Mid-arm muscle circumference cutoff points in patients with cirrhosis: Low muscle mass related to malnutrition predicts mortality.

OBJECTIVES: Muscle loss is one of the phenotypic criteria of malnutrition, is highly prevalent in patients with cirrhosis, and is associated with adverse outcomes. Mid-arm muscle circumference (MAMC) estimates the skeletal muscle mass and is especially helpful in cases of fluid overload. This study aimed to propose MAMC cutoff points for patients with cirrhosis and demonstrate its association with 1-year mortality. METHODS: This is an analysis of cohort databases from five reference centers in Brazil that included inpatients and outpatients with cirrhosis aged ≥18 y. The nutritional variables obtained were the MAMC (n = 1075) and the subjective global assessment (n = 629). We established the MAMC cutoff points stratified by sex based on the subjective global assessment as a reference standard for malnutrition diagnosis, considering the sensitivity, specificity, and Youden index. An adjusted Cox regression model was used to test the association of MAMC cutoff points and 1-year mortality. RESULTS: We included 1075 patients with cirrhosis, with a mean age of 54.8 ± 11.3 y; 70.4% (n = 757) male. Most patients had alcoholic cirrhosis (47.1%, n = 506) and were classified as Child-Pugh B (44.7%, n = 480). The MAMC cutoff points for moderate and severe depletion were ≤21.5 cm and ≤24.2 cm; ≤20.9 cm and ≤22.9 cm for women and men, respectively. According to these cutoff points, 13.8% (n = 148) and 35.1% (n = 377) of the patients had moderate or severe MAMC depletion, respectively. The 1-year mortality rate was 17.3% (n = 186). In the multivariate analysis adjusted for sex, age, MELD-Na, and Child-Pugh scores, a severe depletion in MAMC was an independent increased risk factor for 1-year mortality (HR: 1.71, 95% CI: 1.24-2.35, P < 0.001). Each increase of 1 cm in MAMC values was associated with an 11% reduction in 1-year mortality risk (HR: 0.89, 95% CI: 0.85-0.94, P < 0.001). CONCLUSIONS: Low MAMC classified according to the new cutoff points predicts mortality risk in patients with cirrhosis and could be used in clinical practice.

High Prevalence of Energy and Nutrients Inadequacy among Brazilian Older Adults.

Poor nutrition increases the risk of diseases and adverse health outcomes in older adults. We evaluated the potential inadequacy of nutrient intake among older adults in Brazil and its association with body anthropometry and composition outcomes. Dietary intake was obtained from 295 community-living older adults (>60 years old), of both genders, using a seven-day food record. Nutrient inadequacy was further identified based on the Dietary Reference Intakes and European Guidelines. Skeletal muscle mass (SM), strength and performance, and the diagnosis of sarcopenia were assessed using reference methods. Nutritional inadequacy was high, with energy, dietary fiber, and six micronutrients exhibiting the greatest inadequacy levels (>80%). Energy intake was correlated with SM strength (p = 0.000) and performance (p = 0.001). Inadequate energy, fiber, and protein intakes influenced BMI, while inadequate intake of vitamin B6 directly affected the diagnosis of sarcopenia (p ≤ 0.005). Further research is required to investigate whether these inadequacies can be associated with other clinical health outcomes.

New anthropometric and biochemical models for estimating appendicular skeletal muscle mass in male patients with cirrhosis.

OBJECTIVES: The use of easily accessible methods to estimate skeletal muscle mass (SMM) in patients with cirrhosis is often limited by the presence of edema and ascites, precluding a reliable diagnosis of sarcopenia. The aim of this study was to design predictive models using variables derived from anthropometric and/or biochemical measures to estimate SMM; and to validate their applicability in diagnosing sarcopenia in patients with cirrhosis. METHODS: Anthropometric and biochemical data were obtained from 124 male patients (18-76 y of age) with cirrhosis who also underwent dual-energy x-ray absorptiometry (DXA) and handgrip strength (HGS) assessments to identify low SMM and diagnose sarcopenia using reference cutoff values. Univariate analyses for variable selection were applied to generate predictive decision tree models for low SMM. Model accuracy for the prediction of low SMM and sarcopenia (when associated with HGS) was tested by comparison with reference cutoff values (appendicular SMM index, obtained by DXA) and clinical sarcopenia diagnoses. The prognostic value of the models for the prediction of sarcopenia and mortality at 104 wk of follow up was further tested using Kaplan-Meier graphics and Cox models. RESULTS: The models with anthropometric variables, alone and combined with biochemical variables, showed good accuracy (0.89 [0.83; 0.94] and 0.90 [0.84; 0.95], respectively) and sensitivity (0.72 [0.56; 0.85] and 0.74 [0.59; 0.86], respectively) and excellent specificity (0.96 [0.90; 0.99] and 0.97 [0.92; 0.99], respectively) in predicting SMM. Both models showed excellent accuracy (0.94 [0.89; 0.98], good sensitivity (0.68 [0.45; 0.86]), and excellent specificity (1.00 [0.96; 1.00]) in predicting sarcopenia. The models predicted mortality in patients with sarcopenia, with the likelihood of death sixfold greater relative to patients not predicted to have sarcopenia. CONCLUSIONS: Our simple and inexpensive models provided a practical and safe approach to diagnosing sarcopenia patients with cirrhosis along with an estimate of their mortality risk when other reference methods are unavailable.

Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission.

OBJECTIVES: Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr METHODS: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. RESULTS: Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. CONCLUSIONS: RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.

Gut Microbiota Profile of Obese Diabetic Women Submitted to Roux-en-Y Gastric Bypass and Its Association with Food Intake and Postoperative Diabetes Remission.

Gut microbiota composition is influenced by environmental factors and has been shown to impact body metabolism. OBJECTIVE: To assess the gut microbiota profile before and after Roux-en-Y gastric bypass (RYGB) and the correlation with food intake and postoperative type 2 diabetes remission (T2Dr). DESIGN: Gut microbiota profile from obese diabetic women was evaluated before (n = 25) and 3 (n = 20) and 12 months (n = 14) after RYGB, using MiSeq Illumina-based V4 bacterial 16S rRNA gene profiling. Data on food intake (7-day record) and T2Dr (American Diabetes Association (ADA) criteria) were recorded. RESULTS: Preoperatively, the abundance of five bacteria genera differed between patients with (57%) and without T2Dr (p < 0.050). Preoperative gut bacteria genus signature was able to predict the T2Dr status with 0.94 accuracy ROC curve (receiver operating characteristic curve). Postoperatively (vs. preoperative), the relative abundance of some gut bacteria genera changed, the gut microbial richness increased, and the Firmicutes to Bacteroidetes ratio (rFB) decreased (p < 0.05) regardless of T2Dr. Richness levels was correlated with dietary profile pre and postoperatively, mainly displaying positive and inverse correlations with fiber and lipid intakes, respectively (p < 0.05). CONCLUSIONS: Gut microbiota profile was influenced by RYGB and correlated with diet and T2Dr preoperatively, suggesting the possibility to assess its composition to predict postoperative T2Dr.

Phase angle as a marker for sarcopenia in cirrhosis.

BACKGROUND: In patients with cirrhosis nutritional disturbances can progress to sarcopenia, worsening the disease prognosis. Phase angle (PA) may be a useful marker for sarcopenia in this clinical population reflecting the cellular integrity level. This cross-sectional and prospective study evaluated the association between low PA values and clinical/nutritional variables in cirrhosis with emphasis on sarcopenia. METHODS: Male patients with cirrhosis (n = 122) were grouped according their PA values (>4.9° or ≤ 4.9°) after performing electrical bioimpedance. Sarcopenia diagnosis was assessed by considering appendicular skeletal muscle mass indexes <7.0 kg/m2 (dual-energy X-ray absorptiometry) and non-dominant handgrip strength (HGS) < 27 kg (dynamometry). Logistic regression model was used to examine the correlation between clinical/nutritional variables and PA values and the ROC curve area was calculated to identify the power of PA values in predicting sarcopenia. RESULTS: Sarcopenic patients presented lower HGS (19.57 vs. 30.55, p = 0.000), PA value (4.18 vs. 5.39, p = 0.005), SM (17.17 vs. 22.00 (p = 0.05), reactance (36.76 vs. 51.11, p = 0.023), and albumin (3.10 vs. 3.75, p = 0.037), as well as higher resistance values (512.56 vs. 457.01, p = 0.021) and CRP levels (7.89 vs. 3.53, p = 0.040) than non-sarcopenic patients. Furthermore, the PA values ≤ 5.05° were able to predict with high sensitivity the diagnosis of sarcopenia in the studied population. CONCLUSION: In male patients with cirrhosis, low PA values may reflect disease prognosis by correlating to sarcopenia among other clinical/nutritional changes and performed as a good marker for this main nutritional complication when ≤5.05°.

Reduced intestinal FADS1 gene expression and plasma omega-3 fatty acids following Roux-en-Y gastric bypass.

BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) limits food ingestion and may alter the intestinal expression of genes involved in the endogenous synthesis of polyunsaturated fatty acids (PUFAs). These changes may decrease the systemic availability of bioactive PUFAs after RYGB. To study the impact of RYGB on the dietary ingestion and plasma concentration of PUFAs and on the intestinal expression of genes involved in their endogenous biosynthesis in severely obese women with type 2 diabetes. METHODS: Before, and 3 and 12 months after RYGB, obese women (n = 20) self-reported a seven-day dietary record, answered a food frequency query and provided plasma samples for alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acid assessment by gas chromatography. Intestinal biopsies (duodenum, jejunum and ileum) were collected through double-balloon endoscopy before and 3 months after RYGB for gene expression analysis by microarray (Human GeneChip 1.0 ST array) and RT-qPCR validation. RESULTS: Compared to the preoperative period, patients had decreased intakes of PUFAs, fish and soybean oil (p < 0.05) and lower plasma concentrations of ALA and EPA (p < 0.001) 3 and 12 months after RYGB. FADS1 gene expression was lower in duodenum (RT-qPCR fold change = -1.620, p < 0.05) and jejunum (RT-qPCR fold change = -1.549, p < 0.05) 3 months following RYGB, compared to before surgery. CONCLUSION: RYGB decreased PUFA ingestion, plasma ALA and EPA levels, and intestinal expression of FADS1 gene. The latter encodes a key enzyme involved in endogenous biosynthesis of PUFAs. These data suggest that supplementation of omega-3 PUFAs may be required for obese patients undergoing RYGB. Clinical Trial Registry number and website: www.clinicaltrials.gov - NCT01251016; Plataforma Brasil - 19339913.0.0000.0068.

A new anthropometric index for body fat estimation in patients with severe obesity.

BACKGROUND: Body mass index (BMI) has been used to assess body adiposity, but it cannot adequately reflect body fat (BF) amount. The body adiposity index (BAI) has been shown a better performance than BMI for this purpose, but it can be inaccurate to estimate BF under extreme amounts of fat. Here, we propose a new anthropometric index, the Belarmino-Waitzberg (BeW) index, for specific estimation of BF in severely obese patients. METHODS: In 144 adult patients with severe obesity, BF was estimated by air displacement plethysmography (ADP), as the reference method, along with the follow anthropometric measurements: height, abdominal circumference (AC), hip circumference (HC), weight, BMI (weight/ height2) and BAI ([HC(cm) / height (m)1.5) - 18] × 100). Patients were proportionately distributed into two distinct databases, the building model database (BMD) and the validation model database (VMD), which were applied to develop and validate the BeW index, respectively. The BeW index was tested for gender and ethnicity adjustment as independent variables. The agreement of BF% values obtained by the new index and by BAI with ADP was also assessed. RESULTS: The BF% was 52.05 ± 5.42 for ADP and 59.11 ± 5.95 for the BeW index (all results are expressed as the mean ± standard deviation). A positive Pearson correlation (r = 0.74), a good accuracy (Cb = 0.94), and a positive Lin's concordance correlation (CCC = 0.70) were observed between the two groups. The 95% limits of individual agreement between the BeW index and ADP were 6.8 to 7.9%, compared to - 7.5 to 14.8% between the BAI and ADP. The new index, called the Belarmino-Waitzberg (BeW) index, showed an improvement of 2.1% for the R2 value and a significant gender effect, therefore resulting in two different indexes for females and males, as follows: Female BeW = - 48.8 + 0.087 × AC(cm) + 1.147 × HC(cm) - 0.003 × HC(cm)2 and Male BeW = - 48.8 + 0.087 × AC(cm) + 1.147 × HC(cm) - 0.003 × HC(cm)2-7.195. CONCLUSIONS: The new BeW index showed a good performance for BF estimation in patients with severe obesity and can be superior to the BAI for this purpose.

Diagnosing Sarcopenia in Male Patients With Cirrhosis by Dual-Energy X-Ray Absorptiometry Estimates of Appendicular Skeletal Muscle Mass.

BACKGROUND: Ascites in cirrhotic patients interfere with accurate assessment of skeletal muscle when diagnosing sarcopenia. We hypothesized measurement of appendicular skeletal muscle index (ASMI) with dual-energy x-ray absorptiometry (DXA) improves the diagnosis of sarcopenia in cirrhotic patients as ASMI does not include the fluid-filled abdominal compartment. OBJECTIVE: To evaluate if ASMI is influenced by ascites, lower limb edema (LLE) and predicts mortality alone or combined with handgrip strength (HGS) in cirrhotic patients. DESIGN: ASMI, HGS, and 36-month mortality were obtained in 144 men with cirrhosis. ASMI was compared before and after paracentesis in 20 men with ascites and to results from 20 matched controls. The prognostic value of ASMI alone and with HGS was tested in a survival. Survival probabilities were obtained for sarcopenia diagnosed by standard ASMI and HGS European Working Group on Sarcopenia in Older People (EWGSOP) cutoffs and a new cutoff calculated from our ASMI + HGS tertiles. RESULTS: ASMI did not change after paracentesis, was lower in patients than in controls (P < .001), and was not influenced by LLE (D = 0.30 kg/m2, P = .068; R2 = 2.40%). Mortality was influenced by ASMI and HGS (Pinteraction = 0.028). Sarcopenia diagnosed by EWGSOP was also diagnosed by our new cutoff; both predicted mortality with the latter more sensitive for mortality risk prediction (P = .011). CONCLUSIONS: DXA-measured ASMI is not influenced by ascites or LLE in cirrhotic patients; can diagnose low skeletal muscle/sarcopenia; and predicts mortality, particularly when combined with HGS.

Phase angle obtained by bioelectrical impedance analysis independently predicts mortality in patients with cirrhosis.

AIM: To evaluate the prognostic value of the phase angle (PA) obtained from bioelectrical impedance analysis (BIA) for mortality prediction in patients with cirrhosis. METHODS: In total, 134 male cirrhotic patients prospectively completed clinical evaluations and nutritional assessment by BIA to obtain PAs during a 36-mo follow-up period. Mortality risk was analyzed by applying the PA cutoff point recently proposed as a malnutrition marker (PA ≤ 4.9°) in Kaplan-Meier curves and multivariate Cox regression models. RESULTS: The patients were divided into two groups according to the PA cutoff value (PA > 4.9°, n = 73; PA ≤ 4.9°, n = 61). Weight, height, and body mass index were similar in both groups, but patients with PAs > 4.9° were younger and had higher mid-arm muscle circumference, albumin, and handgrip-strength values and lower severe ascites and encephalopathy incidences, interleukin (IL)-6/IL-10 ratios and C-reactive protein levels than did patients with PAs ≤ 4.9° (P ≤ 0.05). Forty-eight (35.80%) patients died due to cirrhosis, with a median of 18 mo (interquartile range, 3.3-25.6 mo) follow-up until death. Thirty-one (64.60%) of these patients were from the PA ≤ 4.9° group. PA ≤ 4.9° significantly and independently affected the mortality model adjusted for Model for End-Stage Liver Disease score and age (hazard ratio = 2.05, 95%CI: 1.11-3.77, P = 0.021). In addition, Kaplan-Meier curves showed that patients with PAs ≤ 4.9° were significantly more likely to die. CONCLUSION: In male patients with cirrhosis, the PA ≤ 4.9° cutoff was associated independently with mortality and identified patients with worse metabolic, nutritional, and disease progression profiles. The PA may be a useful and reliable bedside tool to evaluate prognosis in cirrhosis.

Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass.

OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9±6.2 years; body mass index, 46.5±5.3 kg/m2) with adult-onset type 2 diabetes (fasting plasma glucose ≥126 mg/dl; hemoglobin A1c≥6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P≤0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P≤0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.

The SURMetaGIT study: Design and rationale for a prospective pan-omics examination of the gastrointestinal response to Roux-en-Y gastric bypass surgery.

Objective To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study's design and challenges faced in its application are detailed. Methods This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission. Results Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation. Conclusion The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.

Body adiposity index performance in estimating body fat in a sample of severely obese Brazilian patients.

BACKGROUND/OBJECTIVES: The body adiposity index (BAI) estimates the amount of body fat (BF) in humans. In Mexican-American and African-American populations, BAI has performed better than body mass index (BMI). The aim of this study was to evaluate the performance of BAI in estimating percentage (BF%) in severely obese Brazilian patients, with air displacement plethysmography (ADP) used as the reference method. SUBJECTS/METHODS: Estimation of BF% by ADP, anthropometric measurements (height, abdominal and hip circumferences, body weight, and BMI) and BAI calculation were performed in 72 obese subjects (BMI ≥ 30 kg/m(2)) aged 30-55 years. RESULTS: The mean BF% estimates ± standard deviation were 52.1 ± 5.7 % for ADP and 47.7 ± 7.4% for BAI, with a positive Pearson correlation (rp = 0.66) and a positive Lin's concordance correlation (rc = 0.479) observed between these methods. The 95% limits of individual agreement between BAI and ADP ranged from -5.769% to 16.036%, with BAI exhibiting an average positive bias of 5.13% compared to the reference method. For each studied variable, BAI exhibited a systematic bias, as evidenced by a tendency for low BF% values to be overestimated. CONCLUSION: For Brazilian patients with severe obesity, BAI does not provide an accurate estimate of BF%.