Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.
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SUBMITTER: Sutton EF
PROVIDER: S-EPMC5990470 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
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Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.
Sutton Elizabeth F EF Beyl Robbie R Early Kate S KS Cefalu William T WT Ravussin Eric E Peterson Courtney M CM
Cell metabolism 20180510 6
Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian ...[more]
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Project description:BACKGROUND:Altering the temporal distribution of energy intake (EI) and introducing periods of intermittent fasting (IF) exert important metabolic effects. Restricting EI to earlier in the day [early time-restricted feeding (eTRF)] is a novel type of IF. OBJECTIVES:We assessed the chronic effects of eTRF compared with an energy-matched control on whole-body and skeletal muscle insulin and anabolic sensitivity. METHODS:Sixteen healthy males (aged 23 ± 1 y; BMI 24.0 ± 0.6 kg·m-2) were assigned to 2 groups that underwent either 2 wk of eTRF (n = 8) or control/caloric restriction (CON:CR; n = 8) diet. The eTRF diet was consumed ad libitum and the intervention was conducted before the CON:CR, in which the diet was provided to match the reduction in EI and body weight observed in eTRF. During eTRF, daily EI was restricted to between 08:00 and 16:00, which prolonged the overnight fast by ?5 h. The metabolic responses to a carbohydrate/protein drink were assessed pre- and post-interventions following a 12-h overnight fast. RESULTS:When compared with CON:CR, eTRF improved whole-body insulin sensitivity [between-group difference (95% CI): 1.89 (0.18, 3.60); P = 0.03; ?2p = 0.29] and skeletal muscle uptake of glucose [between-group difference (95% CI): 4266 (261, 8270) ?mol·min-1·kg-1·180 min; P = 0.04; ?2p = 0.31] and branched-chain amino acids (BCAAs) [between-group difference (95% CI): 266 (77, 455) nmol·min-1·kg-1·180 min; P = 0.01; ?2p = 0.44]. eTRF caused a reduction in EI (?400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01) that was matched in CON:CR (-1.24 ± 0.35 kg; P = 0.01). CONCLUSIONS:Under free-living conditions, eTRF improves whole-body insulin sensitivity and increases skeletal muscle glucose and BCAA uptake. The metabolic benefits of eTRF are independent of its effects on weight loss and represent chronic adaptations rather than the effect of the last bout of overnight fast. This trial was registered at clinicaltrials.gov as NCT03969745.
| S-EPMC7528549 | biostudies-literature
Project description:BackgroundTime-restricted feeding is an emerging dietary intervention that is becoming increasingly popular. There are, however, no randomised clinical trials of time-restricted feeding in overweight patients with type 2 diabetes. Here, we explored the effects of time-restricted feeding on glycaemic regulation and weight changes in overweight patients with type 2 diabetes over 12 weeks.MethodsOverweight adults with type 2 diabetes (n = 120) were randomised 1:1 to two diet groups: time-restricted feeding (n = 60) or control (n = 60). Sixty patients participated in a 10-h restricted feeding treatment program (ad libitum feeding from 8:00 to 18:00 h; fasting between 18:00 and 8:00 h) for 12 weeks.ResultsHaemoglobin A1c and body weight decreased in the time-restricted feeding group (- 1.54% ± 0.19 and - 2.98 ± 0.43 kg, respectively) relative to the control group over 12 weeks (p < 0.001). Homeostatic model assessment of β-cell function and insulin resistance changed in the time-restricted feeding group (0.73 ± 0.21, p = 0.005; - 0.51 ± 0.08, p = 0.02, respectively) compared with the control group. The medication effect score, SF-12 score, and the levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol were improved in the time-restricted feeding group (- 0.66 ± 0.17, p = 0.006; 5.92 ± 1.38, p < 0.001; - 0.23 ± 0.08 mmol/L, p = 0.03; - 0.32 ± 0.07 mmol/L, p = 0.01; - 0.42 ± 0.13 mmol/L, p = 0.02, respectively) relative to the control group. High-density lipoprotein cholesterol was not significantly different between the two groups.ConclusionThese results suggest that 10-h restricted feeding improves blood glucose and insulin sensitivity, results in weight loss, reduces the necessary dosage of hypoglycaemic drugs and enhances quality of life. It can also offer cardiovascular benefits by reducing atherosclerotic lipid levels.Trial registrationThis study was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006371).
| S-EPMC8499480 | biostudies-literature
Project description:Disturbance of the circadian clock has been associated with increased risk of cardio-metabolic disorders. Previous studies showed that optimal timing of food intake can improve metabolic health. We hypothesized that time-restricted feeding could be a strategy to minimize long term adverse metabolic health effects of shift work and jetlag. In this study, we exposed female FVB mice to weekly alternating light-dark cycles (i.e. 12 h shifts) combined with ad libitum feeding, dark phase feeding or feeding at a fixed clock time, in the original dark phase. In contrast to our expectations, long-term disturbance of the circadian clock had only modest effects on metabolic parameters. Mice fed at a fixed time showed a delayed adaptation compared to ad libitum fed animals, in terms of the similarity in 24 h rhythm of core body temperature, in weeks when food was only available in the light phase. This was accompanied by increased plasma triglyceride levels and decreased energy expenditure, indicating a less favorable metabolic state. On the other hand, dark phase feeding accelerated adaptation of core body temperature and activity rhythms, however, did not improve the metabolic state of animals compared to ad libitum feeding. Taken together, restricting food intake to the active dark phase enhanced adaptation to shifts in the light-dark schedule, without significantly affecting metabolic parameters.
| S-EPMC6536683 | biostudies-literature
Project description:The purpose of this study was to evaluate the effects of a 4-week low-carbohydrate diet (LC) with or without exercise training on cardiometabolic health-related profiles in overweight/obese women. Fifty overweight/obese Chinese women (age: 22.2 ± 3.3 years, body mass index (BMI): 25.1 ± 3.1 kg·m-2) were randomized to either a LC control group (LC-CON, n = 16), a LC and high-intensity interval training group (LC-HIIT, n = 17), or a LC and moderate-intensity continuous training group (LC-MICT, n = 17). All groups consumed LC for 4 weeks, while the LC-HIIT and LC-MICT groups followed an additional five sessions of HIIT (10 × 6 s cycling sprints and 9 s rest intervals, 2.5 min in total) or MICT (cycling continuously at 50-60% of peak oxygen uptake (VO2peak) for 30 min) weekly. Blood pressure, fasting glucose, insulin sensitivity, and several metabolic or appetite regulating hormones were measured before and after intervention. Significant reductions in body weight (- ~2.5 kg, p < 0.001, η2 = 0.772) and BMI (- ~1 unit, p < 0.001, η2 = 0.782) were found in all groups. Systolic blood pressure was reduced by 5-6 mmHg (p < 0.001, η2 = 0.370); fasting insulin, leptin, and ghrelin levels were also significantly decreased (p < 0.05), while insulin sensitivity was improved. However, there were no significant changes in fasting glucose, glucagon, and gastric inhibitory peptide levels. Furthermore, no group differences were found among the three groups, suggesting that extra training (i.e., LC-HIIT and LC-MICT) failed to trigger additional effects on these cardiometabolic profiles. The short-term carbohydrate restriction diet caused significant weight loss and improved blood pressure and insulin sensitivity in the overweight/obese women, although the combination with exercise training had no additional benefits on the examined cardiometabolic profiles. Moreover, the long-term safety and effectiveness of LC needs further study.
| S-EPMC8229341 | biostudies-literature
Project description:CONTEXT:Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance. OBJECTIVE:The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function. DESIGN:This was a randomized, double-blind, placebo-controlled study. SETTING:This trial was conducted at Vanderbilt Clinical Research Center. PARTICIPANTS:Participants included overweight individuals with prediabetes. INTERVENTIONS:Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment. MAIN OUTCOME MEASURES:The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion. RESULT:Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per ?U/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per ?U/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 ?g/mg Cr. This effect persisted 3 months after sildenafil discontinuation. CONCLUSIONS:Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.
| S-EPMC4667163 | biostudies-literature
Project description:Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes). Design: Randomized double-blind placebo-controlled pilot trial. Methods: Twenty-three obese men (BMI≥35 kg/m2), 35-65 years old, were randomized to weight loss (diet and exercise) plus either anastrozole (AI+WL, n = 12) at 1 mg daily or placebo (PBO+WL, n = 11) for 6 months. Inclusion criteria: total testosterone <300 ng/mL (average of 2 measurements), estradiol≥10.9 pg/ml, LH <9 IU/l. Symptoms of hypogonadism by questionnaires; muscle strength by Biodex dynamometer; body composition and bone mineral density by dual-energy X-ray absorptiometry; bone microarchitecture and finite element analysis by high resolution peripheral quantitative-computed tomography. Results: After 6 months of therapy, AI+WL group had higher testosterone (p = 0.003) and lower estradiol (p = 0.001) compared to PBO+WL. Changes in symptoms and muscle strength did not differ between groups. AI+WL resulted in higher fat mass loss than PBO+WL (p = 0.04) without differences in changes in lean mass. Total and LDL cholesterol reduced more in the PBO+WL group compared to AI+WL (p = 0.03 for both), who experienced a minimal increase with unlikely meaningful clinical impact. Tibial trabecular bone area decreased more in PBO+WL than AI+WL group for which it remained stable (p = 0.03). Conclusions:Although AI+WL is effective in reversing the hormonal profile of HHG in severely obese men without causing major side effects, it does not lead to greater improvements in muscle strength and symptoms of hypogonadism compared to WL alone. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02959853.
| S-EPMC7243137 | biostudies-literature
Project description:The quantity and quality of food intake have been considered crucial for peoples' wellness. Only recently has it become appreciated that the timing of food intake is also critical. Nondipping blood pressure (BP) is prevalent in diabetic patients and is associated with increased cardiovascular events. However, the causes and mechanisms of nondipping BP in diabetes are not fully understood. Here, we report that food intake and BP were arrhythmic in diabetic db/db mice fed a normal chow diet ad libitum. Imposing a food intake diurnal rhythm by time-restricted feeding (TRF; food was only available for 8 h during the active phase) prevented db/db mice from developing nondipping BP and effectively restored the already disrupted BP circadian rhythm in db/db mice. Interestingly, increasing the time of food availability from 8 h to 12 h during the active dark phase in db/db mice prompted isocaloric feeding and still provided robust protection of the BP circadian rhythm in db/db mice. In contrast, neither 8-h nor 12-h TRF affected BP dipping in wild-type mice. Mechanistically, we demonstrate that TRF protects the BP circadian rhythm in db/db mice via suppressing the sympathetic activity during the light phase when they are inactive and fasting. Collectively, these data reveal a potentially pivotal role of the timing of food intake in the prevention and treatment of nondipping BP in diabetes.
| S-EPMC8237651 | biostudies-literature
Project description:Excessive adipose tissue mass underlies much of the metabolic health complications in obesity. Although exercise training is known to improve metabolic health in individuals with obesity, the effects of exercise training without weight loss on adipose tissue structure and metabolic function remain unclear. Thirty-six adults with obesity (body mass index = 33 ± 3 kg · m-2 ) were assigned to 12 weeks (4 days week-1 ) of either moderate-intensity continuous training (MICT; 70% maximal heart rate, 45 min; n = 17) or high-intensity interval training (HIIT; 90% maximal heart rate, 10 × 1 min; n = 19), maintaining their body weight throughout. Abdominal subcutaneous adipose tissue (aSAT) biopsy samples were collected once before and twice after training (1 day after last exercise and again 4 days later). Exercise training modified aSAT morphology (i.e. reduced fat cell size, increased collagen type 5a3, both P ≤ 0.05, increased capillary density, P = 0.05) and altered protein abundance of factors that regulate aSAT remodelling (i.e. reduced matrix metallopeptidase 9; P = 0.02; increased angiopoietin-2; P < 0.01). Exercise training also increased protein abundance of factors that regulate lipid metabolism (e.g. hormone sensitive lipase and fatty acid translocase; P ≤ 0.03) and key proteins involved in the mitogen-activated protein kinase pathway when measured the day after the last exercise session. However, most of these exercise-mediated changes were no longer significant 4 days after exercise. Importantly, MICT and HIIT induced remarkably similar adaptations in aSAT. Collectively, even in the absence of weight loss, 12 weeks of exercise training induced changes in aSAT structure, as well as factors that regulate metabolism and the inflammatory signal pathway in adults with obesity. KEY POINTS: Exercise training is well-known to improve metabolic health in obesity, although how exercise modifies the structure and metabolic function of adipose tissue, in the absence of weight loss, remains unclear. We report that both 12 weeks of moderate-intensity continuous training (MICT) and 12 weeks of high-intensity interval training (HIIT) induced modifications in adipose tissue structure and factors that regulate adipose tissue remodelling, metabolism and the inflammatory signal pathway in adults with obesity, even without weight loss (with no meaningful differences between MICT and HIIT). The modest modifications in adipose tissue structure in response to 12 weeks of MICT or HIIT did not lead to changes in the rate of fatty acid release from adipose tissue. These results expand our understanding about the effects of two commonly used exercise training prescriptions (MICT and HIIT) on adipose tissue remodelling that may lead to advanced strategies for improving metabolic health outcomes in adults with obesity.
| S-EPMC9058215 | biostudies-literature
Project description:AimsAccumulating evidence indicates gut microbiota dysbiosis is involved in metabolic disorders, including prediabetes. The prebiotic inulin has been frequently reported to exert beneficial effects on the host metabolism. Here, we aimed to evaluate whether dietary supplementation with inulin modulates gut microbiota structure in prediabetes, affecting glucose and lipid metabolism.MethodsWe performed a prospective single-arm study. A total of 49 subjects with prediabetes (WHO 1999 criteria) were voluntarily enrolled. Each subject received a daily supplement with 15 g of inulin for 6 months. Glucose and lipid metabolic parameters and gut microbiota were analyzed at baseline and at 3 and 6 months after inulin intervention. Intestinal microbiota profile was evaluated using the Illumina MiSeq platform based on V3-V4 bacterial 16S rRNA gene.ResultsThe mean age of 49 subjects was 56.6 ± 6.9 years and BMI was 25.07 ± 3.02 kg/m2. After 24 weeks of prevention, inulin significantly decreased fasting insulin (2.38 ± 0.50 vs. 2.22 ± 0.62, P=0.03) and 2-hour post-OGTT insulin (4.01 ± 0.77 vs. 3.74 ± 0.76, P=0.02) and improved HOMA-IR (1.05 ± 0.53 vs. 0.85 ± 0.66, P=0.03). Gut microbiota analysis indicated that inulin supplement resulted in an increase in the relative abundance of Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, Lactobacillaceae, Bifidobacterium, Lactobacillus, and Anaerostipes both at 3 and 6 months, while with a decrease in the relative abundance of Alistipes. Spearman correlation analysis revealed altered microbial community was associated with glucose and lipids metabolic parameters.ConclusionsInulin supplementation improves insulin resistance of prediabetes and exerts beneficial effects on modulating the intestinal microbiota composition. These findings suggest that insulin may be a potentially novel and inexpensive intervention for prediabetes.
| S-EPMC8261184 | biostudies-literature
Project description:BackgroundRenal innate immune cell accumulation and inflammation are associated with hypertension. Time restricted feeding (TRF) has been reported to decrease inflammation and blood pressure. Whether TRF can decrease blood pressure by decreasing renal innate immune cells in hypertension is unknown.Methods and resultsWe determined whether TRF can decrease blood pressure in two separate mouse models of hypertension, N(G)-nitro-L-arginine methyl ester hydrochloride-induced hypertension (LHTN) and salt-sensitive hypertension (SSHTN). Once hypertension was established after 2 days, TRF (12-h food/12-h no food) for 4 weeks significantly decreased systolic blood pressure in both LHTN and SSHTN mice despite no differences in the amount of food eaten or body weight between groups. Activated macrophages and dendritic cells in the kidneys of both LHTN and SSHTN mice were decreased significantly in mice that underwent TRF. This was associated with an improvement in kidney function (decreased serum creatinine, decreased fractional excretion of sodium, and increased creatinine clearance) which achieved significance in LHTN mice and trended towards improvement in SSHTN mice.ConclusionsOur findings demonstrate that TRF can significantly decrease renal innate immune cells and blood pressure in two mouse models of hypertension.
| S-EPMC9444961 | biostudies-literature