Composition Biomarkers Research Articles

Artificial intelligence modeling of biomarker-based physiological age: Impact on phase 1 drug-metabolizing enzyme phenotypes.

Age and aging are important predictors of health status, disease progression, drug kinetics, and effects. The purpose was to develop ensemble learning-based physiological age (PA) models for evaluating drug metabolism. National Health and Nutrition Examination Survey (NHANES) data were modeled with ensemble learning to obtain two PA models, PA-M1 and PA-M2. PA-M1 included body composition, blood and urine biomarkers, and disease variables as predictors. PA-M2 had blood and urine-derived variables as predictors. Activity phenotypes for cytochrome-P450 (CYP) CYP2E1, CYP1A2, CYP2A6, xanthine oxidase (XO), and N-acetyltransferase-2 (NAT-2) and telomere attrition were assessed. Bayesian networks were used to obtain mechanistic systems pharmacology model structures for PA. The study included n = 22,307 NHANES participants (51.5% female, mean age 46.0 years, range: 18-79 years). The PA-M1 and PA-M2 distributions had greater dispersion across age strata with a right skew for younger age strata and a left skew for older age strata. There was no evidence of algorithmic bias based on sex or race/ethnicity. Klotho, lean body mass, glycohemoglobin, and systolic blood pressure were the top four predictors for PA-M1. Glycohemoglobin, serum creatinine, total cholesterol, and urine creatinine were the top four predictors for PA-M2. The models also performed satisfactorily in independent validation. Model-predicted PA was associated with CYP2E1, CYP1A2, CYP2A6, XO, and NAT-2 activity. Telomere attrition was associated with greater PA-M1 and PA-M2. Ensemble learning models provide robust assessments of PA from easily obtained blood and urine biomarkers. PA is associated with Phase I drug-metabolizing enzyme phenotypes.

Insights into respiratory microbiome composition and systemic inflammatory biomarkers of bronchiectasis patients.

The population of microorganisms on/in the human body resides in distinct local microbiomes, including the respiratory microbiome. It remains unclear what defines a healthy and a diseased respiratory microbiome. We investigated the respiratory microbiome in chronic pulmonary infectious disease, i.e., bronchiectasis, and researched correlations between microbiome composition, systemic inflammatory biomarkers, and disease characteristics. The bronchoalveolar microbiome of 47 patients was sequenced, and their serum inflammatory mediators were quantified. The microbiomes were grouped based on their content and diversity. In addition, patients were also grouped into low- and high-response groups according to their inflammatory biomarkers' levels. Certain microbiome compositions, mainly single-species dominated, were associated with high levels of inflammatory cytokines, whereas others correlated with low inflammatory response and remained diverse. We conclude that respiratory microbiome composition is a valuable resource for the diagnostics and personalized management of bronchiectasis, which may include preserving microbiome diversity and introducing possible probiotics.

A generalized health index: automated thoracic CT-derived biomarkers predict life expectancy.

To identify image biomarkers associated with overall life expectancy from low-dose computed tomography and integrate them as an index for assessing an individual's health. Two categories of CT image features, body composition tissues and cardiopulmonary vasculature characteristics, were quantified from LDCT scans in the Pittsburgh Lung Screening Study cohort(n = 3,635). Cox proportional-hazards models identified significant image features which were integrated with subject demographics to predict the subject's overall hazard. Subjects were stratified using composite model predictions and feature-specific risk stratification thresholds. The model's performance was validated extensively, including 5-fold cross-validation on PLuSS baseline, PLuSS follow-up examinations, and the National Lung Screening Trial (NLST). The composite model had significantly improved prognostic ability compared to the baseline model (p < 0.01) with AUCs of 0.774 (95% CI: 0.757-0.792) on PLuSS, 0.723 (95% CI: 0.703-0.744) on PLuSS follow-up, and 0.681 (95% CI: 0.651-0.710) on the NLST cohort. The identified high-risk stratum were several times more likely to die, with mortality rates of 79.34% on PLuSS, 76.47% on PLuSS follow-up, and 46.74% on NLST. Two cardiopulmonary structures (intrapulmonary artery vein ratio, intrapulmonary vein density) and two body composition tissues (SM density, bone density) identified high-risk patients. Body composition and pulmonary vasculatures are predictive of an individual's health risk; their integrations with subject demographics facilitate the assessment of an individual's overall health status or susceptibility to disease. CT-computed body composition and vasculature biomarkers provide improved prognostic value. The integration of CT biomarkers and patient demographic information improves subject risk stratification.

Effects of Human Milk Oligosaccharide 2′-Fucosyllactose Ingestion on Weight Loss and Markers of Health

Background: 2′-Fucosyllactose (2′-FL) is an oligosaccharide contained in human milk and possesses prebiotic and anti-inflammatory effects, which may alleviate skeletal muscle atrophy under caloric restriction. This study evaluated the impacts of 12 weeks of 2′-FL supplementation in conjunction with exercise (10,000 steps/day, 5 days/week) and energy-reduced (−300 kcals/day) dietary interventions on changes in body composition and health-related biomarkers. Methods: A total of 41 overweight and sedentary female and male participants (38.0 ± 13 years, 90.1 ± 15 kg, 31.6 ± 6.6 kg/m2, 36.9 ± 7% fat) took part in a randomized, double-blind, and placebo-controlled study. The participants underwent baseline assessments and were then assigned to ingest 3 g/day of a placebo (PLA) or Momstamin 2′-F while initiating the exercise and weight-loss program. Follow-up tests were performed after 6 and 12 weeks. Data were analyzed using general linear model statistics with repeated measures and mean changes from baseline values with 95% confidence intervals (CIs). Results: No group × time × sex interaction effects were observed, so group × time effects are reported. Participants in both groups saw comparable reductions in weight. However, those with 2′-FL demonstrated a significantly greater reduction in the percentage of body fat and less loss of the fat-free mass. Additionally, there was evidence that 2′-FL supplementation promoted more favorable changes in resting fat oxidation, peak aerobic capacity, IL-4, and platelet aggregation, with some minimal effects on the fermentation of short-chain fatty acids and monosaccharides in fecal samples. Moreover, participants’ perceptions regarding some aspects of the functional capacity and ratings of the quality of life were improved, and the supplementation protocol was well tolerated, although a small, but significant, decrease in BMC was observed. Conclusions: The results support contentions that dietary supplementation of 2′-FL (3 g/d) can promote fat loss and improve exercise- and diet-related markers of health and fitness in overweight sedentary individuals initiating an exercise and weight-loss program. Further research is needed to explore the potential health benefits of 2′-FL supplementation in both healthy and elderly individuals (Registered clinical trial #NCT06547801).

8462 Synergistic Outcomes Of hCG And GLP1-RA Combination Therapy: Improved Body Composition And Carbohydrate Metabolism

Abstract Disclosure: F. Comite: None. K. O'Malley: None. Objective: Precision medicine prevents and reverses diseases of aging by way of systematic analysis of body composition and extensive blood biomarkers. Andropause, the age-related reduction of free testosterone (FT) in males, elicits symptoms primarily of muscle loss, decreased libido, and diminished energy. Exogenous testosterone therapy (TTx) subsequently increases lean body mass (LBM) and improves both libido and energy levels in affected males. More recently, stimulation of endogenous testosterone from the testes, human Chorionic Gonadotropin (hCG) has emerged as a compelling physiologic alternative to TTx. Common comorbidities to andropause are DMII and/or obesity. Recent literature surrounds the use of GLP-1 receptor agonists to improve insulin sensitivity in these disorders of carbohydrate metabolism. A primary benefit secondary to GLP-1 use is reduction of fat mass; however, concerns of this monotherapy surround loss of muscle.[1] Remarkably, when treated adjunctly with GLP-1s, hCG therapy significantly mitigates muscle loss while maintaining optimal carbohydrate biomarkers. The efficacy and benefits of hormonal optimization through hCG therapy simultaneous to GLP-1 intervention were investigated. Methods: In this retrospective analysis, a cohort of 20 males ≥30 years of age were reviewed at baseline timepoints and 18 months post treatment-initiation. Participants underwent biweekly hCG and weekly GLP-1 subcutaneous injections. Exclusion criteria restricted use of alternative GLP-1/GIP combination medication. Paired T-Tests were used to determine a relationship between LBM, FT, percent body fat (PBF), fasting glucose (FG), fasting insulin (FI), and HbA1c at each timepoint. Results: Body composition analysis as shown via bioelectrical impedance proved baseline PBF (mean=24.60) significantly reduced post-treatment (p&amp;lt;0.05, mean=18.08) for all participants. In addition, relevant carbohydrate metabolic biomarkers FG, FI, and HbA1c provided significant reductions (p&amp;lt;0.05). Initial FT (mean=67.76) and LBM (mean=150.36) increased significantly at follow-up (p&amp;lt;0.05) with values of 167.55 and 154.91, respectively. Discussion: Using metrics of precision medicine, our interpretation reveals a promising combination therapy for males experiencing andropause. The novel use of hCG to optimize FT levels enhances muscle, while simultaneously, fat loss and reversal of harmful carbohydrate metabolic markers resultant from GLP-1 therapy are achieved. Muscle loss due to overall weight loss is thus ameliorated. Our findings merit further investigation of the magnitude of downstream improvements, particularly in energy and libido.

Evaluation of Body Composition and Biochemical Parameters in Adult Phenylketonuria

Background/Objectives: Phenylketonuria is a hereditary metabolic disorder characterized by a deficiency of phenylalanine hydroxylase. The main treatment for PKU is a phenylalanine-restricted diet. The exclusion of protein rich natural foods and inclusion of low-Phe substitutes may give rise to an imbalanced diet, and the increased risk of overweight and obesity in PKU is a cause for concern. We aimed to evaluate the body composition and nutritional biochemical biomarkers in adult PKU patients who are on Phe-restricted and essential amino acid-supplemented nutrition therapy and to investigate the relationships between these parameters and patient gender, adherence to dietary therapy, and disease type, defined as mild or classic PKU. Methods: The study group comprised 37 PKU patients and 26 healthy siblings as controls. The participants were assessed based on an analysis of anthropometric parameters, body composition, and biochemical test results. Results: PKU patients do not have a higher incidence of overweight and obesity than healthy controls, the proportion of energy derived from carbohydrates in their diets was below the recommended level, and their total energy intake was below the recommended daily allowance. It was remarkable that patients with a treatment adherence ratio of &lt;50% displayed a higher prevalence of overweight and abdominal obesity in comparison to those with a more favorable treatment adherence ratio. Conclusions: In view of the growing prevalence of overweight in the general population, PKU patients should be kept under close long-term follow-up. Particularly in the group with low treatment compliance, more caution should be taken in terms of adverse outcomes.

Correlation of HbA1c levels with CT-based body composition biomarkers in diabetes mellitus and metabolic syndrome

Diabetes mellitus and metabolic syndrome are closely linked with visceral body composition, but clinical assessment is limited to external measurements and laboratory values including hemoglobin A1c (HbA1c). Modern deep learning and AI algorithms allow automated extraction of biomarkers for organ size, density, and body composition from routine computed tomography (CT) exams. Comparing visceral CT biomarkers across groups with differing glycemic control revealed significant, progressive CT biomarker changes with increasing HbA1c. For example, in the unenhanced female cohort, mean changes between normal and poorly-controlled diabetes showed: 53% increase in visceral adipose tissue area, 22% increase in kidney volume, 24% increase in liver volume, 6% decrease in liver density (hepatic steatosis), 16% increase in skeletal muscle area, and 21% decrease in skeletal muscle density (myosteatosis) (all p < 0.001). The multisystem changes of metabolic syndrome can be objectively and retrospectively measured using automated CT biomarkers, with implications for diabetes, metabolic syndrome, and GLP-1 agonists.

Effects of Small-Sided Soccer Games on Physical Fitness and Cardiometabolic Health Biomarkers in Untrained Children and Adolescents: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis aimed to determine the benefits of an exercise intervention based on small-sided soccer games (SSSGs) on health-related physical fitness and cardiometabolic health in previously untrained children and adolescents. Methods: A systematic search on PubMed/MEDLINE, Web of Science, Scopus, Cochrane, and EBSCO databases was performed. Randomized or non-randomized controlled trials conducted in previously untrained children or adolescents (age < 18 years) that assessed the effect of SSSG-based intervention on health-related physical fitness and cardiometabolic risk biomarkers were included. Primary outcomes were cardiorespiratory fitness and waist circumference. Evidence was synthesized as the mean difference or standardized mean difference using a random-effects meta-analysis. The quality of evidence was assessed using ROB2 and ROBINS-I tools. Results: Sixteen studies (n = 2872 participants) were included in this meta-analysis. SSSGs significantly improved cardiorespiratory fitness (SMD, 0.12 [0.01; 0.23]) and showed a non-significant trend in decreased waist circumference (-7.49 cm [-15.03; 0.06]). Additionally, SSSGs significantly decreased systolic (MD, -3.85 mmHg [-5.75; -1.94]) and diastolic blood pressure (MD, -1.26 mmHg [-2.44; -0.08]) and triglycerides (-30.34 mg·dL-1 [-45.99; -14.69]). No effects on body composition or other cardiometabolic risk biomarkers were observed. After a sensitivity analysis, waist circumference and muscle strength were also shown to improve significantly following SSSGs. Comparisons between SSSG and other types of exercise interventions showed no differences in improved physical fitness or cardiometabolic risk. Conclusions: SSSG-based interventions effectively improve cardiorespiratory fitness, blood pressure, triglycerides, muscle strength, and waist circumference. There is less evidence of the effects of SSSGs on other health markers. Particular attention should be given to improving SSSG protocol reporting in future studies.

Effects of Different Resistance Training Frequencies on Body Composition, Muscular Strength, Muscle Quality, and Metabolic Biomarkers in Sarcopenic Older Women.

Dos Santos, VR, Antunes, M, dos Santos, L, Nascimento, MA, Pina, FLC, Carneiro, NH, Trindade, MCC, Venturini, D, Barbosa, DS, and Cyrino, ES. Effects of different resistance training frequencies on body composition, muscular strength, muscle quality, and metabolic biomarkers in sarcopenic older women. J Strength Cond Res 38(9): e521-e528, 2024-Resistance training (RT) can ameliorate outcomes related to sarcopenia by promoting beneficial changes in muscular strength, skeletal muscle mass (SMM), and muscle quality. This study compared the effects of 12 weeks of RT performed 2 and 3 sessions a week on body composition, muscular strength, muscle quality, and metabolic biomarkers in sarcopenic older women. Thirty-four sarcopenic older women (>60 years) were randomly assigned to perform a whole-body RT program, either 2 (G2X, n = 18) or 3 (G3X, n = 16) sessions a week during 12 weeks (8 exercises, single set of 10-15 repetitions). Body composition, muscular strength, muscle quality, and metabolic biomarkers were assessed before and after the intervention. Both groups increased (p < 0.05) 1 repetition maximum total muscular strength (G2X = +20.4% and G3X = +21.0%), SMM (G2X = +4.0% and G3X = +7.0%), and improved muscle quality (G2X = +16.7% and G3X = +13.6%), with no differences between groups (p > 0.05). No change over time was found for IGF-1 and testosterone (p > 0.05). Our results suggest that 12 weeks of RT performed at a lower weekly frequency is as effective as a higher frequency in improving muscular strength, SMM, and muscle quality in sarcopenic older women.

A study protocol for a randomized clinical trial on exposure and effects of pesticides consumption - the PEST-EXPO Brazil study

Randomized clinical trials are considered the gold standard for studies with dietary interventions, which is mainly due to the fact that they can establish causal relationships between food exposure and body composition measures or biomarkers. The aim of this study was to describe the details of a double-blind, randomized, clinical trial protocol to identify, characterize and evaluate the effects of human dietary exposure to pesticide residues in food. Specific aspects of planning (development of a research question, determination of objectives, selection of participants, randomization and blinding) and performance (recruitment of participants, measures to improve adherence, data collection, follow-up and evaluation of results) are addressed in this study. The study design proved effective in characterizing dietary patterns with foods originating from both conventional and organic agriculture. A total of 148 individuals were recruited for the study. The conventional group was represented by 47 % of the sample and the organic group was represented by 53 %. The practice of evidence-based nutrition has demanded that trials be well designed and systematically performed in the field of clinical nutrition. Therefore, this clinical trial emphasizes the importance of improving studies with toxicological nutrition that assess sources of exposure through food.•This double-blind, randomized clinical trial details the protocol for identifying, characterizing, and evaluating the effects of dietary exposure to pesticide residues.•The protocol demonstrates that well-designed and systematically conducted trials emphasize the importance of robust methodologies in evidence-based nutrition.•In the face of the global climate crisis, this clinical trial underscores the importance of enhancing studies in toxicological nutrition, particularly those evaluating sources of exposure through food, to better understand the dietary impacts on health.

Childhood Nutritional Factors and Cardiometabolic Outcomes at 9–11 y of Age: Findings from the ROLO Longitudinal Birth Cohort Study

BackgroundChildhood represents a critical period of nutritional risk in the programming of later chronic disease. Few longitudinal studies have explored repeated measures of nutrition throughout the first decade of life in relation to preteen cardiometabolic outcomes. ObjectivesThis research aimed to explore associations of early feeding practices (human milk exposure and duration and timing of introduction to solids) and childhood dietary quality and inflammatory scores (at 5 and 9–11 y and change during childhood) on preteen cardiometabolic outcomes. MethodsThis is an analysis of children from the ROLO longitudinal birth cohort study (n = 399). Information on early feeding practices were obtained at postnatal study visits. Food frequency questionnaires collected maternal-reported dietary intakes for each child at 5 and 9–11 y of age. Healthy Eating Index (HEI)-2015 and the Children’s Dietary Inflammatory Index (C-DII) scores were calculated. Anthropometry, body composition, blood pressure, heart rate, cardiorespiratory endurance, and blood biomarkers were obtained at 9–11 y. Crude and adjusted linear regression models examined nutritional exposure associations with preteen cardiometabolic outcomes. ResultsIn the adjusted model, any human milk exposure was associated with lower body fat (%) at 9–11 y (β: −2.86; 95% confidence interval [CI]: −5.46, −0.27; P = 0.03), than never receiving human milk. At 5 y, diet scores were favorably associated with lean mass at 9–11 y (P < 0.05 for both). Higher preteen HEI-2015 scores were associated with lower preteen leptin levels (tertile 3 compared with tertile 1—β: −2.92; 95% CI: −5.64, −0.21; P = 0.03). Diet quality significantly deteriorated (HEI-2015 score decreased) and became more proinflammatory (C-DII score increased) from 5 to 9–11 y of age. Diet quality/inflammation deterioration (compared with improvement) or overall change in dietary scores were not related to preteen cardiometabolic outcomes. ConclusionsExposure to human milk in early life was associated with lower preteen adiposity, irrespective of duration. Diet quality/inflammatory potential deteriorated between early childhood and the preteen years, highlighting a potential period for intervention.

The Effect of Dietary Nitrate on the Oral Microbiome and Salivary Biomarkers in Individuals with High Blood Pressure

BackgroundGreen leafy vegetables (GLV) contain inorganic nitrate, an anion with potential prebiotic effects on the oral microbiome. However, it remains unclear whether GLV and pharmacological supplementation [potassium nitrate (PN)] with a nitrate salt induce similar effects on the oral microbiome. ObjectivesThis study aimed to compare the effect of GLV with PN supplementation on the oral microbiome composition and salivary biomarkers in individuals with high blood pressure. MethodsSeventy individuals were randomly allocated to 3 different groups to follow a 5-wk dietary intervention. Group 1 consumed 300 mg/d of nitrate in form of GLV. Group 2 consumed pills with 300 mg/d of PN and low-nitrate vegetables. Group 3 consumed pills with potassium chloride (placebo: PLAC) and low-nitrate vegetables. The oral microbiome composition and salivary biomarkers of oral health were analyzed before and after the dietary intervention. ResultsThe GLV and PN groups showed similar microbial changes, probably nitrate-dependent, including an increase in the abundance of Neisseria, Capnocytophaga, Campylobacter species, and a decrease in Veillonella, Megasphaera, Actinomyces, and Eubacterium species after the treatment. Increased abundance of Rothia species, and reduced abundance of Streptococcus, Prevotella, Actinomyces, and Mogibacterium species were observed in the GLV group, which could be nitrate-independent. GLV and PN treatments increased salivary pH, but only GLV treatment showed an increase in the salivary buffering capacity and a reduction of lactate. ConclusionThe combination of nitrate-dependent and nitrate-independent microbial changes in the GLV group has a stronger effect to potentially improve oral health biomarkers compared with PN.

Effects of brisk walking with or without music on body composition, standing balance, cardiovascular parameters, and salivary biomarkers in older women.

This study aimed to assess and compare changes in body composition, standing balance, cardiovascular parameters, and salivary biomarkers, particularly salivary antioxidant status, after brisk walking training with or without music in older women. Twenty-four subjects were randomly assigned to brisk walking groups: with music (BWM) (n=12) or without music (BW) (n=12). Eighteen subjects completed the exercise training (9 in each group), and their data were used for analysis. The research protocols were classified into three phases: pretraining phase, training phase, and posttraining phase, while the data collection was divided into four sessions: resting condition, during treadmill exercise testing, immediately posttreadmill exercise testing, and 5-min posttreadmill exercise testing defined as after the cool-down session. The results showed that 8 weeks of home-based brisk walking with or without music did not improve standing balance, blood pressure, salivary biomarkers including total protein concentration, and antioxidant status but maintained or prevented the decline of these parameters. Only the BWM group reduced fat mass relative to increasing fat-free mass (P<0.05) and improved recovery heart rate (P<0.05) by modifying cardiac autonomic control in posttreadmill exercise testing. Therefore, brisk walking with preferred music can be a tool to delay the progression of cardiovascular dysfunction in older women. A longer duration of the exercise program and larger groups of participants are needed for further investigation of brisk walking with or without music on physiological and biochemical changes.

Occupational Exposure to Metal-Based Nanomaterials: A Possible Relationship between Chemical Composition and Oxidative Stress Biomarkers.

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of "NanoExplore Project" [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations-Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers-TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance.

Temporal Trends in Body Composition and Metabolic Markers Prior to Diagnosis of Pancreatic Ductal Adenocarcinoma

Changes in body composition and metabolic factors may serve as biomarkers for the early detection of pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to capture the longitudinal changes in body composition and metabolic factors before diagnosis of PDAC. We performed a retrospective cohort study in which all patients (≥18 years) diagnosed with PDAC from 2002 to 2021 were identified. We collected all abdominal computed tomography scans and 10 different blood-based biomarkers up to 36 months before diagnosis. We applied a fully automated abdominal segmentation algorithm previously developed by our group for 3-dimensional quantification of body composition on computed tomography scans. Longitudinal trends of body composition and blood-based biomarkers before PDAC diagnosis were estimated using linear mixed models, compared across different time windows, and visualized using spline regression. We included 1690 patients in body composition analysis, of whom 516 (30.5%) had ≥2 prediagnostic computed tomography scans. For analysis of longitudinal trends of blood-based biomarkers, 3332 individuals were included. As an early manifestation of PDAC, we observed a significant decrease in visceral and subcutaneous adipose tissue (β= -1.94 [95% confidence interval (CI), -2.39 to -1.48] and β= -2.59 [95% CI, -3.17 to -2.02]) in area (cm2)/height (m2) per 6 months closer to diagnosis, accompanied by a decrease in serum lipids (eg, low-density lipoprotein [β= -2.83; 95% CI, -3.31 to -2.34], total cholesterol [β= -2.69; 95% CI, -3.18 to -2.20], and triglycerides [β= -1.86; 95% CI, -2.61 to -1.11]), and an increase in blood glucose levels. Loss of muscle tissue and bone volume was predominantly observed in the last 6 months before diagnosis. This study identified significant alterations in a variety of soft tissue and metabolic markers that occur in the development of PDAC. Early recognition of these metabolic changes may provide an opportunity for early detection.

Abdominal CT metrics in 17,646 patients reveal associations between myopenia, myosteatosis, and medical phenotypes: a phenome-wide association study

BackgroundDeep learning facilitates large-scale automated imaging evaluation of body composition. However, associations of body composition biomarkers with medical phenotypes have been underexplored. Phenome-wide association study (PheWAS) techniques search for medical phenotypes associated with biomarkers. A PheWAS integrating large-scale analysis of imaging biomarkers and electronic health record (EHR) data could discover previously unreported associations and validate expected associations. Here we use PheWAS methodology to determine the association of abdominal CT-based skeletal muscle metrics with medical phenotypes in a large North American cohort. MethodsAn automated deep learning pipeline was used to measure skeletal muscle index (SMI; biomarker of myopenia) and skeletal muscle density (SMD; biomarker of myosteatosis) from abdominal CT scans of adults between 2012-2018. A PheWAS was performed with logistic regression using patient sex and age as covariates to assess for associations between CT-derived muscle metrics and 611 common EHR-derived medical phenotypes. PheWAS P values were considered significant at a Bonferroni corrected threshold (α=0.05/1222). Findings17,646 adults (mean age, 56 years +/- 19 [SD]; 57.5% women) were included. CT-derived SMI was significantly associated with 268 medical phenotypes; SMD with 340 medical phenotypes. Previously unreported associations with the highest magnitude of significance included higher SMI with decreased cardiac dysrhythmias (OR [95%CI], 0.59 [0.55-0.64]; P<0.0001), decreased epilepsy (OR, 0.59 [0.50-0.70]; P<0.0001), and increased elevated prostate-specific antigen (OR, 1.84 [1.47-2.31]; P<0.0001), and higher SMD with decreased decubitus ulcers (OR, 0.36 [0.31-0.42]; P<0.0001), sleep disorders (OR, 0.39 [0.32-0.47]; P<0.0001), and osteomyelitis (OR, 0.43 [0.36-0.52]; P<0.0001). InterpretationPheWAS methodology reveals previously unreported associations between CT-derived biomarkers of myopenia and myosteatosis and EHR medical phenotypes. The high-throughput PheWAS technique applied on a population scale can generate research hypotheses related to myopenia and myosteatosis and can be adapted to research possible associations of other imaging biomarkers with hundreds of EHR medical phenotypes.

Short-Term Changes in Weight, Body Composition, and Metabolic Biomarkers After Laparoscopic Sleeve Gastrectomy in Patients with Obesity: A Comparative Prospective Study.

To investigate the changes in weight, body composition, and metabolic biomarkers in patients with obesity after laparoscopic sleeve gastrectomy (LSG) and compare those changes between patients with and without metabolic syndrome (MS). This retrospective longitudinal study included 76 patients who underwent LSG, among whom 32 had complete 1-year postoperative body composition and metabolic biomarkers. Body composition was measured by quantitative CT. Weight changes were compared between the MS and non-MS groups at 1-, 3-, 6-, and 12-month post-LSG in all patients; changes in body compositions and metabolic biomarkers from one day pre-LSG to 12-month post-LSG were also compared in those 32 patients. MS occurred in 46% (35/76) of all patients and 44% (14/32) of patients with complete follow-up data. Excess weight loss was lower in the MS group than that in the non-MS group at 1-, 3-, 6-, and 12-month post-LSG; the 12-month difference was significant (MS vs. non-MS: 0.91 ± 0.22 vs. 1.07 ± 0.42, P = 0.04). The greatest rate of visceral fat area (VFA) change occurred 12-month post-LSG in both the non-MS [0.62(0.55,0.7)] and MS [0.6(0.51,0.63)] groups. The most significant reduction in ectopic fat occurred in liver fat (LF) [non-MS, 0.45(0.22,0.58); MS, 0.39(0.23,0.58)]. LGS significantly improves weight, body composition, and metabolic biomarkers in populations with obesity, regardless of whether they have MS. Among the body composition, VFA and LF were the most significantly improved body composition measurements.

Dietary Amino Acid Composition and Glycemic Biomarkers in Japanese Adolescents.

Protein intake reportedly increases the risk of diabetes; however, the results have been inconsistent. Diabetes in adulthood may be attributed to early life dietary amino acid composition. This study aimed to investigate the association between amino acid composition and glycemic biomarkers in adolescents. Dietary intake was assessed using a food frequency questionnaire, and fasting glucose and insulin levels were measured in 1238 eighth graders. The homeostatic model assessment (HOMA) indices (insulin resistance and β-cell function) were calculated. Anthropometrics were measured and other covariates were obtained from a questionnaire. Amino acid composition was isometric log transformed according to the compositional data analysis, which was used as explanatory variables in multivariate linear regression models for glucose, insulin, and HOMA indices. Only the association between glucose and leucine was significant. In replacement of other amino acids with leucine, an increase of 0.1% of total amino acids correlated with a lower glucose level (-1.02 mg/dL). One-to-one substitution of leucine for isoleucine or methionine decreased glucose (-2.98 and -2.28 mg/dL, respectively). Associations with other biomarkers were not observed. In conclusion, compositional data analysis of amino acids revealed an association only with glucose in adolescents; however, the results of this study should be verified in other populations.

Comparison of Normocalcemic vs Hypercalcemic Primary Hyperparathyroidism in a Hypercalciuric Renal Stone Population.

Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet. Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P = .01) likely explained by a lesser PTH decrease (P = .02). However, a strong negative association (P < .0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group. Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones.

Effects of High-Intensity Interval Training vs Moderate-Intensity Continuous Training on Body Composition and Blood Biomarkers in Coronary Artery Disease Patients: A Randomized Controlled Trial.

Cardiac rehabilitation (CR) is essential in reducing cardiovascular mortality and morbidity. High-intensity interval training (HIIT) has emerged as a promising exercise intervention for enhancing clinical outcomes in cardiac patients. This study aimed to investigate the effects of two short-term exercise-based programs employing HIIT and moderate-intensity continuous training (MICT) in comparison to a control group concerning blood pressure, body composition, and blood biomarkers in patients diagnosed with coronary artery disease (CAD). Seventy-two CAD patients (14% women) underwent randomization into three groups: HIIT, MICT, and control. The training programs encompassed six weeks of supervised treadmill exercises, conducted thrice weekly. MICT targeted 70-75% of peak heart rate (HRpeak), while HIIT was tailored to 85-95% of HRpeak. The control group received guidance on adopting healthy lifestyles. Outcome measurements included evaluations of blood pressure, body composition, and blood biomarkers. In contrast to MICT, the HIIT exhibited superior improvements in body fat mass ( %HIIT: 4.5%, p 0.001 vs. %MICT: 3.2%, p 0.001), waist circumference ( %HIIT: 4.1%, p = 0.002 vs. %MICT: 2.5%, p = 0.002), hemoglobin A1c (HbA1c) ( %HIIT: 10.4%, p 0.001 vs. %MICT: 32.3%, p 0.001) and thyrotropin (TSH) ( %HIIT: 16.5%, p = 0.007 vs. %MICT: 3.1%, p = 0.201). Both HIIT and MICT induced significant enhancements across all variables compared to the control group. HIIT and MICT emerged as effective modalities for enhancing systolic and diastolic function, body composition, and blood biomarkers in CAD patients, with HIIT demonstrating incremental improvements over MICT. The absence of participation in exercise-based programs following cardiovascular events yielded less favorable outcomes. HIIT holds promise as an adjunct intervention in CR programs for CAD patients. https://clinicaltrials.gov/ct2/show/NCT03538119.