Growth differentiation factor-15 and metabolic features in chronic heart failure: Insights from the SUPPORT Trial -GDF15 across the BMI spectrum.

BACKGROUND: GDF15 plays pivotal metabolic roles in nutritional stress and serves as a physiological regulator of energy balance. However, the patterns of GDF15 levels in underweight or obese patients with chronic heart failure (CHF) are not well-understood. METHODS: We assessed serum GDF15 levels at baseline and 3 years and the temporal changes in 940 Japanese patients (642 paired samples), as a sub-analysis of the SUPPORT trial (age 65.9 ± 10.1 years). The GDF15 levels were analyzed across BMI groups (underweight [<18.5 kg/m2; n = 50], healthy weight [18.5-22.9; n = 27 5], overweight [23-24.9; n = 234], and obese [≥25; n = 381]), following WHO recommendations for the Asian-Pacific population. Landmark analysis at 3 years assessed the association between GDF15 levels and HF hospitalization or all-cause death. RESULTS: Compared to the healthy weight group, the underweight group included more females (54.0%) with advanced HF (NYHA class III; 20.0%) and exhibited increased GDF15 level (1764 pg/mL [IQR 1067-2633]). Obese patients, younger (64.2 years) and diabetic (53%), had a similar GDF15 level to the healthy weight group. A higher baseline GDF15 level was associated with worse outcomes across the BMI spectrum. GDF15 increased by 208 [21-596] pg/mL over 3 years, with the most substantial increase observed in the underweight group (by +28.9% [6.2-81.0]). Persistently high GDF15 levels (≥1800 pg/mL) was independently associated with worse outcomes after 3 years (adjusted HR 1.8 [95%CI 1.1-2.9]). CONCLUSIONS: In underweight patients with CHF, GDF15 level was elevated at baseline and experienced the most significant increase over 3 years. Its consistent elevation suggested a worse outcome.

Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men.

Lack of interleukin-6 (IL-6) leads to expansion of adipose tissue mass in rodents and humans. The exact underlying mechanisms have not been identified. In this placebo-controlled, non-randomized, participant-blinded crossover study, we use the IL-6 receptor antibody tocilizumab to investigate the role of endogenous IL-6 in regulating systemic energy metabolism at rest and during exercise and recovery in lean and obese men using tracer dilution methodology. Tocilizumab reduces fatty acid appearance in the circulation under all conditions in lean and obese individuals, whereas lipolysis (the rate of glycerol appearance into the circulation) is mostly unaffected. The fact that fatty acid oxidation is unaffected by IL-6 receptor blockade suggests increased re-esterification of fatty acids. Glucose kinetics are unaffected. We find that blocking endogenous IL-6 signaling with tocilizumab impairs fat mobilization, which may contribute to expansion of adipose tissue mass and, thus, affect the health of individuals undergoing anti-IL-6 therapy (Clinicaltrials.gov: NCT03967691).

The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial.

Purpose: Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes. Methods: In a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5-10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen. Results: WP reduced PPG area under the curve [AUC0-60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects. Conclusion: Pre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual's insulin resistance, their obese state, or other obesity-related ailments needs further investigation. Clinical Trial Registration: ISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.

Is Serum BDNF Altered in Acute, Short- and Long-Term Recovered Restrictive Type Anorexia Nervosa?

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all.

Effect of Treatment of Periodontitis on Incretin Axis in Obese and Nonobese Individuals: A Cohort Study.

CONTEXT: Periodontitis confers an increased risk of developing type 2 diabetes and, in patients with obesity, it might interfere with the incretin axis. The effect of periodontal treatment on glucoregulatory hormones remains unknown. OBJECTIVE: To evaluate the effect of periodontal treatment on incretin axis in obese and lean nondiabetic individuals. SETTING: King's College Dental Hospital and Institute, London, UK. PARTICIPANTS AND METHODS: The metabolic profile of obese and normal-body-mass-index individuals affected by periodontitis was studied at baseline, 2, and 6 months after intensive periodontal treatment, by measuring plasma insulin, glucagon, glucagon-like peptide-1(GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) and markers of systemic inflammation and oxidative stress. MAIN OUTCOME MEASURE(S): Circulating levels of incretins and inflammatory markers. RESULTS: At baseline, periodontal parameters were worse for obese than nonobese; this was accompanied by higher levels of circulating high-sensitivity C-reactive protein (hs-CRP), insulin, and GLP-1. The response to periodontal treatment was less favorable in the obese group, without significant variations of hs-CRP or malondialdehyde. Glucoregulatory hormones changed differently after treatment: while insulin and glucagon did not vary at 2 and 6 months, GLP-1 and GIP significantly increased at 6 months in both groups. In particular, GLP-1 increased more rapidly in obese participants, while the increase of GIP followed similar trends across visits in both groups. CONCLUSIONS: Nonsurgical treatment of periodontitis is associated with increased GLP-1 and GIP levels in nonobese and obese patients; changes in GLP-1 were more rapid in obese participants. This might have positive implications for the metabolic risk of these individuals.

Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).

BACKGROUND: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. RESULTS: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. CONCLUSIONS: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean women with polycystic ovary syndrome: insights from a large Caucasian cohort.

PURPOSE: Polycystic ovary syndrome (PCOS), considered a lifelong condition, manifests mainly as a cluster of hyperandrogenic symptoms during the early reproductive years, with the affected woman gradually developing an adverse cardiometabolic profile over the years. However, some data point to the possibility of differences in the evolution of PCOS according to a woman's weight. The aim of the present study was to evaluate the metabolic and hormonal profiles of women with PCOS over time. METHODS: A total of 763 lean women with PCOS (BMI 20-25 kg/m2) and 376 controls were included. The study group was further divided into three age groups representing women post-adolescence, of reproductive age, and of late reproductive age. All subjects were assessed clinically, biochemically, and hormonally. RESULTS: Waist circumference, lipids, androgens, and insulin resistance index (homeostasis model assessment of IR index (HOMA-IR)) were significantly higher in the PCOS group compared with controls. Age subgroup analysis showed a progressive decrease of HOMA-IR and waist circumference, and lipid levels were comparable between PCOS and controls in all age groups. Androgens remained significantly higher in PCOS, but they gradually decreased through time. A significant negative association of age with waist circumference, androgens, insulin, and HOMA-IR was revealed. Univariate and multivariate regression analysis disclosed a strong correlation of HOMA-IR with age (p = 0.014, ß - 0.19, SE coefficient 0.008) as a single parameter or in combination with total cholesterol (TC) (p < 0.001, age: ß - 0.023, SE 0.10; TC: ß 0.084, SE 0.027). CONCLUSION: Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean PCOS women. We hypothesize that if these women do not gain weight with the passage of time, there is a high probability that their cardiometabolic risk will be attenuated.

Serum betatrophin levels are significantly increased in obese patients compared to lean patients regardless to the presence of PCOS.

Betatrophin, which regulates glucose metabolism, is primarily expressed in liver and fat tissue. We aimed to investigate betatrophin levels in patients with polycystic ovary syndrome (PCOS) that is the most common endocrine pathology in women of reproductive age. A total of 69 women were included in this prospective study: 35 patients with PCOS (18 obese and 17 lean) and 34 healthy controls (17 obese and 17 lean). Patients who met the criteria were compared regarding betatrophin levels and other hormonal values. Serum betatrophin level did not differ between obese PCOS patients and obese controls, and lean PCOS patients and lean controls; while significantly increased in obese PCOS patients and controls compared to lean PCOS patients and controls. Total testosterone and androstenedione were significantly higher in patients with PCOS than in controls both in the obese and lean groups, while sex hormone-binding globulin was significantly lower in patients with PCOS than in controls both in the obese and lean groups. However, remaining hormone values were similar between groups. Betatrophin level was significantly increased in obese patients compared to lean patients independent to the presence of PCOS.

Associations of Fat and Lean Body Mass with Circulating Amino Acids in Older Men and Women.

Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62-74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking, and fasting glucose. Higher lean mass index (LMI) was associated with higher concentrations of branched-chain amino acids in both sexes (p ≤ .001). In men, LMI was also positively associated with tyrosine (p = .006) and inversely with glycine (p < .001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p ≤ .008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.

Ingestion of lean meat elevates muscle inositol hexakisphosphate kinase 1 protein content independent of a distinct post-prandial circulating proteome in young adults with obesity.

BACKGROUND: We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS: We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS: Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ±â€¯0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ±â€¯0.17], 10 overweight (BMI: 27.1 ±â€¯0.5; HOMAIR: 1.25 ±â€¯0.11), and 10 obese (BMI: 35.9 ±â€¯1.3; HOMAIR: 5.82 ±â€¯0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS: Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS: These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.

Relationship between adipocytokines and angiotensin converting enzyme gene insertion/deletion polymorphism in lean women with and without polycystic ovary syndrome.

This study was designed to investigate the relationship between the levels of select adipocytokines (adiponectin, visfatin and apelin) and angiotensin in converting enzyme (ACE) gene insertion/deletion (ID) polymorphism in lean women with and without polycystic ovary syndrome (PCOS). The PCOS group (N = 94) was identified according to the Rotterdam criteria. The Control group (N = 68) included age- and body mass index (BMI)-matched healthy volunteers. Serum levels of adipocytokines were measured using enzyme immunoassays (EIA) and ACE genes were evaluated by polymerase chain reaction (PCR). The PCOS group, when compared to the Control group had lower adiponectin (p < .001) but higher visfatin (p < .001) and apelin (p = .003). There was no significant correlation of the levels of these adipocytokines with BMI, fasting glucose, fasting insulin or Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The PCOS and the Control groups also differed with regard to the ACE ID genotype distribution (p < .001). The ID, DD, and II genotype frequencies were, respectively, 34, 57 and 9% in the PCOS group and 49, 22 and 29% in the Control group. When stratified according to individual ID genotypes, the levels of adipocytokines in the PCOS and the Control groups remained significantly different. There was no statistically significant relationship between the levels of adipocytokines and ACE ID genotypes.

The role of the adipocytokines vaspin and visfatin in vascular endothelial function and insulin resistance in obese children.

BACKGROUND: We measured the concentrations of the adipocytokines vaspin and visfatin in obese Chinese children. Furthermore, we studied the correlation of these adipocytokines with early-onset metabolic and vascular sequelae among these children. METHODS: A total of 244 children (160 obese and 84 lean) were included in this study. Vaspin and visfatin were detected using enzyme-linked immunosorbent assays. We also assayed other metabolic and cardiovascular parameters. The associations of serum vaspin and visfatin concentrations with metabolic and cardiovascular parameters were determined. RESULTS: We found a significant elevation in the concentrations of vaspin and visfatin in obese children compared to the concentrations in lean children. Additionally, we found a significant positive correlation between visfatin and vaspin levels, as well as inflammatory cell infiltration and markers of endothelial activation, but these factors did not affect insulin resistance in obese children. Multiple regression analyses confirmed that vaspin is the strongest predictor of higher tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), angiotensin-2 (Ang-2), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin levels. We also found a significant association between visfatin and Ang-2, IL-6, VCAM-1, and E-selectin levels. CONCLUSION: The adipocytokines vaspin and visfatin are significantly interrelated, and both adipocytokines play a role in vascular endothelial function and inflammation.

Lean non-alcoholic fatty liver disease and development of diabetes: a cohort study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD), a condition associated with multiple metabolic abnormalities, is frequently observed in normal weight individuals (lean NAFLD). The metabolic consequences of lean NAFLD, however, are not well characterized. Thus, this study aimed to evaluate the risk of incident diabetes in lean NAFLD. METHODS: This is a cohort study of 51,463 adults without diabetes, history of liver disease or cancer at baseline who participated in a regular health screening exam. Fatty liver was diagnosed by ultrasonography. The study outcome was the development of diabetes during follow-up. RESULTS: During 236,446.6 person-years of follow-up (median follow-up of 4.0 years), 5370 participants developed diabetes. In fully adjusted models, the hazard ratios (HRs) for incident diabetes comparing lean participants with NAFLD, overweight/obese participants without NAFLD and overweight/obese participants with NAFLD to lean participants without NAFLD, were 1.18 (95% CI: 1.03-1.35), 1.06 (0.98-1.14) and 1.45 (1.34-1.57), respectively. The fully adjusted HR for incident diabetes for lean NAFLD participants with low NAFLD fibrosis score (NFS) (<-1.455) and with intermediate-to-high NFS (≥-1.455) compared to lean participants without NAFLD were 1.32 (1.14-1.53) and 2.73 (2.10-3.55), respectively. CONCLUSIONS: In this large cohort study, the presence and severity of NAFLD in normal weight adults was associated with an increased incidence of diabetes independently of established risk factors. Indeed, isolated lean NAFLD was a stronger risk factor for incident diabetes than the presence of overweight/obesity without NAFLD. Subjects with lean NAFLD require careful monitoring for the development of metabolic abnormalities.

Safety and efficacy of autologous mononuclear cell and stem cell apheresis in very low-weight children-Experience at a single center.

BACKGROUND: Apheresis in children with low body weight is technically limited by their tolerance of the extracorporeal blood volume. STUDY DESIGN AND METHODS: This paper presents a single-center experience with 23 procedures in 12 children with weights between 5.2 and 9.5 kg using the Spectra Optia mononuclear cell (MNC) protocol with blood priming. RESULTS: The average procedure duration was 158 minutes, and the median processed blood volume was 316 mL/kg. The white blood cell (WBC), platelet (PLT), and hemoglobin (HGB) values showed a downward trend with increased volume of processed blood. The post-apheresis HGB concentration was increased in all procedures due to initial priming with packed red blood cells (PRBCs), but this effect disappeared at a level of ~400 mL of processed blood/kg. The median volume of the cellular product was 36 mL, the WBC count was 153 K/µL, the hematocrit (HCT) was 1.5%, the PLT count was 602 K/µL, the WBC collection efficacy (CE2) was 13.2%, and the PLT CE2 was 9.5%. The median CD34+ CE2 was 28%, and interpolation of the CD34+ CE2 yielded a Y-intercept value of 32%. Higher pre-collection CD34+ counts resulted in higher CD34+ yields. No correlation was found between the pre-collection CD34+ results and CD34+ CE2. CONCLUSION: The analyzed data demonstrated the feasibility and safety of apheresis in very low-weight children. The laboratory abnormalities were asymptomatic and citrate toxicity was mild. Visual control of clogging with manual adjustment of the citrate infusion rate is important to reduce exposure to citrate.

Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is becoming a major health problem worldwide. Inflammation plays an important role in disease pathogenesis and recent studies have shown a potential role for the neutrophil serine proteases (NSPs) proteinase-3 (PR3) and neutrophil elastase (NE) in NAFLD as well as an imbalance between NSPs and their natural inhibitor alpha-1 antitrypsin (AAT). The aim of this study was to investigate whether PR3 and NE plasma concentrations are associated with NAFLD and/or type 2 diabetes. METHODS: To explore this hypothesis we used several cohorts: a cohort of 271 obese individuals with liver steatosis, a cohort of 41 patients with biopsy-proven NAFLD, a cohort of 401 obese type 2 diabetes patients and a cohort of 205 lean healthy controls; and measured PR3 and NE plasma concentrations. In addition, we measured AAT plasma concentrations in order to investigate if the ratios between NSPs and their natural inhibitor were altered in NAFLD and type 2 diabetes when compared to healthy controls. RESULTS: Our data shows an increase in PR3 and NE concentrations and a decrease in AAT concentrations in obese patients when compared to controls. Moreover, PR3 plasma concentrations are increased in patients with liver steatosis. Furthermore, PR3 and NE concentrations in the liver are associated with the advanced stages of NAFLD characterized by NASH and/ or liver fibrosis. Additionally, PR3 and NE concentrations were up-regulated in patients with type 2 diabetes when compared to lean and obese controls. CONCLUSION: We conclude that circulating levels of NSPs associate with obesity-related metabolic disorders. Further research is needed to clearly establish the role of these proteases and investigate whether they could be used as non-invasive markers for NAFLD and/or type 2 diabetes.

Associations of Overweight, Obesity, and Underweight With High Serum Total Cholesterol Level Over 30 Years Among the Japanese Elderly: NIPPON DATA 80, 90, and 2010.

BACKGROUND: The trend of association between overweight and high serum total cholesterol (TC) among the elderly is unclear. In addition, there is little evidence of risk of underweight for high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data. METHODS: Data of the National Survey on Circulatory Disorders and National Health and Nutrition Survey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was defined as 220 mg/dL and above. For participants aged ≥50 years, sex-specific odds ratios (ORs) of overweight or underweight compared with normal body mass index participants for high TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia. RESULTS: A total of 5,734, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980, 1990, 2000, and 2010, respectively. Although overweight was positively and significantly associated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83-3.24 and 0.92; 95% CI, 0.66-1.27 among men and 1.43; 95% CI, 1.18-1.72 and 1.08; 95% CI, 0.81-1.44 among women, respectively). While underweight was inversely and significantly associated with high TC in 1980, the association also gradually weakened among women (ORs in 1980 and 2010 were 0.28; 95% CI, 0.12-0.60 and 0.37; 95% CI, 0.10-1.28 among men and 0.39; 95% CI, 0.26-0.57 and 0.96; 95% CI, 0.58-1.57 among women, respectively). CONCLUSIONS: These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.

Basal and metoclopramide induced prolactin secretion in lean PCOS women.

Polycystic ovary syndrome (PCOS) as well as hyperprolactinemia can cause infertility. In retrospective study the prolactin levels during the oral metoclopramide test among lean PCOS woman according to four phenotypes and free androgen index (FAI) were compared. The study population consisted of 314 lean PCOS women. The population was divided into four groups according to the FAI and menstrual cycle regularity. The group A consisted 126 women with FAI≥5 and irregular menstruation, the group B- 53 patients with FAI≥5 and regular menstruation. Group C- 70 patients with FAI<5 and irregular menstruation, group D - 65 patients with FAI<5 and regular menstruation. The ratio of prolactin value in 120th minute in the metoclopramide test to the basal prolactin value was higher in group D than in groups A and B. The prolactin basal concentration was higher in patients with FAI≥5 than in patients with FAI<5, (262.9 vs 228.9 µIU/ml; p<0.001). The ratio of prolactin in 60th minute (12.3 vs 16.7; p=0.006) and in the 120th minute (10.9 versus 13.3; p<0.001) of the metoclopramide test to the basal prolactin were lower in patients with FAI≥5. The prolactin secretion in lean PCOS women may be associated with their FAI.

A study of ghrelin and leptin levels and their relationship to metabolic profiles in obese and lean Saudi women with polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as one of the most frequently encountered hormonal pathologies in women during their reproductive years. Leptin and ghrelin, peptide hormones with adipostatic and orexigenic effect, respectively, seem to be involved in the metabolic changes that occur in PCOS. The aim of this study was to determine serum ghrelin and leptin levels in obese and lean Saudi women with PCOS and to investigate their relationship to the metabolic profiles in these women. METHODS: This study was conducted as a prospective, observational, cross-sectional, case-control study, at the Department of Obstetrics and Gynecology, Al-Noor Hospital, Makkah, Kingdom of Saudi Arabia. The study population included 252 women [130 women with PCOS (diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus, 2003) and 122 normo-ovulatory women as matched controls] attending the outpatient Gynecology Clinic. Demographic details were recorded, blood was extracted following overnight fast and serum was used for the determination of serum ghrelin and leptin levels and other hormonal and biochemical parameters including total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, and insulin. Insulin resistance and sensitivity were calculated as HOMA-IR and HOMA-S. RESULTS: No significant differences in ghrelin (P = 0.1830) and leptin (P = 0.8329) levels were detected between the PCOS and control groups. However, ghrelin levels were significantly lower; and leptin levels were significantly higher in obese PCOS patients in comparison with lean patients (P = 0.0001 for both). In the PCOS group, there were significant correlations between ghrelin and leptin levels with Body Mass Index (BMI), waist-hip ratio, total cholesterol, triglycerides, HDL, LDL and insulin levels. Multiple regression analysis demonstrated that insulin was the main determinant for ghrelin (R2 = 0.316) and leptin (R2 = 0.352) levels (P = 0.0001 for both). CONCLUSIONS: Although serum ghrelin and leptin levels were found to be normal in women with PCOS; yet, there is a relationship, possibly linked to obesity, hyperinsulinemia and insulin resistance between these levels and metabolic profile of Saudi PCOS.

Inflammatory signatures distinguish metabolic health in African American women with obesity.

Obesity-driven Type 2 diabetes (T2D) is a systemic inflammatory condition associated with cardiovascular disease. However, plasma cytokines and tissue inflammation that discriminate T2D risk in African American women with obese phenotypes are not well understood. We analyzed 64 circulating cytokines and chemokines in plasma of 120 African American women enrolled in the Black Women's Health Study. We used regression analysis to identify cytokines and chemokines associated with obesity, co-morbid T2D and hypertension, and compared results to obese women without these co-morbidities, as well as to lean women without the co-morbidities. We then used hierarchical clustering to generate inflammation signatures by combining the effects of identified cytokines and chemokines and summarized the signatures using an inflammation score. The analyses revealed six distinct signatures of sixteen cytokines/chemokines (P = 0.05) that differed significantly by prevalence of T2D (P = 0.004), obesity (P = 0.0231) and overall inflammation score (P < E-12). Signatures were validated in two independent cohorts of African American women with obesity: thirty nine subjects with no metabolic complications or with T2D and hypertension; and thirteen breast reduction surgical patients. The signatures in the validation cohorts closely resembled the distributions in the discovery cohort. We find that blood-based cytokine profiles usefully associate inflammation with T2D risks in vulnerable subjects, and should be combined with metabolism and obesity counselling for personalized risk assessment.

Examining the relationship between blood lead level and stunting, wasting and underweight- A cross-sectional study of children under 2 years-of-age in a Bangladeshi slum.

Elevated blood lead level (BLL) is known to cause cardiac, immune, and cognitive damage but had not been thoroughly studied in relation to stunting among children under two years of age. We primarily aimed to assess the relationship between elevated BLL, the accumulation of concerned amount of the metal lead in blood and stunting and secondarily-wasting and underweight amongst Bangladeshi children less than two years of age. For this cross-sectional study, BLL measurements, anthropometric data, and socioeconomic indicator information were collected and analyzed for 729 children under two years of age upon enrollment in the MAL-ED study conducted in a Bangladeshi slum area. Univariate, bivariate and multivariate analyses were carried out to observe the proportion and mean and contribution of elevated BLL and other relevant variables in explaining the occurrence of stunting. Of the enrolled subjects, 39.0% were stunted [length-for-age z score (LAZ<-2)], 50.3% were male, and 86.6% had an elevated BLL (≥5µg/dL). Mean BLL of stunted children was 8.47 ± 3·37 µg/dL and 8.10 ± 3·80 µg/dL for non-stunted children. Proportion of children with elevated BLL was not significantly different between the stunted and non-stunted groups (p>0.05). When adjusted for other variables, elevated BLL was found to be a significant predictor of stunting and underweight (p<0.05) but not wasting (p>0.05). Elevated BLL (p<0·01), child's gender and weight (p<0·001), maternal body mass index (BMI) (p<0.05) and severe household food insecurity (p<0·05) were all significantly associated with stunting in the multivariate model. Increased odds of stunting was also observed for increased BLL. The findings suggest that chronic lead poisoning is significantly associated with high level of stunting among child slum dwellers in Bangladesh. These findings strengthen the argument for improved lead reduction efforts in Bangladesh, where lead poisoning and stunting are both highly prevalent.