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The effect of exenatide on fasting bile acids in newly diagnosed type 2 diabetes mellitus patients, a pilot study.
Li, B, Hu, Y, Wang, G, Liu, L
BMC pharmacology & toxicology. 2020;(1):44
Abstract
BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrated good glycemic efficacy in patients with type 2 diabetes mellitus (T2DM) recent years, whereas studies on GLP-1 RAs' biliary effects were limited. Therefore, we aimed to assess the effect of exenatide on bile acids (BAs) and investigate the role of BAs in the glycemic control effect of exenatide. METHODS Thirty-eight newly diagnosed T2DM participants without glucose-lowering drugs intake were recruited. Plasma total bile acids in fasting state (FTBAs) and other parameters were tested at baseline. Then exenatide were applied to the T2DM participants for 12 weeks. FTBAs and glycemic parameters were measured again after exenatide treatment, and correlation analysis between changes of FTBAs and glycemic parameters were conducted to investigate the role of BAs in the glycemic control effect of exenatide. RESULTS The baseline FTBAs level of T2DM patients had no significance (3.84 ± 2.06 vs. 3.87 ± 2.89, P = 0.954) compared with healthy subjects. After 12-week exenatide treatment for the T2DM patients, FTBAs were decreased from 3.84 ± 2.06 μmol/L to 3.06 ± 1.27 μmol/L (P < 0.01). The correlation analysis showed that changes of FTBAs was positively correlated with changes of FPG (r = 0.355, P < 0.05). CONCLUSIONS Our results demonstrated a decreased FTBAs level after exenatide treatment for 12 weeks, without the interference of metformin and other glucose-lowering drugs. The reduction of FTBAs might not exert a positive role in the glycemic control effect of exenatide. TRIAL REGISTRATION Trial registration number: NCT04303819. Registered in March 11, 2020 - Retrospectively registered.
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Performance evaluation of a self-administered home oral glucose tolerance test kit in a controlled clinical research setting.
Dunseath, GJ, Bright, D, Jones, C, Dowrick, S, Cheung, WY, Luzio, SD
Diabetic medicine : a journal of the British Diabetic Association. 2019;(7):862-867
Abstract
AIM: To evaluate the performance of the current, pre-production version of a novel home oral glucose tolerance test (Home OGTT) device when administered by trained research nurses, compared with a reference laboratory glucose analyser and a second laboratory analyser, incorporating a sample processing delay to simulate normal practice. METHODS One hundred women (aged 19-48 years), with and without known glucose intolerance were recruited. Following an overnight fast, participants attended for a 75-g OGTT. A fasting capillary sample was applied to the Home OGTT device with a corresponding venous sample collected and measured immediately on the reference YSI 2300 stat plus analyser, and following a 1-h delay on the Randox Daytona Plus analyser. The sampling process was repeated 2 h after the oral glucose load. RESULTS Some 97% of tested devices gave complete data for analysis. Good agreement was observed between the reference glucose analyser and the Home OGTT device, with the Home OGTT device displaying a small negative bias (-0.18 mmol/l, -1.75 to 1.39 mmol/mol; -1.0%, -26.4% to 24.5%; absolute and relative mean, 95% limits of agreement). When classified as normal glucose tolerant or glucose intolerant, the Home OGTT device showed 100% and 90% sensitivity, and 99% and 99% specificity using fasting plasma glucose and 2-h glucose respectively. Similar sensitivity (100% and 100%) and specificity (96% and 99%) for fasting plasma glucose and 2-h glucose were observed using the secondary analyser. CONCLUSIONS The novel Home OGTT device was reliable and easy to use and showed excellent agreement with two separate laboratory analysers. The Home OGTT offers potential as an effective alternative for clinic-based OGTT testing.
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A nonrandomized controlled clinical pilot trial on 8 wk of intermittent fasting (24 h/wk).
Kessler, CS, Stange, R, Schlenkermann, M, Jeitler, M, Michalsen, A, Selle, A, Raucci, F, Steckhan, N
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:143-152.e2
Abstract
OBJECTIVE The aim of the study was to evaluate whether intermittent fasting (IF) is an effective preventive measure, and whether it is feasible for healthy volunteers under every day conditions. METHODS A nonrandomized controlled clinical trial on IF was performed with healthy volunteers over a period of 8 wk, and a subsequent 4-mo follow-up. Outcomes were assessed at baseline, after 8 wk, and after 6 mo. Volunteers who were not interested in fasting served as a control group. Participants in the fasting group were asked to continue their regular nutritional habits on the nonfasting days, whereas the control group maintained their habitual nutrition throughout the whole period. Outcomes included changes of metabolic parameters (insulin, glucose, insulin resistance, insulin-like growth factor-1, brain-derived neurotropic factor, lipids, liver enzymes, hemoglobin A1c) and coagulation markers; bioelectrical impedance analysis; body mass index; abdominal girth; blood pressure; general quality of life (five-item World Health Organization Well-Being Index [WHO-5] questionnaire), as well as mood and anxiety (Hospital Anxiety and Depression Scale [HADS], Profile of Mood States, Flourishing-Scale, visual analog scale, Likert scales). The intervention consisted of a fasting day, which was repeated every week for 8 wk, with abstinence from solid food between 00:00 and 23:59 at minimum and a maximum caloric intake of 300 kcal on each fasting day. A per-protocol analysis was performed. P < 0.05 was considered significant. RESULTS Thirty-six volunteers were included; 22 allocated themselves to the fasting group, and 14 to the control group. Thirty-three data sets were included in the final analysis. Although significant in-group changes were observed in both groups for a number of outcomes after 8 wk and 6 mo, no significant between-group differences were observed for any outcome other than overall body fat mass after 8 wk as well as for the HADS total score and the WHO-5 total score after 6 mo, all in favor of the fasting group. However, none of the between-group differences were clinically relevant. CONCLUSIONS We did not find any clinically relevant differences between groups in this controlled clinical pilot trial of 8 wk of IF in healthy volunteers. Further clinical research in this field is warranted to further analyze mechanisms and effects of IF.
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Timing of food intake during simulated night shift impacts glucose metabolism: A controlled study.
Grant, CL, Coates, AM, Dorrian, J, Kennaway, DJ, Wittert, GA, Heilbronn, LK, Pajcin, M, Della Vedova, C, Gupta, CC, Banks, S
Chronobiology international. 2017;(8):1003-1013
Abstract
Eating during the night may increase the risk for obesity and type 2 diabetes in shift workers. This study examined the impact of either eating or not eating a meal at night on glucose metabolism. Participants underwent four nights of simulated night work (SW1-4, 16:00-10:00 h, <50 lux) with a daytime sleep opportunity each day (10:00-16:00 h, <3 lux). Healthy males were assigned to an eating at night (NE; n = 4, meals; 07:00, 19:00 and 01:30 h) or not eating at night (NEN; n = 7, meals; 07:00 h, 09:30, 16:10 and 19:00 h) condition. Meal tolerance tests were conducted post breakfast on pre-night shift (PRE), SW4 and following return to day shift (RTDS), and glucose and insulin area under the curve (AUC) were calculated. Mixed-effects ANOVAs were used with fixed effects of condition and day, and their interactions, and a random effect of subject identifier on the intercept. Fasting glucose and insulin were not altered by day or condition. There were significant effects of day and condition × day (both p < 0.001) for glucose AUC, with increased glucose AUC observed solely in the NE condition from PRE to SW4 (p = 0.05) and PRE to RTDS (p < 0.001). There was also a significant effect of day (p = 0.007) but not condition × day (p = 0.825) for insulin AUC, with increased insulin from PRE to RTDS in both eating at night (p = 0.040) and not eating at night (p = 0.006) conditions. Results in this small, healthy sample suggest that not eating at night may limit the metabolic consequences of simulated night work. Further study is needed to explore whether matching food intake to the biological clock could reduce the burden of type 2 diabetes in shift workers.
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Effect of phytic acid, tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium.
Jaramillo, Á, Briones, L, Andrews, M, Arredondo, M, Olivares, M, Brito, A, Pizarro, F
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2015;:112-7
Abstract
OBJECTIVE To determine the effect of phytic acid, tannic acid and pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium. RESEARCH METHODS Twenty-eight apparently healthy adult females participated in two iron absorption studies using radioactive iron isotopes ((59)Fe and (55)Fe). One group received 5mg of iron (as FeSO4) alone (control), together with 10mg of phytic acid, 100mg of tannic acid and 250mg of pectin (study A), on different days. The second group received the same iron doses and compounds as the other group, plus 800mg of calcium (CaCl2) (study B). The compounds were administered after an overnight fast, and no food or beverages were consumed for the following 3h. Iron status and circulating radioactivity were measured in venous blood samples. RESULTS The geometric means of iron bioavailability (range±1SD) for iron alone, iron with phytic acid, iron with tannic acid, and iron with citrus pectin were 25.0% (11.9-52.0); 18.9% (9.9-35.8); 16.8% (8.7-32.3); and 21.1% (10.2-43.9), respectively (repeated-measures ANOVA, p<0.02 (Dunnett's post hoc: control vs tannic acid p<0.05). When 800mg of calcium was added (study B), iron bioavailability was 16.7% (10.1-27.5); 13.2% (7.1-24.6); 14.8% (8.8-25.1); and 12.6% (5.5-28.8), respectively (repeated-measures ANOVA, NS). CONCLUSIONS Tannic acid decreases the fasting bioavailability of non-heme iron, however this effect did not exist in the presence of calcium. No effect was observed by phytic acid or citrus pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium.
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Influence of Inspiratory Muscle Training on Changes in Fasting Hyperglycemia in the Older Adult: The Epidoso Project.
Dos Santos Silva, M, Ramos, LR, Tufik, S, Togeiro, SM, Lopes, GS
Journal of diabetes science and technology. 2015;(6):1352-3
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Metabolic response to 36 hours of fasting in young men born small vs appropriate for gestational age.
Jørgensen, SW, Brøns, C, Bluck, L, Hjort, L, Færch, K, Thankamony, A, Gillberg, L, Friedrichsen, M, Dunger, DB, Vaag, AA
Diabetologia. 2015;(1):178-87
Abstract
AIMS/HYPOTHESIS Being born small for gestational age (SGA) is associated with an increased risk of type 2 diabetes in an affluent society, but could confer an improved chance of survival during sparse living conditions. We studied whether insulin action and other metabolic responses to prolonged fasting differed between 21 young adults born SGA and 18 matched controls born appropriate for gestational age (AGA). METHODS A frequently sampled IVGTT and indirect calorimetry measurements were performed after a 36 h fast. Endogenous glucose production, insulin sensitivity (SI), first-phase insulin secretion and glucose effectiveness were estimated by stable isotope tracer techniques and minimal modelling. Muscle and fat biopsies were obtained after 35 h of fasting. RESULTS During fasting, SGA individuals experienced a more pronounced decrease in serum insulin and lower plasma triacylglycerol levels compared with AGA individuals. In addition, energy expenditure decreased in SGA but increased in AGA individuals. After fasting, SGA individuals displayed lower fat oxidation than AGA individuals. SG was reduced in SGA compared with AGA individuals, whereas hepatic or whole body insulin action (SI) did not differ between groups. SGA individuals had increased muscle PPARGC1A DNA methylation. We found no differences in adipose tissue PPARGC1A DNA methylation, muscle and adipose tissue PPARGC1A mRNA expression, or muscle glycogen levels between the groups. CONCLUSION Compared with AGA individuals, SGA individuals displayed a more energy-conserving and potentially beneficial [corrected] cardiometabolic response to 36 h fasting. The role of increased muscle PPARGC1A DNA methylation in mediating this response requires further study.
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Hepatic glucose sensing is impaired, but can be normalized, in people with impaired fasting glucose.
Perreault, L, Færch, K, Kerege, AA, Bacon, SD, Bergman, BC
The Journal of clinical endocrinology and metabolism. 2014;(7):E1154-62
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Abstract
OBJECTIVE Abnormal endogenous glucose production (EGP) is a characteristic feature in people with impaired fasting glucose (IFG). We sought to determine whether impaired hepatic glucose sensing contributes to abnormal EGP in IFG and whether it could be experimentally restored. METHODS Glucose production (rate of appearance; Ra) and flux (glucose cycling) were assessed during a hyperglycemic-euinsulinemic somatostatin clamp with an infusion of [6,6-(2)H2-]glucose and [2-(2)H]glucose before and after enhanced hepatic glucokinase activity via an infusion of low-dose fructose in people with IFG and normal glucose tolerance (NGT). RESULTS During euglycemia, neither endogenous glucose production [(6,6-(2)H2)-glucose Ra; P = 0.53] or total glucose output (TGO; [2-(2)H]-glucose Ra; P = .12) was different between groups, but glucose cycling ([2-(2)H]glucose Ra to [6,6-(2)H2-]glucose Ra; a surrogate measure of hepatic glucokinase activity in the postabsorptive state) was lower in IFG than NGT (P = .04). Hyperglycemia suppressed EGP more in NGT than IFG (P < .01 for absolute or relative suppression, NGT vs IFG), whereas TGO decreased similarly in both groups (P = .77). The addition of fructose completely suppressed EGP in IFG (P < .01) and tended to do the same to TGO (P = .01; no such changes in NGT, P = .39-.55). Glucose cycling (which reflects glucose-6-phosphatase activity during glucose infusion) was similar in IFG and NGT (P = .51) during hyperglycemia and was unchanged and comparable between groups with the addition of fructose (P = .24). CONCLUSIONS In summary, glucose sensing is impaired in IFG but can be experimentally restored with low-dose fructose. Glucokinase activation may prove to be a novel strategy for the prevention of diabetes in this high-risk group.
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Appetite, energy intake and resting metabolic responses to 60 min treadmill running performed in a fasted versus a postprandial state.
Deighton, K, Zahra, JC, Stensel, DJ
Appetite. 2012;(3):946-54
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Abstract
This study investigated the effect of fasted and postprandial exercise on appetite, energy intake and resting metabolic responses. Twelve healthy males (mean±SD: age 23±3 years, body mass index 22.9±2.1 kg m(-2), maximum oxygen uptake 57.5±9.7 mL kg(-1) min(-1)) performed three 10 h experimental trials (control, fasted exercise and postprandial exercise) in a Latin Square design. Trials commenced at 8 am after an overnight fast. Sixty min of treadmill running at ∼70% of maximum oxygen uptake was performed at 0-1 h in the fasted exercise trial and 4-5 h in the postprandial exercise trial. A standardised breakfast was provided at 1.5 h and ad libitum buffet meals at 5.5 and 9.5 h. Appetite ratings and resting expired air samples were collected throughout each trial. Postprandial exercise suppressed appetite to a greater extent than fasted exercise. Ad libitum energy intake was not different between trials, resulting in a negative energy balance in exercise trials relative to control after accounting for differences in energy expenditure (control: 9774±2694 kJ; fasted exercise: 6481±2318 kJ; postprandial exercise: 6017±3050 kJ). These findings suggest that 60 min treadmill running induces a negative daily energy balance relative to a sedentary day but is no more effective when performed before or after breakfast.
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Severe catabolic state after an overnight fast in patients with chronic renal failure.
Nakaya, Y, Shimohata, T, Haraguchi, S, Nakao, T, Minaguchi, J, Sumitani, H, Harada, N, Sakaue, H
Nutrition (Burbank, Los Angeles County, Calif.). 2011;(3):329-32
Abstract
OBJECTIVE Starvation causes more rapid development of a catabolic state in patients with liver cirrhosis than in normal subjects. Because the kidneys have a gluconeogenic activity similar to that of the liver, we tested whether patients with chronic renal failure develop a catabolic state after an overnight fast. METHODS The effect of an overnight fast on diurnal changes in respiratory quotient (RQ) was studied in 12 normal subjects and 12 patients with stable chronic renal failure. Changes in RQ in the early morning after an overnight fast were also studied in 27 patients with chronic renal failure not on dialysis. We also examined the effect on RQ of consuming a light snack in the evening before the measurements. RESULTS The RQ before breakfast, but not at other times, was significantly lower in patients with renal failure than in normal subjects (0.824 ± 0.051 versus 0.868 ± 0.038, P < 0.05). This indicated that patients with renal failure had higher fat use and developed a catabolic state early in the morning. The RQ before breakfast showed significant inverse correlations with creatinine levels (r = -0.604, P < 0.001). Supplementation with a carbohydrate-rich snack in the evening resulted in a significant increase of 0.07 ± 0.04 (P < 0.05) in mean RQ in the early morning. This suggested that a late evening snack is useful for improving the catabolic state of patients with renal failure. CONCLUSION Starvation involving an overnight fast facilitates catabolism of visceral and muscle proteins in renal failure. This suggests that nutritional management of renal failure should focus not only on the contents of a meal, but also on the timing of the meal.