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Effects of intermittent very-low calorie diet on glycemic control and cardiovascular risk factors in obese patients with type 2 diabetes mellitus: A randomized controlled trial.
Umphonsathien, M, Rattanasian, P, Lokattachariya, S, Suansawang, W, Boonyasuppayakorn, K, Khovidhunkit, W
Journal of diabetes investigation. 2022;13(1):156-166
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Various studies have shown that intermittent low-calorie diets are effective in reducing weight and improving glycaemic control. In this randomized controlled trial, two intermittent very-low calorie diets (2 days per week and 4 days per week) were evaluated against a control group with respect to achieving diabetes remission, improving glycemic control, metabolic parameters, and quality of life in Type 2 diabetic patients. There was a significant reduction in HbA1c and insulin resistance in the 2 days/week and 4 days/week intermittent very-low calorie groups at week 20. Both the intervention groups achieved diabetes remission with 29% of participants not requiring glucose-lowering medications at week 20. Both intervention groups also showed a significant reduction in serum triglycerides, body weight, body mass index, and fat mass. Aspartate transaminase and alanine aminotransferase levels, as well as blood pressure, decreased significantly with a 4 day/week intermittent low-calorie diet. Both intervention groups experienced improved quality of life at week 10 and the interventions were generally well tolerated. To generalise the results, longer-term, robust studies are required. These results can help healthcare providers understand the clinical relevance of intermittent very-low calorie diets in managing Type 2 diabetes and obesity.
Abstract
AIMS/INTRODUCTION Very few studies assess the effectiveness of different protocols of intermittent very-low calorie diet (VLCD) in patients with diabetes. This study was designed to compare the effects of 2 days/week and 4 days/week of intermittent VLCD on glycemic control, diabetes remission, metabolic parameters and quality of life in patients with type 2 diabetes and obesity. MATERIALS AND METHODS Participants with obesity and type 2 diabetes were recruited and randomly assigned to three groups, consisting of control, 2 days/week and 4 days/week of intermittent VLCD. In the intermittent VLCD groups, participants received a 600-kcal diet per day on restricted days and ad libitum food consumption on non-restricted days. Glycemic control, rate of diabetes remission, metabolic parameters and quality of life were evaluated at baseline, weeks 2, 10 and 20. RESULTS A total of 40 participants were enrolled. The mean body mass index was 30.1 ± 5.9 kg/m2 , and the mean glycated hemoglobin was 7.4 ± 1.2%. At week 20, there was an improvement in glycemic control in both intermittent VLCD groups with significant decreases in glycated hemoglobin levels and insulin resistance index throughout the study periods. Diabetes remission without the need for medications was equally found in 29% of participants in both intermittent VLCD groups. Serum triglyceride, bodyweight, body mass index and fat mass were also significantly decreased in both VLCD groups. No serious adverse events were encountered. CONCLUSION Intermittent VLCD was highly effective in achieving optimal glycemic control. The effects of 2 days/week and 4 days/week of intermittent VLCD on diabetes remission were relatively similar.
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The Effects of Time-Restricted Eating versus Standard Dietary Advice on Weight, Metabolic Health and the Consumption of Processed Food: A Pragmatic Randomised Controlled Trial in Community-Based Adults.
Phillips, NE, Mareschal, J, Schwab, N, Manoogian, ENC, Borloz, S, Ostinelli, G, Gauthier-Jaques, A, Umwali, S, Gonzalez Rodriguez, E, Aeberli, D, et al
Nutrients. 2021;13(3)
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Metabolic syndrome (MS) is a collection of conditions such as obesity, high blood pressure and impaired ability to balance blood sugars, that increase the sufferers risk of diabetes, stroke, and heart disease. Weight loss and lifestyle modifications are the main recommendations to improve MS. Intermittent fasting is a dietary regime that involves restricting the intake of food to certain times of the day, without restricting calories and has been shown in animal and human studies to result in fat loss and an increased ability to balance blood sugars. This randomised control trial of 218 adults over 6 months aimed to firstly determine relationships between eating duration, unprocessed and processed foods, and lifestyle factors on health and secondly to determine if a 12-hour time restricted eating pattern leads to an improvement in MS. The results showed that higher consumption of processed foods was associated with poorer metabolic health. A 12-hour restricted eating pattern resulted in weight loss, whereas individuals on a standard daily eating pattern did not, however differences between the two groups were not significant. Other measures of metabolic health failed to show any differences between the two groups. It was concluded that a 12-hour restricted eating pattern was feasible over 6 months, however further research is needed to assess if a more restricted time would result in greater weight loss. This study could be used by healthcare professionals to understand that a restricted eating pattern may be of benefit to those with MS, however further research would be needed to determine the optimal timeframe.
Abstract
Weight loss is key to controlling the increasing prevalence of metabolic syndrome (MS) and its components, i.e., central obesity, hypertension, prediabetes and dyslipidaemia. The goals of our study were two-fold. First, we characterised the relationships between eating duration, unprocessed and processed food consumption and metabolic health. During 4 weeks of observation, 213 adults used a smartphone application to record food and drink consumption, which was annotated for food processing levels following the NOVA classification. Low consumption of unprocessed food and low physical activity showed significant associations with multiple MS components. Second, in a pragmatic randomised controlled trial, we compared the metabolic benefits of 12 h time-restricted eating (TRE) to standard dietary advice (SDA) in 54 adults with an eating duration > 14 h and at least one MS component. After 6 months, those randomised to TRE lost 1.6% of initial body weight (SD 2.9, p = 0.01), compared to the absence of weight loss with SDA (-1.1%, SD 3.5, p = 0.19). There was no significant difference in weight loss between TRE and SDA (between-group difference -0.88%, 95% confidence interval -3.1 to 1.3, p = 0.43). Our results show the potential of smartphone records to predict metabolic health and highlight that further research is needed to improve individual responses to TRE such as a shorter eating window or its actual clock time.
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A Delayed Morning and Earlier Evening Time-Restricted Feeding Protocol for Improving Glycemic Control and Dietary Adherence in Men with Overweight/Obesity: A Randomized Controlled Trial.
Parr, EB, Devlin, BL, Radford, BE, Hawley, JA
Nutrients. 2020;12(2)
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Dietary strategies which focus on the timing and duration of eating and fasting, rather than the type, quality or quantity of foods, appear to improve metabolic health independent of weight loss. Time restricted feeding (TRF) refers to an eating pattern where food intake is limited to a certain duration, e.g. 8 hours. The aim of this randomized crossover trial was to compare the effects of TRF versus extended feeding time (EXT). 11 sedentary men with obesity/overweight had their three meals which contained equal calories and macronutrient composition, either at 10:00, 13:00 and 17:00 or at 07:00, 14:00 and 21:00 for 5 days, and after a 10 days wash-out phase, swapped to the other feeding pattern. The TRF improved blood glucose control after breakfast and lunch and at night. The TRF pattern was well accepted by participants who felt that it improved their general wellbeing, helped them reduce snacking and the structure encouraged good habits. Work, social and family life schedules were noted as potential barriers to adopting TRF.
Abstract
We determined the effects of time-restricted feeding (TRF; 8 h/d) versus extended feeding (EXF; 15 h/d) on 24-h and postprandial metabolism and subjective opinions of TRF in men with overweight/obesity. In a randomized crossover design, 11 sedentary males (age 38 ± 5 y; BMI: 32.2 ± 2.0 kg/m2) completed two isoenergetic diet protocols for 5 days, consuming meals at 1000, 1300 and 1700 h (TRF) or 0700, 1400 and 2100 h (EXF). On Day 5, participants remained in the laboratory for 24 h, and blood samples were collected at hourly (0700-2300 h) then 2-hourly (2300-0700 h) intervals for concentrations of glucose, insulin and appetite/incretin hormones. Structured qualitative interviews were conducted following completion of both dietary conditions and investigated thematically. Total 24-h area under the curve (AUCtotal) [glucose] tended to be lower for TRF versus EXF (-5.5 ± 9.0 mmol/L/h, P = 0.09). Nocturnal glucose AUC was lower in TRF (-4.2 ± 5.8 mmol/L/h, P = 0.04), with no difference in waking glucose AUC or AUCtotal for [insulin]. Attitudes towards TRF were positive with improved feelings of well-being. Barriers to TRF were work schedules, family commitments and social events. Compared to extended feeding, short-term TRF improved nocturnal glycemic control and was positively perceived in men with overweight/obesity.
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PROFAST: A Randomized Trial Assessing the Effects of Intermittent Fasting and Lacticaseibacillus rhamnosus Probiotic among People with Prediabetes.
Tay, A, Pringle, H, Penning, E, Plank, LD, Murphy, R
Nutrients. 2020;12(11)
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The prevalence of diabetes is increasing worldwide, and with it, the risk of cardiovascular disease is also increasing. Intermittent fasting has been shown to reduce weight and improve glycaemic control. Weight control and glycaemic control were also improved with probiotic Lacticaseibacillus rhamnosus HN001 supplementation. This pilot, 12-week, double-blinded, two-armed, randomized 1:1 study aimed to investigate the combined effects of intermittent fasting with daily probiotic Lacticaseibacillus rhamnosus HN001 supplementation on glycaemic management in participants with prediabetes. For two days, participants restricted their calorie intake to 600-650 kcal, followed by five days of ad libitum consumption (5:2). Intermittent fasting for 12 weeks improved glycaemic control (reduced HbA1c) and reduced body weight by 5%. The supplementation with Lacticaseibacillus rhamnosus HN001 did not significantly improve these outcomes. Probiotic supplementation significantly improved mental health and social functioning in participants. There is a need for further large, robust studies to assess the effects of intermittent fasting alone and when it is combined with different exercise forms and different prebiotic and probiotic supplements on cardiometabolic markers and mental health. The findings of this study may be useful to healthcare professionals in understanding the effects of fasting on metabolism as well as the psychological benefits of Lacticaseibacillus rhamnosus HN001 supplementation.
Abstract
Both intermittent fasting and specific probiotics have shown promise in improving glucose tolerance with a potential for synergistic effects through alterations to gut microbiota. In this randomized, double-blinded, two-arm feasibility study, we investigated whether intermittent fasting, supplemented with Lacticaseibacillus rhamnosus HN001 probiotic, reduces HbA1c in individuals with prediabetes. All participants with HbA1c 40-50 mmol/mol commenced intermittent fasting (2 days per week of calorie restriction to 600-650 kcal/day) and were randomized 1:1 to either daily probiotic (Lacticaseibacillus rhamnosus HN001) or placebo for 12 weeks. The primary outcome was a change in HbA1c. Secondary outcomes included changes in anthropometry, body composition, glucoregulatory markers, lipids, hunger hormones, liver enzymes, inflammatory markers, gut hormones, calorie and macronutrient intake, quality of life, hunger, mood and eating behavior. Of 33 participants who commenced the trial, 26 participants (mean age 52 years, body mass index (BMI) 34.7 kg/m2) completed the intervention (n = 11 placebo, n = 15 probiotic). HbA1c decreased from 43 ± 2.7 mmol/mol to 41 ± 2.3 mmol/mol, p < 0.001, with average of 5% weight loss. No significant between-group differences were seen in primary or secondary outcomes except for social functioning (p = 0.050) and mental health (p = 0.007) scores as improvements were seen in the probiotic group, but not in the placebo group. This study shows additional psychological benefits of probiotic supplementation during intermittent fasting to achieve weight loss and glycemic improvement in prediabetes.
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Effects of Intermittent Energy Restriction Combined with a Mediterranean Diet on Reducing Visceral Adiposity: A Randomized Active Comparator Pilot Study.
Panizza, CE, Lim, U, Yonemori, KM, Cassel, KD, Wilkens, LR, Harvie, MN, Maskarinec, G, Delp, EJ, Lampe, JW, Shepherd, JA, et al
Nutrients. 2019;11(6)
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Excess adiposity is known to contribute to many metabolic diseases. Intermittent energy restriction (IER) has emerged as a favourable method of calorie reduction, and combining IER with the Mediterranean diet has shown promising results for reducing body fat and improving insulin resistance. The aim of this pilot study was to explore efficacy of an IER and Mediterranean diet in adiposity reduction in 60 Japanese Americans. Participants were randomised to either consume the IER + Mediterranean diet (22) or a control anti-hypertension diet (26) for 12 weeks. At baseline and 12-weeks, visceral adipose tissue and total fat mass were measured. Phone check-ins were completed weekly for the 12-weeks and both groups had equivalent dietetic support. This study found significant reductions in total fat mass in the IER + Mediterranean group compared with the control group, and found diet adherence to be high. Based on these results, the authors conclude the IER and Mediterranean diet combined can lower total adiposity and potentially improve liver function among Japanese Americans.
Abstract
Intermittent energy restriction combined with a Mediterranean diet (IER+MED) has shown promise to reduce body fat and insulin resistance. In the Multiethnic Cohort Adiposity Phenotype Study, Japanese Americans had the highest visceral adipose tissue (VAT) when adjusting for total adiposity. We conducted this pilot study to demonstrate feasibility and explore efficacy of following IER+MED for 12 weeks to reduce VAT among East Asians in Hawaii. Sixty volunteers (aged 35-55, BMI 25-40 kg/m2, VAT ≥ 90 cm2 for men and ≥ 80 cm2 for women) were randomized to IER+MED (two consecutive days with 70% energy restriction and 5 days euenergetic MED) or an active comparator (euenergetic Dietary Approaches to Stop Hypertension (DASH) diet). Participants and clinic staff (except dietitians) were blinded to group assignments. IER+MED had significantly larger reductions in DXA-measured VAT and total fat mass (-22.6 ± 3.6 cm2 and -3.3 ± 0.4 kg, respectively) vs. DASH (-10.7 ± 3.5 cm2 and -1.6 ± 0.4 kg) (p = 0.02 and p = 0.005). However, after adjusting for total fat mass, change in VAT was not statistically different between groups; whereas, improvement in alanine transaminase remained significantly greater for IER+MED vs. DASH (-16.2 ± 3.8 U/L vs. -4.0 ± 3.6 U/L, respectively, p = 0.02). Attrition rate was 10%, and participants adhered well to study prescriptions with no reported major adverse effect. Results demonstrate IER+MED is acceptable, lowers visceral and total adiposity among East Asian Americans, and may improve liver function more effectively than a healthful diet pattern. ClinicalTrials.gov Identifier: NCT03639350.
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Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.
Wegman, MP, Guo, MH, Bennion, DM, Shankar, MN, Chrzanowski, SM, Goldberg, LA, Xu, J, Williams, TA, Lu, X, Hsu, SI, et al
Rejuvenation research. 2015;18(2):162-72
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It has been repeatedly shown that calorie restriction is beneficial for health by delaying the onset of age-related diseases. Long term calorie restriction is difficult to maintain. It is thought that benefits are due to increased oxidative stress which triggers expression of protective genes, resulting in an overall health benefit. Intermittent fasting (IF), where days of fasting and feasting are alternated, can result is similar benefits. In this double-crossover, double-blinded, randomised clinical trial seventeen young, healthy adults followed either IF + placebo or IF + antioxidants for three weeks each. The provided food was based on American Dietary Guidelines and the antioxidant supplements were vitamins C and E. Participants ate 25% of calories on fast days and 175% of calories on feast days to achieve overall neutral calorie balance. The aim of the trial was to show if benefits were due to intermittent periods of fasting rather than overall calorie reduction commonly seen with other IF trials. Further, if antioxidant supplements would reduce expression of the protective genes. Markers of oxidative stress and gene expression were measured. Results showed that IF decreases insulin, but IF + antioxidants did not, suggesting that the insulin lowering effect might be triggered by IF oxidative stress. Results also suggested IF mildly raised measured gene expression, including expression of sirtuin 3 (SIRT3), but IF + antioxidant reduced or reversed rises. However, none of the gene expression results were statistically significant, SIRT3 was closest. The authors stated that the findings suggest that IF may have some benefits on metabolism and potentially longevity, even in healthy individuals.
Abstract
Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.
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Three 15-min bouts of moderate postmeal walking significantly improves 24-h glycemic control in older people at risk for impaired glucose tolerance.
DiPietro, L, Gribok, A, Stevens, MS, Hamm, LF, Rumpler, W
Diabetes care. 2013;36(10):3262-8
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The insulin response is known to decline with age, which puts older people at risk of hyperglycaemia after eating. Insulin and exercise stimulate the uptake of glucose into skeletal muscle so exercise could aid insulin in age-related impaired glucose tolerance (IGT). This small randomised controlled trial (RCT) used a multiple crossover design to compare the effect of exercise timing and frequency on glycaemia control in older people. The ten trial subjects were at risk of impaired glucose tolerance (IGT), but were otherwise healthy with an average age of sixty-nine years old. Subjects were housed in whole room calorimeters, fed three standardised meals a day and glucose levels were monitored. Subjects were randomly assigned to walk on a treadmill for either fifteen minutes after each of the three meals, or walk for forty-five minutes either at mid-morning or mid-afternoon. It was found that that both the morning walk and the post-meal walking decreased 24 hour glucose concentration, whilst the afternoon walk had little impact. Post-meal walking was effective at lowering glucose levels after each meal including dinner, where the other exercise protocols were not. The author concluded that the timing of the exercise may be as important, if not more, than volume. Short (15 minute) bouts of post-meal walking could be manageable for older people and appears to be an effective way of controlling post eating hyperglycaemia.
Abstract
OBJECTIVE The purpose of this study was to compare the effectiveness of three 15-min bouts of postmeal walking with 45 min of sustained walking on 24-h glycemic control in older persons at risk for glucose intolerance. RESEARCH DESIGN AND METHODS Inactive older (≥60 years of age) participants (N=10) were recruited from the community and were nonsmoking, with a BMI<35 kg/m2 and a fasting blood glucose concentration between 105 and 125 mg dL(-1). Participants completed three randomly ordered exercise protocols spaced 4 weeks apart. Each protocol comprised a 48-h stay in a whole-room calorimeter, with the first day serving as the control day. On the second day, participants engaged in either 1) postmeal walking for 15 min or 45 min of sustained walking performed at 2) 10:30 a.m. or 3) 4:30 p.m. All walking was on a treadmill at an absolute intensity of 3 METs. Interstitial glucose concentrations were determined over 48 h with a continuous glucose monitor. Substrate utilization was measured continuously by respiratory exchange (VCO2/VO2). RESULTS Both sustained morning walking (127±23 vs. 118±14 mg dL(-1)) and postmeal walking (129±24 vs. 116±13 mg dL(-1)) significantly improved 24-h glycemic control relative to the control day (P<0.05). Moreover, postmeal walking was significantly (P<0.01) more effective than 45 min of sustained morning or afternoon walking in lowering 3-h postdinner glucose between the control and experimental day. CONCLUSIONS Short, intermittent bouts of postmeal walking appear to be an effective way to control postprandial hyperglycemia in older people.
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Oral sensory and cephalic hormonal responses to fat and non-fat liquids in bulimia nervosa.
Bello, NT, Coughlin, JW, Redgrave, GW, Moran, TH, Guarda, AS
Physiology & behavior. 2010;99(5):611-7
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Bulimia nervosa (BN) is characterised by episodes of compulsive binge eating and compensatory behaviours such as restriction/fasting, over exercising or self-induced purging. Research suggests that sufferers may have alterations in their food evaluations and the cephalic phase of eating. This study explores whether the oral sensory responses from high fat liquids compared to non-fat liquids were different in BN subjects compared to healthy controls. The hormonal responses to each liquid were qualified by measuring glucose, insulin, ghrelin and pancreatic polypeptides (which have been found to be associated with cephalic phase of eating solid foods). Subjective hunger levels were also measured. Participants were 10 women aged between 18 and 42 years, and the control group consisted of 11 women without an eating disorder. The study found not significant differences between the fat and non-fat liquids in terms of hunger levels or hormonal responses. However, there were differences between the BN group and the control. BN compared to controls had higher levels of hunger at baseline. BN's also rated the liquids 'fattier' tasting regardless of the fat content of the liquids and also reported a 'fear of swallowing' more than the control group. There were also differences between the BN and control group in baseline hormonal levels - BN's had significantly elevated ghrelin and pancreatic polypeptide levels. BN's also had elevated ghrelin levels throughout. The authors concluded that BN women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.
Abstract
Sensory evaluation of food involves endogenous opioid mechanisms. Bulimics typically limit their food choices to low-fat "safe foods" and intermittently lose control and binge on high-fat "risk foods". The aim of this study was to determine whether the oral sensory effects of a fat versus a non-fat milk product (i.e., traditional versus non-fat half-and-half) resulted in different subjective and hormonal responses in bulimic women (n=10) compared with healthy women (n=11). Naltrexone (50mg PO) or placebo was administered 1h before, and blood sampling began 30 min prior to and 29 min after, a 3 min portion controlled modified sham-feeding trial. Following an overnight fast, three morning trials (fat, naltrexone; fat, placebo; and non-fat, placebo) were administered in a random double-blind fashion separated by at least 3 days. Overall, there were no differences between Fat and Non-Fat trials. Hunger ratings (p<0.001) and pancreatic polypeptide levels (p<0.05) were higher for bulimics at baseline. Bulimics also had overall higher ratings for nausea (p<0.05), fatty taste (p<0.01), and fear of swallowing (p<0.005). Bulimics had approximately 40% higher total ghrelin levels at all time points (p<0.001). Hormones and glucose levels were not altered by the modified sham-feeding paradigm. Naltrexone, however, resulted in an overall increase in blood glucose and decrease in ghrelin levels in both groups (p<0.05, for both). These data suggest that bulimic women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.