Medication use before and after bariatric surgery: 5-year results from a randomised controlled trial of banded Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with obesity and type 2 diabetes.

AIM: Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. METHODS: This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. RESULTS: After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. CONCLUSION: Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.

Pacific Islands Families Study: Household Food Security during Pregnancy and Secondary School Educational Achievement.

Nutritional environment in early life is a key factor for brain development and function. It is important to understand the relationship between nutrition in early life and academic achievement in adolescence. The birth cohort of the Pacific Islands Families (PIF) study was born in the year 2000. When their child was six weeks old, mothers were asked questions concerning food security over the past year. Two binary measures of food security were derived as previously used in PIF and also by the Ministry of Health (MOH). In 2020, records of academic achievement from the National Certificate of Educational Achievement (NCEA) for 649 (317 female, 332 male) cohort members showed progressive achievement at levels 1, 2, and 3 of NCEA and allowed University Entrance (UE) to be assessed. The prevalence of food insecurity was not different for sex but high at 29% and 42% using the PIF and MOH definitions of food insecurity, respectively. More females (27%) than males (18%) achieved UE as their highest qualification, and more males (40%) than females (31%) achieved NCEA levels 1 or 2 as their highest qualification. UE was achieved by 25% of those born into food-secure households and 17% from food-insecure households. Logistic regression demonstrated that the odds of achieving UE were 1.8-fold (95% CI 1.2, 2.6, p = 0.003) higher in females than males and, independently, 1.6-fold (95% CI 1.1, 2.5 p = 0.026) higher if the household was food secure. This work emphasises the importance of maternal and early-life food security for subsequent academic achievement and the well-being of future generations.

Metformin in Gestational Diabetes The Offspring Follow Up (MiGTOFU): Associations between maternal characteristics and size and adiposity of boys and girls at nine years.

Data from 98 women recruited in the Metformin in Gestational Diabetes trial and dual-energy X-ray absorptiometry studies of their children at nine years were analysed to investigate associations between maternal measures during pregnancy and their children's size and adiposity. Mothers of boys (n = 56) and girls (n = 42) had been randomised to metformin or insulin treatment at 30.1 ± 2.8 and 29.3 ± 4.1 weeks gestation, respectively. In boys, fat-free mass indexed to height squared was associated with maternal weight, body mass index, maternal glycaemia and metformin treatment. In boys and girls, fat mass indexed to height squared was associated with maternal glycaemia measures before gestational diabetes treatment.

Magnetic resonance study of visceral, subcutaneous, liver and pancreas fat changes after 12 weeks intermittent fasting in obese participants with prediabetes.

BACKGROUND: It is not clear whether there are differences in proportions of fat loss from visceral:subcutaneous depots by probiotic supplementation, ethnicity or sex during weight loss; or whether visceral/pancreatic fat depot changes are related to changes in HbA1c. Our objective is to investigate whether weight loss from different fat depots is related to these factors during weight loss achieved by intermittent fasting. METHOD: Prediabetes participants on 5:2 intermittent fasting were randomized 1:1 to either daily probiotic or placebo for 12 weeks. Twenty-four patients had magnetic resonance imaging data at baseline and 12 weeks. RESULTS: After 12 weeks of intermittent fasting, subcutaneous fat (%) changed from 35.9 ± 3.1 to 34.4 ± 3.2, visceral fat (%) from 15.8 ± 1.3 to 14.8 ± 1.2, liver fat (%) from 8.7 ± 0.8 to 7.5 ± 0.7 and pancreatic fat (%) from 7.7 ± 0.5 to 6.5 ± 0.5 (all p < 0.001). Changes in weight, HbA1c, SAT, VAT, LF and PF did not differ significantly between probiotic and placebo groups. CONCLUSION: Overall weight loss was correlated with fat loss from subcutaneous depots. Losses from different fat depots did not correlate with changes in HbA1c or differ by probiotic supplementation, ethnicity or sex.

Seven-Year Results of a Randomized Trial Comparing Banded Roux-en-Y Gastric Bypass to Sleeve Gastrectomy for Type 2 Diabetes and Weight Loss.

INTRODUCTION: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are common bariatric procedures that are effective in treating type 2 diabetes (T2D) in patients with obesity. Limited data from randomized trials are available comparing longevity of diabetes remission directly between the two procedures beyond 5 years. METHODS: A prospective, randomized, parallel, two-arm, clinical trial comparing the outcomes of silastic ring (SR)-LRYGB versus LSG was conducted at a single (Auckland, New Zealand) center. Patients and researchers were blinded until the 5-year mark and follow-up after this was unblinded. Eligible patients had T2D of > 6 months duration with a BMI 35--65 kg/m2 and were aged 20-55 years. Randomization was 1:1 to SR-LRYGB and LSG following induction of anesthesia and was stratified by age group, BMI group, ethnicity, diabetes duration, and insulin therapy. The primary outcome was T2D remission, defined as HbA1c < 6% (42 mmol/mol), without the use of glucose-lowering medications. RESULTS: A total of 114 patients were randomized of whom 6 died before the 7-year follow-up (2 SR-LRYGB, 4 LSG). Diabetes remission, assessed in 89 (82.4%) of the remaining patients, was seen in 23/50 (46.0%) after SR-LRYGB and 12/39 (30.8%) after LSG (adjusted OR 4.64, 95% CI 1.39, 15.52, p = 0.013). Percentage total body weight loss was greater after SR-LRYGB than LSG (26.2% vs 13.4%; absolute difference 12.8%; 95% CI 7.2%, 18.2%; p < 0.001). Complication rates were similar between groups. CONCLUSION: SR-LRYGB was superior to LSG for diabetes remission and weight loss at 7 years following surgery, with acceptable complication rates.

Bariatric Surgery and Psychological Health: A Randomised Clinical Trial in Patients with Obesity and Type 2 Diabetes.

PURPOSE: This study investigated the impact of either Roux-en-Y gastric bypass with silastic ring (SR-RYGB) or sleeve gastrectomy (SG) types of bariatric surgery on psychological health and explored the role of pre-existing depressive symptoms on weight loss. MATERIALS AND METHODS: A total of 114 participants with obesity and type 2 diabetes were randomized to receive SR-RYGB or SG at a single centre. Data from the Hospital Anxiety and Depression Scale (HADS), RAND 36-item Health Survey and body weight were collected before surgery and annually for 5 years. RESULTS: Sixteen patients were lost to follow-up at 5 years. Of the 98 patients who completed 5-year psychological follow-up assessments, 13 had mild to severe depressive symptoms (SR-RYGB n = 6, SG n = 7). SR-RYGB and SG resulted in similar psychological health improvement but percent weight loss at 5 years was greater for SR-RYGB by 10.6% (95% CI: 7.2 to 14.0, P < 0.0001). Scores for depressive symptoms and most RAND-36 domains improved significantly from baseline to 5 years in both groups. Patients with pre-existing depressive symptoms had similar percent weight loss at 5 years compared to patients without depressive symptoms, irrespective of procedural type. CONCLUSION: Patients receiving either SR-RYGB or SG had comparable psychosocial functioning, which was maintained to 5 years post-surgery. Pre-existing depressive symptoms did not affect weight loss achieved at 5 years. These findings confirm previous longitudinal studies demonstrating that bariatric surgery is generally associated with improved psychosocial functioning.

Exploring the relationship between pancreatic fat and insulin secretion in overweight or obese women without type 2 diabetes mellitus: A preliminary investigation of the TOFI_Asia cohort.

OBJECTIVE: While there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects ß-cell function and insulin secretion in women with overweight or obesity but without T2DM. METHODS: 20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups. RESULTS: No ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p<0.0001), insulin (p<0.0001) and ISR (p = 0.02) increased significantly from baseline in both high and low PPF groups but did not differ between the two groups at any given time during the test (PPF x time, p > 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05). CONCLUSION: In women with overweight or obesity but without T2DM, PPF did not modify ß-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation.

An Adapted Deep Convolutional Neural Network for Automatic Measurement of Pancreatic Fat and Pancreatic Volume in Clinical Multi-Protocol Magnetic Resonance Images: A Retrospective Study with Multi-Ethnic External Validation.

Pancreatic volume and fat fraction are critical prognoses for metabolic diseases like type 2 diabetes (T2D). Magnetic Resonance Imaging (MRI) is a required non-invasive quantification method for the pancreatic fat fraction. The dramatic development of deep learning has enabled the automatic measurement of MR images. Therefore, based on MRI, we intend to develop a deep convolutional neural network (DCNN) that can accurately segment and measure pancreatic volume and fat fraction. This retrospective study involved abdominal MR images from 148 diabetic patients and 246 healthy normoglycemic participants. We randomly separated them into training and testing sets according to the proportion of 80:20. There were 2364 recognizable pancreas images labeled and pre-treated by an upgraded superpixel algorithm for a discernible pancreatic boundary. We then applied them to the novel DCNN model, mimicking the most accurate and latest manual pancreatic segmentation process. Fat phantom and erosion algorithms were employed to increase the accuracy. The results were evaluated by dice similarity coefficient (DSC). External validation datasets included 240 MR images from 10 additional patients. We assessed the pancreas and pancreatic fat volume using the DCNN and compared them with those of specialists. This DCNN employed the cutting-edge idea of manual pancreas segmentation and achieved the highest DSC (91.2%) compared with any reported models. It is the first framework to measure intra-pancreatic fat volume and fat deposition. Performance validation reflected by regression R2 value between manual operation and trained DCNN segmentation on the pancreas and pancreatic fat volume were 0.9764 and 0.9675, respectively. The performance of the novel DCNN enables accurate pancreas segmentation, pancreatic fat volume, fraction measurement, and calculation. It achieves the same segmentation level of experts. With further training, it may well surpass any expert and provide accurate measurements, which may have significant clinical relevance.

Gains in body mass and body water in pregnancy and relationships to birth weight of offspring in rural and urban Pune, India.

Maternal size, weight gain in pregnancy, fetal gender, environment and gestational age are known determinants of birth weight. It is not clear which component of maternal weight or gained weight during pregnancy influences birth weight. We evaluated the association of maternal total body water measured by the deuterium dilution technique (TBW-D2O) at 17 and 34 weeks of gestation with birth weight. A secondary aim was to examine the utility of bioimpedance spectroscopy (BIS) to determine total body water (TBW-BIS) in pregnancy. At 17 and 34 weeks of pregnancy, ninety-nine women (fifty-one rural and forty-eight urban) from Pune, India had measurements of body weight, TBW-D2O, TBW-BIS and offspring birth weight. At 17 weeks of gestation, average weights for rural and urban women were 45⋅5 ± 4⋅8 (sd) and 50⋅7 ± 7⋅8 kg (P < 0⋅0001), respectively. Maternal weight gains over the subsequent 17 weeks for rural and urban women were 6⋅0 ± 2⋅2 and 7⋅5 ± 2⋅8 kg (P = 0⋅003) and water gains were 4⋅0 ± 2⋅4 and 4⋅8 ± 2⋅8 kg (P = 0⋅092), respectively. In both rural and urban women, birth weight was positively, and independently, associated with gestation and parity. Only for rural women, between 17 and 34 weeks, was an increase in dry mass (weight minus TBW-D2O) or a decrease in TBW-D2O as a percentage of total weight associated with a higher birth weight. At both 17 and 34 weeks, TBW-BIS increasingly underestimated TBW-D2O as the water space increased. Differences in body composition during pregnancy between rural and urban environments and possible impacts of nutrition transition on maternal body composition and fetal growth were demonstrated.

Identifying metabolic syndrome in migrant Asian Indian adults with anthropometric and visceral fat action points.

BACKGROUND: Metabolic syndrome (MetS) is a clustering of metabolic risk factors, including large waist circumference (WC). Other anthropometric parameters and visceral fat mass (VFM) predicted from these may improve MetS detection. Our aim was to assess the ability of such parameters to predict this clustering in a cross-sectional, diagnostic study. METHOD: Participants were 82 males and 86 females, aged 20-74 years, of Asian Indian ethnicity. VFM was estimated by dual-energy X-ray absorptiometry (DXA) through identification of abdominal subcutaneous fat layer boundaries. Non-anthropometric metabolic risk factors (triglycerides, HDL cholesterol, blood pressure and glucose) were defined using MetS criteria. We estimated the ability of anthropometry and VFM to detect ≥ 2 of these factors by receiver operating characteristic (ROC) and precision-recall curves. RESULTS: Two or more non-anthropometric metabolic risk factors were present in 45 (55%) males and 29 (34%) females. The area under the ROC curve (AUC) to predict ≥ 2 of these factors using WC was 0.67 (95% confidence interval: 0.55-0.79) in males and 0.65 (0.53-0.77) in females. Optimal WC cut-points were 92 cm for males (63% accuracy) and 79 cm for females (53% accuracy). VFM, DXA-measured sagittal diameter and suprailiac skinfold thickness yielded higher AUC point estimates (by up to 0.06), especially in females where these measures improved accuracy to 69%, 69% and 65%, respectively. Pairwise combinations that included WC further improved accuracy. CONCLUSION: Our findings indicate that cut-points for readily obtained measures other than WC, or in combination with WC, may provide improved detection of MetS risk factor clusters.

Effect of Banded Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy on Diabetes Remission at 5 Years Among Patients With Obesity and Type 2 Diabetes: A Blinded Randomized Clinical Trial.

OBJECTIVE: To determine whether silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) or laparoscopic sleeve gastrectomy (LSG) produces superior diabetes remission at 5 years. RESEARCH DESIGN AND METHODS: In a single-center, double-blind trial, 114 adults with type 2 diabetes and BMI 35-65 kg/m2 were randomly assigned to SR-LRYGB or LSG (1:1; stratified by age-group, BMI group, ethnicity, diabetes duration, and insulin therapy) using a web-based service. Diabetes and other metabolic medications were adjusted according to a prespecified protocol. The primary outcome was diabetes remission assessed at 5 years, defined by HbA1c <6% (42 mmol/mol) without glucose-lowering medications. Secondary outcomes included changes in weight, cardiometabolic risk factors, quality of life, and adverse events. RESULTS: Diabetes remission after SR-LRYGB versus LSG occurred in 25 (47%) of 53 vs. 18 (33%) of 55 patients (adjusted odds ratios 4.5 [95% CI 1.6, 15.5; P = 0.009] and 4.2 [1.3, 13.4; P = 0.015] in the intention-to-treat analysis). Percent body weight loss was greater after SR-LRYGB than after LSG (absolute difference 10.7%; 95% CI 7.3, 14.0; P < 0.001). Improvements in cardiometabolic risk factors were similar, but HDL cholesterol increased more after SR-LRYGB. Early and late complications were similar in both groups. General health and physical functioning improved after both types of surgery, with greater improvement in physical functioning after SR-LRYGB. People of Maori or Pacific ethnicity (26%) had lower incidence of diabetes remission than those of New Zealand European or other ethnicities (2 of 25 vs. 41 of 83; P < 0.001). CONCLUSIONS: SR-LRYGB provided superior diabetes remission and weight loss compared with LSG at 5 years, with similar low risks of complications.

Brain temperature as an indicator of neuroinflammation induced by typhoid vaccine: Assessment using whole-brain magnetic resonance spectroscopy in a randomised crossover study.

Prior studies indicate a pathogenic role of neuroinflammation in psychiatric disorders; however, there are no accepted methods that can reliably measure low-level neuroinflammation non-invasively in these individuals. Magnetic resonance spectroscopic imaging (MRSI) is a versatile, non-invasive neuroimaging technique that demonstrates sensitivity to brain inflammation. MRSI in conjunction with echo-planar spectroscopic imaging (EPSI) measures brain metabolites to derive whole-brain and regional brain temperatures, which may increase in neuroinflammation. The validity of MRSI/EPSI for measurement of low level neuroinflammation was tested using a safe experimental model of human brain inflammation - intramuscular administration of typhoid vaccine. Twenty healthy volunteers participated in a double-blind, placebo-controlled crossover study including MRSI/EPSI scans before and 3 h after vaccine/placebo administration. Body temperature and mood, assessed using the Profile of Mood States, were measured every hour up to four hours post-treatment administration. A mixed model analysis of variance was used to test for treatment effects. A significant proportion of brain regions (44/47) increased in temperature post-vaccine compared to post-placebo (p < 0.0001). For temperature change in the brain as a whole, there was no significant treatment effect. Significant associations were seen between mood scores assessed at 4 h and whole brain and regional temperatures post-treatment. Findings indicate that regional brain temperature may be a more sensitive measure of low-level neuroinflammation than whole-brain temperature. Future work where these measurement techniques are applied to populations with psychiatric disorders would be of clinical interest.

Pancreas Fat, an Early Marker of Metabolic Risk? A Magnetic Resonance Study of Chinese and Caucasian Women: TOFI_Asia Study.

Objective: Prevalence of type 2 diabetes (T2D) is disproportionately higher in younger outwardly lean Asian Chinese compared to matched Caucasians. Susceptibility to T2D is hypothesised due to dysfunctional adipose tissue expansion resulting in adverse abdominal visceral and organ fat accumulation. Impact on early risk, particularly in individuals characterised by the thin-on-the-outside-fat-on-the-inside (TOFI) phenotype, is undetermined. Methods: Sixty-eight women [34 Chinese, 34 Caucasian; 18-70 years; body mass index (BMI), 20-45 kg/m2] from the TOFI_Asia study underwent magnetic resonance imaging and spectroscopy to quantify visceral, pancreas, and liver fat. Total body fat was (TBF) assessed by dual-energy x-ray absorptiometry, and fasting blood biomarkers were measured. Ethnic comparisons, conducted using two-sample tests and multivariate regressions adjusted for age, % TBF and ethnicity, identified relationships between abdominal ectopic fat depots with fasting plasma glucose (FPG), insulin resistance (HOMA2-IR), and related metabolic clinical risk markers in all, and within ethnic groups. Results: Despite being younger and of lower bodyweight, Chinese women in the cohort had similar BMI and % TBF compared to their Caucasian counterparts. Protective high-density lipoprotein cholesterol, total- and high-molecular weight adiponectin were significantly lower, while glucoregulatory glucagon-like peptide-1 and glucagon significantly higher, in Chinese. There were no ethnic differences between % pancreas fat and % liver fat. However, at low BMI, % pancreas and % liver fat were ∼1 and ∼2% higher in Chinese compared to Caucasian women. In all women, % pancreas and visceral adipose tissue had the strongest correlation with FPG, independent of age and % TBF. Percentage (%) pancreas fat and age positively contributed to variance in FPG, whereas % TBF, amylin and C-peptide contributed to IR which was 0.3 units higher in Chinese. Conclusion: Pancreas fat accumulation may be an early adverse event, in TOFI individuals, with peptides highlighting pancreatic dysfunction as drivers of T2D susceptibility. Follow-up is warranted to explore causality.

The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition.

OBJECTIVE: The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Maori and peoples of Polynesia), with a frequency of up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It remains unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. METHODS: We undertook body composition analysis using DXA in 189 young men of Maori and Pacific descent living in Aotearoa New Zealand. Further investigation was carried out in two orthologous Arg458Gln knockin mouse models on FVB/NJ and C57BL/6j backgrounds. RESULTS: The rs373863828 A allele was associated with lower fat mass when adjusted for BMI (p < 0.05) and was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p < 0.05). Supporting the human data, significant reductions in adipose tissue mass were observed in the knockin mice. This was more significant in older mice in both backgrounds and appeared to be the result of reduced age-associated increases in fat mass. The older male knockin mice on C57BL/6j background also had increased grip strength (p < 0.01) and lower levels of myostatin (p < 0.05). CONCLUSION: Overall, these results prove that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contribute to an age-dependent lowering of fat mass, at least in males.

Relationships between physical function, body composition and metabolic health in Pacific Island youth.

The Pacific Islands Families (PIF) study is a birth cohort study designed to increase knowledge about the growth and development of Pacific children living in Auckland, New Zealand. Adolescence is a critical time of growth and development, yet the roles of physical function and body composition in metabolic health at this life stage are not clear. We aimed to investigate associations between measures of physical function (the 6-minute-walk-test (6MWT)), heart rate changes before and after the 6MWT, handgrip strength, body composition including appendicular skeletal muscle mass (ASMM) measured by dual-energy X-ray absorptiometry and biomarkers of metabolic health from a fasting blood sample.A total of 200 youth (98 girls, 102 boys) aged 14-15 years, from the birth-cohort of children in the Pacific Islands families study were measured. In girls, the proportion of ASMM was lower and fat higher than in boys. Controlling for age, a 1% increase in ASMM predicted a longer walk distance (+6.3, 95%CI 2.2, 10.4 m in girls; +7.1, 95%CI 4.4, 9.1 m in boys) and lower heart rate following the 6MWT. ASMM and fat mass were independently predictive of maximal handgrip strength which was increased by 1.4 (1.0,1.8) kg in girls and 1.7 (1.3, 2.0) kg in boys for each kg increase in ASMM and reduced by 0.23 (0.08, 0.38) kg in girls and 0.26 (0.14, 0.37) kg in boys for each kg increase in fat mass. Lower total cholesterol and LDL were associated with an increase in distance walked in boys only. For each year of age, distance walked was reduced by 34 (15, 53) m in girls and 59 (36,84) m in boys. These findings should be explored further in the context of other influences such as food security, opportunities for physical activity and cultural expectations.

[ESPEN Practical Guideline: clinical nutrition in liver disease]. / Guía Práctica ESPEN: nutrición clínica en las enfermedades del hígado.

Introduction: Background: the Practical Guideline is based on the current scientific ESPEN guide on Clinical Nutrition in Liver Disease. Methods: it has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. Results: a total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. Disease-related recommendations are preceded by general recommendations on the diagnosis of nutritional status in liver patients and on liver complications associated with medical nutrition. Conclusion: this Practical Guideline gives guidance to health care providers involved in the management of liver disease on how to offer optimal nutritional care.

Introducción: Introducción: la Guía Práctica se basa en la actual guía científica de la ESPEN sobre nutrición clínica en las enfermedades hepáticas. Métodos: se ha reducido y transformado en diagramas de flujo para facilitar su uso en la práctica clínica. La guía está dedicada a todos los profesionales, incluidos médicos, dietistas, nutricionistas y enfermeras, que trabajan con pacientes con enfermedad hepática crónica. Resultados: la guía presenta un total de 103 pronunciamientos y recomendaciones con breves comentarios para el manejo nutricional y metabólico de pacientes con (i) insuficiencia hepática aguda grave, (ii) esteatohepatitis alcohólica, (iii) enfermedad hepática grasa no alcohólica, (iv) cirrosis hepática, y (v) cirugía o trasplante de hígado. Conclusión: las recomendaciones relacionadas con enfermedades están precedidas por recomendaciones generales sobre el diagnóstico del estado nutricional en los pacientes hepáticos y sobre las complicaciones hepáticas asociadas a la nutrición médica.

Predicted estimates of resting energy expenditure have limited clinical utility in patients with cirrhosis.

BACKGROUND & AIMS: Malnutrition is associated with adverse clinical outcomes in patients with cirrhosis. Accurate assessment of energy requirements is needed to optimize dietary intake. Resting energy expenditure (REE), the major component of total energy expenditure, can be measured using indirect calorimetry (mREE) or estimated using prediction equations (pREE). This study assessed the usefulness of predicted estimates of REE in this patient population. METHODS: Individual mREE data were available for 900 patients with cirrhosis (mean [±1 SD] age 55.7±11.6 years-old; 70% men; 52% south-east Asian) and 282 healthy controls (mean age 36.0±12.8 years-old; 52% men; 18% south-east Asian). Metabolic status was classified using thresholds based on the mean ± 1 SD of the mREE in the healthy controls. Comparisons were made between mREE and pREE estimates obtained using the Harris-Benedict, Mifflin, Schofield and Henry equations. Stepwise regression was used to build 3 new prediction models which included sex, ethnicity, body composition measures, and model for end-stage liver disease scores. RESULTS: The mean mREE was significantly higher in patients than controls when referenced to dry body weight (22.4±3.8 cf. 20.8±2.6 kcal/kg/24 hr; p <0.001); there were no significant sex differences. The mean mREE was significantly higher in Caucasian than Asian patients (23.1±4.4 cf. 21.7±2.9 kcal/kg/24 hr; p <0.001). Overall, 37.1% of Caucasian and 25.3% of Asian patients were classified as hypermetabolic. The differences between mREE and pREE were both statistically and clinically relevant; in the total patient population, pREE estimates ranged from 501 kcal/24 hr less to 548 kcal/24 hr more than the mREE. Newly derived prediction equations provided better estimates of mREE but still had limited clinical utility. CONCLUSIONS: Prediction equations do not provide useful estimates of REE in patients with cirrhosis. REE should be directly measured. LAY SUMMARY: People with cirrhosis are often malnourished and this has a detrimental effect on outcome. Provision of an adequate diet is very important and is best achieved by measuring daily energy requirements and adjusting dietary intake accordingly. Prediction equations, which use information on age, sex, weight, and height can be used to estimate energy requirements; however, the results they provide are not accurate enough for clinical use, particularly as they vary according to sex and ethnicity.

Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes.

Mitochondrial-derived peptides (MDPs) are encoded by the mitochondrial genome and hypothesised to form part of a retrograde signalling network that modulates adaptive responses to metabolic stress. To understand how metabolic stress regulates MDPs in humans we assessed the association between circulating MOTS-c and SHLP2 and components of metabolic syndrome (MS), as well as depot-specific fat mass in participants without overt type 2 diabetes or cardiovascular disease. One-hundred and twenty-five Chinese participants (91 male, 34 female) had anthropometry, whole body dual-energy X-ray absorptiometry scans and fasted blood samples analysed. Chinese female participants and an additional 34 European Caucasian female participants also underwent magnetic resonance imaging and spectroscopy (MRI/S) for visceral, pancreatic and liver fat quantification. In Chinese participants (age = 41 ± 1 years, BMI = 27.8 ± 3.9 kg/m2), plasma MOTS-c (315 ± 27 pg/ml) and SHLP2 (1393 ± 82 pg/ml) were elevated in those with MS (n = 26). While multiple components of the MS sequelae positively associated with both MOTS-c and SHLP2, including blood pressure, fasting plasma glucose and triglycerides, the most significant of these was waist circumference (p < 0.0001). Android fat had a greater effect on increasing plasma MOTS-c (p < 0.004) and SHLP2 (p < 0.009) relative to whole body fat. Associations with MRI/S parameters corrected for total body fat mass revealed that liver fat positively associated with plasma MOTS-c and SHLP2 and visceral fat with SHLP2. Consistent with hepatic stress being a driver of circulating MDP concentrations, plasma MOTS-c and SHLP2 were higher in participants with elevated liver damage markers and in male C57Bl/6j mice fed a diet that induces hepatic lipid accumulation and damage. Our findings provide evidence that in the absence of overt type 2 diabetes, components of the MS positively associated with levels of MOTS-c and SHLP2 and that android fat, in particular liver fat, is a primary driver of these associations. MOTS-c and SHLP2 have previously been shown to have cyto- and metabolo-protective properties, therefore we suggest that liver stress may be a mitochondrial peptide signal, and that mitochondrial peptides are part of a hepatic centric-hormetic response intended to restore metabolic balance.

Feasibility and Provisional Efficacy of Embedding High-Intensity Interval Training Into Physical Education Lessons: A Pilot Cluster-Randomized Controlled Trial.

PURPOSE: The aim of this study was to determine the feasibility of generalist school teachers delivering curriculum connected high-intensity interval training in a school's physical education class time. METHOD: Two schools volunteered to participate. A total of 84 students (11.9 [0.5] y, M = 64 and F = 19) volunteered to participate. Four classes from 2 schools were randomized to either intervention (n = 53) or control (n = 31) for one school term (8 wk). Intervention class teachers participated in a 1-day workshop instructing them how to deliver twice weekly, high-intensity interval training sessions. The control classes continued with their usual physical education curriculum. Recruitment, intervention fidelity, and program satisfaction were assessed. Preliminary efficacy (primary outcome cardiorespiratory fitness) was quantified using generalized linear mixed models, expressed as effect size. A range of secondary outcomes was also assessed. RESULTS: The recruitment rate was 88%. About 84% of the sessions were delivered. The heart rate peak over all sessions was 89.6% (13%) of the predicted maximum. The intervention teachers reported high levels of satisfaction. Almost all student participants were positive about participating. No adverse events occurred. The adjusted between-group difference for cardiorespiratory fitness was trivial (effect size 0.02). CONCLUSIONS: This teacher-delivered high-intensity interval training program was feasible and acceptable to both teachers and student participants. It is therefore potentially scalable.

The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Maori and Pacific ancestry.

AIMS/HYPOTHESIS: The minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased BMI, but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Maori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes. METHODS: A mixed meal tolerance test was completed by 172 men (56 with the A allele) of Maori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled IVGTT and hyperinsulinaemic-euglycaemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation. RESULTS: The A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins glucagon-like polypeptide-1 or gastric inhibitory polypeptide. Consistent with this point, following an i.v. infusion of a glucose bolus, participants with an A allele had higher early (p < 0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p > 0.05) in insulin sensitivity index or glucose disposal during hyperinsulinaemic-euglycaemic clamp. CONCLUSIONS/INTERPRETATION: rs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase insulin release to reduce the risk of type 2 diabetes.