI) and Waist Circumference (WC). Mixed-effect logistic regression models were conducted to accommodate sib-pair design and adjust for potential confounders.

Results

After controlling for potential confounders, the risk of being obese (BMI≥25 kg/m²) was lower among women (OR = 0.57;95%CI:0.43−0.76;p≤0.0001) and men (OR = 0.67;95%CI: 0.51−0.87;p = 0.005), and the risk of a high WC (men: >90 cm; women: >80 cm) was lower among men (OR = 0.71;95%CI:0.54−0.93;p = 0.005) and women (OR = 0.79;95%CI:0.59−1.05;p>0.05) who consume ≥1 portions of plain milk daily than those who do not consume any milk. The inverse association between daily plain milk consumption and obesity was also confirmed in sibling-pair analyses. Daily tea consumption of ≥1 portion was associated with obesity (OR = 1.51;95%CI:1.00−2.25;p>0.050) and high WC (OR = 1.65;95%CI:1.08−2.51;p>0.019) among men but not among women but there was no strong evidence of association of curd and buttermilk/lassi consumption with obesity and high waist circumference among both men and women.

Conclusions

The independent, inverse association of daily plain milk consumption with the risk of being obese suggests that high plain milk intake may lower the risk of obesity in adult Indians. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. Therefore, confirmatory studies are needed to clarify this relationship.     

Effect of Modest Caloric Restriction on Oxidative Stress in Women,a Randomized Trial

Objectives

It is not established to what extent caloric intake must be reduced to lower oxidative stress in humans. The aim of this study was to determine the effect of short-term, moderate caloric restriction on markers of oxidative stress and inflammation in overweight and obese premenopausal women.

Materials/Methods

Randomized trial comparison of 25% caloric restriction (CR) or control diet in 40 overweight or obese women (body mass index 32±5.8 kg/m²) observed for 28 days and followed for the next 90 days. Weight, anthropometry, validated markers of oxidative stress (F₂-isoprostane) and inflammation (C-reactive protein), adipokines, hormones, lipids, interleukins, and blood pressure were assessed at baseline, during the intervention, and at follow-up.

Results

Baseline median F₂-isoprostane concentration (57.0, IQR = 40.5–79.5) in the CR group was 1.75-fold above average range for normal weight women (32.5 pg/ml). After starting of the caloric restriction diet, F₂-isoprostane levels fell rapidly in the CR group, reaching statistical difference from the control group by day 5 (median 33.5, IQR = 26.0–48.0, P<0.001) and remained suppressed while continuing on the caloric restriction diet. Three months after resuming a habitual diet, concentrations of F₂-isoprostane returned to baseline elevated levels in ∼80% of the women.

Conclusions

Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00808275","term_id":"NCT00808275"}}NCT00808275     

Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

Background

Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls.

Research Design and Methods

Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method).

Results

Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons).

Conclusion

Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.     

Morbid Obesity as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic Influenza A(H1N1) Disease

Background

Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications.

Methodology/Principal Findings

We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April–July, 2009, with a cohort of the U.S. population estimated from the 2003–2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m²); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among ≥20 year olds, hospitalization was associated with being morbidly obese (BMI≥40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4–9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3–17.2). Among 2–19 year olds, hospitalization was associated with being underweight (BMI≤5^th percentile) among those with (OR = 12.5, 95%CI 3.4–45.5) and without (OR = 5.5, 95%CI 1.3–22.5) ACIP-recognized chronic conditions. Death was not associated with BMI category among individuals 2–19 years old. Among individuals aged ≥20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5–6.6) and morbid obesity (OR = 7.6, 95%CI 2.1–27.9).

Conclusions/Significance

Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.     

Prevention of Contrast-Induced Acute Kidney Injury: Is Simple Oral Hydration Similar To Intravenous? A Systematic Review of the Evidence

Background

Pre-procedural intravenous fluid administration is an effective prophylaxis measure for contrast-induced acute kidney injury. For logistical ease, the oral route is an alternative to the intravenous. The objective of this study was to compare the efficacy of the oral to the intravenous route in prevention of contrast-induced acute kidney injury.

Study Design

A systematic review and meta-analysis of randomised trials with a stratified analysis and metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE (1947 to week 47 2011), Cochrane CENTRAL (3^rd quarter 2011). Two reviewers identified relevant trials and abstracted data.

Settings and Population

Trials including patients undergoing a contrast enhanced procedure.

Selection Criteria

Randomised controlled trial; adult (>18 years) population; comparison of oral versus intravenous volume expansion.

Intervention

Oral route of volume expansion compared to the intravenous route.

Outcomes

Any measure of acute kidney injury, need for renal replacement therapy, hospitalization and death.

Results

Six trials including 513 patients met inclusion criteria. The summary odds ratio was 1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two routes of volume expansion. There was significant heterogeneity (Cochran’s Q = 11.65, p = 0.04; I² = 57). In the stratified analysis, inclusion of the five studies with a prespecified oral volume expansion protocol resulted in a shift towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also resolved the heterogeneity (Q = 3.19, P = 0.53; I² = 0).

Limitations

Small number of studies identified; lack of hard clinical outcomes.

Conclusion

The oral route may be as effective as the intravenous route for volume expansion for contrast-induced acute kidney injury prevention. Adequately powered trials with hard endpoints should be done given the potential advantages of oral (e.g. reduced patient burden and cost) over intravenous volume expansion.     

Gestational weight gain and body mass index in children: results from three german cohort studies

Introduction

Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring’s body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.

Methods

We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring’s mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5–6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.

Results

In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m² of ‘real’ BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.

Discussion

Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers.     

Deficiency in Clonogenic Endometrial Mesenchymal Stem Cells in Obese Women with Reproductive Failure – a Pilot Study

Objectives

The mechanisms of obesity associated reproductive complications remain poorly understood. Endometrial mesenchymal stem-cells are critical for cyclic renewal and uterine function. Recently, W5C5⁺ cells, with high clonogenicity, capable of producing endometrial stroma in vivo, have been described. We sought to investigate the abundance and cloning efficiency of W5C5⁺ and W5C5⁻ endometrial cells in relation to Body Mass Index, age and reproductive outcome.

Design

W5C5⁺ and W5C5⁻ cells were purified from mid-luteal endometrial biopsies (n = 54) by magnetic bead separation and subjected to in vitro colony-forming assays.

Results

First trimester pregnancy losses were significantly higher in obese subjects (n = 12) compared to overweight (n = 20) and subjects with normal Body Mass Index (n = 22) (P<0.05, P<0.01, respectively). W5C5⁺ cells (%) were significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). W5C5⁺ cloning efficiency was significantly lower in obese subjects compared to overweight and subjects with normal Body Mass Index (P<0.05, respectively). W5C5⁻ cloning efficiency was significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). Body Mass Index was significantly negatively correlated with W5C5⁺ cloning efficiency and W5C5⁻ cloning efficiency (P<0.01, respectively), and positively correlated with first trimester loss (P<0.01). We found no significant results with age (P>0.05).

Conclusions

Our observations suggest that the regenerative capacity and plasticity of the endometrium of obese women is suboptimal, which in turn may account for the increased risk of reproductive complications associated with obesity.     

Metabolic Signatures of Cultured Human Adipocytes from Metabolically Healthy versus Unhealthy Obese Individuals

Background and Aims

Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO) can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-specific metabolic signatures and functional biomarkers for MHO versus MUHO.

Methods

10 insulin-resistant (IR) vs. 10 insulin-sensitive (IS) non-diabetic morbidly obese (BMI >40 kg/m²) Caucasians were matched for gender, age, BMI, and percentage of body fat. From subcutaneous fat biopsies, primary preadipocytes were isolated and differentiated to adipocytes in vitro. About 280 metabolites were investigated by a targeted metabolomic approach intracellularly, extracellularly, and in plasma.

Results/Interpretation

Among others, aspartate was reduced intracellularly to one third (p = 0.0039) in IR adipocytes, pointing to a relative depletion of citric acid cycle metabolites or reduced aspartate uptake in MUHO. Other amino acids, already known to correlate with diabetes and/or obesity, were identified to differ between MUHO''s and MHO''s adipocytes, namely glutamine, histidine, and spermidine. Most species of phosphatidylcholines (PCs) were lower in MUHO''s extracellular milieu, though simultaneously elevated intracellularly, e.g., PC aa C32∶3, pointing to increased PC synthesis and/or reduced PC release. Furthermore, altered arachidonic acid (AA) metabolism was found: 15(S)-HETE (15-hydroxy-eicosatetraenoic acid; 0 vs. 120pM; p = 0.0014), AA (1.5-fold; p = 0.0055) and docosahexaenoic acid (DHA, C22∶6; 2-fold; p = 0.0033) were higher in MUHO. This emphasizes a direct contribution of adipocytes to local adipose tissue inflammation. Elevated DHA, as an inhibitor of prostaglandin synthesis, might be a hint for counter-regulatory mechanisms in MUHO.

Conclusion/Interpretation

We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.     

Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

Objectives

Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants.

Methods

suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register.

Results

For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1^st to the 4^th quartile (HR = 1.72, 95% CI: 1.11–2.69). For women, it increased by 108% from the 1^st to the 4^th quartile (HR = 2.08, 95% CI: 1.45–2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002).

Conclusions

High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression.     

Impact of Baseline BMI on Glycemic Control and Weight Change with Metformin Monotherapy in Chinese Type 2 Diabetes Patients: Phase IV Open-Label Trial

Background

Differences exist between treatment recommendations regarding the choice of metformin as first-line therapy for type 2 diabetes patients according to body mass index (BMI). This study compared the efficacy of metformin monotherapy among normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes.

Methods

In this prospective, multicenter, open-label study in China, patients aged 23–77 years were enrolled 1∶1:1 according to baseline BMI: normal-weight (BMI 18.5−23.9 kg/m²; n = 125); overweight (BMI 24.0−27.9 kg/m²; n = 122) or obese (BMI ≥28 kg/m²; n = 124). Extended-release metformin was administered for 16 weeks (500 mg/day, up-titrated weekly to a maximum 2,000 mg/day). The primary efficacy endpoint was the effect of baseline BMI on glycemic control with metformin monotherapy, measured as the change from baseline in glycosylated hemoglobin (HbA_1c) at week 16 compared among BMI groups using ANCOVA. Other endpoints included comparisons of metformin’s effects on fasting plasma glucose (FPG), lipid levels and body weight.

Results

Mean HbA_1c decreases at week 16, adjusted for baseline values, were –1.84%, –1.78% and –1.78% in normal-weight, overweight and obese patients, (P = 0.664); body weight decreased by 2.4%, 3.9% and 3.5%, respectively. FPG levels decreased similarly over time in all BMI groups (P = 0.461) and changes from baseline in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) did not differ significantly among BMI groups at week 16 (P = 0.143 and 0.451, respectively).

Conclusions

Baseline BMI had no impact on glycemic control, weight change or other efficacy measures with metformin monotherapy. These data suggest that normal-weight type 2 diabetes patients would derive the same benefits from first-line treatment with metformin as overweight and obese patients, and are not at increased risk of excess weight loss.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00778622","term_id":"NCT00778622"}}NCT00778622     

Twenty-Four Hour Total and Dietary Fat Oxidation in Lean,Obese and Reduced-Obese Adults with and without a Bout of Exercise

Background

It has been hypothesized that obese and reduced-obese individuals have decreased oxidative capacity, which contributes to weight gain and regain. Recent data have challenged this concept.

Objective

To determine (1) whether total and dietary fat oxidation are decreased in obese and reduced-obese adults compared to lean but increase in response to an acute exercise bout and (2) whether regular physical activity attenuates these metabolic alterations.

Design

We measured 24-hr total (whole-room calorimetry) and dietary fat (¹⁴C-oleate) oxidation in Sedentary Lean (BMI = 21.5±1.6; n = 10), Sedentary Obese (BMI = 33.6±2.5; n = 9), Sedentary Reduced-Obese (RED-SED; BMI = 26.9±3.7; n = 7) and in Physically Active Reduced-Obese (RED-EX; BMI = 27.3±2.8; n = 12) men and women with or without an acute exercise bout where energy expended during exercise was not replaced.

Results

Although Red-SED and Red-EX had a similar level of fatness, aerobic capacity and metabolic profiles were better in Red-EX only compared to Obese subjects. No significant between-group differences were seen in 24-hr respiratory quotient (RQ, Lean: 0.831±0.044, Obese: 0.852±0.023, Red-SED: 0.864±0.037, Red-EX: 0.842±0.039), total and dietary fat oxidation. A single bout of exercise increased total (+27.8%, p<0.0001) and dietary (+6.6%, p = 0.048) fat oxidation across groups. Although exercise did not impact RQ during the day, it decreased RQ during sleep (p = 0.01) in all groups. Red-EX oxidized more fat overnight than Red-SED subjects under both resting (p = 0.036) and negative energy balance (p = 0.003) conditions, even after adjustment for fat-free mass.

Conclusion

Obese and reduced-obese individuals oxidize as much fat as lean both under eucaloric and negative energy balance conditions, which does not support the hypothesis of reduced oxidative capacity in these groups. Reduced-obese individuals who exercise regularly have markers of metabolic health similar to those seen in lean adults. Both the acute and chronic effects of exercise were primarily observed at night suggesting an important role of sleep in the regulation of lipid metabolism.