-
1.
Inter-Day Reliability of Resting Metabolic Rate and Maximal Fat Oxidation during Exercise in Healthy Men Using the Ergostik Gas Analyzer.
Robles-González, L, Gutiérrez-Hellín, J, Aguilar-Navarro, M, Ruiz-Moreno, C, Muñoz, A, Del-Coso, J, R Ruiz, J, Amaro-Gahete, FJ
Nutrients. 2021;(12)
Abstract
The attainment of high inter-day reliability is crucial to determine changes in resting metabolic rate (RMR), respiratory exchange ratio (RER), maximal fat oxidation during exercise (MFO) and the intensity that elicits MFO (Fatmax) after an intervention. This study aimed to analyze the inter-day reliability of RMR, RER, MFO and Fatmax in healthy adults using the Ergostik gas analyzer. Fourteen healthy men (age: 24.4 ± 5.0 years, maximum oxygen uptake (VO2max): 47.5 ± 11.9 mL/kg/min) participated in a repeated-measures study. The study consisted of two identical experimental trials (Day 1 and Day 2) in which the participants underwent an indirect calorimetry assessment at resting and during an incremental exercise test. Stoichiometric equations were used to calculate energy expenditure and substrate oxidation rates. There were no significant differences when comparing RMR (1999.3 ± 273.9 vs. 1955.7 ± 362.6 kcal/day, p = 0.389), RER (0.87 ± 0.05 vs. 0.89 ± 0.05, p = 0.143), MFO (0.32 ± 0.20 vs. 0.31 ± 0.20 g/min, p = 0.776) and Fatmax (45.0 ± 8.6 vs. 46.4 ± 8.4% VO2max, p = 0.435) values in Day 1 vs. Day 2. The inter-day coefficient of variation for RMR, RER, MFO and Fatmax were 4.85 ± 5.48%, 3.22 ± 3.14%, 7.78 ± 5.51%, and 6.51 ± 8.04%, respectively. In summary, the current results show a good inter-day reliability when RMR, RER, MFO and Fatmax are determined in healthy men using the Ergostik gas analyzer.
-
2.
Free fatty acid processing diverges in human pathologic insulin resistance conditions.
Sekizkardes, H, Chung, ST, Chacko, S, Haymond, MW, Startzell, M, Walter, M, Walter, PJ, Lightbourne, M, Brown, RJ
The Journal of clinical investigation. 2020;(7):3592-3602
-
-
Free full text
-
Abstract
BACKGROUNDPostreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g., insulin receptor pathogenic variants, INSR) causes hyperglycemia without steatosis. We examined 4 pathologic conditions of IR in humans to examine pathways controlling lipid metabolism and gluconeogenesis.METHODSCross-sectional study of severe receptor IR (INSR, n = 7) versus postreceptor IR that was severe (lipodystrophy, n = 14), moderate (type 2 diabetes, n = 9), or mild (obesity, n = 8). Lipolysis (glycerol turnover), hepatic glucose production (HGP), gluconeogenesis (deuterium incorporation from body water into glucose), hepatic triglyceride (magnetic resonance spectroscopy), and hepatic fat oxidation (plasma β-hydroxybutyrate) were measured.RESULTSLipolysis was 2- to 3-fold higher in INSR versus all other groups, and HGP was 2-fold higher in INSR and lipodystrophy versus type 2 diabetes and obesity (P < 0.001), suggesting severe adipose and hepatic IR. INSR subjects had a higher contribution of gluconeogenesis to HGP, approximately 77%, versus 52% to 59% in other groups (P = 0.0001). Despite high lipolysis, INSR subjects had low hepatic triglycerides (0.5% [interquartile range 0.1%-0.5%]), in contrast to lipodystrophy (10.6% [interquartile range 2.8%-17.1%], P < 0.0001). β-hydroxybutyrate was 2- to 7-fold higher in INSR versus all other groups (P < 0.0001), consistent with higher hepatic fat oxidation.CONCLUSIONThese data support a key pathogenic role of adipose tissue IR to increase glycerol and FFA availability to the liver in both receptor and postreceptor IR. However, the fate of FFA diverges in these populations. In receptor-level IR, FFA oxidation drives gluconeogenesis rather than being reesterified to triglyceride. In contrast, in postreceptor IR, FFA contributes to both gluconeogenesis and hepatic steatosis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778556, NCT00001987, and NCT02457897.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases, US Department of Agriculture/Agricultural Research Service 58-3092-5-001.
-
3.
Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study.
Araujo, DB, Dantas, JR, Silva, KR, Souto, DL, Pereira, MFC, Moreira, JP, Luiz, RR, Claudio-Da-Silva, CS, Gabbay, MAL, Dib, SA, et al
Frontiers in immunology. 2020;:993
Abstract
Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.
-
4.
Deep Learning-Based Quantification of Epicardial Adipose Tissue Volume and Attenuation Predicts Major Adverse Cardiovascular Events in Asymptomatic Subjects.
Eisenberg, E, McElhinney, PA, Commandeur, F, Chen, X, Cadet, S, Goeller, M, Razipour, A, Gransar, H, Cantu, S, Miller, RJH, et al
Circulation. Cardiovascular imaging. 2020;(2):e009829
-
-
Free full text
-
Abstract
BACKGROUND Epicardial adipose tissue (EAT) volume (cm3) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography. METHODS Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction. RESULTS At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P<0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72-0.96]; P=0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm3 and coronary artery calcium ≥100 AU and was highest in subjects with both (P<0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers. CONCLUSIONS Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.
-
5.
Metabolic rate and substrate utilisation resilience in men undertaking polar expeditionary travel.
Hattersley, J, Wilson, AJ, Thake, CD, Facer-Childs, J, Stoten, O, Imray, C
PloS one. 2019;(8):e0221176
Abstract
The energy expenditure and substrate utilisation were measured in 5 men pre- and post- a 67 day, 1750km unassisted Antarctic traverse from the Hercules Inlet to the Ross Sea Ice via the South pole pulling sledges weighing 120kg whilst experiencing temperatures as low as -57°C. A 36-hours protocol in a whole body calorimeter was employed to measure periods of rest, sleep and three periods of standardised stepping exercises at 80, 100 and 120 steps min-1; participants were fed isocalorically. Unlike previous expeditions where large weight loss was reported, only a modest loss of body weight (7%, P = 0.03) was found; fat tissue was reduced by 53% (P = 0.03) together with a small, but not statistically significant, increase in lean tissue weight (P = 0.18). This loss occurred despite a high-energy intake (6500 kcal/day) designed to match energy expenditure. An energy balance analysis suggested the loss in body weight could be due to the energy requirements of thermoregulation. Differences in energy expenditure [4.9 (0.1) vs 4.5 (0.1) kcal/min. P = 0.03], carbohydrate utilisation [450 (180) vs 569 (195) g/day; P = 0.03] and lipid utilisation [450 (61) vs 388 (127) g/day, P = 0.03] at low levels of exertion were different from pre-expedition values. Only carbohydrate utilisation remained statistically significant when normalised to body weight. The differences in energy expenditure and substrate utilisation between the pre- and post-expedition for other physiological states (sleeping, resting, higher levels of exercise, etc) were small and not statistically significant. Whilst inter-subject variability was large, there was a tendency for increased carbohydrate utilisation, post-expedition, when fasted that decreased upon feeding.
-
6.
Food Overconsumption in Healthy Adults Triggers Early and Sustained Increases in Serum Branched-Chain Amino Acids and Changes in Cysteine Linked to Fat Gain.
Elshorbagy, AK, Samocha-Bonet, D, Jernerén, F, Turner, C, Refsum, H, Heilbronn, LK
The Journal of nutrition. 2018;(7):1073-1080
-
-
Free full text
-
Abstract
BACKGROUND Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes. OBJECTIVE We investigated amino acid changes during food overconsumption. METHODS Forty healthy men and women with a body mass index (mean ± SEM) of 25.6 ± 0.6 were overfed by 1250 kcal/d for 28 d, increasing consumption of all macronutrients. Insulin sensitivity and body composition were assessed at baseline (day 0) and day 28. Fasting serum amino acids were measured at days 0, 3, and 28. Linear mixed-effects models evaluated the effect of time in the total group and separately in those with low and high body fat gain (below compared with at or above median fat gain, 1.95 kg). At days 0 and 28, insulin-induced suppression of serum amino acids during a hyperinsulinemic-euglycemic clamp test and, in a subset (n = 20), adipose tissue mRNA expression of selected amino acid metabolizing enzymes were assessed. RESULTS Weight increased by 2.8 kg. High fat gainers gained 2.6 kg fat mass compared with 1.1 kg in low fat gainers. Valine and isoleucine increased at day 3 (+17% and +22%, respectively; P ≤ 0.002) and remained elevated at day 28, despite a decline in valine (P = 0.019) from day 3 values. Methionine, cystathionine, and taurine were unaffected. Serum total cysteine (tCys) transiently increased at day 3 (+11%; P = 0.022) only in high fat gainers (P-interaction = 0.043), in whom the cysteine catabolic enzyme cysteine dioxygenase (CDO1) was induced (+26%; P = 0.025) in adipose tissue (P-interaction = 0.045). Overconsumption did not alter adipose tissue mRNA expression of the BCAA-metabolizing enzymes branched-chain keto acid dehydrogenase E1α polypeptide (BCKDHA) or branched-chain amino transferase 1 (BCAT1). In the total population at day 0, insulin infusion decreased all serum amino acids (-11% to -47%; P < 0.01), except for homocysteine and tCys, which were unchanged, and glutathione, which was increased by 54%. At day 28, insulin increased tCys (+8%), and the insulin-induced suppression of taurine and phenylalanine observed at day 0, but not that of BCAAs, was significantly impaired. CONCLUSIONS These findings highlight the role of nutrient oversupply in increasing fasting BCAA concentrations in healthy adults. The link between cysteine availability, CDO1 expression, and fat gain deserves investigation. This trial was registered at www.clinicaltrials.gov as NCT00562393.
-
7.
First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.
Grønhøj, C, Jensen, DH, Glovinski, PV, Jensen, SB, Bardow, A, Oliveri, RS, Specht, L, Thomsen, C, Darkner, S, Kiss, K, et al
Trials. 2017;(1):108
Abstract
BACKGROUND Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. METHODS This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. DISCUSSION The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. TRIAL REGISTRATION EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.
-
8.
Spillover of Fatty acids during dietary fat storage in type 2 diabetes: relationship to body fat depots and effects of weight loss.
Almandoz, JP, Singh, E, Howell, LA, Grothe, K, Vlazny, DT, Smailovic, A, Irving, BA, Nelson, RH, Miles, JM
Diabetes. 2013;(6):1897-903
-
-
Free full text
-
Abstract
Spillover of lipoprotein lipase-generated fatty acids from chylomicrons into the plasma free fatty acid (FFA) pool is an important source of FFA and reflects inefficiency in dietary fat storage. We measured spillover in 13 people with type 2 diabetes using infusions of a [(3)H]triolein-labeled lipid emulsion and [U-(13)C]oleate during continuous feeding, before and after weight loss. Body fat was measured with dual energy X-ray absorptiometry and computed tomography. Participants lost ∼14% of body weight. There was an ∼38% decrease in meal-suppressed FFA concentration (P < 0.0001) and an ∼23% decrease in oleate flux (P = 0.007). Fractional spillover did not change (P = NS). At baseline, there was a strong negative correlation between spillover and leg fat (r = -0.79, P = 0.001) and a positive correlation with the trunk-to-leg fat ratio (R = 0.56, P = 0.047). These correlations disappeared after weight loss. Baseline leg fat (R = -0.61, P = 0.027) but not trunk fat (R = -0.27, P = 0.38) negatively predicted decreases in spillover with weight loss. These results indicate that spillover, a measure of inefficiency in dietary fat storage, is inversely associated with lower body fat in type 2 diabetes.
-
9.
A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome.
Miller, JL, Lynn, CH, Shuster, J, Driscoll, DJ
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2013;(1):2-9
-
-
Free full text
-
Abstract
BACKGROUND Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. METHODS Sixty-three children, aged 2-10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. RESULTS Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P < 0.001) and weight management (body mass index SD score 0.3 versus 2.23; P < 0.001) than those whose parents followed the energy intake recommendations but did not alter the macronutrient composition of the diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). CONCLUSIONS Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet.
-
10.
Change in body fat during a family-based treatment of obesity in children: the relative importance of energy intake and physical activity.
Steinsbekk, S, Wichstrøm, L, Odegård, R, Mehus, I
Obesity facts. 2012;(4):515-26
Abstract
OBJECTIVE The aim of the current study was to examine to what extent changes in reported energy intake and physical activity predict changes in body fat during a family-based outpatient treatment of obesity in children. METHODS Total body fat (DXA), reported energy intake (4-day diet record), and physical activity (accelerometer) was measured in 99 children (age 7-12 years, mean BMI SDS = 2.99) at baseline as well as after 6 months 2 years of treatment. Repeated measures (GLM), growth modeling, and structural equation modeling (SEM) were applied in the data analyses. RESULTS There was significant decrease in body fat, reported energy intake, and physical activity at both follow-ups (p < 0.001) compared to baseline. Changes in reported energy intake from baseline to 6 months predicted a decrease in body fat from baseline to 6 months (β = 0.68, p < 0.001). In addition, changes in reported energy intake had a strong indirect effect on body fat at 2-year follow-up, mediated by changes in body fat from baseline to 6 months (indirect β = 0.50, p < 0.001). Changes in physical activity did not predict changes in body fat during treatment. CONCLUSIONS Changes in reported energy intake significantly affected body fat at 6 months and indirectly predicted the amount of body fat at 2-year follow-up. The indirect effect was mediated by a decrease in body fat obtained during the first phase of treatment.