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.

Quantifying time from last dose: do direct oral anticoagulant assays correlate with patient's reported last dose.

INTRODUCTION: In the absence of a patient's last direct oral anticoagulant (DOAC) dose time, best practice regarding preoperative DOAC cessation remains unclear. The aim of this study was to investigate, in a real-life patient cohort, if there was an association between subjective patient recall and objective DOAC assay titre. METHODS/MATERIALS: A multicentre cohort study of consecutive surgical inpatients was conducted. DOAC assays were 'expected' if they satisfied both time and titre-based guidelines. RESULTS: Patient-recalled last dose and DOAC assay was available in 285 individuals. DOAC assay titres correlated strongly with the expected levels based on a patient's reported last dose time(rho = 0.70, P value < 0.0001). However, underweight (<50 kg; P  = 0.0339) and elderly (>80 years; P  = 0.0134) were more likely to have an unexpectedly high assay titre. CONCLUSIONS: A significant portion (∼25%) of patients had unexpected DOAC titres. DOAC levels can be clinically impactful in a significant percentage of patients, particularly in elderly and/or underweight.

Higher Peripheral Cholesterol and a Positive Correlation With Risk for Large-For-Gestational-Age Neonates in Pre-Pregnancy Underweight Women.

Objective: As the high proportion of underweight pregnant women, omission of their weight gain and blood lipids management during gestation might lead to adverse pregnancy outcomes. This study aimed to determine the relationship between lipid profile and risks for adverse pregnancy outcomes in pre-pregnancy underweight women. Methods: This study was part of an ongoing cohort study including Chinese gravidas delivered from January 2015 to December 2016. Included subjects were grouped into underweight, normal-weight, and overweight by BMI before conception. Logistic regression was used to assess the association between lipid profiles during second trimester and adverse obstetric outcomes in each group. A subgroup analysis according to the gestational weight gain, in which subjects in each group were divided into above and within the Institute of Medicine (IOM) recommendations, was performed. Results: A total of 6, 223 women were included. The proportion of underweight (19.3%) was similar to that of overweight women (19.4%) in South China. Peripheral total cholesterol (TC) level in underweight women was significantly higher than that in overweight women (P <0.001). After adjusting maternal age, TC level was positively correlated to the risk for large-for-gestational-age (LGA) [aOR =2.24, 95%CI (1.08, 4.63)], and negatively related to the risk for small-for-gestational age (SGA) [aOR =0.71, 95%CI (0.59, 0.85)] in underweight women, but not in normal-weight or overweight women. The subgroup analysis showed that maternal TC level was positively correlated with the risk of LGA only in underweight women who gained weight more than the IOM recommendations. Conclusion: Underweight pregnant women with high TC levels had a higher risk for LGA, especially among women whose gestational weight gain were above the IOM recommendations. Therefore, clinical management of lipids and weight gain during gestation should also be recommended for underweight women.

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).

Leanness and Low Plasma Leptin in GPR17 Knockout Mice Are Dependent on Strain and Associated With Increased Energy Intake That Is Not Suppressed by Exogenous Leptin.

Previous studies have shown that agonists of GPR17 stimulate, while antagonists inhibit feeding. However, whole body knockout of GPR17 in mice of the C57Bl/6 strain did not affect energy balance, whereas selective knockout in oligodendrocytes or pro-opiomelanocortin neurons provided protection from high fat diet-induced obesity and impaired glucose homeostasis. We reasoned that whole body knockout of GPR17 in mice of the 129 strain might elicit more marked effects because the 129 strain is more susceptible than the C57Bl/6 strain to increased sympathetic activity and less susceptible to high fat diet-induced obesity. Consistent with this hypothesis, compared to wild-type mice, and when fed on either a chow or a high fat diet, GPR17 -/- mice of the 129 strain displayed increased expression of uncoupling protein-1 in white adipose tissue, lower body weight and fat content, reduced plasma leptin, non-esterified fatty acids and triglycerides, and resistance to high fat diet-induced glucose intolerance. Not only energy expenditure, but also energy intake was raised. Administration of leptin did not suppress the increased food intake in GPR17 -/- mice of the 129 strain, whereas it did suppress food intake in GPR17 +/+ mice. The only difference between GPR17 +/- and GPR17 +/+ mice of the C57Bl/6 strain was that the body weight of the GPR17 -/- mice was lower than that of the GPR17 +/+ mice when the mice were fed on a standard chow diet. We propose that the absence of GPR17 raises sympathetic activity in mice of the 129 strain in response to a low plasma fuel supply, and that the consequent loss of body fat is partly mitigated by increased energy intake.

Is BMI associated with anemia and hemoglobin level of women and children in Bangladesh: A study with multiple statistical approaches.

BACKGROUND: The coexistence of undernutrition and obesity is an emerging problem for developing countries like Bangladesh. Anemia is another critical public health threat, prevalent predominantly among women and children. Undernutrition is linked with a higher risk of anemia, and lower dietary iron intake might be the possible reason. However, the risk of anemia among obese/overweight individuals is controversial. The study explores the relation of BMI with anemia and blood hemoglobin level among women and children in Bangladesh. METHODS: Multiple statistical approaches were employed to nationally representative secondary data (BDHS 2011) on women (n = 5680) age 15-49 years and children (n = 2373) age 6-59 months to illuminate the relation between BMI and anemia. BMI was categorized according to the WHO recommended BMI category for Asian people. Descriptive statistics were used to measure mean hemoglobin level. Chi-square test, Pearson correlation, Two-way ANOVA, binary, ordinal, and restricted cubic splines (RCS) regression were used to study the association of BMI with anemia and hemoglobin level. RESULTS: Chi-square test reveals significant association, though not intense, among BMI and anemia categories of women (15-49 years) (χ2 ≥99, p<2.2e-16 and Cramér's V = 0.0799-0.1357). From ANOVA analysis, a significant difference in blood hemoglobin level was found among women (total sample and nonpregnant) with different BMI categories (p≤0.05). Binary (Severely Underweight: OR 1.2680, 95% CI 0.755-2.161; Obese: OR 0.4038, 95% CI 0.120-1.177), Ordinal logistic regression (Severely Underweight: OR 1.337, 95% CI 0.842-2.115; Obese: OR 0.504, 95% CI 0.153-1.411) and restricted cubic spline regression (Severely Underweight: OR >1.5; Obese: OR ~0.5) reveal that the risk of anemia was higher among underweight and lower among obese/overweight women compared to normal women. Lower anemia risk among richest women indicates probable higher dietary iron intake among obese/overweight women. CONCLUSION: In the current study, women with overweight/obesity from Bangladesh were shown to have lower likelihood of being anemic, while underweight women more likely to be anemic. However, no relation between BMI and anemia was found among children.

Lean non-alcoholic fatty liver disease and associated metabolic disturbance: A Saudi Arabian cross-sectional study.

Non-alcoholic liver disease (NAFLD) is a metabolic liver disease associated with visceral adiposity and insulin resistance. Recently, NAFLD has been described in lean individuals who additionally have impaired metabolic parameters similar to their non-lean counterparts. We aimed to explore this further in Saudi Arabia. From 2016 to 2019, we prospectively studied a group of newly diagnosed NAFLD patients at a tertiary hospital in Saudi Arabia. Patients were classified into three groups: lean (body mass index [BMI] <25), overweight (BMI ≥25 and <30), and obese (BMI ≥30). We made comparisons between these groups on basic clinical, demographic, and laboratory parameters. In total, 1753 patients were recruited and 1262 patients met the inclusion criteria. Altogether, 159 (12.6%), 365 (29%), and 737 (58.4%) patients were in the lean, overweight, and obese categories, respectively. Lean NAFLD patients were, on average, younger than those in the overweight group (mean 49.95 ± 15.3) and had a significantly higher high-density lipoprotein value (HDL) (mean 52.56 ± 16.27). Sex, hyperlipidemia, type 2 diabetes, and hypertension were significantly associated with BMI. Lean NAFLD patients displayed the features of metabolic syndrome including elevated glycosylated hemoglobin and abnormal lipid profile but had higher serum HDL. This is in contrast to the widely held belief that lean individuals have no dysmetabolic changes compared to overweight individuals. Recognition of this problem is essential so that lean NAFLD patients can be screened for metabolic changes and managed appropriately to prevent complications.

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/.

Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.

INTRODUCTION: Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals. METHODS: BAT 18F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography-high-resolution mass spectrometry. RESULTS: In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity. CONCLUSION: Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.

Decreased Abundance of Akkermansia muciniphila Leads to the Impairment of Insulin Secretion and Glucose Homeostasis in Lean Type 2 Diabetes.

Although obesity occurs in most of the patients with type 2 diabetes (T2D), a fraction of patients with T2D are underweight or have normal weight. Several studies have linked the gut microbiome to obesity and T2D, but the role of gut microbiota in lean individuals with T2D having unique clinical characteristics remains unclear. A metagenomic and targeted metabolomic analysis is conducted in 182 lean and abdominally obese individuals with and without newly diagnosed T2D. The abundance of Akkermansia muciniphila (A. muciniphila) significantly decreases in lean individuals with T2D than without T2D, but not in the comparison of obese individuals with and without T2D. Its abundance correlates inversely with serum 3ß-chenodeoxycholic acid (ßCDCA) levels and positively with insulin secretion and fibroblast growth factor 15/19 (FGF15/19) concentrations. The supplementation with A. muciniphila is sufficient to protect mice against high sucrose-induced impairment of glucose intolerance by decreasing ßCDCA and increasing insulin secretion and FGF15/19. Furthermore, ßCDCA inhibits insulin secretion and FGF15/19 expression. These findings suggest that decreased abundance of A. muciniphila is linked to the impairment of insulin secretion and glucose homeostasis in lean T2D, paving the way for new therapeutic options for the prevention or treatment of diabetes.

Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC). METHODS: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10-22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal. RESULTS: Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037). CONCLUSIONS: ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets.

The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population.

BACKGROUND: The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. METHODS: The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. RESULTS: The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. CONCLUSIONS: This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

Iodine Nutritional Status and Related Factors among Chinese School-Age Children in Three Different Areas: A Cross-Sectional Study.

We evaluated the iodine nutritional status and related factors among school-age children based on the 2016 National Nutrition and Health Surveillance of Children and Lactating Women; 3808 children from Hebei, Guangxi, and Zhejiang province were included in the study. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), body mass index (BMI), vitamin A (VA), and vitamin D (VD) were measured. The abnormal rate of UIC and TSH were assessed. Relationships between UIC/TSH and the possible factors were analyzed. The overall median UIC was 185.14 µg/L, and the median UIC of children aged 8-10 was 164.60 µg/L. Prevalence of iodine deficiency and excess was 13.84% and 14.36%, respectively, and 12.87% of children showed TSH excess. UIC, as well as the abnormal rates of iodine deficiency (ID) and TSH, were significantly different among the three provinces. The median UICs and excess rates increased with age, reaching 211.45 µg/L and 21.35% at age of 14~, while TSH showed the opposite trend. Overweight children tended to have lower UIC and higher TSH. Higher UIC and TSH were found in VA sufficient group (p < 0.01). Further, the VD deficient group had a higher TSH compared to the sufficient group (p < 0.01). Moreover, UI and TSH distribution was obviously different among different vitamin A/D status (p < 0.05). Although the median UIC of school-age children was optimal, there were pockets of inadequate and excessive UI in the three provinces. Compared to the national IDD monitoring results in 2014, the iodine nutritional status of children was greatly improved. Considerations of region, age, BMI, VA, or VD are needed in the future iodine evaluation and surveillance.

Pediatric Reference Intervals for Thyrotropin, Free Triiodothyronine, and Free Thyroxine and the Relevance of Body Mass Index and Puberty in Measurement Interpretation.

Background: The present study aimed to establish age- and sex-specific reference intervals for serum concentrations of thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) in healthy children and adolescents. Additionally, we investigated the association of TSH, fT3, and fT4 with putative influencing factors, such as sex, body mass index (BMI), and puberty. Methods: A total of 9404 blood serum samples from 3140 children and adolescents without thyroid affecting diseases were included in determining TSH, fT3, and fT4 levels and age- and sex-specific reference ranges. To investigate the association of TSH, fT3, and fT4 with age, sex, weight status, and the role of puberty-based changes, the hormone levels and BMI values were converted to standard deviation scores (SDS). Results: In general, TSH, fT3, and fT4 were found to be age- and sex-dependent. Puberty was accompanied by decreased TSH, decreased fT3 with a temporary peak in males, and a temporary nadir of fT4 in Tanner stage 3 for both sexes. BMI-SDS was positively associated with TSH-SDS (ß = 0.081, p < 0.001); the effect was more pronounced in overweight subjects (ß = 0.142, p < 0.01) and insignificantly negative in underweight subjects (ß = -0.047, p > 0.05). BMI-SDS was positively associated with fT3-SDS (ß = 0.066, p < 0.001) and negatively associated with fT4-SDS (ß = -0.135, p < 0.001), with the effect insignificantly less negative in overweight children (ß = -0.055, p > 0.05). Conclusions: Age- and sex-specific reference intervals are important for the interpretation of measurements of TSH, fT3, and fT4 in children and adolescents. Influencing factors such as BMI and puberty should be taken into consideration when using measurements of TSH and thyroid hormones in the diagnosis, treatment, and monitoring of thyroid diseases. Clinical Trial Registration number: NCT02550236.

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.

Nutritional status, hemoglobin level and their associations with soil-transmitted helminth infections between Negritos (indigenous) from the inland jungle village and resettlement at town peripheries.

This study compared the current nutritional status, hemoglobin levels and their associations with soil-transmitted helminth (STH) infections between two categories of Negritos (indigenous): (i) Inland Jungle Villages (IJV) (ii) and Resettlement Plan Scheme (RPS) near town peripheries, decades after redevelopment and demarginalization. A total of 416 Negritos (IJV: 149; RPS: 267) was included for nutritional profiling based on anthropometric analysis. However, only 196 (IJV: 64; RPS: 132) individuals consented to blood taking for the hemoglobin (Hb) measurements. Subsequently, the association of undernutrition and anemia with STH infections were determined based on univariate and multivariate logistic regression analyses. The overall prevalence of stunting, wasting, and underweight amongst children and adolescents (n = 343) were 45.8%, 42.3% and 59.1%, respectively. In adults (n = 73), the prevalence of underweight was low (6.8%) but overweight and obese was prominent (26.0%). For anemia (n = 196), an overall prevalence rate of 68.4% were observed with 80% and 70.4% of children aged 2-6 y/o and aged 7-12 y/o, respectively being anemic. Comparatively, the prevalence of underweight (WAZ) was significantly higher in the RPS versus the IJV (P = 0.03) In the IJV, children aged ≤ 6 y/o and having STH poly-parasitism were associated with underweight (P = 0.01) and moderate-severe T. trichiura infection was associated with anemia. Whilst in the RPS, underweight was highly associated with only T. trichiura infection (P = 0.04). Wasting was significantly associated with young children aged ≤10 in both IJV (P = 0.004) and RPS (P = 0.02). Despite efforts in improving provision of facilities and amenities among the indigenous, this study highlighted a high magnitude of nutritional issues among the Negritos especially those in the RPS and their likely association with STH infections and decades of demarginalization. Joint nutritional intervention strategies with mass anti-helminthic treatment are imperative and urgently needed to reduce the undernutrition problems especially among indigenous children.

Nutritional Status and Serum Levels of Micronutrients in an Elderly Group Who Participate in the Program for Complementary Food in Older People (PACAM) from the Metropolitan Region, Santiago de Chile.

The increase in the Chilean elderly population has promoted public policies to favor an adequate nutrition in later life. This study evaluated the nutritional status, micronutrients intake and serum micronutrients levels of an elderly group beneficiary of the PACAM from the Metropolitan Region, Santiago de Chile. Anthropometric and dietary survey (24 h food recalls) were assessed in 182 elderly individuals (60 and 80 years old). Blood serum collection was used to measure the micronutrient status. The sample was comprised by 12.6%, 46.1%, 28.0% and 13.2% of underweight, normal weight, overweight and obese subjects, respectively. Women presented 11% of underweight, 45% of normal weight and 44% of overweight and obese, while men-18%, 50% and 32%, respectively. Only the 63% of the elderlies consumed PACAM foods, reaching average daily intakes below (50%) the recommended daily serving. Serum deficiencies of 25-hydroxyvitamin D (88%), vitamin B12 (33%) and calcium (36%) were observed, being the highest ones in the PACAM foods women (60-75 years old). Chilean elderlies presented mainly a normal weight; however, an important proportion of overweight/obese subjects was observed. Although PACAM foods consumption significantly increased the micronutrient intake, it was not enough to ensure an adequate serum micronutrient levels in the elderly.

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.

Childhood Malnutrition and Association of Lean Mass with Metabolome and Hormone Profile in Later Life.

This study aimed to determine the associations of targeted metabolomics and hormone profiles data with lean mass index (LMI), which were estimated using bioelectrical impedance, in survivors of child severe malnutrition (SM) (n = 69) and controls (n = 77) in Malawi 7 years after being treated. Linear associations between individual metabolite or hormone and LMI were determined, including their interaction with nutrition status 7 years prior. Path analysis was performed to determine structural associations. Lastly, predictive models for LMI were developed using the metabolome and hormone profile by elastic net regularized regression (EN). Metabolites including several lipids, amino acids, and hormones were individually associated (p < 0.05 after false discovery rate correction) with LMI. However, plasma FGF21 (Control: ß = -0.02, p = 0.59; Case: ß = -0.14, p < 0.001) and tryptophan (Control: ß = 0.15, p = 0.26; Case: ß = 0.70, p < 0.001) were associated with LMI among cases but not among controls (both interaction p-values < 0.01). Moreover, path analysis revealed that tryptophan mediates the association between child SM and LMI. EN revealed that most predictors of LMI differed between groups, further indicating altered metabolic mechanisms driving lean mass accretion among SM survivors later in life.

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.