Nana Gletsu Miller Research Collection

Permanent link for this collectionhttps://hdl.handle.net/2022/24683

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Modifying Eating Behavior: Novel Approaches for Reducing Body Weight, Preventing Weight Regain, and Reducing Chronic Disease Risk
(American Society for Nutrition, 2014-11-03) Gletsu-Miller, Nana; McCrory, Megan A.
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.
Mineral Malnutrition Following Bariatric Surgery
(American Society for Nutrition, 2013-09-05) Gletsu-Miller, Nana; Wright, Breanne N.
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.
A Sulfur Amino Acid–Free Meal Increases Plasma Lipids in Humans
(American Society for Nutrition, 2011-06-15) Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei; Strobel, Fred; Gletsu-Miller, Nana; Accardi, Carolyn J.; Lee, Kichun S.; Wu, Shaoxiong; Ziegler, Thomas R.; Jones, Dean P.
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.
Postprandial Cysteine/Cystine Redox Potential in Human Plasma Varies with Meal Content of Sulfur Amino Acids
(American Society for Nutrition, 2010-04) Park, Youngja; Ziegler, Thomas R.; Gletsu-Miller, Nana; Liang, Yongliang; Yu, Tianwei; Accardi, Carolyn Jonas; Jones, Dean P.
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 (E$_h$CySS) 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 E$_h$CySS 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 E$_h$CySS.
The Effects of Gastric Surgery on Systemic Ghrelin Levels in the Morbidly Obese
(Archives of Surgery, 2004-07) Gletsu-Miller, Nana; Lin, Edward; Fugate, Kim; McClusky, David; Gu, Li H.; Ramshaw, Bruce J.; Papanicolaou, Dimitris A.; Ziegler, Thomas R.; Smith, C. Daniel; Zhu, Juan-Li
Hypothesis: Circulating ghrelin, produced primarily in the stomach, is a powerful orexigen. Ghrelin levels are elevated in states of hunger, but rapidly decline postprandially. Early alterations in ghrelin levels in morbidly obese patients undergoing weight reduction surgery may be attributed to gastric partitioning. Design and Patients: Thirty-four patients underwent Roux-en-Y gastric bypass with a completely divided gastroplasty to create a 15-mL vertically oriented gastric pouch. Eight other patients underwent other gastric procedures that did not involve complete division of the stomach, including 4 vertical banded gastroplasties and 4 antireflux surgical procedures. Six additional patients undergoing antireflux surgery served as lean control subjects. Plasma samples were obtained before surgery and immediately after surgery. In a substudy, plasma was collected after Roux-en-Y limb formation and after dividing the stomach to identify any changes in plasma ghrelin levels. Setting: Tertiary university medical center. Main Outcome Measures: Ghrelin levels at different stages of surgical intervention. Results: Mean ± SEM preoperative and postoperative ghrelin levels in the gastric bypass group were 355 ± 20 and 246 ± 13 pg/mL, respectively (P<.001). In the vertical banded gastroplasty group and in all patients undergoing antireflux surgery, ghrelin levels were not significantly changed. Conclusions: Compared with morbidly obese humans, lean controls had significantly higher plasma ghrelin levels at baseline. A divided gastroplasty creating a small proximal gastric pouch results in significant early declines in circulating ghrelin levels that are not observed with other gastric procedures. This may explain, in part, the loss of hunger sensation and rapid weight loss observed following gastric bypass surgery.
Surgical Stress Induces an Amplified Inflammatory Response in Patients with Type 2 Diabetes
(ISRN Obesity, 2013) Gletsu-Miller, Nana; Lin, Edward
Background. Morbid obesity is believed to be an extreme of the metabolic spectrum. Moreover, diabetes is hypothesized to be associated with a chronic inflammatory state that is not observed in nondiabetic healthy individuals. We investigated the differences in expression of inflammatory cytokines induced by surgical stress between diabetic and nondiabetic individuals. Method. 39 morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass (9 with type 2 diabetes mellitus) were compared with 8 nonobese euglycemic patients undergoing laparoscopic antireflux surgery. Cytokine levels for IL-6, IL-10, and IL-18 were measured 15 minutes before surgery and immediately after surgery. Results. IL-6 and IL-10 levels were elevated from baseline following surgery, but morbidly obese patients exhibited a much higher elevation than lean patients. Individuals with type 2 diabetes had the most pronounced IL-6 and IL-10 elevations. Baseline IL-18 levels were significantly higher in diabetic patients compared with nondiabetic or lean patients. However, IL-18 levels were not changed in response to surgery. Conclusions. Diabetes and morbid obesity are associated with augmented cytokine expression in response to surgical trauma that is several folds higher than in nonobese euglycemic patients. Diabetic patients exhibit a chronic elevation in IL-18 that is not changed by surgical stress.
Measurement of Copper Deficiency in Humans: CCS as a Novel Biomarker of Copper Status in Bariatric Surgery Patients
(Journal of Purdue Undergraduate Research, 2016) Gletsu-Miller, Nana; Watson, Emily
Bariatric surgery is a popular and effective treatment for obesity. However, an unfavorable consequence for patients who have had bariatric surgery is copper (Cu) deficiency. Current screening methods used for Cu deficiency are neither sensitive nor specific enough to diagnose Cu deficiency or detect changes in Cu status. The purpose of this research is to determine if concentrations of copper chaperone for superoxide dismutase (CCS) in erythrocytes are associated with serum Cu concentrations in bariatric surgery patients, by assessing whether changes in CCS concentrations can be observed in response to altering Cu status when patients are supplemented with Cu (8 mg/day) or iron (Fe) (195 mg/day) for 8 weeks. Blood samples were obtained from subjects who had undergone bariatric surgery and serum Cu concentrations were measured. Concentrations of CCS in erythrocytes were measured using Western blotting. CCS and serum Cu were not significantly correlated (p > 0.05), though there were significant increases in CCS for patients supplemented with Fe (p < 0.05). This indicates that CCS increases as a result of Fe supplementation. Because serum Cu and erythrocyte CCS were not significantly correlated, it is unclear if CCS is representative of Cu status. Future research should focus on improving the reliability of the methods and increasing the sample size.
Antioxidant Vitamins and Atherosclerosis
(Current Topics in Pharmacology, 1993) Gletsu-Miller, Nana; Basu, Tapan K.
Oxidative modification of low-density lipoproteins (LDL) plays an important role in atherogensis. Oxidized LDL can be formed in vitro by smooth muscle cells, endothelial cells and monocyte-derived cells, all of which are found in the arterial wall. Human and animal atherosclerotic leasions have been found to contain oxidized LDL. It is thought that oxidized LDL particles are ligands for the ‘scavanger’ receptors on macrophages and can therefore converted to the cholesterol-loaded foam cells characteristic of the early atherosclerotic leasions, the fatty streak. In recent years, the use of nutritional antioxidants, including vitamins E and C, carotenes, and selenium, in the prevention of atherosclerosis has gained heightened interest. Many in vitro experiments and studies in animals have shown that the antioxidant protect cells from oxidative destruction. Epidemiological studies provide evidence supporting the results from these in vitro and animal studies. The potential anti-antherogenic value of the antioxidant vitamins is further indicated by the inverse relationship between plasma levels of vitamins C and E and carotene, and the risk of coronary heart disease. The scope of this review is to present evidence supporting the use of vitamin antioxidants in the prevention of atherosclerosis, including their mechanisms of action, synergistic effects, and future research merited in this controversial field of study.
Dual mechanism for type-2 diabetes resolution after Roux-en-Y gastric bypass
(American Surgeon, 2009-06) Gletsu-Miller, Nana; Lin, Edward; Davis, S. Scott; Srinivasan, Jahnavi; Sweeney, John F.; Ziegler, Thomas R.; Phillips, Lawrence
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.
Discovery of metabolite features for the modelling and analysis of high-resolution NMR spectra
(International Journal of Data Mining and Bioinformatics, 2008) Gletsu-Miller, Nana; Cho, Hyun-Woo; Kim, Seoung Bum; Jeong, Myong K.; Park, Youngja; Ziegler, Thomas R.; Jones, Dean P.
This study presents three feature selection methods for identifying the metabolite features in nuclear magnetic resonance spectra that contribute to the distinction of samples among varying nutritional conditions. Principal component analysis, Fisher discriminant analysis, and Partial Least Square Discriminant Analysis (PLS-DA) were used to calculate the importance of individual metabolite feature in spectra. Moreover, an Orthogonal Signal Correction (OSC) filter was used to eliminate unnecessary variations in spectra. We evaluated the presented methods by comparing the ability of classification based on the features selected by each method. The result showed that the best classification was achieved from an OSC-PLS-DA model.
Bariatric Surgery or Medical Therapy for Obesity
(New England Journal of Medicine, 2012-08-02) Gletsu-Miller, Nana; Ziegler, Thomas R.
Mingrone et al. and Schauer et al. (April 26 issue) report the results of rigorous randomized, controlled trials comparing various types of bariatric surgery with medical therapy for obesity-associated type 2 diabetes. However, we would like to raise the important issue of micro-nutrient assessment and management in pa-tients undergoing bariatric surgery. The risk of deficiency (of thiamine; vitamins B6, B12, and D; calcium; iron; or copper, zinc, or both) is increasingly recognized after malabsorptive bariatric surgery, but these deficiencies may be inadequately diagnosed. For example, we recently described the incidence and prevalence of copper deficiency after Roux-en-Y gastric bypass surgery as 18.8% and 9.6%, respectively.
Abnormal Primary Tissue Collagen Composition in the Skin of Recurrent Incisional Hernia Patients
(American Surgeon, 2007-12) Gletsu-Miller, Nana; White, Brent; Jeansonne, Louis; Baghai, Mercedeh; Sherman, Melanie; C. Daniel, Smith; Ramshaw, Bruce; Lin, Edward
Recurrence of incisional hernia may be as high as 50 per cent. Abnormal collagen I/III ratios have been observed within scar tissue of patients with recurrent incisional hernias. We sought to determine whether collagen composition in primary, nonscarred tissue was similarly affected in these patients. In this prospective, case–control study, nonscarred, primary abdominal wall skin and fascia biopsies were obtained in 12 patients with a history of recurrent incisional hernias and 11 control subjects without any history of hernia while undergoing abdominal laparoscopic surgery. Tissue protein expression of collagen I and III was assessed by immunohistochemistry followed by densitometry analysis. The collagen I/III ratio in skin biopsies from the recurrent hernia group was significantly less compared with control subjects (0.88 ± 0.01 versus 0.98 ± 0.04, respectively, P < 0.05). Fascia biopsies from patients with recurrent hernias was not significantly decreased in collagen I/III ratio compared with control subjects (0.90 ± 0.04 versus 0.94 ± 0.03, respectively, P = 0.17). Decreased collagen I/III ratios within the skin of patients with recurrent hernias not involved with scar or healing tissue suggest an underlying collagen composition defect. Such a primary collagen defect, in addition to abnormal scar formation, likely plays a significant role in the pathogenesis of recurrent incisional hernias.
Proceedings of the 2017 ASPEN Research Workshop— Gastric Bypass: Role of the Gut
(Journal of Parenteral and Enteral Nutrition, 2018-02) Gletsu-Miller, Nana; Jain, Ajay Kumar; le Roux, Carel W; Puri, Puneet; Tavakkoli, Ali; Laferrère, Blandine; Kellermayer, Richard; DiBaise, John K.; Martindale, Robert G.; Wolfe, Bruce M.
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.
Dietary Intervention for Glucose Tolerance In Teens (DIG IT): Protocol of a randomized controlled trial using health coaching to prevent youth-onset type 2 diabetes
(Contemporary Clinical Trials, 2017-02) Gletsu-Miller, Nana; Wagner, Kelly A; Braun, Ethan; Armah, Seth M; Horan, Diarmuid; Smith, Lisa G; Pike, Julie; Tu, Wanzhu; Hamilton, Marc T.; Delp, Edward J.; Campbell, Wayne W; Boushey, Carol J; Hannon, Tamara S
Background: Youth-onset type 2 diabetes (T2D) is a disease that is newly emerging and behavioral strategies for its prevention are limited. Interventions that target the lifestyle behaviors of adolescents, to improve poor dietary quality and reduce excessive sedentariness, promise to reduce the risk of developing T2D. Health coaching is effective for promoting healthy behaviors in patients who have chronic disease, but few experimental studies are in adolescents. This randomized controlled trial, in adolescents with prediabetes, will determine the effectiveness of a health coaching intervention to facilitate adoption of healthy diet and activity behaviors that delay or prevent development of T2D. Methods/design: The Dietary Intervention for Glucose Tolerance In Teens (DIG IT) trial will involve an evaluation of a health coaching intervention in adolescents with prediabetes. Eligible participants will be randomized to receive 6 months of health coaching or a single dietary consultation that is standard-of-care. The primary outcome will be 2-hour oral glucose tolerance test concentration. Secondary outcomes will include measures of glycemia and insulin action as well as dietary, physical activity and sedentary behaviors measured using an electronic food record, and by inclinometer. Data will be collected before and after the intervention (at 6 months) and at 12 months (to assess sustainability). Discussion:This trial will determine whether a health coaching intervention, a personalized and low-cost approach to modify dietary and activity behaviors, is effective and sustainable for prevention of youth-onset T2D, relative to standard-of-care. Health coaching has the potential to be widely implemented in clinical or community settings.
Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery
(International Journal of Obesity, 2012-03) Gletsu-Miller, Nana; Broderius, M; Frediani, JK; Zhao, VM; Griffith, DP; Davis, SS Jr; Sweeney, JF; Lin, E; Prohaska, JR; Ziegler, TR
Introduction and Objectives: 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. Design and Methods: 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. Results: 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<0.05), but plasma zinc concentrations did not change. A simultaneous decrease in white blood cells was observed (P<0.05). The incidence of copper deficiency in these subjects was determined to be 18.8%. Conclusions: The prevalence and incidence of copper deficiency following RYGB surgery was determined to be 9.6% and 18.8%, respectively, with many patients experiencing mild-to-moderate symptoms. Given that copper deficiency can lead to serious and irreversible complications if untreated, frequent monitoring of the copper status of RYGB patients is warranted.
Sagittal Abdominal Diameter and Visceral Adiposity: Correlates of Beta-Cell Function and Dysglycemia in Severely Obese Women
(Obesity Surgery, 2013-07) Gletsu-Miller, Nana; Kahn, Henry S.; Gasevic, Danijela; Liang, Zhe; Frediani, Jennifer K.; Torres, William E.; Ziegler, Thomas R.; Phillips, Lawrence S.; Lin, Edward
Background: 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/m2) 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. Methods: 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. Results: Compared to fasting normoglycemic women, individuals with dysglycemia had greater VAT (P < 0.001) 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 P < 0.05). 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. Conclusions: 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.
Determination of ebselen-sensitive reactive oxygen metabolites(ebROM) in human serum based upon N,N′-diethyl-1,4-phenylenediamine oxidation
(Clinica Chimica Acta, 2012-12) Gletsu-Miller, Nana; Liang, Yongliang; Roede, James R.; Dikalov, Sergey; Dudley, Samuel C. Jr; Quyyumi, Arshed; Jones, Dean P.
Background: Oxidative stress occurs through free radical- and non-radical-mediated oxidative mechanisms, but these are poorly discriminated by most assays. A convenient assay for oxidants in human serum is based upon the Fe2+-dependent decomposition of peroxides to oxidize N,N′-diethyl-1,4-phenylenediamine (DEPPD) to a stable radical cation which can be measured spectrophotometrically. Methods: We investigated modification of the DEPPD oxidation assay to discriminate color formation due to non-radical oxidants, including hydroperoxides and endoperoxides, which are sensitive to ebselen. Results: Use of serum, which has been pretreated with ebselen as a reference, provides a quantitative assay for non-radical, reactive oxidant species in serum, including hydroperoxides, endoperoxides and epoxides. In a set of 35 human serum samples, non-radical oxidants largely accounted for DEPPD oxidation in 86% of the samples while the remaining 14% had considerable contribution from other redox-active chemicals. Conclusions: The simple modification in which ebselen-pretreated sample is used as a reference provides means to quantify non-radical oxidants in human serum. Application of this approach could enhance understanding of the contribution of different types of oxidative stress to disease.
Contribution of Adipose Tissue to Plasma 25-Hydroxy vitamin D Concentrations During Weight Loss Following Gastric Bypass Surgery
(Obesity, 2011-03) Gletsu-Miller, Nana; Lin, Edward; Armstrong-Moore, Dereka; Liang, Zhe; Sweeney, John F.; Torres, William E.; Ziegler, Thomas R.; Tangpricha, Vin
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.
Dietary Sulfur Amino Acid Effects on Fasting Plasma Cysteine/Cystine Redox Potential in Humans
(Nutrition, 2011-02) Gletsu-Miller, Nana; Jones, Dean P.; Park, Youngja; Yu, Tianwei; Ziegler, Thomas R.; Liang, Yongliang; Accardi, Carolyn Jonas
Objective: Oxidation of plasma cysteine/cystine (Cys/CySS) redox potential (EhCySS) 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 EhCySS in human plasma under fasting conditions. Methods: 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 EhCySS. Results: The SAA-free diet significantly (P < 0.05) decreased plasma-free Cys concentrations and oxidized EhCySS 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 EhCySS 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 EhCySS. Conclusions:These results show that free Cys and Cys/CySS redox potential (EhCySS) 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.
Loss of Total and Visceral Adipose Tissue Mass Predicts Decreases in Oxidative Stress After Weight Loss Surgery
(Obesity, 2009-03) Gletsu-Miller, Nana; Hansen, Jason M.; Jones, Dean P.; Go, Young-Mi; Torres, William E.; Ziegler, Thomas R.; Lin, Edward
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.

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