Change in carbohydrate intake one year after Roux-en-Y gastric bypass: A prospective study.

Background and objectives: To investigate the effect of carbohydrate intake before laparoscopic Roux-en-Y gastric bypass (LRYGB) on body weight, body composition and glycaemic status after surgery. Methods: In a tertiary centre cohort study, dietary habits, body composition and glycaemic status were evaluated before and 3, 6 and 12 months after LRYGB. Detailed dietary food records were processed by specialized dietitians on the basis of a standard protocol. The study population was subdivided according to relative carbohydrate intake before surgery. Results: Before surgery, 30 patients had a moderate relative carbohydrate intake (26%-45%, M-CHO), a mean body mass index (BMI) of 40.4 ± 3.9 kg/m² and a mean glycated haemoglobin A1c (A1C) of 6.5 ± 1.2% compared to 20 patients with a high relative carbohydrate intake (> 45%, H-CHO), mean BMI of 40.9 ± 3.7 kg/m² (non-significant, NS) and a mean A1C of 6.2% (NS). One year after surgery, body weight, body composition and glycaemic status were similar in the M-CHO (n = 25) and H-CHO groups (n = 16), despite less caloric intake in the H-CHO group (1317 ± 285 g vs. 1646 ± 345 g in M-CHO, p < 0.01). Their relative carbohydrate intake converged to 46% in both groups, but the H-CHO group reduced the absolute total carbohydrate consumption more than the M-CHO group (190 ± 50 g in M-CHO vs. 153 ± 39 g in H-CHO, p < 0.05), and this was especially pronounced for the mono- and disaccharides (86 ± 30 g in M-CHO vs. 65 ± 27 g in H-CHO, p < 0.05). Conclusion: A high relative carbohydrate intake before LRYGB, did not influence the change in body composition or diabetes status after surgery, despite a significantly lower total energy intake and less mono- and disaccharide consumption after surgery.

Impact of gastrointestinal physiology on drug absorption in special populations--An UNGAP review.

The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.

Predicting iron absorption from an effervescent iron supplement in obese patients before and after Roux-en-Y gastric bypass: a preliminary study.

BACKGROUND & AIMS: Oral iron absorption is hampered in obese and bariatric patients, especially after Roux-en-Y gastric bypass (RYGB). As a result, iron deficiency, which is common in both patient groups, can be difficult to treat by oral supplements, often necessitating a switch to parenteral administration. The aim of this study was to find possible predictors of the extent of absorption of an effervescent iron gluconate oral supplement, which enables to pre-emptively identify those patients in which oral supplementation is likely to fail. METHODS: The pharmacokinetic properties of 695 mg effervescent iron gluconate (80 mg Fe2+) were assessed in 13 obese patients (female = 10; mean age ± SD: 45.2 ± 12.5years) pre- and six months post-RYGB by measuring serum iron concentrations during 24 hours and by calculating the adjusted for baseline AUC0-24h, Cmax and Tmax. A multivariate regression analysis was performed to investigate the effect of hepcidin concentration, iron and hematologic indices, personal and anthropometric characteristics on iron absorption. Subsequently, Receiver Operating Characteristic (ROC) curves were used to propose the cut-off value for hepcidin concentrations above which obese patients are unlikely to benefit from oral iron supplementation. Data are expressed as mean ± SD. RESULTS: Low iron status persisted after surgery as there was no significant difference observed in TSAT (17.3 ± 5.2 vs. 20.2 ± 6.6%), ferritin (91.8 ± 68.6 vs. 136.2 ± 176.9 µg/L) and hepcidin concentration (32.0 ± 30.1 vs. 28.3 ± 21.3 ng/mL) after RYGB. The absorption of effervescent iron gluconate was similar pre- and post-RYGB [AUC0-24h,pre-RYGB: 28.6 ± 10.8 µg/dL*h; AUC0-24h,post-RYGB: 27.5 ± 9.11 µg/dL*h (P = 0.84)]. Post-RYGB, iron AUC0-24h showed a strong negative correlation with both hepcidin concentrations and TSAT (R=-0.51; P = 0.08 and R=-0.81; P = 0.001), respectively. Pre-RYGB, there was a clear trend for the same negative correlations for hepcidin concentrations and TSAT (R=-0.47; P = 0.11 ;R=-0.41; P = 0.16), respectively. Taking pre-and post-RYGB data together, the negative correlations were confirmed for hepcidin concentrations and TSAT (R=-0.54; P = 0.004; R=-0.60; P = 0.001), respectively. The AUCROC = 0.87 (95%CI 0.71; 1.00) showed an optimal sensitivity/specificity cut-off at hepcidin concentrations of 26.8 ng/mL. CONCLUSIONS: The iron AUC0-24h showed a negative correlation with the hepcidin concentration and TSAT of obese patients, in particular post-RYGB. Therefore, our data support the use of hepcidin concentration and TSAT to distinguish potential responders from non-responders for iron supplementation particularly post-RYGB. Additionally, this study showed that the pharmacokinetic properties of iron gluconate from an effervescent tablet were unaffected by RYGB-surgery.

At similar weight loss, dietary composition determines the degree of glycemic improvement in diet-induced obese C57BL/6 mice.

BACKGROUND: Achieving weight loss is the cornerstone of the treatment of the metabolic consequences of obesity, in particular of glucose intolerance. OBJECTIVE: To determine whether improvement in glucose control depends on dietary macronutrient composition of the diet at identical weight loss. MATERIALS AND METHODS: Twenty-two weeks old diet-induced obese C57BL/6 mice lost weight through caloric restriction on normal chow (R-NC) or high fat diet (R-HF). Control mice were fed normal chow (LEAN) or high fat diet (OBESE) ad libitum. Body weight and composition were assessed after 8 weeks of dietary intervention. Glucose homeostasis was evaluated by intraperitoneal glucose tolerance tests (IPGTT). Epididymal white adipose (eWAT) and hepatic tissues were analyzed by immunohistochemistry and RT-qPCR. RESULTS: By 30 weeks of age, the body weight of the mice on R-NC (31.6±1.7g, mean±SEM) and R-HF (32.3±0.9g) was similar to LEAN mice (31.9±1.4g), while OBESE mice weighed 51.7±2.4g. Glucose tolerance in R-NC was better than in LEAN mice (69% AUC IPGTT, P 0.0168) whereas R-HF mice remained significantly less glucose tolerant (125% AUC IPGTT, P 0.0279 vs LEAN), despite identical weight loss. The eWAT pads and adipocyte size were similar in LEAN and R-NC mice, while the eWAT pad size of R-HF was 180% of R-NC (P < 0.0001) and the average adipocyte size of R-HF mice was 134% of R-NC fed mice (P 0.0285). No LEAN or R-NC mice had hepatic steatosis, in contrast to 28.6% of R-HF mice. Compared to OBESE mice, inflammatory markers were lower in eWAT and liver tissue of R-NC, but not in R-HF mice. Measures of visceral adiposity correlated well with glucose tolerance parameters. CONCLUSIONS: In mice, caloric restriction on a normal chow diet improved glucose tolerance significantly more when identical weight loss was achieved on a high fat diet.

The relevance of dietary protein after bariatric surgery: what do we know?

PURPOSE OF REVIEW: The growing obesity epidemic is associated with an increased demand for bariatric surgery with Roux-en-Y Gastric Bypass and Sleeve Gastrectomy as the most widely performed procedures. Despite beneficial consequences, nutritional complications may arise because of anatomical and physiological changes of the gastrointestinal tract. The purpose of this review is to provide an update of the recent additions to our understanding of the impact of bariatric surgery on the intake, digestion and absorption of dietary protein. RECENT FINDINGS: After bariatric surgery, protein intake is compromised because of reduced gastric capacity and aversion for certain foods. A minority of patients reaches the recommended protein intake of minimal 60 g per day, which results in the loss of fat-free mass rather than the desired loss of fat mass. Despite inadequate protein intake, protein digestion and absorption do not seem to be impaired suggesting that other mechanisms could counteract the reduced secretion of digestive enzymes and their delayed inlet. SUMMARY: After bariatric surgery, protein supplementation or diet enrichment could attribute to achieve the minimal recommended protein intake and benefit the amount and composition of postoperative weight loss.

Micronutrient intake, from diet and supplements, and association with status markers in pre- and post-RYGB patients.

BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) is associated with an increased risk for micronutrient deficiencies. This study aimed to assess total (dietary and supplement) intake and association with iron (including hepcidin), vitamin B12, vitamin C and zinc status markers before and after Roux-en-Y gastric bypass (RYGB). METHODS: This prospective study included patients with a planned RYGB in University Hospitals Leuven, Belgium; who were followed until 12 months post-RYGB. Patients completed an estimated dietary record of two non-consecutive days before and 1, 3, 6 and 12 months post-RYGB and supplement/drug use was registered. Associations between total micronutrient intake and status markers were analyzed. RESULTS: Fifty-four patients (21 males; mean age: 48.0 [95%CI 46.6; 49.3] years; mean preoperative BMI: 40.4 [95%CI 39.4; 41.4] kg/m2) were included. One month post-RYGB, usual dietary intake of the studied micronutrients was significantly decreased compared to pre-RYGB, but gradually increased until 12 months post-RYGB, remaining below baseline values. By including micronutrient supplement intake, 12 months post-RYGB values were higher than baseline, except for zinc. Hemoglobin, ferritin, vitamin B12 and C-reactive protein serum concentrations were significantly decreased and transferrin saturation and mean corpuscular volume were significantly increased 12 months post-RYGB. Serum hepcidin concentration was significantly decreased 6 months post-RYGB. CONCLUSIONS: Medical nutritional therapy is essential following RYGB as dietary intake of iron, vitamin B12, vitamin C, copper and zinc was markedly decreased postoperatively and some patients still had an inadequate total intake one year post-RYGB.

Drug disposition before and after gastric bypass: fenofibrate and posaconazole.

AIMS: Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate (bile salt-dependent solubility) and posaconazole (gastric pH-dependent dissolution) - before and after RYGB in the same individuals. METHODS: A single-dose pharmacokinetic study with two model compounds - namely, 67 mg fenofibrate (Lipanthyl®) and 400 mg posaconazole (Noxafil®) - was performed in 12 volunteers pre- and post-RYGB. After oral administration, blood samples were collected at different time points up to 48 h after administration. Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration-time curve up to 48 h (AUC0-48 h ), the peak plasma concentration (Cmax) and the time to reach peak concentration (Tmax ). RESULTS: After administration of fenofibrate, no relevant differences in AUC0-48 h , Cmax and Tmax between the pre- and postoperative setting were observed. The geometric mean of the ratio of AUC0-48 h post/pre-RYGB for fenofibrate was 1.10 [95% confidence interval (CI) 0.87, 1.40; P = 0.40]. For posaconazole, an important decrease in AUC0-48 h and Cmax following RYGB was shown; the geometric mean of the AUC0-48 h post/pre-RYGB ratio was 0.68 (95% CI 0.48, 0.96; P = 0.03) and the geometric mean of the Cmax pre/post-RYGB ratio was 0.60 (95% CI 0.39, 0.94; P = 0.03). The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB. No difference for Tmax was observed. CONCLUSIONS: The disposition of fenofibrate was not altered after RYGB, whereas the oral disposition of posaconazole was significantly decreased following RYGB.

Barriers in the Approach of Obese Patients Undergoing Bariatric Surgery in Flemish Hospitals.

BACKGROUND: Bariatric surgery is associated not only with weight loss and improvement of comorbidities of obesity but also with short and long-term complications. Preoperative screening and lifelong follow-up of these patients are important to optimize the effect of bariatric surgery and minimize complications. The objective of this study was to create an inventory of the current care offered to bariatric patients before and after surgery in Flemish hospitals, Belgium and to identify barriers for optimal care. METHODS: Semi-structured interviews with healthcare professionals involved in screening and follow-up of bariatric patients in 12 hospitals in Flanders, Belgium were performed. Interviews were transcribed verbatim and analyzed with NVivo 10.0. RESULTS: In each participating hospital, except one, biochemical screening before and after bariatric surgery was performed, but the extent and timing varied between hospitals. In ten hospitals, a standard multivitamin preparation was started in all patients after surgery, but there was a large variation for timing of initiation and duration between hospitals. The interviewees indicated that the knowledge about appropriate dosage and formulation adjustments after surgery was limited. Most of the performed drug adjustments were due to improvement of comorbidities. In 9 out of 12 hospitals, a multidisciplinary team was involved, but the approach varied widely. Only in 3 out of 12 hospitals, eligibility of patients for bariatric surgery was discussed in team meetings. CONCLUSIONS: Strategies to implement existing guidelines are required in order to obtain more uniform, interdisciplinary support for bariatric patients, resulting in an increase of efficiency of surgery and improved patient care.

Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations.

AIMS: The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB. METHODS: A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6-8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB. RESULTS: After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC(0-24 h)) was shown, although a tendency towards an increased oral exposure could be observed as the AUC(0-24 h) was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled-release formulation, respectively. This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity. CONCLUSIONS: The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation.

Medication cost is significantly reduced after Roux-en-Y gastric bypass in obese patients.

BACKGROUND: This study aims to determine the influence of Roux-en-Y gastric bypass (RYGB) on medication-related costs. METHODS: The study analyzed the types, dosages, and costs of drugs and medical devices prescribed before and after surgery (1, 3, 6, and 12 months and yearly thereafter) in patients who underwent RYGB between June 2004 and May 2010 and had an outpatient visit between December 2009 and May 2010 at Pitié-Salpêtrière University Hospital, Paris, France. RESULTS: The cohort included 143 patients (78 % female; mean age, 42.9 years; mean BMI, 48.6 kg/m(2)). Total prescription costs were significantly lower (-32 %, p < 0.001) 1 year after RYGB compared with preoperative costs. However, the cost for medications to prevent RYGB side effects (in particular nutritional deficiencies) displayed a 36-fold increase in the first month postsurgery, but then decreased progressively over time. Importantly, the cost related to the treatment of the two most frequent obesity-related diseases significantly decreased 1 year after surgery. Indeed, prescription costs for treatment of type 2 diabetes (T2D) and obstructive sleep apnea (OSA) (namely CPAP therapy considered as the gold standard treatment) were reduced 1 year after surgery by 85 and by 63 % (both p < 0.001), respectively. We also observed a trend toward a decrease in the prescription costs of other obesity-related diseases, although it did not reach significance in our cohort. CONCLUSIONS: Considering medication to treat both obesity-related diseases and prevention of secondary effects of bariatric surgery, we observed that overall postoperative medication costs were significantly reduced one year after surgery, especially for T2D and OSA.

Iron deficiency after Roux-en-Y gastric bypass: insufficient iron absorption from oral iron supplements.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) may reduce the absorption of iron, but the extent to which this absorption is impeded is largely unknown. First, we determined the prevalence of iron deficiency following RYGB and explored the risk factors for its development. Second, we examined to what extent oral iron supplements are absorbed after RYGB. METHODS: Monocentric retrospective study in 164 patients (123 females, 41 males; mean age 43 years) who underwent RYGB between January 2006 and November 2010 was done. Pre- and postoperative data on gender, age, BMI, serum levels of iron, ferritin, hemoglobin, vitamin B12, 25-hydroxy vitamin D, and use of proton pump inhibitors and H2 antagonists were collected. Generalized linear mixed models were used for the analysis of the data. In 23 patients who developed iron deficiency after surgery, an oral challenge test with 100 mg FeSO4 · 7H2O was performed. RESULTS: Following RYGB, 52 (42.3 %) female patients and 9 male (22.0 %) patients developed iron deficiency (serum ferritin concentration ≤ 20 µg/L). The prevalence of iron deficiency was significantly higher in females than males (p = 0.0170). Young age (p = 0.0120), poor preoperative iron status (p = 0.0004), vitamin B12 deficiency (p = 0.0009), and increasing time after surgery (p < 0.0001) were also associated with iron deficiency. In the oral iron challenge test, only one patient out of 23 showed sufficient iron absorption. CONCLUSIONS: Iron deficiency is extremely frequent after RYGB and is linked with different risk factors. Iron supplementation seems essential, but the effect of oral tablets may be limited as absorption of oral iron supplements is insufficient post-RYGB.