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Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization.We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide.Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD.Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Background Severe acute respiratory syndrome coronavirus 2 is a respiratory virus that poses risks to the nutrition status and survival of infected patients, yet there is paucity of data to inform evidence‐based quality care. Methods We collected data on the nutrition care provided to patients with coronavirus disease 2019 (COVID‐19) by registered dietitian nutritionists (RDNs). Results Hospitalized COVID‐19 patients (N = 101) in this cohort were older adults and had elevated body mass index. The most frequent nutrition problems were inadequate oral intake (46.7%), inadequate energy intake (18.9%), and malnutrition (18.4%). These problems were managed predominantly with enteral nutrition, food supplements, and multivitamin‐multimineral supplement therapy. Over 90% of documented problems required a follow‐up. Conclusion This data set is the first of its kind to report on the types of nutrition diagnoses and interventions for COVID‐19 cases used by RDNs and highlights the need for increased and continued nutrition care.

Increased risk of type 2 diabetes mellitus (T2D) among individuals with overweight or obesity is well-established; however, questions remain about the temporal dynamics of weight change (gain or loss) on the natural course of T2D in this at-risk population. Existing epidemiologic evidence is limited to studies that discretely sample and assess excess weight and T2D risk at different ages with limited follow-up, yet changes in weight may have time-varying and possibly non-linear effects on T2D risk. Predicting the impact of weight change on the risk of T2D is key to informing primary prevention. We critically review the relationship between weight change, trajectory groups (i.e., distinct weight change patterns), and T2D risk among individuals with excess weight in recently published T2D prevention randomized controlled trials (RCTs) and longitudinal cohort studies.Overall, weight trajectory groups have been shown to differ by age of onset, sex, and patterns of insulin resistance or beta-cell function biomarkers. Lifestyle (diet and physical activity), pharmacological, and surgical interventions can modify an individual's weight trajectory. Adolescence is a critical etiologically relevant window during which onset of excess weight may be associated with higher risk of T2D. Changes in insulin resistance and beta-cell function biomarkers are distinct but related correlates of weight trajectory groups that evolve contemporaneously over time. These multi-trajectory markers are differentially associated with T2D risk. T2D risk may differ by the age of onset and duration of excess body weight, and the type of weight loss intervention. A better understanding of the changes in weight, insulin sensitivity, and beta-cell function as distinct but related correlates of T2D risk that evolve contemporaneously over time has important implications for designing and targeting primary prevention efforts.

Background:Nutritional deficiencies are common following Roux-en-Y Gastric Bypass (RYGB). Aetiology is diverse; including non-compliance, altered diet, unresolved preoperative deficiency and differential degrees of post-operative malabsorption occurring as function of length of bypassed intestine. Iron and calcium/vitamin D deficiency occur in up to 50% of patients following RYGB. Currently, treatment strategies recommend the prescription of oral supplements for those who become deficient. Meanwhile, debate exists regarding the absorption capacity of these post-operatively and their efficacy in treating deficiency.Objective:To examine the disposition of oral iron and calcium/vitamin D supplementation following RYGB. Methods: A literature review was carried out using PubMed and Embase. Data from the key interventional studies investigating iron and calcium/vitamin D oral supplement absorption and efficacy following RYGB was summarized.Results:Absorption of both iron and vitamin D/calcium is adversely affected following RYGB. Distribution and metabolism may be altered by the predominance of paracellular absorption pathways which promote unregulated influx into the circulatory system. Overall, studies indicate that current supplementation strategies are efficacious to a degree in treating deficiency following RYGB, generally restoration of optimal status is not achieved.Conclusion:Oral supplement disposition is altered following RYGB. As a result, patients are required to take regimens of oral supplementation indefinitely. The dosage which confers optimum health benefit while avoiding potential toxicity and tolerability issues remains unknown. Novel preparations with improved disposition could help limit the extent of post-RYGB nutritional deficiencies.

Background Preoperative optimization of iron status is a priority in candidates for bariatric surgery. Inflammation is strongly associated with obesity, and as a consequence, functional iron deficiency (ID) is potentially an underreported issue in surgical candidates. Objectives In light of updated practice guidelines, to retrospectively review preoperative iron status in an Irish cohort of bariatric surgery candidates, taking account of the relative incidence rate of functional ID. Setting A tertiary care obesity service with bariatric surgery referral in Ireland. Methods Baseline nutritional biochemistry records were reviewed between February 2017 and February 2020 in a hospital, Dublin, Ireland. Absolute ID was defined as serum ferritin 5 mg/L. Anemia was indexed with reference to hemoglobin and qualified by vitamin B12 and folate status to rule out anemia unrelated to primary ID. Results The analysis included 120 patients, 68% female, 49.6 ± 9.3 years, and body mass index, 52.0 ± 9.6 kg/m2. The prevalence of absolute and functional ID was 11.7% and 30.8%, respectively (P = .0003). Anemia was associated with absolute ID and functional ID in 14.3% and 10.8% of patients (P = .29). Folate and vitamin B12 deficiency occurred in Conclusion In patients seeking bariatric surgery for severe obesity, the prevalence of baseline functional ID is substantial and can be associated with anemia. These findings raise queries with regard to how best to optimize preoperative iron status in the context of ongoing inflammation.

Bariatric surgery induces deficiencies in a combination of B vitamins. However, high costs and a large blood volume requirement are barriers to routine screening. We adapted and validated a method coupling tandem mass spectrometry (MS/MS) with high-performance liquid chromatography (HPLC) to facilitate cost-effective analysis for simultaneous detection of B vitamins in low volumes of plasma. Based on existing methods, pooled plasma was extracted using hexane and acetonitrile and seven B vitamin analytes were separated using HPLC. Detection was performed with an Agilent 6460 triple quadrupole tandem mass spectrometer (MS/MS) using electrospray ionization in the positive ion mode. We evaluated linearity, recovery, precision, and limit of detection, as well as costs of the assay. We evaluated seven B vitamins from plasma, five (riboflavin, nicotinamide, pantothenic acid, pyridoxine, and biotin) were detected and quantified with precision and linearity. Recovery ranged from 63 to 81% for each of the vitamins, except for nicotinamide&mdash, the recovery of which was suppressed to 40%, due to plasma matrix effects. We demonstrated the feasibility of the HPLC&ndash, MS/MS method for use in patients who undergo bariatric surgery by analyzing pooled plasma from patients with a lower cost and blood volume than had we sent the samples to a commercial laboratory. It is advantageous and feasible, in terms of low cost and blood volume requirement, to simultaneously measure plasma concentrations of B vitamins using HPLC&ndash, MS/MS. With further improvements, the method may enable personalized nutritional assessment for the nutritionally compromised, bariatric surgery population.

The goal of the National Institutes of Health-funded American Society for Parenteral and Enteral Nutrition 2017 research workshop (RW) "Gastric Bypass: Role of the Gut" was to focus on the exciting research evaluating gut-derived signals in modulating outcomes after bariatric surgery. Although gastric bypass surgery has undoubted positive effects, the mechanistic basis of improved outcomes cannot be solely explained by caloric restriction. Emerging data suggest that bile acid metabolic pathways, luminal contents, energy balance, gut mucosal integrity, as well as the gut microbiota are significantly modulated after bariatric surgery and may be responsible for the variable outcomes, each of which was rigorously evaluated. The RW served as a timely and novel academic meeting that brought together clinicians and researchers across the scientific spectrum, fostering a unique venue for interdisciplinary collaboration among investigators. It promoted engaging discussion and evolution of new research hypotheses and ideas, driving the development of novel ameliorative, therapeutic, and nonsurgical interventions targeting obesity and its comorbidities. Importantly, a critical evaluation of the current knowledge regarding gut-modulated signaling after bariatric surgery, potential pitfalls, and lacunae were thoroughly addressed.

We submit a letter to the editor regarding “Interventioneffects of a kindergarten-based health promotion programme on obesity related behavioural outcomes and BMI percentiles” by Kobel et al. becauseof 4 issues: 1) clustering is ignored in the analysis, 2) outcomes wereswitched compared to the preregistration, 3) there is spin in theabstract, and 4) concerns about the self-reported outcomes. We believethat reanalysis of the results is necessary as accounting for clusteringmay change the conclusions of the study.

To determine the influence of dietary behaviors, assessed in a clinical setting, on measures of glycemia in overweight and obese adolescents.The study is a retrospective, cross-sectional chart review. Eligible participants were overweight youth (N = 146, age 9-21 years) who attended the Youth Diabetes Prevention Clinic in Indianapolis, IN. Glycemic status was assessed during a 2-hour oral glucose tolerance test (OGTT). In the Bright Futures Questionnaire, a recommended clinical tool for assessing unhealthy behaviors in youth, nutrition-specific questions were modified to quantify dietary habits. Associations between dietary habits and measures of glycemia were determined using multiple linear regression models. Skewed data are presented as geometric means and 95% confidence intervals.Of the 146 adolescents who were assessed [60% girls, age 13.7 years (13.3, 14.0), BMI 33.9 kg/m(2) (33.3, 34.5)], 40% were diagnosed with prediabetes. Higher intake of dessert foods was associated with increased glucose levels at 2 hours following the OGTT (β = 0.23, p = 0.004), and higher intake of packaged snack foods was associated with elevated levels of hemoglobin A1c (β = 0.04, p = 0.04), independent of adiposity.In obese youth, high intakes of dessert and packaged snack items were associated with elevated concentrations of glucose at 2 hours following the OGTT and hemoglobin A1c. Findings demonstrate the usefulness of a modified Bright Futures Questionnaire, used in a clinical setting, for identifying dietary behaviors associated with hyperglycemia in obese adolescents. ClinicalTrials.gov registration number: NCT02535169.

Iron deficiency is common after Roux-en-Y gastric bypass (RYGB) surgery, but there is no consensus on the optimal diet quality and quantity for restoring and preserving iron status.The authors explored the impact of dietary and supplemental sources of iron and absorptive factors on iron status.Academic, United States.In a cross-sectional cohort of individuals who underwent RYGB, nutrient intakes from food and supplements were measured using 3-day food records. Blood biomarkers of iron status, including concentrations of ferritin, total iron binding capacity, serum transferrin receptor (sTfR), and the sTfR:ferritin ratio, were assessed by a reference laboratory; iron deficiency was defined as having at least 2 abnormal measures. Associations between iron status biomarkers and dietary predictors were determined using regression analysis.Of the 36 participants, 97% were female, the mean age was 45 years (95% confidence interval, 41-48 years), and body mass index was 32 (30-35) kg/m(2). Iron deficiency was found in 42% of participants. Dietary intake of heme iron, found in meats, was favorably associated with 3 iron status biomarkers (ferritin, β = .366; sTfR:ferritin ratio, β = -.459; and total iron binding capacity, β = -18.26; all P.05), independent of obesity-induced inflammation. Intake of vitamin C from food contributed to iron status (ferritin, β = .010 and sTfR:ferritin ratio, β = -.011; P.05). Use of supplementary non-heme iron, at doses recommended for prophylaxis (45 mg/d), was positively associated with serum ferritin (β = .964; P = .029).For patients who have undergone RYGB, consuming high, but realistic amounts of heme iron in meat, vitamin C from food, and adherence to recommended iron supplements can prevent iron deficiency.

OBJECTIVES: Most studies used serum magnesium concentration and total urine magnesium as nutrition biomarkers of magnesium, but whether these biomarkers are sensitive to changes in dietary intake of magnesium is uncertain. Whole blood ionized magnesium (iMg(2+)) is the free bioactive form of magnesium in the body, and therefore it could be more sensitive to the changes in magnesium intake. Thus, we aimed to compare the responses of iMg(2+), serum magnesium concentration, and total urine magnesium following an oral dose of magnesium. METHODS: Healthy adults participated in a randomized, single-blind, placebo-controlled crossover trial. They were randomly assigned to 300 mg of magnesium chloride (MgCl(2), ReMag®) or placebo, taken with a low-magnesium breakfast after 8-hours of fasting. Timed blood and urine samples were obtained beginning 15-minutes before breakfast, and then at 0, 0.5, 1, 2, 4, 6, 8, and 24-hours timepoints following breakfast. Pharmacokinetic analyses included area under the curve (AUC), the maximum concentration (C(max)), and the time to maximum concentration (T(max)) for iMg(2+), serum magnesium concentration, and total urine magnesium. Data were analyzed using paired t-test and Wilcoxon signed-rank test, and reported as mean ± standard deviation, or as median and range, depending on normality. RESULTS: Seventeen participants were included in the data analyses. Responses were observed following MgCl(2) compared to placebo for iMg(2+) (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82, and C(max) = 1.38 ± 0.13 vs. 1.32 ± 0.07, both P 0.05. CONCLUSIONS: The response of iMg(2+) to a single oral dose of magnesium was more pronounced than the responses of serum magnesium concentration and total urine magnesium. Therefore, iMg(2+) may be a more sensitive nutrition biomarker for magnesium intake. FUNDING SOURCES: Funding for this study was provided through an unrestricted educational grant from Think Healthy Group Inc.

Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag&reg, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean &plusmn, standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 &plusmn, 0.96 vs. 0.84 &plusmn, 0.82 mg/dL&middot, 24h, Cmax = 1.38 &plusmn, 0.13 vs. 1.32 &plusmn, 0.07 mg/dL, respectively, both p &lt, 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL&middot, Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 &plusmn, 161.63 vs. 139.30 &plusmn, 92.84 mg&middot, Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL, p &gt, 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.

BACKGROUND: Neurobehavioral symptoms and cognitive dysfunction related to mood disorders are present in individuals with severe obesity. We sought to determine acute improvements in these symptoms and relationships with adiposity, inflammation, and insulin sensitivity after roux-en-y gastric bypass (RYGB) surgery. METHODS: The self-report Zung Depression Rating (ZDRS) and Neurotoxicity Rating (NRS) scales were administered before, and at 6-months after RYGB surgery in severely obese women (body mass index > 35 kg/m(2); N=19). Symptom domains corresponding to depressed mood/suicide ideation, anxiety, cognitive, somatic, and neurovegetative symptoms were assessed. Biologic measures were of adiposity [leptin, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue], inflammation [IL-6, C-reactive protein (CRP)], and insulin sensitivity (Si). Spearman correlations and linear regression (adjusted for biologic measures) assessed relationships between changes in biologic measures and changes in neurobehavioral domains. RESULTS: By 6-months after RYGB, VAT, SAT, Si, CRP, and IL-6 had improved (p

Although patients experience hair loss and dry skin which may be attributable to deficiency in essential fatty acids (EFAs), the impact of bariatric surgeries on EFA status is unknown. This study aimed to assess plasma phospholipid fatty acid profiles following adjustable gastric banding (AGB), which restricts dietary fat intake, versus Roux-en-Y gastric bypass (RYGB), which also promotes fat malabsorption. Serial measures were obtained before and 1 and 6 months from women undergoing RYGB (N = 13) and AGB (N = 5). Measures included the composition of plasma fatty acids in phospholipids, dietary intake, and body fat mass. Friedman and Mann–Whitney tests were used to assess differences over time and between groups, respectively, p

The evidence behind recommendations for treatment of iron deficiency (ID) following roux-en-y gastric bypass surgery (RYGB) lacks high quality studies. Academic, United States The objective of the study is to compare the effectiveness of oral iron supplementation using non-heme versus heme iron for treatment of iron deficiency in RYGB patients. In a randomized, single-blind study, women post-RYGB and iron deficient received non-heme iron (FeSO4, 195 mg/day) or heme iron (heme-iron-polypeptide, HIP, 31.5 to 94.5 mg/day) for 8 weeks. Measures of iron status, including blood concentrations of ferritin, soluble transferrin receptor (sTfR), and hemoglobin, were assessed. At baseline, the mean ± standard deviation for age, BMI, and years since surgery of the sample was 41.5 ± 6.8 years, 34.4 ± 5.9 kg/m2, and 6.9 ± 3.1 years, respectively; and there were no differences between FeSO4 (N = 6) or HIP (N = 8) groups. Compliance was greater than 94%. The study was stopped early due to statistical and clinical differences between groups. Values before and after FeSO4 supplementation, expressed as least square means (95% CI) were hemoglobin, 10.8 (9.8, 11.9) to 13.0 (11.9, 14.0) g/dL; sTfR, 2111 (1556, 2864) to 1270 (934, 1737) μg/L; ferritin, 4.9 (3.4, 7.2) to 15.5 (10.6, 22.6) μg/L; and sTfR:ferritin ratio, 542 (273, 1086) to 103 (51, 204); all p 0.05). In accordance with recommendations, oral supplementation using FeSO4, but not HIP, was efficacious for treatment of iron deficiency after RYGB.

Background and objectives Severe obesity is associated with fatigue, however, the effects of weight loss after bariatric surgery on particular dimensions of fatigue are unknown. In a secondary analysis of a prospective cohort study of women undergoing roux-en-y gastric bypass (RYGB) we explored relationships among multiple dimensions of fatigue and improving adiposity, insulin resistance and inflammation. Methods Before, and 1 and 6 months after RYBG, dimensions of fatigue were assessed using the validated, self-report, Multidimensional Fatigue Inventory. Total, abdominal visceral (VAT) and subcutaneous (SAT) adiposity, insulin sensitivity (Si and HOMA) and plasma concentrations of leptin, C-reactive protein (CRP) and interleukin-6 (Il-6) were measured using air displacement plethysmography, computed tomography, glucose tolerance testing and enzyme-linked immunoassay. Associations were assessed using Spearman correlations and linear regression. Results At baseline, the majority of our female participants (N = 19, body mass index, 46.5 kg/m2, age 37.2 years) were experiencing elevated levels of fatigue. By 6 months, dimensions of physical (−43%), reduced activity (−43%), reduced motivation (−38%), general (−31%; all p Conclusions In the 6 months after RYGB, fatigue improved, especially physical fatigue. Decreases in mental fatigue were strongly associated with decreases in visceral adiposity. Nevertheless, the biologic mechanisms underlying changes in these specific fatigue dimensions remain undetermined.

Moderate/severe obesity is on the rise in the United States. Weight management includes bariatric surgery, which is effective and can alleviate morbidity and mortality from obesity-associated diseases. However, many individuals are dealing with nutritional complications. Risk factors include: 1) preoperative malnutrition (e.g., vitamin D, iron); 2) decreased food intake (due to reduced hunger and increased satiety, food intolerances, frequent vomiting); 3) inadequate nutrient supplementation (due to poor compliance with multivitamin/multimineral regimen, insufficient amounts of vitamins and/or minerals in supplements); 4) nutrient malabsorption; and 5) inadequate nutritional support (due to lack of follow-up, insufficient monitoring, difficulty in recognizing symptoms of deficiency). For some nutrients (e.g., protein, vitamin B-12, vitamin D), malnutrition issues are reasonably addressed through patient education, routine monitoring, and effective treatment strategies. However, there is little attention paid to other nutrients (e.g., zinc, copper), which if left untreated may have devastating consequences (e.g., hair loss, poor immunity, anemia, defects in neuro-muscular function). This review focuses on malnutrition in essential minerals, including calcium (and vitamin D), iron, zinc, and copper, which commonly occur following popular bariatric procedures. There will be emphasis on the complexities, including confounding factors, related to screening, recognition of symptoms, and, when available, current recommendations for treatment. There is an exceptionally high risk of malnutrition in adolescents and pregnant women and their fetuses, who may be vulnerable to problems in growth and development. More research is required to inform evidence-based recommendations for improving nutritional status following bariatric surgery and optimizing weight loss, metabolic, and nutritional outcomes.

The frequency of copper deficiency and clinical manifestations following roux-en-y gastric bypass (RYGB) surgery is not yet clear. Objectives were to determine the prevalence and incidence of copper deficiency in patients who have undergone RYGB. We sought to determine the number of RYGB patients undergoing medical and nutritional follow-up visits at the Emory Bariatric Center who experienced copper deficiency and associated hematological and neurological complaints (n=136). Separately, in patients followed longitudinally before and during 6 and 24 months following RYGB surgery, we obtained measures of copper status (n=16). Systemic blood cell counts and measures of copper, zinc and ceruloplasmin were determined using standardized assays in reference laboratories including atomic absorption spectrometry and immunoassays. Thirteen patients were identified to have copper deficiency suggesting a prevalence of copper deficiency of 9.6%, and the majority of these had concomitant complications including anemia, leukopenia and various neuro-muscular abnormalities. In the longitudinal study, plasma copper concentrations and ceruloplasmin activity decreased over 6 and 24 months following surgery, respectively (P

Oxidation of plasma cysteine/cystine (Cys/CySS) redox potential (E(h)CySS) has been associated with risk factors for cardiovascular disease in humans. Cys and CySS are derived from dietary sulfur amino acids (SAA), but the specific effects of SAA depletion and repletion on Cys/CySS redox indices are unknown. The present study examined the effect of dietary SAA intake level on free Cys, free CySS, and E(h)CySS in human plasma under fasting conditions.Healthy individuals aged 18-36 y (n = 13) were equilibrated to foods providing the RDA for SAA and then fed chemically defined diets without SAA (0 mg · kg(-1) · d(-1); n = 13) followed by SAA at levels approximating the mean (56 mg · kg(-1) · d(-1); n = 8) or 99th percentile (117 mg · kg(-1) · d(-1); n = 5) intake levels of Americans. Fasting plasma samples were collected daily during 4-d study periods and analyzed for free Cys, free CySS, and the E(h)CySS.The SAA-free diet significantly (P0.05) decreased plasma-free Cys concentrations and oxidized E(h)CySS values after 4 d of SAA depletion. With SAA repletion at 56 mg · kg(-1) · d(-1), plasma-free Cys increased significantly and values for E(h)CySS became more reduced. Administration of a diet providing a higher dose of SAA (117 mg · kg(-1) · d(-1)) resulted in a significantly higher level of free Cys and a more reduced E(h)CySS.These results show that free Cys and Cys/CySS redox potential (E(h)CySS) in fasting plasma are affected by dietary SAA intake level in humans. Significant changes occur slowly over 4 d with insufficient SAA intake, but rapidly (after 1 d) with repletion.

This article is a summary of the symposium "Modifying Eating Behavior: Novel Approaches for Reducing Body Weight, Preventing Weight Regain, and Reducing Chronic Disease Risk" held 29 April 2014 at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 in San Diego, CA. In this symposium, novel approaches to modifying eating behavior were highlighted, including 1) alteration of meal timing and macronutrient composition and 2) retraining and provision of feedback about eating behavior. Dr. Ciampolini discussed a method for teaching individuals to recognize a decrease in blood glucose concentration, and therefore the need for energy, by learning the associated physical sensations (signifying hunger). Dr. Madar and Sigal Sofer presented their work on reducing hunger during energy reduction by feeding carbohydrate only in the evening. Dr. Hamilton-Shield reviewed studies on the Mandometer (Mikrodidakt), a device for training individuals to slow eating rate. Finally, Dr. Sazonov presented information on a wearable device, the Automatic Ingestion Monitor, which senses jaw motion and/or hand-to-mouth gestures to detect and characterize food intake. His goal is to use the instrument to prevent overeating by providing feedback to the user to stop ingestion at a predetermined limit.

Glycemic disorders resolve following Roux-en-Y gastric bypass (RYGB) surgery, but early and longer-term mechanisms regarding effects on β-cell dysfunction as well as relationships with decreasing adiposity are not well understood. We evaluated longitudinal changes in peripheral insulin sensitivity (Si), the acute insulin response to glucose (AIRg), and the composite estimate of β-cell function, the disposition index (DI), over 24 mo via frequently sampled intravenous glucose tolerance testing in severely obese women who had fasting normoglycemia ( n = 16) and hyperglycemia ( n = 11) before RYGB surgery; homeostatic model assessment (HOMA-IR) estimated insulin resistance; air displacement plethysmography determined adipose tissue mass. At baseline, subjects with normoglycemia had adequate DI associated with elevated AIRg, but DI was markedly reduced in subjects with hyperglycemia. Within 1–6 mo post-RYGB, glycemic control was normalized in subjects with hyperglycemia related to reduced HOMA-IR (−54% at 1 mo, P < 0.005) and increased DI (23-fold at 6 mo vs. baseline, P < 0.05). Over 24 mo, DI improved in subjects with hyperglycemia (15-fold vs. baseline, P < 0.005) and also modestly in subjects with normoglycemia (58%, P < 0.05), due largely to increased Si. Decreasing adiposity correlated with longer-term HOMA-IR and Si values at 6 and 24 mo, respectively. In patients exhibiting fasting hyperglycemia before surgery, β-cell function improved early following RYGB, due largely to increases in insulin secretion. For both normoglycemic and hyperglycemic subjects, further improvement or stabilization of β-cell function over the 2 yr is due largely to improved Si associated with reduced adiposity.

Few data are available on plasma redox responses to sulfur amino acid (SAA) loads. In this study, we had 2 aims: to determine whether the SAA content of a meal affected postprandial plasma cysteine (Cys), cystine (CySS), or redox potential (EhCySS) in humans and whether SAA intake level (adequate or inadequate) in the days preceding the meal challenge affected these postprandial levels. Eight healthy individuals aged 18–36 y were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (inadequate SAA) and then fed isoenergetic, isonitrogenous meals with adequate SAA for 5 d. On the first and last days with the chemically defined meals, a morning meal containing 60% of the daily food intake was given, and plasma Cys, CySS, and EhCySS were determined over an 8-h postprandial time course. Following equilibration to adequate intake, provision of the meal with SAA resulted in increased plasma Cys and CySS concentrations and more reduced plasma EhCySS compared with the postprandial values following the same meal without SAA. Equilibration to inadequate SAA intake for the days preceding the meal challenge did not affect this response. The magnitude of the difference in postprandial plasma EhCySS (10 mV) due to meal content of SAA was comparable to those which alter physiologic signaling and/or are associated with disease risk. Consequently, the SAA content of meals could affect physiologic signaling and associated disease mechanisms in the postprandial period by changes in Cys, CySS, or EhCySS.

Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose-insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.

It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 ± 0.8 kg/m2 to 43.3 ± 0.8 kg/m2 (1 month), 35.2 ± 0.8 kg/m2 (6 months), and 30.2 ± 1.2 kg/m2 (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6-month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6-month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high-density lipoprotein (HDL) at 1 and 6 months after surgery (r = −0.38 and −0.42). This study found longitudinal associations between general, and more specifically intra-abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.

Obesity-related glucose intolerance is a function of hepatic (homeostatic model assessment-insulin resistance [HOMA-IR]) and peripheral insulin resistance (Si) and β-cell dysfunction. We determined relationships between changes in these measures, visceral (VAT) and subcutaneous (SAT) adipose tissue, and systemic adipocytokine biomarkers 1 and 6 months after surgical weight loss. HOMA-IR decreased significantly (−50%) from baseline by 1 month and decreased further (−67%) by 6 months, and Si was improved by 6 months (2.3-fold) weight loss. Plasma concentrations of leptin decreased and adiponectin increased significantly by 1 month, and decreases in interleukin-6, C-reactive protein (CRP), and tumor necrosis factor-α were observed at 6 months of weight loss. Longitudinal decreases in CRP (r = −0.53, P < 0.05) were associated with increases in Si, and decreases in HOMA-IR were related to increases in adiponectin (r = −0.37, P < 0.05). Decreases in VAT were more strongly related to increases in adiponectin and decreases in CRP than were changes in general adiposity or SAT. Thus, in severely obese women, specific loss of VAT leads to acute improvements in hepatic insulin sensitivity mediated by increases in adiponectin and in peripheral insulin sensitivity mediated by decreases in CRP.

Roux-en-y gastric bypass surgery (RYGB) is effective for weight loss, but is commonly associated with anemia. Anemia may be caused by decreased dietary intake and intestinal absorption of nutrients...

In the context of increasing obesity prevalence, the relationship between large visceral adipose tissue (VAT) volumes and type 2 diabetes mellitus (T2DM) is unclear. In a clinical sample of severely obese women (mean body mass index [BMI], 46 kg/m(2)) with fasting normoglycemia (n = 40) or dysglycemia (impaired fasting glucose + diabetes; n = 20), we sought to determine the usefulness of anthropometric correlates of VAT and associations with dysglycemia.VAT volume was estimated using multi-slice computer tomography; anthropometric surrogates included sagittal abdominal diameter (SAD), waist circumference (WC) and BMI. Insulin sensitivity (Si), and beta-cell dysfunction, measured by insulin secretion (AIRg) and the disposition index (DI), were determined by frequently sampled intravenous glucose tolerance test.Compared to fasting normoglycemic women, individuals with dysglycemia had greater VAT (P0.001) and SAD (P = 0.04), but BMI, total adiposity and Si were similar. VAT was inversely associated with AIRg and DI after controlling for ancestry, Si, and total adiposity (standardized beta, -0.32 and -0.34, both P0.05). In addition, SAD (beta = 0.41, P = 0.02) was found to be a better estimate of VAT volume than WC (beta = 0.32, P = 0.08) after controlling for covariates. Receiver operating characteristic analysis showed that VAT volume, followed by SAD, outperformed WC and BMI in identifying dysglycemic participants.Increasing VAT is associated with beta-cell dysfunction and dysglycemia in very obese women. In the presence of severe obesity, SAD is a simple surrogate of VAT, and an indicator of glucose dysregulation.

The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR ((1)H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (18-36 y, 5 males and 3 females) were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (depletion), and then fed isoenergetic, isonitrogenous meals containing 56 mg·kg(-1)·d(-1) SAA for 4.5 d (repletion). On the first and last day of consuming the chemically defined meals, a morning meal containing 60% of the daily food intake was given and plasma samples were collected over an 8-h postprandial time course for characterization of metabolic changes by (1)H-NMR spectroscopy. SAA-free food increased peak intensity in the plasma (1)H-NMR spectra in the postprandial period. Orthogonal signal correction/partial least squares-discriminant analysis showed changes in signals associated with lipids, some amino acids, and lactate, with notable increases in plasma lipid signals (TG, unsaturated lipid, cholesterol). Conventional lipid analyses confirmed higher plasma TG and showed an increase in plasma concentration of the lipoprotein lipase inhibitor, apoC-III. The results show that plasma (1)H-NMR spectra can provide useful macronutrient profiling following a meal challenge protocol and that a single meal with imbalanced SAA content alters postprandial lipid metabolism.

Objective This pilot study was designed to determine if metabolic effects in different brain regions (left and right parietal lobes, midbrain) caused by 3 d of food consumption without methionine or cysteine could be detected by proton magnetic resonance spectroscopy. Methods Healthy individuals 18 to 36 y old ( n = 8) were studied by magnetic resonance spectroscopy after receiving a diet with adequate sulfur amino acids (SAAs) or with zero SAA for 3 d. Pulse sequences were used to selectively measure glutathione (GSH), and linear combination modeling of spectra was used to measure other high-abundance brain metabolites and expressed relative to creatine (Cr). Results Although dietary SAAs are required to maintain GSH, the 3-d SAA insufficiency resulted in no significant change in GSH/Cr in the three brain regions. Principal component analysis of 16 metabolites measured by linear combination modeling showed that the metabolic pattern in the midbrain, but not in the parietal lobes, was distinguished according to the dietary SAAs. Multivariate statistical analysis showed that the major discriminating factors were signals of glutamate/Cr, (glutamate + glutamine)/Cr, and myoinositol/Cr. Correlation analyses between midbrain metabolites and GSH-related metabolites in plasma showed that midbrain glutamate/Cr had an inverse correlation with plasma cystine. Conclusion The data show that magnetic resonance spectroscopy is a non-invasive tool suitable for nutritional assessment and suggest that nutritional imbalance caused by 3 d of SAA-free food more selectively affects the midbrain than the parietal lobes.

Roux-en-y gastric bypass (RYGB) surgery is associated with dramatic improvements in obesity-related comorbidity, but also with nutritional deficiencies. Vitamin D concentrations are depressed in the severely obese, but the impact of weight loss via RYGB is unknown. We determined associations between adiposity and systemic 25-hydroxyvitamin D (25(OH)D) during weight loss and the immediate and longer-term effects of RYGB. Plasma 25(OH)D concentrations and fat mass (FAT) were determined by immunoassay and air displacement plethysmography, respectively, at 0 (before RYGB surgery), and at 1, 6, and 24 months in severely obese white and African American (AA) women (n = 20). Decreases in adiposity were observed at 1, 6, and 24 months following RYGB (P < 0.05). Plasma 25(OH)D concentrations increased at 1 month (P = 0.004); a decreasing trend occurred over the remainder months after surgery (P = 0.02). Despite temporary improvement in vitamin D status, a high prevalence of vitamin D insufficiency was observed (76, 71, 67, and 82%, at baseline, 1, 6, and 24 months, respectively), and plasma 25(OH)D concentrations were lower in AA compared to white patients (P < 0.05). Strong positive baseline and 1 month cross-sectional correlations between FAT and plasma 25(OH)D were observed, which remained after adjustment for age and race subgroup (β = 0.76 and 0.61, respectively, P = 0.02). In conclusion, 25(OH)D concentrations increased temporarily and then decreased during the 24 months following RYGB. The acute increase and the positive associations observed between adipose tissue mass and systemic 25(OH)D concentrations suggest storage in adipose tissue and release during weight loss.

High-resolution Nuclear Magnetic Resonance (NMR) spectroscopy in combination with multivariate statistical methods has been widely used to investigate metabolic fluctuations in biological systems. This study presents three feature selection methods for identifying the metabolite features that contribute to the distinction of spectral samples among varying nutritional conditions in human plasma. Loading vectors of Principal Component Analysis (PCA), the optimal discriminant direction of Fisher discriminant analysis, and index values of the Variable Importance in Projection (VIP) in a Partial Least Square Discriminant Analysis (PLS-DA) were used to calculate the importance of individual metabolite feature in spectra. In addition, an Orthogonal Signal Correction (OSC) filter was used to eliminate unnecessary variations in NMR spectra and its effectiveness was demonstrated through PCA and kernel PCA. For the evaluation of presented feature selection methods, we compared the ability of classification based on the metabolite features selected by each method. The results have shown that the best classification was achieved using VIP values from an OSC-PLS-DA model.