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1.
The effect of bedtime snacks on fasting blood glucose levels in gestational diabetes mellitus.
Henze, M, Burbidge, H, Nathan, E, Graham, DF
Diabetic medicine : a journal of the British Diabetic Association. 2022;(3):e14718
Abstract
AIM: To investigate the effect of different bedtime snacks (higher carbohydrate versus lower carbohydrate versus no snack) on first morning fasting blood glucose levels (BGLs) in women with diet-controlled gestational diabetes mellitus (GDM) and borderline fasting glucose levels. METHODS This prospective randomised crossover trial enrolled women with diet controlled GDM between 24 and 34 weeks gestation who had two or more first morning fasting BGLs between 4.7 and 5.4 mmol/L in the week prior to recruitment. The women were randomly allocated to 6 different orders of 5 days each of a standardised higher carbohydrate bedtime snack, a lower carbohydrate bedtime snack and no bedtime snack. The primary outcome was fasting capillary BGL as measured with a home glucometer, and the secondary outcome was requirement for insulin as assessed by a physician. RESULTS A total of 68 women with GDM were enrolled in and completed the study at a median gestation of 30.8 weeks. Compared with no bedtime snack, the higher carbohydrate snack (4.96 vs 4.87 mmol/L, mean difference: 0.09 mmol/L, 95% CI 0.05-0.13, p < 0.001) and the lower carbohydrate snack (5.01 vs 4.87 mmol/L, mean difference: 0.14 mmol/L, 95% CI 0.09-0.18, p < 0.001) were both associated with a slightly higher fasting BGL the following morning. CONCLUSIONS Taking a bedtime snack was associated with slightly higher fasting BGLs in women with diet-controlled GDM compared with no bedtime snack (Clinical trial registration: ACTRN12617000659303).
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2.
Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.
Herz, CT, Kulterer, OC, Prager, M, Langer, FB, Prager, G, Marculescu, R, Fauler, G, Hacker, M, Kautzky-Willer, A, Trauner, M, et al
Molecular and cellular endocrinology. 2021;:111403
Abstract
INTRODUCTION Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals. METHODS BAT 18F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography-high-resolution mass spectrometry. RESULTS In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity. CONCLUSION Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.
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3.
Pre-Exercise Carbohydrate or Protein Ingestion Influences Substrate Oxidation but Not Performance or Hunger Compared with Cycling in the Fasted State.
Rothschild, JA, Kilding, AE, Broome, SC, Stewart, T, Cronin, JB, Plews, DJ
Nutrients. 2021;(4)
Abstract
Nutritional intake can influence exercise metabolism and performance, but there is a lack of research comparing protein-rich pre-exercise meals with endurance exercise performed both in the fasted state and following a carbohydrate-rich breakfast. The purpose of this study was to determine the effects of three pre-exercise nutrition strategies on metabolism and exercise capacity during cycling. On three occasions, seventeen trained male cyclists (VO2peak 62.2 ± 5.8 mL·kg-1·min-1, 31.2 ± 12.4 years, 74.8 ± 9.6 kg) performed twenty minutes of submaximal cycling (4 × 5 min stages at 60%, 80%, and 100% of ventilatory threshold (VT), and 20% of the difference between power at the VT and peak power), followed by 3 × 3 min intervals at 80% peak aerobic power and 3 × 3 min intervals at maximal effort, 30 min after consuming a carbohydrate-rich meal (CARB; 1 g/kg CHO), a protein-rich meal (PROTEIN; 0.45 g/kg protein + 0.24 g/kg fat), or water (FASTED), in a randomized and counter-balanced order. Fat oxidation was lower for CARB compared with FASTED at and below the VT, and compared with PROTEIN at 60% VT. There were no differences between trials for average power during high-intensity intervals (367 ± 51 W, p = 0.516). Oxidative stress (F2-Isoprostanes), perceived exertion, and hunger were not different between trials. Overall, exercising in the overnight-fasted state increased fat oxidation during submaximal exercise compared with exercise following a CHO-rich breakfast, and pre-exercise protein ingestion allowed similarly high levels of fat oxidation. There were no differences in perceived exertion, hunger, or performance, and we provide novel data showing no influence of pre-exercise nutrition ingestion on exercise-induced oxidative stress.
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4.
The Effects of Exercise on β-Hydroxybutyrate Concentrations over a 36-h Fast: A Randomized Crossover Study.
Deru, LS, Bikman, BT, Davidson, LE, Tucker, LA, Fellingham, G, Bartholomew, CL, Yuan, HL, Bailey, BW
Medicine and science in sports and exercise. 2021;(9):1987-1998
Abstract
PURPOSE This study assessed β-hydroxybutyrate (BHB) concentration during a short-term fast and the degree to which an initial bout of exercise influences the rate of ketogenesis. METHODS Twenty subjects (11 male, 9 female) completed two 36-h fasts, with one protocol requiring the subject to complete a treadmill exercise session at the beginning of the fast. BHB levels were assessed via portable meter every 2 h, along with mood and hunger ratings. Venipuncture was performed every 12 h. RESULTS The mean (SD) areas under the curve for BHB concentration were 19.19 (2.59) mmol·L-1 (nonexercised) and 27.49 (2.59) mmol·L-1 (exercised), yielding a difference of 8.30 mmol·L-1 between conditions (95% posterior probability interval (PPI), 1.94 to 14.82 mmol·L-1; posterior probability (PP) = 0.99). The mean (SD) times to BHB concentration of 0.5 mmol·L-1 were 21.07 (2.95) h (nonexercised) and 17.5 (1.69) h (exercised), a 3.57-h difference (95% PPI, -2.11 to 10.87 h; PP = 0.89). The differences in area under the curve between conditions were 5.07 μU·mL-1 (95% PPI, -21.64 to 36.18 μU·mL-1; PP = 0.67) for insulin, 97.13 pg·mL-1 (95% PPI, 34.08 to 354.21 pg·mL-1; PP = 0.98) for glucagon, and 20.83 (95% PPI, 4.70 to 24.22; PP = 0.99) for the insulin/glucagon ratio. CONCLUSIONS Completing aerobic exercise at the beginning of a fast accelerates the production of BHB throughout the fast without altering subjective feelings of hunger, thirst, stomach discomfort, or mood. Insulin and the insulin/glucagon ratio experience a marked reduction within the first 12 h of fasting and was not altered with exercise. Thus, exercising at the beginning of a fast may improve the metabolic outcomes of fasting.
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5.
Effects of tree nut and groundnut consumption compared with those of l-arginine supplementation on fasting and postprandial flow-mediated vasodilation: Meta-analysis of human randomized controlled trials.
Smeets, ETHC, Mensink, RP, Joris, PJ
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1699-1710
Abstract
INTRODUCTION l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD). METHODS Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. RESULTS A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of l-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P < 0.001; I2: 76.7%, P < 0.001), while l-arginine supplementation (daily range: 3-21 g) increased fasting FMD by 0.53 PP (95% CI: 0.12, 0.93; P = 0.012; I2: 91.6%, P < 0.001). Effects between treatments were not statistically different (P = 0.31). Tree nut and groundnut consumption did not affect postprandial FMD responses (1.25 PP, 95% CI: -0.31, 2.81, P = 0.12; I2: 91.4%, P < 0.001), whereas l-arginine supplementation (range: 3-15 g) improved FMD during the postprandial phase by 2.02 PP (95% CI: 0.92, 3.13, P < 0.001; I2: 99.1%, P < 0.001). However, treatment effects did not differ significantly (P = 0.60). Overall, these results derive from high-quality evidence. CONCLUSION Longer-term consumption of tree nuts and groundnuts, as well as l-arginine supplementation did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of l-arginine in these nuts. Only l-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD.
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6.
Comparing the Fasting and Random-Fed Metabolome Response to an Oral Glucose Tolerance Test in Children and Adolescents: Implications of Sex, Obesity, and Insulin Resistance.
LaBarre, JL, Hirschfeld, E, Soni, T, Kachman, M, Wigginton, J, Duren, W, Fleischman, JY, Karnovsky, A, Burant, CF, Lee, JM
Nutrients. 2021;(10)
Abstract
As the incidence of obesity and type 2 diabetes (T2D) is occurring at a younger age, studying adolescent nutrient metabolism can provide insights on the development of T2D. Metabolic challenges, including an oral glucose tolerance test (OGTT) can assess the effects of perturbations in nutrient metabolism. Here, we present alterations in the global metabolome in response to an OGTT, classifying the influence of obesity and insulin resistance (IR) in adolescents that arrived at the clinic fasted and in a random-fed state. Participants were recruited as lean (n = 55, aged 8-17 years, BMI percentile 5-85%) and overweight and obese (OVOB, n = 228, aged 8-17 years, BMI percentile ≥ 85%). Untargeted metabolomics profiled 246 annotated metabolites in plasma at t0 and t60 min during the OGTT. Our results suggest that obesity and IR influence the switch from fatty acid (FA) to glucose oxidation in response to the OGTT. Obesity was associated with a blunted decline of acylcarnitines and fatty acid oxidation intermediates. In females, metabolites from the Fasted and Random-Fed OGTT were associated with HOMA-IR, including diacylglycerols, leucine/isoleucine, acylcarnitines, and phosphocholines. Our results indicate that at an early age, obesity and IR may influence the metabolome dynamics in response to a glucose challenge.
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7.
Effect of Moderate Hepatic Impairment on the Pharmacokinetics of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor.
Chavan, A, Burke, L, Sawant, R, Navarro-Gonzales, P, Vargo, D, Paulson, SK
Clinical pharmacology in drug development. 2021;(8):950-958
Abstract
Vadadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor in development for the treatment of anemia of chronic kidney disease. This phase 1, open-label, parallel-group, single-dose study evaluated the pharmacokinetics of 450-mg vadadustat in adults with moderate hepatic impairment (Child-Pugh class B) vs those with normal hepatic function. Primary end points were area under the plasma concentration-time curve (AUC) from dosing to last concentration and to infinity, as well as maximum concentration (Cmax ); additional pharmacokinetic parameters included time to Cmax (Tmax ) and half-life. Safety and tolerability were also assessed. All enrolled participants (n = 16) completed the study. Demographics were similar in both groups (overall, 100% White; 62.5% female; mean age, 59.2 years). Vadadustat plasma exposure was higher in the moderate hepatic impairment group, whereas maximum concentration was similar between groups. Point estimates of the hepatic impairment : normal geometric mean ratios (90% confidence interval) for AUC from dosing to last concentration, AUC from dosing to infinity, and Cmax were 1.05 (0.82-1.35), 1.06 (0.82-1.36), and 1.02 (0.79-1.32), respectively. Mean elimination half-life was 5.8 and 7.8 hours in the normal and hepatic impairment groups, respectively. Treatment-emergent adverse events were mostly mild in severity, and vadadustat was generally well tolerated. In conclusion, moderate hepatic impairment did not significantly impact vadadustat systemic exposure, and mild hepatic impairment is unlikely to alter vadadustat exposure.
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8.
Application of a Backpropagation Artificial Neural Network in Predicting Plasma Concentration and Pharmacokinetic Parameters of Oral Single-Dose Rosuvastatin in Healthy Subjects.
Xu, Y, Lou, H, Chen, J, Jiang, B, Yang, D, Hu, Y, Ruan, Z
Clinical pharmacology in drug development. 2020;(7):867-875
Abstract
A backpropagation artificial neural network (BPANN) model was established for the prediction of the plasma concentration and pharmacokinetic parameters of rosuvastatin (RVST) in healthy subjects. The data (demographic characteristics and results of clinical laboratory tests) were collected from 4 bioequivalence studies using reference 10-mg RVST calcium tablets. After the data were cleaned using extreme gradient boosting, 13 important factors were extracted to construct the BPANN model. The model was fully validated, and mean impact values (MIVs) were calculated. The model was used to predict the plasma concentration and pharmacokinetic parameters of oral single-dose RVST in healthy subjects under fasting and fed conditions. The predicted and measured values were compared in order to evaluate the accuracy of prediction. The constructed model performed well in validation. The top 3 factors ranked by MIV related to RVST concentration are fasting/fed, time, and creatinine clearance. The time-concentration profiles of the measured and predicted data agreed well. There were no significant differences (P > .05) in the area under the concentration-time curve from 0 to the last measurable concentration (AUC0-t ) and extrapolated to infinity (AUC0-∞ ), half-time of elimination, peak concentration, and time to peak concentration of the measured data and data predicted by BPANN. The BPANN model has an accurate prediction ability and can be used to predict RVST concentration and pharmacokinetic parameters in healthy subjects.
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9.
Predictive value of random blood glucose versus fasting blood glucose on in-hospital adverse events in patients with ST-segment elevation acute myocardial infarction.
Qin, Y, Yan, G, Qiao, Y, Wang, D, Luo, E, Hou, J, Tang, C
BMC cardiovascular disorders. 2020;(1):95
Abstract
BACKGROUND We aim to find out the relationship between random blood glucose (RBG), fasting blood glucose (FBG) and in-hospital adverse events in ST-segment elevation acute myocardial infarction (STEMI) patients. We evaluate and compare the predictive value of RBG and FBG on in-hospital adverse events, and give an appropriate cut-off value of RBG and FBG. METHOD A retrospective study enrolled 958 consecutive AMI patients undergoing emergency coronary angiography at Zhongda Hospital were enrolled from January 1, 2016, to December 31, 2018 was performed. RBG and FBG, baseline data and adverse events were recorded. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as death, nonfatal recurrent myocardial infarction and stroke. Other adverse events included malignant arrhythmia, cardiac shock and hemorrhage. Patients with RBG > 11.1 mmol/L were divided into elevated RBG group. Patients with FBG > 6.1 mmol/L were divided into elevated FBG group. The incidence of in-hospital adverse events were compared in elevated RBG/FBG group and the control group. ROC curve was used to evaluate the predictive value of RBG and FBG on in-hospital adverse events. RESULT The incidence of death, hemorrhage, cardiac shock and malignant arrhythmia significantly increases in elevated RBG and FBG group. Binary logistic regression showed that age, hypertension, diabetes, FBG and RBG were independent risk factors for in-hospital adverse events in STEMI patients. The AUC and 95% CI of RBG and FBG in predicting death of AMI patients were 0.789, 0.759~0.816; 0.810, 0.783~0.835, respectively. The cut-off values were 13.82 and 7.35 mmol/L. RBG and FBG also had fine predictive value on cardiac shock and malignant arrhythmia, no statistical difference was found in the predictive value on in-hospital adverse events (P = 0.462, P = 0.570, P = 0.694). CONCLUSION Incidence of in-hospital adverse events significantly increases in AMI patients combined with elevated RBG or FBG. Both RBG and FBG were independent risk factors for in-hospital adverse events, they had good value on predicting in-hospital adverse events and there was no statistical difference in their predictive value.
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10.
Influence of Fasting Glucose Levels on Achieving Glycemic Target in Individuals with Type 2 Diabetes: a Post Hoc Analysis.
Ma, J, Lei, M, Li, Y, Zhang, X, Cui, N, Yang, W
Advances in therapy. 2020;(9):3816-3826
Abstract
INTRODUCTION FPG GOAL was a 24-week, open-label, treat-to-target randomized controlled trial which demonstrated that the optimal self-monitored fasting blood glucose (SM-FBG) target for most Chinese individuals with type 2 diabetes (T2D) using insulin glargine 100 IU/mL was 3.9-6.1 mmol/L. Individuals who achieved lower fasting plasma glucose (FPG) levels might achieve the target HbA1c of < 7% without increasing the risk of hypoglycemia. METHODS For this post hoc analysis, individuals were redivided into three groups based on their actual laboratory FPG levels at 24 weeks: level 1, ≤ 5.6 mmol/L; level 2, > 5.6 to ≤ 6.1 mmol/L; and level 3, > 6.1 to ≤ 7.0 mmol/L. RESULTS At week 24, 863 individuals with diabetes had available FPG data and 179, 122, and 179 individuals achieved FPG levels 1, 2, and 3, respectively. The proportion of individuals with HbA1c < 7% or HbA1c < 7% without hypoglycemia (≤ 3.9 or ≤ 3.0 mmol/L) was significantly higher in FPG levels 1 (p < 0.01) and 2 (p < 0.05) than in level 3. The least squares mean changes from baseline in HbA1c (- 1.77% and - 1.66% vs - 1.34%; both p < 0.001) and 2-h postprandial glucose (- 3.88 mmol/L and - 3.98 mmol/L vs - 3.22 mmol/L; both p < 0.05) were also significantly higher in FPG levels 1 and 2 compared with level 3. Linear regression analysis showed a moderate relationship between FPG and HbA1c levels at 24 weeks (r = 0.449). CONCLUSIONS Chinese individuals with T2D who achieved lower FPG levels with insulin glargine 100 IU/mL were more likely to achieve the recommended target HbA1c of < 7% compared with those with higher FPG levels. ClinicalTrials.gov identifier NCT02545842.