Hormonal and dietary influences on true fractional calcium absorption in women: role of obesity.

UNLABELLED: The goal in this study was to examine the hormonal and dietary predictors of true fractional Ca absorption (TFCA) in adult women and to determine whether TFCA differs due to body weight. Results showed that TFCA is higher in obese individuals and dietary fat, estradiol, and 1,25-dihydroxy vitamin D are the most significant positive predictors of TFCA in adult women. INTRODUCTION: Calcium absorption is an important determinant of calcium balance and is influenced by several factors. Previous studies have identified that age, intake of protein, fat and fiber, and hormones such as 1, 25-dihyroxyvitamin D (1,25(OH)(2)D(3)) influence absorption. The determinants of TFCA using the double isotope method, the gold standard estimate of absorption, have not been examined previously in adult women nor has the role of obesity been addressed. METHODS: In this study, we examined the hormonal and dietary predictors of TFCA in adult women with a wide range of age, body weights, and nutrient intake. TFCA was measured using dual stable isotope ((42)Ca and (43)Ca) technique. Serum was analyzed for bone-regulating hormones, and dietary information was obtained through food records. The independent dietary factors and hormonal predictors (25-hydroxyvitamin D, 1,25(OH)(2)D(3), parathyroid hormone, and estradiol) of TFCA were analyzed using multiple regression analysis. RESULTS: Two hundred twenty-nine women aged 54 ± 11 years old (24-75 years) and with BMI of 31 ± 7.0 kg/m(2) were eligible and were categorized into tertiles of body mass index (BMI) into leaner, overweight, and obese. In the entire group of women, total fat intake, estradiol, and 1,25(OH)(2)D(3) are significant positive predictors (p < 0.05). As expected, age is a significant negative predictor of TFCA (R (2) = 26%). TFCA is higher in obese women compared to non-obese women (p < 0.05). CONCLUSION: Together, these data show that dietary fat is the most significant positive predictor of TFCA which may have implications for dietary intake for non-obese individuals who are more likely to have lower and potentially compromised Ca absorption.

Gastric bypass.

Nearly all morbidly obese patients with satisfactory postoperative weight loss experience substantial improvement in the quality of their lives. Improved health status is characterized by increased exercise tolerance and improvement or resolution of obesity-related comorbidities. Improvement of obesity-related medical problems (discussed in the article by Klein elsewhere in this issue) is a primary goal of gastric bypass. The patient's ability to interact with others in social situations is also enhanced. At present, RYGB may be the only bariatric operation that has produced durable long-term weight loss at an acceptable level of risk.

Gastric bypass surgery in adolescents with morbid obesity.

OBJECTIVE: The objective was to review retrospectively all patients undergoing bariatric surgery at a large university medical center. METHODS: Ten adolescents 17 years or younger underwent gastric bypass surgery; 7 of 10 adolescents had severe obesity-related morbidities. Follow-up >1 year was present in 9 of 10 adolescents. RESULTS: The average weight before surgery was 148 +/- 37 kg. Postoperative recovery was uneventful in all adolescents; 9 of 10 adolescents had weight loss in excess of 30 kg (mean weight loss was 53.6 +/- 25.6 kg). Obesity related morbidities resolved in all adolescents. Five adolescents had mild iron deficiency anemia, and 3 adolescents had transient folate deficiency. Late complications requiring operative treatment occurred in 4 of the adolescents. CONCLUSION: Gastric bypass surgery was an effective method for weight reduction in morbidly obese adolescents. The procedure was well tolerated, with few unanticipated side effects. Gastric bypass remains a last resort option for severely obese adolescents for whom other dietary and behavioral approaches to weight loss have been unsuccessful.

Regulation of the leptin content of obese human adipose tissue.

The objective of this study was to determine whether obese human adipose tissue contains preformed stores of leptin and their relationship to secreted leptin. Detergent increased detectable leptin by about twofold, suggesting that leptin is stored in a membrane-bound location. Subcutaneous tissue leptin was approximately 1.6-fold higher than omental, paralleling known differences in leptin secretion and expression. The amount of leptin secreted during a 3-h incubation was similar to that of extractable tissue leptin. Tissue leptin levels were maintained over the incubation. Inhibition of protein synthesis decreased tissue leptin content but did not decrease leptin secretion until after 3 h of incubation. Culture of adipose tissue for 2 days with the combination of insulin and dexamethasone, but not with either hormone alone, increased tissue leptin content about twofold in both depots. Although insulin did not affect tissue leptin content, it potentiated leptin secretion (as a % of tissue stores). These data suggest that adipose tissue leptin storage and secretion per se are regulated. Regulation of the release of preformed leptin may modulate serum leptin levels in obese humans.

Lipid risk profile and weight stability after gastric restrictive operations for morbid obesity.

There are no longitudinal data that address weight loss stability and lipid levels in bariatric surgical patients. The goal of this study was to determine whether weight regain adversely affected reduction in lipid levels after gastric bariatric operations. Of 651 consecutive patients undergoing gastric restrictive surgery for morbid obesity, 227 (35%) had increased serum levels of total cholesterol (TC), triglycerides, or both preoperatively. High-density lipoprotein cholesterol (HDL-C) levels were subnormal (/=15% mean reduction in TC and a >/=50% mean reduction in triglycerides, both of which were significant in comparison with preoperative levels (P /=15% of their lost weight or lost less than 50% of excess weight (N = 37). Although mean excess weight loss and body mass index were significantly different between the two groups (P <0.0001) at 2 years, there was no difference in the lipid profile (TC/HDL) between the two groups at any interval through 5 years. These results show that abnormal lipid profiles can be permanently improved after gastric bariatric surgery and are not adversely affected by mediocre weight loss or regaining >/=15% of lost weight. DRY appears to be a superior operation for TC reduction in comparison with GP and RYGB.

Assessment of eating disorders in bariatric surgery candidates: self-report questionnaire versus interview.

OBJECTIVE: To compare the Eating Disorder Examination (EDE), an investigator-based interview for the assessment of the specific psychopathology of eating disorders, with the EDE-Q, a self-report questionnaire based directly on it. METHOD: Ninety-eight morbidly obese gastric bypass surgery candidates were administered both instruments. RESULTS: The four subscale scores (Restraint, Eating Concern, Weight Concern, and Shape Concern) generated by the EDE and EDE-Q were significantly correlated, although the questionnaire scores were significantly higher. Eating Concern and Shape Concern exhibited the lowest levels of agreement. Frequency of binges (objective bulimic episodes) as rated by the EDE and EDE-Q was significantly correlated and was not significantly different. However, variability in ratings contributed to only modest agreement with respect to classification of patients as binge eaters. DISCUSSION: Overall, there were lower levels of agreement between the EDE and EDE-Q than have been previously found in other samples.

Staphylococcal enterotoxin B induces potent cytotoxic activity by intraepithelial lymphocytes.

In food poisoning, Staphylococcus aureus secretes staphylococcal enterotoxin B (SEB), a superantigen that causes intense T-cell proliferation and cytotoxicity. The effects of SEB on lytic activity by human intestinal intraepithelial lymphocytes (IEL) were investigated. Jejunal IEL, from morbidly obese individuals undergoing gastric bypass operations, were tested for SEB-induced cytotoxicity against C1R B-lymphoblastoid cells, HT-29 adenocarcinoma cells, or CD1d-transfected cells using the 51Cr-release assay. Fas and Fas ligand expression were detected by immunofluorescence and flow cytometry and soluble ligand by enzyme-linked immunosorbent assay (ELISA). In the presence of SEB, IEL became potently cytotoxic against C1R cells and interferon-gamma (IFN-gamma)-precultured HT-29 cells, causing 55+/-10% and 31+/-6% lysis, respectively, greater than that by phytohaemagglutinin (PHA)-, interleukin-2 (IL-2)-, or anti-T-cell receptor (TCR)-activated IEL. SEB-stimulated peripheral blood (PB) CD8+ T cells lysed similar numbers of C1R cells but fewer HT-29 cells (53+/-13% and 8+/-5%, respectively). IEL killing of C1R cells involved interaction of major histocompatibility complex (MHC) class II with TCR, CD2 with CD58, and CD11a with CD54, and was perforin mediated. SEB-induced IEL lysis of HT-29 cells, in contrast, was caused by an unknown target cell structure, not MHC class II or CD1d, and resulted from a combination of perforin and Fas-mediated events. The potent cytotoxic activities of IEL promoted by SEB utilize two different mechanisms, depending on the surface receptors expressed by the target cells.

Efficacy and safety of patient-controlled analgesia for morbidly obese patients following gastric bypass surgery.

BACKGROUND: Adequate postoperative pain control is important to reduce potential cardiopulmonary complications. It is often difficult to determine dosages of narcotics for morbidly obese patients following Roux-en-Y gastric bypass (RYGBP) due to respiratory depression. Individualization of analgesic therapy, patient-controlled analgesia (PCA), can provide optimal dosage for pain control and minimize the side-effects. METHOD: 25 morbidly obese patients who received PCA with morphine sulfate following RYGBP. PCA settings we re as follows: morphine, 20 microg/kg of ideal body weight, 10-minute lock out interval and 80 % of a calculated amount for a 4-hour limit. W e measured arterial blood gas, heart rate, mean arterial pressure, arterial oxygen saturation, respiratory rate, opioid amount, patient satisfaction, visual analog pain scale (VAS), and the incidence of nausea, vomiting, pruritus and sedation. RESULTS: Average morphine usage was 44.2+/-28.7 mg during the day of surgery (DOS); 49.1+/-27.4 mg during POD (postoperative day) #1; and 36.6+/-22.8 mg during POD#2 (p < 0.01). 24 patients were satisfied with their pain control on POD#1. VAS was 5.4+/-2.1 on the day of surgery, but remained below 4 thereafter. Arterial oxygen saturation and vital signs were maintained without significant changes. 5 patients experienced mild sedation on the day of surgery and 3 patients experienced mild sedation on POD#1. 1 patient experienced nausea and vomiting and 4 patients had pruritus; however, none required treatment. CONCLUSION: PCA is safe and effective for morbidly obese patients following RYGBP.

Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen.

Intraepithelial lymphocytes (IELs) from human intestinal epithelium are memory CD8+ T cells that bind to epithelial cells through human mycosal lymphocyte (HML)-1 and to mesenchymal cells through very late activation antigen-4 (VLA-4). Their binding of extracellular matrix proteins and the mechanism involved were tested. Activated 51Cr-labelled lymphocytes were incubated in protein-coated microwells with various additives. After washing, the adherent cells were detected by radioactivity. The percentages of activated IELs that bound to collagen types I and IV were 20 and 31%, respectively; fewer bound to fibronectin or laminin. Compared to interleukin-2-activated peripheral blood CD8+ T lymphocytes, more IELs bound collagen IV and fewer bound fibronectin. IEL adhesion to collagen (but not fibronectin or laminin) was up-regulated by antibody ligation of CD2 or by protein kinase C stimulation by phorbol ester; staurosporine reduced binding, while herbimycin, phytohaemagglutinin and CD3 ligation had no effect. Antibody-blocking of integrin VLA-1 subunits alpha1 (CD49a) and beta1 (CD18) inhibited adhesion to collagen type I by 82+/-6% and to type IV by 94+/-1% (P<0.001), implicating VLA-1 as the main collagen receptor for IELs. Cell adhesion was dependent on extracellular divalent cations, a characteristic event of VLA-1 never before shown for IELs: manganese and magnesium ions supported binding in a dose-dependent manner; calcium ions inhibited their effectiveness. Therefore, IELs bind collagen through integrin alpha1beta1 after protein kinase C activation. Adhesion is modulated by divalent cations.

Survey of vitamin and mineral supplementation after gastric bypass and biliopancreatic diversion for morbid obesity.

BACKGROUND: The authors investigated whether practice patterns of bariatric surgeons correlate with published data regarding metabolic deficiencies after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). METHODS: 109 surgeons completed a questionnaire to determine use of supplements and frequency of lab tests. RESULTS: Regarding supplements routinely prescribed after RYGB, 96% of surgeons gave multivitamins, 63% gave iron, and 49% gave vitamin B12. After BPD, 96% of surgeons gave multivitamins, 67% gave iron, 42% gave vitamin B12, 97% gave calcium, 63% gave fat-soluble vitamins, and 21% gave protein supplements. Regarding laboratory tests obtained routinely after RYGB, 95% of surgeons do complete blood counts, 56% do iron determinations, 66% do vitamin B12 determinations, 58% do folate determinations, 76% do electrolyte determinations, and 8% test for proteins. After BPD, 96% of surgeons do complete blood counts, 80% do iron determinations, 67% do vitamin B12 determinations, 71% do folate determinations, 88% do electrolyte determinations, 84% do protein determinations, and 46% test for fat-soluble vitamins. Regarding frequency of blood tests, after RYGB, 22% of surgeons obtain them after 3 months, 33% after 6 months, and 41% after 12 months; 4% do not routinely obtain postoperative laboratory tests. After BPD, 46% of surgeons obtain them after 3 months, 33% after 6 months, and 16% after 12 months; one does not obtain laboratory tests. Surgeons estimated these deficiencies after RYGB: 16% iron, 12% vitamin B12, 14% anemia, 5% protein, and 3% calcium. They estimated these deficiencies after BPD: 26% iron, 11% vitamin B12, 21% anemia, 18% protein, 16% calcium, and 6% fat-soluble vitamins. The estimated incidence of deficiencies after RYGB was considerably lower than the published incidence. Unnecessary tests were commonly performed (electrolytes after RYGB). CONCLUSION: Despite wide variations in the performance of laboratory tests and the use of supplements, the practice patterns of most surgeons protect patients from developing severe metabolic deficiencies after RYGB and BPD.

Effect of aging on intestinal ischemia and reperfusion injury.

Intestinal ischemia/reperfusion (I/R) is a serious disorder that is prevalent in elderly patients. Reactive oxygen species are implicated in the pathogenesis of intestinal I/R injury. Reactive oxygen species are also implicated in cellular senescence and aging. To test the hypothesis that aging exacerbates intestinal I/R injury, the effects of intestinal I/R on tissue injury were compared between young (3 month old) and aged (12 month old) mice. Intestinal ischemia was induced by occluding the superior mesenteric artery with a microbulldog clamp. Reperfusion was initiated by removing the clamp. Mortality due to intestinal ischemia followed by reperfusion was significantly higher in aged mice. There were no differences in the baseline levels of malondialdehyde or myeloperoxidase activity (indicators of lipid peroxidation and neutrophil infiltration, respectively) between young and aged mice. Although intestinal I/R caused a significant increase in malondialdehyde levels and myeloperoxidase activity in aged mice, similar increases were also observed in young mice. There were no significant differences in the activities of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and catalase between young and aged mice that underwent sham operation. Intestinal I/R caused a significant decrease in catalase activity only in aged mice. In conclusion, our results indicate that aged mice are more susceptible to mortality due to intestinal I/R and that an age-dependent decrease in catalase activity may contribute to the observed mortality.

Performance standards in bariatric surgery.

A bariatric surgeon is a fully trained general or gastrointestinal surgeon who has demonstrated specialized knowledge in the management of patients who suffer from morbid obesity and its complications. In addition to appropriate formal surgical training, preceptorships with experienced surgeons, preferably members of international bariatric societies, are highly desirable. Active participation in meetings of these societies, continuing medical education and knowledge of the current literature are necessary to maintain the required skills to treat these complex patients. Bariatric surgery should be performed at institutions that provide the necessary equipment, facilities and support systems for this particular population. When analysing outcomes of obesity surgery, long-term weight loss reports should include the number of patients followed and the time period of follow-up. Complications and re-operations should be presented, as well as modifications of techniques when various operations are compared. Weight loss should not be the only criterion used to define success or failure. Objective assessment of improvement in medical conditions related to obesity, and reliable measurements of quality of life after surgery should also be included in the final outcome analysis.

Effects of bariatric surgery on binge eating and related psychopathology.

The Beck Depression Inventory (BDI), the Three-Factor Eating Questionnaire (TFEQ), and the Eating Disorder Examination (EDE) were administered to 50 morbidly obese patients before and after gastric bypass surgery. Subjects were classified as non-binge or binge eaters prior to surgery. Though the two groups differed markedly before operation, they were largely indistinguishable 4 months afterward. All binge eating had ceased and mood had improved markedly. TFEQ Restraint scores increased, and Disinhibition and Hunger scores decreased. EDE Eating Concern, Shape Concern, and Weight Concern scores dropped. EDE Restraint scores decreased in non-binge eaters and increased in binge eaters. The overall findings indicate that gastric bypass surgery had a positive short-term impact on non-binge and binge eaters alike.

Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass?

Although iron, vitamin B12, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB) patients. During a 10-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vitamin B12, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years, then annually thereafter. The principal objectives of this study were to determine how readily patients who developed metabolic deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn whether the risk of developing these deficiencies decreases over time. Hemoglobin and hematocrit levels were significantly decreased at all postoperative intervals in comparison to preoperative values. Moreover, at each successive interval through 5 years, hemoglobin and hematocrit were decreased significantly compared to the preceding interval. Folate levels were significantly increased compared to preoperative levels at all time intervals. Iron and vitamin B12 levels were lower than preoperative measurements and remained relatively stable postoperatively. Half of the low hemoglobin levels were not associated with iron deficiency. Taking multivitamin supplements resulted in a lower incidence of folate deficiency but did not prevent iron or vitamin B12 deficiency. Oral supplementation of iron and vitamin B12 corrected deficiencies in 43% and 81% of cases, respectively. Folate deficiency was almost always corrected with multivitamins alone. No patient had symptoms that could be attributed to either vitamin B12 or folate deficiency Conversely, many patients had symptoms of iron deficiency and anemia. Lack of symptoms of vitamin B12 and folate deficiency suggests that these deficiencies are not clinically important after RYGB. Conversely, iron deficiency and anemia are potentially serious problems after RYGB, particularly in younger women. Hence we recommend prophylactic oral iron supplements to premenopausal women who undergo RYGB.

Gastrointestinal surgery for obesity.

Surgery is becoming an increasingly common method for treatment of morbid obesity in the United States. This text includes the presentation of a typical morbidly obese man with a number of obesity related comorbidities who was treated with a modification of Roux-en-Y gastric bypass. Subsequently, the gastrointestinal operations currently in use as treatment for morbid obesity are discussed. Preoperative and postoperative care for this patient population is discussed briefly. The results of the various procedures are also discussed in terms of both complications and improvement of medical comorbidities.

Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone.

We investigated the in vitro regulation of leptin expression in adipose tissue from severely obese women and men before and after culture with insulin (7 nM) and/or dexamethasone (25 nM). Leptin mRNA and leptin secretion were two- to threefold higher in subcutaneous vs. omental adipose tissue before culture. Dexamethasone transiently increased leptin mRNA approximately twofold in both depots after 1 day of culture [P < 0.01 vs. basal (no hormone control)], but leptin secretion was only increased in omental adipose tissue (P < 0.005 vs. basal). Insulin did not increase leptin mRNA in either depot but increased leptin secretion approximately 1.5- to 3-fold in subcutaneous tissue throughout 7 days of culture (P < 0.05 vs. basal). The combination of insulin and dexamethasone increased leptin mRNA and leptin secretion approximately two- to threefold in both depots at day 1 (P < 0.005 vs. basal or insulin) and maintained leptin expression throughout 7 days of culture. We conclude that insulin and glucocorticoid have depot-specific effects and function synergistically as long-term regulators of leptin expression in omental and subcutaneous adipose tissue from obese subjects.

Prophylactic iron supplementation after Roux-en-Y gastric bypass: a prospective, double-blind, randomized study.

OBJECTIVE: To determine whether prophylactic oral iron supplements (320 mg twice daily) would protect women from iron deficiency and anemia after Roux-en-Y gastric bypass. DESIGN: Prospective, double-blind, randomized study in which 29 patients received oral iron and 27 patients received a placebo beginning 1 month after Roux-en-Y gastric bypass. SETTING: Tertiary care medical center. PATIENTS AND INTERVENTIONS: Complete blood cell count and serum levels of iron, total iron binding capacity, ferritin, vitamin B12, and folate were determined preoperatively and at 6-month intervals postoperatively in 56 menstruating women who had Roux-en-Y gastric bypass. MAIN OUTCOME MEASURE: Incidence of iron deficiency and other hematological abnormalities in each treatment group. RESULTS: Hemoglobin, hematocrit, and vitamin B12 levels were significantly decreased compared with preoperative values in both groups. Conversely, folate levels increased significantly over time in both groups. Oral iron consistently prevented development of iron deficiency in the iron group. Ferritin levels did not change significantly in the iron group. However, in placebo-treated patients, ferritin levels 2 years postoperatively were significantly decreased compared with preoperative levels. There was no difference in the incidence of anemia between the 2 groups. However, the incidence of microcytosis was substantially greater (P=.07) in placebo-treated than iron-treated patients. CONCLUSIONS: Prophylactic oral iron supplements successfully prevented iron deficiency in menstruating women after Roux-en-Y gastric bypass but did not consistently protect these women from developing anemia. On the basis of these results we now routinely recommend prophylactic iron supplements to menstruating women who have Roux-en-Y gastric bypass.

Binge eating in bariatric surgery patients.

OBJECTIVE: Eating behavior, attitudes toward eating and body weight and shape, and depression were assessed in a sample of 64 morbidly obese gastric bypass surgery candidates. METHOD: The Beck Depression Inventory (BDI), the Three-Factor Eating Questionnaire (TFEQ), and the Eating Disorder Examination (EDE) were administered at the first preoperative visit. RESULTS: Twenty-five subjects (39%) reported at least one binge episode per week on average over the 3 months prior to seeking treatment. Binge eaters had significantly higher TFEQ Disinhibition and Hunger scores than nonbinge eaters. Binge eaters also differed from nonbinge eaters in terms of attitudes toward eating, shape, and weight. DISCUSSION: A significant number of gastric bypass surgery candidates report binge eating. The findings are consistent with other studies showing binge eaters to be a distinctive subgroup of the obese.