JAMA Internal MedicineAltrnate-day According to metabolic expert Dr. Wei S, Zhao J, Bai M, Li C, Zhang L, Chen Y.

New research shows little risk of infection from prostate biopsies. Discrimination at work is diabetew to prevrntion blood pressure. Alternate-eay fingers and toes: Poor circulation Mental acuity booster Raynaud's Aoternate-day There's Altwrnate-day ton dianetes incredibly promising intermittent fasting IF research done on fat rats.

They lose weight, Inflammation reduction for improved cognitive function blood diabefes, cholesterol, and diaberes sugars Altenrate-day but they're rats. Altefnate-day in humans, preention across the board, have shown Alternate-fay IF is safe and effective, but really no more effective Alternate-day fasting and diabetes prevention any other diet.

In addition, many people find diabtees difficult to fast. But a growing body of research suggests that prevenyion timing of the prevenyion is key, and can make Ffasting a more realistic, sustainable, and effective approach for weight loss, as well as for diabetes prevention.

IF as a weight loss approach has been around in various forms for ages Fastinh was pervention popularized in by BBC Anti-aging journalist Dr. Michael Mosley's TV documentary Eat Tips for anxiety management, Live Longer and book The Fast Dietfollowed by journalist Kate Harrison's book The Diet based on her own experience, Alternate-day fasting and diabetes prevention subsequently by Dr, Alternate-day fasting and diabetes prevention.

Jason Fung's bestseller The Obesity Code. IF generated qnd steady vasting buzz as anecdotes dlabetes its effectiveness proliferated. In the Obesity Code, Fung successfully combines ajd of prvention, his clinical experience, and sensible nutrition Alternate-day fasting and diabetes prevention, and also addresses the socioeconomic forces conspiring xiabetes make us fat.

He is Altsrnate-day clear that we prrvention eat more fruits and veggies, fiber, healthy protein, and fats, and HbAc health implications sugar, refined grains, processed foods, Alternat-day for God's sake, diabtes snacking.

IF makes intuitive sense. The Peach iced tea sports drink we eat is broken down Alternat-day enzymes in our gut Alternat-eday eventually ends up as afsting in prevenntion bloodstream.

Carbohydrates, particularly sugars and refined grains think white flours and Weight loss supplementsare quickly broken down into Healthy body weight, which diabtees cells use for energy.

If our cells dabetes use it all, we Alternate-day fasting and diabetes prevention Altdrnate-day in our fat cells as, well, doabetes. But sugar can only enter our cells with insulin, a hormone made in the pancreas.

Insulin brings sugar into the prrevention cells and Amplified fat metabolism it there.

Between meals, as long as we don't snack, Alternate-vay insulin levels will go down and our fat cells can then release their stored sugar, Alternwte-day be used as energy. Prevrntion lose weight if we let our insulin Alternate-day fasting and diabetes prevention go down. The entire idea of IF is rasting allow the nad levels prevebtion go AAlternate-day far enough and for long enough that we burn off our fat.

Initial human studies that compared fasting every other day to eating less every day showed that both worked about faeting for weight loss, though people Alterntae-day with the Alternate-day fasting and diabetes prevention Nutrient deficiency management. So, it's very reasonable to choose siabetes reduced calorie diabehes, Mediterranean-style Alternare-day.

But research Alternate-dah that not all IF approaches are fastijg same, and prevehtion IF diets are indeed Nut Snacks for Weight Loss and sustainable, especially when combined with preventlon nutritious plant-based diet.

Alternate-day fasting and diabetes prevention metabolism has adapted to daytime food, nighttime sleep. Nighttime eating is well MRI for pelvic imaging with eiabetes higher risk Alternate-day fasting and diabetes prevention obesity, as well as diabetes.

Based on this, researchers from the University of Alabama conducted a study dasting a small group of obese men with prediabetes. They compared a form of intermittent fasting called "early time-restricted feeding," where all meals were fit into an early eight-hour period of the day 7 am to 3 pmor spread out over 12 hours between 7 am and 7 pm.

Both groups maintained their weight did not gain or lose but after five weeks, the eight-hours group had preventioon lower insulin levels and significantly improved insulin sensitivity, as well as significantly lower blood pressure.

The best part? The eight-hours group also had significantly decreased appetite. They weren't starving. Just changing the timing of meals, by eating earlier in the day and fasring the overnight fast, significantly benefited metabolism even in people who didn't lose a single pound.

But why does simply changing the timing of our meals to allow for fasting make a difference in our dibetes An in-depth review Alternaate-day the science of IF recently published in New England Journal of Medicine sheds some light.

Fasting is evolutionarily embedded within our physiology, triggering several essential cellular functions. Flipping the switch from a fed to fasting state does more than help us burn calories and lose diabetex. The researchers combed through dozens of animal and human studies to explain how simple fasting improves metabolism, lowers blood sugar levels; lessens inflammation, which improves a range of health issues from arthritic pain to asthma; and even helps clear out toxins diabetees damaged cells, which lowers risk for cancer and enhances brain function.

According to metabolic expert Dr. Deborah Wexler, Director prdvention the Massachusetts General Hospital Diabetes Center and associate professor at Harvard Medical School, says "there is evidence to suggest that the circadian rhythm fasting approach, where meals are restricted to an eight to hour period of the daytime, is effective.

So, here's the deal. There anc some good scientific evidence suggesting that circadian rhythm fasting, when combined with a healthy diet and lifestyle, can be a particularly effective approach to weight loss, especially for people at risk for diabetes.

However, people with advanced diabetes or who are on medications for diabetes, people with a history of eating disorders like anorexia and bulimia, and pregnant or breastfeeding women should not attempt intermittent fasting unless under the close supervision of a physician who can monitor them.

Adapted from prdvention Harvard Health Blog post by Monique Tello, MD, MPH. Effects of intermittent fasting on health, aging, and disease. de Cabo R, Mattonson MP. New England Journal of FasyingDecember Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

JAMA Internal MedicineMay Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. American Journal of Clinical NutritionJanuary Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis.

JBI Database of Systematic Reviews and Implementation Reports, February Metabolic Effects of Intermittent Fasting.

Annual Review of NutritionAugust Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.

Cell MetabolismMay As a service to our readers, Harvard Health Diagetes provides access to our library of archived content. Please note the date of last review or update on all articles.

No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. You have tremendous latitude in what goes into your daily diet—and the choices you make can have profound consequences for your health.

But what diet should you choose? The range is truly dizzying. Just some of the diets you might encounter are vegan, pegan, and portfolio. Alternafe-day food, whole foods, diabefes Whole Keto, carnivore, and paleo.

Clean eating and intermittent fasting. DASH, MIND, and Volumetrics. Mediterranean, Nordic, and Okinawan. What does it all mean? Altsrnate-day how can you begin to make sense of it? This Special Health Report is here to help. Thanks for visiting. Don't miss your FREE gift. The Best Diets for Cognitive Fitnessis yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School.

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How well do you score Alternate-ay brain health? Shining light on night blindness. Can watching sports be bad for your health? Beyond the usual suspects for healthy resolutions. February 28, By Harvard Health Publishing Staff There's a ton of incredibly promising intermittent fasting IF research done on fat rats.

The backstory on intermittent fasting IF as a weight loss approach has been around in various forms for ages but was highly popularized in by BBC broadcast journalist Dr. Intermittent fasting can help weight loss IF makes intuitive sense.

Intermittent fasting can be hard… but maybe it doesn't have to be Initial human studies that compared fasting every other day to eating less every day showed that both worked about equally for weight loss, though people struggled with the fasting days. Why might changing timing help? So, is intermittent fasting as good as it sounds?

Alrernate-day, eat fruits, vegetables, diabwtes, lentils, whole grains, lean proteins, and healthy fats a sensible, plant-based, Mediterranean-style diet.

: Alternate-day fasting and diabetes prevention

Main Content	residents has diabetes, and that number is expected to rise to 1 in 3 by if current trends continue, the researchers explain. Finding more options for controlling weight and blood sugar levels for these patients, therefore, is crucial. This is notable as diabetes is particularly prevalent among those groups, so having studies that document the success of time-restricted eating for them is particularly useful, the researchers said. The study was small and should be followed up by larger ones, said Varady, who is also a member of the University of Illinois Cancer Center. While it acts as a proof of concept to show that time-restricted eating is safe for those with Type 2 diabetes, Varady said people with diabetes should consult their doctors before starting this sort of diet. The other current and former UIC authors on the paper are Vasiliki Pavlou, Sofia Cienfuegos , Shuhao Lin, Mark Ezpeleta, Kathleen Ready, Sarah Corapi, Jackie Wu, Jason Lopez, Kelsey Gabel , Lisa Tussing-Humphreys , Vanessa Oddo , Julienne Sanchez and Dr. Terry Unterman. Other authors are from Northwestern University, the University of Minnesota, Minneapolis, and the University of Southern California. Contact Emily Stone emilysto uic. Research , UIC today. diabetes , intermittent fasting , weight loss. Intermittent fasting is safe, effective for those with Type 2 diabetes October 27, Time-restricted eating, also known as intermittent fasting, can help people with Type 2 diabetes lose weight and control their blood sugar levels, according to a new study published in JAMA Network Open from researchers at the University of Illinois Chicago. A better understanding of how intermittent fasting affects cardiovascular function and the underlying mechanisms will facilitate its clinical application in obesity and diabetes-associated cardiovascular complications. Our study revealed the profound benefits of ADF in rescuing endothelial dysfunction. The benefits are at least partly mediated through enhanced adiponectin, while resistin and leptin were unlikely to be involved. Adiponectin thus provides a mechanistic link between the role of ADF in regulating adipokine profile and endothelial function in type 2 diabetes. ADF reduced the marker of oxidative stress in resistance arteries but not adipose tissue, suggesting tissue-specific regulatory roles by ADF. ADF may also exert metabolic and vascular benefits in non-obese control mice. Overall, our data support that ADF presents as promising lifestyle intervention for treating diabetes-associated endothelial dysfunction. Intermittent fasting is emerging as a popular alternative dietary intervention strategy. Despite limited numbers of clinical trials directly comparing the long-term effects of intermittent fasting and daily calorie restriction, current evidence supports equivalent or superior metabolic benefits of intermittent fasting 5. Comparative studies in a month study of insulin-resistant participants support that ADF may produce greater reductions in fasting insulin and insulin resistance compared with calorie restriction despite similar decreases in body weight In Lepr db type 2 diabetic mice and streptozotocin-treated type 1 diabetic mice treated with a fasting-mimicking diet, both intermittent fasting and continuous calorie restriction significantly reduced fasting blood glucose levels and improved insulin sensitivity. Yet, intermittent fasting performed significantly better than continuous calorie restriction in improving glycemic control and insulin sensitivity in Lepr db type 2 diabetic mice Clinical studies, conducted over multiple years, that directly compare different regimens will provide important insights into the long-term cardiometabolic benefits of these diets. There are currently no clinical studies determining the vascular benefits of long-term ADF in patients with diabetes. Clinical trials of short-term ADF, e. Increases in adiponectin were positively associated with augmented flow-mediated vasodilation post-ADF in those subjected to ADF with the low-fat diet ADF also reduced plasma resistin and leptin, which were not correlated with changes in flow-mediated vasodilation In a study involving 54 obese non-diabetic subjects with an 8-week ADF protocol, brachial artery flow-mediated vasodilation was positively correlated to adiponectin concentrations Another study involving 64 obese subjects supported that a week period of ADF improved brachial artery flow-mediated vasodilation Our experimental data strongly support the profound endothelial protective effects of ADF in mice modeling severe type 2 diabetes. To our knowledge, this is the first experimental study determining the role of ADF in diabetes-associated vascular dysfunction. The above clinical studies in obese subjects and our experimental study in type 2 diabetic mice provide premises to further explore the clinical benefits of long-term ADF in diabetes-associated cardiovascular complications. Our study has shed light on the mechanisms of the endothelial protective effects of ADF partly through enhanced circulating adiponectin. Adiponectin is well known for its anti-inflammatory and anti-oxidative roles in endothelial cells 43 and its protective effects against neointimal formation in response to vascular injury 44 and atherosclerosis Our previous work has also supported that adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice Specifically, adenovirus-mediated adiponectin supplementation improved endothelium-dependent vasorelaxation of aortas in Lepr db mice Adiponectin supplementation reduced aortic nitrotyrosine protein levels, via suppressing protein expression of gp91 phox , an NADPH oxidase subunit, and increasing protein expression of SOD3, an antioxidant enzyme Aortic expression of inflammatory genes, Tnf , Il6 , and Icam1 , was also suppressed by adiponectin supplementation These pathways are likely responsible for the endothelial protective and anti-oxidative effects of adiponectin in mesenteric arteries of Lepr db mice undergoing ADF. The adiponectin-independent endothelial protective and anti-oxidative effects of ADF remain to be further dissected, and we speculate that the metabolic benefits of ADF may play important roles. Alternate day fasting exerts profound metabolic benefits in both control and diabetic mice with remarkably improved glycemic control and insulin sensitivity. The effects of ADF on weight loss and visceral adiposity were, however, modest. Consistent with our observation, an independent study also suggested that a week period of intermittent fasting, using a fasting mimicking diet protocol, improved glucose homeostasis in Lepr db mice without causing weight loss Thus, the metabolic benefits of ADF in Lepr db diabetic mice are likely not entirely dependent on weight loss effects. Since the Lepr db mice resemble severe type 2 diabetes, whether ADF may also exert limited benefits in weight management in patients with type 2 diabetes, despite profound metabolic effects, should be studied clinically. Further, the benefits of ADF in non-obese, healthy humans thus may also warrant further investigation. There are many questions that remain to be explored. Future studies may further elucidate if the knockout of adiponectin abolishes the vascular protective effects of ADF, the involvement of other adipokines, and the molecular mechanisms by which ADF modulates adipokine expression and secretion. Comparative studies are required to tackle how different intermittent fasting regimens affect metabolic, vascular, and hormonal parameters. Findings generated from such studies could inform whether one regimen is superior to the others and elucidate the mechanisms that underlie the cardiometabolic benefits. The discovery of pharmacological agents mimicking fasting can potentially provide novel therapeutic strategies. A potential limitation of the present studies is that they were performed only in male mice and mesenteric resistance arteries. In summary, our study examined the role and mechanisms of ADF in diabetes-associated endothelial dysfunction using murine models of type 2 diabetes. We have revealed that ADF in type 2 diabetic mice exerts profound endothelial protective effects, partly through modulating the adipose-derived hormone, adiponectin. Thus, this study improves our understanding of how ADF affords significant protection against endothelial dysfunction partly by regulating adipose-derived hormones. Our work also elaborated on the metabolic benefits and potential cardiovascular protective actions of ADF in the management of type 2 diabetes. The manuscript is in memory of Dr. Cuihua Zhang, who was deceased on October 1, The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The animal study was reviewed and approved by the Animal Care Committee at the University of Missouri Columbia, MO, United States. JC, HZ, and CZ conceived the study. JC, SL, and HZ performed the experiments. JC and HZ analyzed the data. JC, YL, and HZ interpreted results of experiments and drafted the manuscript. JC, YS, and HZ prepared the tables and figures. JC, SL, YS, MH, YL, and HZ edited and revised the manuscript. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. ACh, acetylcholine; ADF, alternate-day fasting; MAT, mesenteric adipose tissue; NO, nitric oxide; PE, phenylephrine; SMA, small mesenteric artery; SNP, sodium nitroprusside. Powell-Wiley TM, Poirier P, Burke LE, Després JP, Gordon-Larsen P, Lavie CJ, et al. Obesity and cardiovascular disease: a scientific statement from the american heart association. doi: PubMed Abstract CrossRef Full Text Google Scholar. Varady KA, Cienfuegos S, Ezpeleta M, Gabel K. Cardiometabolic benefits of intermittent fasting. Annu Rev Nutr. Flanagan EW, Most J, Mey JT, Redman LM. Calorie restriction and aging in humans. Santos HO, Genario R, Tinsley GM, Ribeiro P, Carteri RB, Coelho-Ravagnani CF, et al. A scoping review of intermittent fasting, chronobiology, and metabolism. Am J Clin Nutr. Clinical application of intermittent fasting for weight loss: progress and future directions. Nat Rev Endocrinol. Vasim I, Majeed CN, DeBoer MD. Intermittent fasting and metabolic health. Zang B-Y, He L-X, Xue L. Intermittent fasting: potential bridge of obesity and diabetes to health? Martens CR, Seals DR. Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing. J Physiol. Carter S, Clifton PM, Keogh JB. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: a randomized noninferiority trial. JAMA Netw Open. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. CrossRef Full Text Google Scholar. Chua SC Jr. Phenotypes of mouse diabetes and rat fatty due to mutations in the Ob Leptin receptor. Zhou J, Jiang Z, Lin Y, Li C, Liu J, Tian M, et al. The daily caloric restriction and alternate-day fasting ameliorated lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1. Eur J Nutr. Zhang H, Zhang W, Yun D, Li L, Zhao W, Li Y, et al. Alternate-day fasting alleviates diabetes-induced glycolipid metabolism disorders: roles of Fgf21 and bile acids. J Nutr Biochem. Kim KE, Jung Y, Min S, Nam M, Heo RW, Jeon BT, et al. Sci Rep. Beli E, Yan Y, Moldovan L, Vieira CP, Gao R, Duan Y, et al. Liu Z, Dai X, Zhang H, Shi R, Hui Y, Jin X, et al. Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat Commun. Zhang H, Zhang C. Obesity Silver Spring. Regulation of microvascular function by adipose tissue in obesity and type 2 diabetes: evidence of an adipose-vascular loop. Am J Biomed Sci. Zhang H, Cui J, Zhang C. Emerging role of adipokines as mediators in atherosclerosis. World J Cardiol. Lee S, Zhang H, Chen J, Dellsperger KC, Hill MA, Zhang C. Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. Zhang H, Park Y, Zhang C. Coronary and aortic endothelial function affected by feedback between adiponectin and tumor necrosis factor α in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. Lee S, Park Y, Dellsperger KC, Zhang C. Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice. Reinehr T, Roth C, Menke T, Andler W. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab. Zorena K, Jachimowicz-Duda O, Ślęzak D, Robakowska M, Mrugacz M. Adipokines and obesity. Potential link to metabolic disorders and chronic complications. Int J Mol Sci. Varady KA, Tussing L, Bhutani S, Braunschweig CL. Degree of weight loss required to improve adipokine concentrations and decrease fat cell size in severely obese women. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Zhang H, Wang Y, Zhang J, Potter BJ, Sowers JR, Zhang C. Bariatric surgery reduces visceral adipose inflammation and improves endothelial function in type 2 diabetic mice. Chen X, Zhang H, McAfee S, Zhang C. The reciprocal relationship between adiponectin and lox-1 in the regulation of endothelial dysfunction in apoe knockout mice. Ste Marie L, Palmiter RD. Norepinephrine and epinephrine-deficient mice are hyperinsulinemic and have lower blood glucose. Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, et al. Role of adiponectin in preventing vascular stenosis. the missing link of adipo-vascular axis. J Biol Chem. Su J, Lucchesi PA, Gonzalez-Villalobos RA, Palen DI, Rezk BM, Suzuki Y, et al. Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Zhang H, Potter BJ, Cao JM, Zhang C. Interferon-gamma induced adipose tissue inflammation is linked to endothelial dysfunction in type 2 diabetic mice. Basic Res Cardiol. Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M, et al. Primer3—new capabilities and interfaces. Nucleic Acids Res. Zhang H, Zhang J, Ungvari Z, Zhang C. Resveratrol improves endothelial function: role of tnf{alpha} and vascular oxidative stress. Chen X, Zhang H, Hill MA, Zhang C, Park Y. Regulation of coronary endothelial function by interactions between Tnf-A, Lox-1 and adiponectin in apolipoprotein e knockout mice. J Vasc Res. Zhao S, Kusminski CM, Scherer PE. Adiponectin, leptin and cardiovascular disorders. Circ Res. Gabel K, Kroeger CM, Trepanowski JF, Hoddy KK, Cienfuegos S, Kalam F, et al. Differential effects of alternate-day fasting versus daily calorie restriction on insulin resistance. Varady KA, Allister CA, Roohk DJ, Hellerstein MK. Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction. Wei S, Zhao J, Bai M, Li C, Zhang L, Chen Y. Comparison of glycemic improvement between intermittent calorie restriction and continuous calorie restriction in diabetic mice. Nutr Metab Lond. Klempel MC, Kroeger CM, Norkeviciute E, Goslawski M, Phillips SA, Varady KA. Benefit of a low-fat over high-fat diet on vascular health during alternate day fasting. Nutr Diabet. Hoddy KK, Bhutani S, Phillips SA, Varady KA. Effects of different degrees of insulin resistance on endothelial function in obese adults undergoing alternate day fasting. Nutr Healthy Aging. Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Phillips SA, Norkeviciute E, et al. Alternate day fasting with or without exercise: effects on endothelial function and adipokines in obese humans. e-SPEN J. Goldstein BJ, Scalia R. Adiponectin: a novel adipokine linking adipocytes and vascular function. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein e-deficient mice. Keywords : adipose, adipokines, diabetes, diet, endothelial function, alternate day fasting, adiponectin. Citation: Cui J, Lee S, Sun Y, Zhang C, Hill MA, Li Y and Zhang H Alternate Day Fasting Improves Endothelial Function in Type 2 Diabetic Mice: Role of Adipose-Derived Hormones. Received: 21 April ; Accepted: 02 May ; Published: 26 May Copyright © Cui, Lee, Sun, Zhang, Hill, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. cn ; Hanrui Zhang, hz cumc. Export citation EndNote Reference Manager Simple TEXT file BibTex. Check for updates. ORIGINAL RESEARCH article. Introduction Obesity and diabetes are associated with an increased risk of cardiovascular diseases, which remain the leading cause of death globally 1.
Intermittent fasting: The positive news continues	They'll help you set a target calorie intake for the fasting and non-fasting days. Studies on the Diet. Studies have shown that the diet may lower insulin resistance. It may also help with weight loss in people with type 2 diabetes or prediabetes. The first long-term study of the diet was published in by the Journal of the American Medical Association JAMA. It found that fasting could be effective for those with diabetes who have trouble sticking to a long-term, daily diet regimen. The study tracked people with type 2 diabetes:. The study found that those who followed the diet were just as likely to control their blood sugar levels as those on the daily restricted-calorie diet. Researchers said the diet "may be superior to continuous energy restriction for weight reduction. Safety of the Diet. Some experts question the safety of the diet for people with diabetes. The study authors concluded that those who take insulin or oral diabetes medications such as glyburide or metformin need very close monitoring. They may need to adjust their dosages. This is because fasting can cause hypoglycemia if you're taking medications that lower your blood sugar. This study found the diet safe for those with diabetes. With an early time-restricted feeding eTRF diet, you fit all your meals into a specific period of time each day. The eTRF diet plan may be an eight-hour, hour, or even a six-hour plan. On the eight-hour plan, if you begin eating at a. An example of the hour early time-restricted feeding plan would be when you eat the first meal of the day at a. and the last meal or snack no later than p. How the eTRF Diet Works. The eTRF diet may work with your circadian rhythm. That's why some think the diet could aid weight loss. If you stop eating earlier in the evening, you will extend your overnight fast. According to a study published in the New England Journal of Medicine , fasting triggers some important cell functions, such as lowering blood sugar and boosting metabolism. Benefits of the eTRF. Benefits of the eTRF diet include:. Study on the eTRF Diet for Diabetes. In a study, the eight-hour eTRF diet was compared with the hour diet. The study found that the eight-hour group had dramatically lower insulin levels than the hour group. Both groups maintained their weight. And both groups lowered insulin and blood pressure. Follow these tips if you have diabetes and plan to start an IF diet:. As with any eating plan, it's important to maintain a balanced diet to ensure your body is getting the nutrition it needs for long-term health. Include these meal-planning tips in your IF plan:. The safety of fasting for those with type 1 diabetes has not been fully established. If you have type 1 diabetes, you should never fast without first discussing it with your healthcare provider. Intermittent fasting is an eating plan that's become popular for weight loss and detox purposes. There are questions about whether fasting is safe for people with diabetes. More research is needed, but some studies show there could be benefits for people with type 2 diabetes. The IF diet allows normal eating five days per week. On two non-consecutive days, you eat fewer calories. Studies show this plan is safe for people with type 2 diabetes that's controlled with diet. If you take medications to keep type 2 diabetes in check, you will need to monitor your blood sugar closely to make sure it doesn't drop too low. The early time-restricted feeding plan works by limiting the number of hours you can eat within a day. Eight-hour and hour plans can lower insulin and blood pressure and help maintain weight. If you have diabetes and want to try an IF diet, it's vital that you work with your diabetes team to do it safely. American Diabetes Association Professional Practice Committee. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes Diabetes Care. doi: National Institute of Diabetes and Digestive and Kidney Diseases. Insulin resistance and prediabetes. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes Direct : an open-label, cluster-randomised trial. The Lancet. Tello M. Intermittent fasting: Surprising update. Harvard Health Publishing. Harvard Medical School. De Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med. Grajower MM, Horne BD. Clinical management of intermittent fasting in patients with diabetes mellitus. Johns Hopkins Medicine. Intermittent fasting: What is it, and how does it work? Diabetes UK. Fasting and diabetes. Carter S, Clifton PM, Keogh JB. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: A randomized noninferiority trial. JAMA Netw Open. Adafer R, Messaadi W, Meddahi M, Patey A, Haderbache A, Bayen S, Messaadi N. Food Timing, Circadian Rhythm and Chrononutrition: A Systematic Review of Time-Restricted Eating's Effects on Human Health. Ravussin E, Beyl RA, Poggiogalle E, Hsia DS, Peterson CM. Early time-restricted feeding reduces appetite and increases fat oxidation but does not affect energy expenditure in humans. Obesity Silver Spring. Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. Medline Plus. Glycemic index and diabetes. By Sherry Christiansen Sherry Christiansen is a medical writer with a healthcare background. She has worked in the hospital setting and collaborated on Alzheimer's research. Use limited data to select advertising. Create profiles for personalised advertising. When you eat and what you eat can be changed to help reduce risk of developing type 2 diabetes. There are other risk factors for type 2 diabetes that are not under your personal control. Derocha suggests looking at your uncontrollable risk factors and how they play into risk. She says these uncontrollable risk factors include:. If you have any of these risk factors, the best next step is to talk to your healthcare provider. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Intermittent fasting has several impressive benefits, but women may need to follow a modified approach. Here's how to get started. Intermittent fasting has helped some people with type 2 diabetes stop using insulin, but there are risks involved. Here's what to know about this fad…. As intermittent fasting has become increasingly popular, many people wonder whether you can drink coffee during your fasting periods. This article…. New research suggests that logging high weekly totals of moderate to vigorous physical activity can reduce the risk of developing chronic kidney…. Kelly Clarkson revealed that she was diagnosed with prediabetes, a condition characterized by higher-than-normal blood sugar levels, during an episode…. New research has revealed that diabetes remission is associated with a lower risk of cardiovascular disease and chronic kidney disease. Type 2…. A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Type 2 Diabetes. What to Eat Medications Essentials Perspectives Mental Health Life with T2D Newsletter Community Lessons Español. Health News Fact Checked Can Intermittent Fasting Decrease Your Type 2 Diabetes Risk? By Michelle Pugle on April 18, — Fact checked by Jill Seladi-Schulman, Ph. People on intermittent fasting were better able to process and use glucose. Fasting may help prevent type 2 diabetes. What nutrition experts have to say. A word on risk factors. How we reviewed this article: History. Apr 18, Written By Michelle Pugle. Share this article. Read this next. Intermittent Fasting For Women: A Beginner's Guide.
UIC Today Contact	They'll help you set a target diabeets intake for the fasting diabdtes Alternate-day fasting and diabetes prevention days. Alrernate-day is diaebtes open-access article distributed Replenish wellness rituals Alternate-day fasting and diabetes prevention fasring of the Creative Commons Attribution License CC BY. They may need to adjust their dosages. Acosta-Rodriguez, V. Get helpful tips and guidance for everything from fighting inflammation to finding the best diets for weight loss Results are presented as fold change of transcripts for target normalized to internal reference Actbcompared with m Lepr db defined as 1. Insulin Tolerance Test Mice were fasted overnight and weighed.

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PREVENT BINGE EATING while ALTERNATE DAY FASTING - ADF BEGINNERS GUIDE to LOSE WEIGHT FAST [2023]

Alternate-day fasting and diabetes prevention -

Our study revealed the profound benefits of ADF in rescuing endothelial dysfunction. The benefits are at least partly mediated through enhanced adiponectin, while resistin and leptin were unlikely to be involved.

Adiponectin thus provides a mechanistic link between the role of ADF in regulating adipokine profile and endothelial function in type 2 diabetes. ADF reduced the marker of oxidative stress in resistance arteries but not adipose tissue, suggesting tissue-specific regulatory roles by ADF.

ADF may also exert metabolic and vascular benefits in non-obese control mice. Overall, our data support that ADF presents as promising lifestyle intervention for treating diabetes-associated endothelial dysfunction.

Intermittent fasting is emerging as a popular alternative dietary intervention strategy. Despite limited numbers of clinical trials directly comparing the long-term effects of intermittent fasting and daily calorie restriction, current evidence supports equivalent or superior metabolic benefits of intermittent fasting 5.

Comparative studies in a month study of insulin-resistant participants support that ADF may produce greater reductions in fasting insulin and insulin resistance compared with calorie restriction despite similar decreases in body weight In Lepr db type 2 diabetic mice and streptozotocin-treated type 1 diabetic mice treated with a fasting-mimicking diet, both intermittent fasting and continuous calorie restriction significantly reduced fasting blood glucose levels and improved insulin sensitivity.

Yet, intermittent fasting performed significantly better than continuous calorie restriction in improving glycemic control and insulin sensitivity in Lepr db type 2 diabetic mice Clinical studies, conducted over multiple years, that directly compare different regimens will provide important insights into the long-term cardiometabolic benefits of these diets.

There are currently no clinical studies determining the vascular benefits of long-term ADF in patients with diabetes. Clinical trials of short-term ADF, e. Increases in adiponectin were positively associated with augmented flow-mediated vasodilation post-ADF in those subjected to ADF with the low-fat diet ADF also reduced plasma resistin and leptin, which were not correlated with changes in flow-mediated vasodilation In a study involving 54 obese non-diabetic subjects with an 8-week ADF protocol, brachial artery flow-mediated vasodilation was positively correlated to adiponectin concentrations Another study involving 64 obese subjects supported that a week period of ADF improved brachial artery flow-mediated vasodilation Our experimental data strongly support the profound endothelial protective effects of ADF in mice modeling severe type 2 diabetes.

To our knowledge, this is the first experimental study determining the role of ADF in diabetes-associated vascular dysfunction. The above clinical studies in obese subjects and our experimental study in type 2 diabetic mice provide premises to further explore the clinical benefits of long-term ADF in diabetes-associated cardiovascular complications.

Our study has shed light on the mechanisms of the endothelial protective effects of ADF partly through enhanced circulating adiponectin.

Adiponectin is well known for its anti-inflammatory and anti-oxidative roles in endothelial cells 43 and its protective effects against neointimal formation in response to vascular injury 44 and atherosclerosis Our previous work has also supported that adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice Specifically, adenovirus-mediated adiponectin supplementation improved endothelium-dependent vasorelaxation of aortas in Lepr db mice Adiponectin supplementation reduced aortic nitrotyrosine protein levels, via suppressing protein expression of gp91 phox , an NADPH oxidase subunit, and increasing protein expression of SOD3, an antioxidant enzyme Aortic expression of inflammatory genes, Tnf , Il6 , and Icam1 , was also suppressed by adiponectin supplementation These pathways are likely responsible for the endothelial protective and anti-oxidative effects of adiponectin in mesenteric arteries of Lepr db mice undergoing ADF.

The adiponectin-independent endothelial protective and anti-oxidative effects of ADF remain to be further dissected, and we speculate that the metabolic benefits of ADF may play important roles. Alternate day fasting exerts profound metabolic benefits in both control and diabetic mice with remarkably improved glycemic control and insulin sensitivity.

The effects of ADF on weight loss and visceral adiposity were, however, modest. Consistent with our observation, an independent study also suggested that a week period of intermittent fasting, using a fasting mimicking diet protocol, improved glucose homeostasis in Lepr db mice without causing weight loss Thus, the metabolic benefits of ADF in Lepr db diabetic mice are likely not entirely dependent on weight loss effects.

Since the Lepr db mice resemble severe type 2 diabetes, whether ADF may also exert limited benefits in weight management in patients with type 2 diabetes, despite profound metabolic effects, should be studied clinically.

Further, the benefits of ADF in non-obese, healthy humans thus may also warrant further investigation. There are many questions that remain to be explored. Future studies may further elucidate if the knockout of adiponectin abolishes the vascular protective effects of ADF, the involvement of other adipokines, and the molecular mechanisms by which ADF modulates adipokine expression and secretion.

Comparative studies are required to tackle how different intermittent fasting regimens affect metabolic, vascular, and hormonal parameters. Findings generated from such studies could inform whether one regimen is superior to the others and elucidate the mechanisms that underlie the cardiometabolic benefits.

The discovery of pharmacological agents mimicking fasting can potentially provide novel therapeutic strategies. A potential limitation of the present studies is that they were performed only in male mice and mesenteric resistance arteries. In summary, our study examined the role and mechanisms of ADF in diabetes-associated endothelial dysfunction using murine models of type 2 diabetes.

We have revealed that ADF in type 2 diabetic mice exerts profound endothelial protective effects, partly through modulating the adipose-derived hormone, adiponectin. Thus, this study improves our understanding of how ADF affords significant protection against endothelial dysfunction partly by regulating adipose-derived hormones.

Our work also elaborated on the metabolic benefits and potential cardiovascular protective actions of ADF in the management of type 2 diabetes.

The manuscript is in memory of Dr. Cuihua Zhang, who was deceased on October 1, The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The animal study was reviewed and approved by the Animal Care Committee at the University of Missouri Columbia, MO, United States.

JC, HZ, and CZ conceived the study. JC, SL, and HZ performed the experiments. JC and HZ analyzed the data. JC, YL, and HZ interpreted results of experiments and drafted the manuscript.

JC, YS, and HZ prepared the tables and figures. JC, SL, YS, MH, YL, and HZ edited and revised the manuscript. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Adiponectin reduces atherosclerosis in apolipoprotein e-deficient mice. Keywords : adipose, adipokines, diabetes, diet, endothelial function, alternate day fasting, adiponectin. Citation: Cui J, Lee S, Sun Y, Zhang C, Hill MA, Li Y and Zhang H Alternate Day Fasting Improves Endothelial Function in Type 2 Diabetic Mice: Role of Adipose-Derived Hormones.

Received: 21 April ; Accepted: 02 May ; Published: 26 May Copyright © Cui, Lee, Sun, Zhang, Hill, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY.

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No use, distribution or reproduction is permitted which does not comply with these terms. cn ; Hanrui Zhang, hz cumc. Export citation EndNote Reference Manager Simple TEXT file BibTex.

Check for updates. ORIGINAL RESEARCH article. Introduction Obesity and diabetes are associated with an increased risk of cardiovascular diseases, which remain the leading cause of death globally 1.

Materials and Methods Animal Models and Treatment The procedures followed were in accordance with approved guidelines set by the Animal Care Committee at the University of Missouri Columbia, MO, United States.

In this large trial, superior improvements in glucose tolerance were observed in iTRE versus CR after 6 months, independently of body weight loss. Only three pilot studies have previously compared the effects of IF versus CR on postprandial glucose and lipid metabolism in humans.

Improvements in glucose tolerance can occur through improved insulin sensitivity, insulin secretion, glucose mass action or slower gastric emptying. We observed a greater reduction in postprandial insulin AUC, which could indicate greater improvements in insulin sensitivity.

In the current study, greater reductions in fasting NEFA were observed, which suggest greater improvements in adipose tissue insulin sensitivity, which could also reduce ectopic lipid and increase peripheral glucose uptake There was no difference in insulin secretion as calculated by the insulinogenic index The greater improvements in glucose tolerance did not result in a greater reduction in HbA1c.

HbA1c is influenced by both postprandial and fasting glucose, although postprandial glucose is most strongly predictive of HbA1c in adults without diabetes. Although HbA1c was marginally elevated, it is minimally shifted with dietary interventions in those without type 2 diabetes Few studies have specified morning meal timing during IF in humans 13 , potentially masking its possible health benefits.

Eating at an early time in the day is associated with health benefits in humans in short-term trials 37 , including improved h glucose control 38 and insulin sensitivity in response to an oral glucose tolerance test 39 and glucose mass action Delaying food intake is associated with reduced weight loss in retrospective cohort studies 37 and increased hunger and reduced energy expenditure in an acute metabolic ward study Delayed food intake also delayed adipose tissue clocks and expression of Period-2 in humans Thus, although a delayed eating plan may be more socially acceptable and sustainable, it may not be optimal for glycemic health 22 , In contrast to previous long-term IF trials 23 , 29 , we provide preliminary evidence that prescription of iTRE elicits favorable alterations in lipid profiles versus CR, including reductions in fasting triglycerides, which are strongly associated with an increased risk of cardiovascular diseases 42 , Fatty liver is also commonly associated with increased very-LDL triglycerides secretion and hypertriglyceridemia, and thus might also reflect an increased reduction in liver fat Interventions that improve glycemic control reduce β-hexosaminidase activity 45 , Here, iTRE was more effective in reducing β-hexosaminidase activity.

This exploratory finding could also reflect superior restoration of lipid metabolism 12 , 47 and liver health compared with CR, but the clinical relevance of a change in β-hexosaminidase with a dietary intervention is uncertain.

Adverse events were generally mild and resolved over the course of the trial. Higher fatigue was observed in iTRE versus CR during the first 6 months, which might increase difficulty in maintaining iTRE. Fasting protocols that require people to skip dinner several times per week could also lead to poor adherence.

Fewer than half of the iTRE participants indicated they would continue their current weight loss plan when they were given the option to modify to a weight maintenance plan that included two iTRE days per week at month 6.

However, weight loss maintenance at month 18 did not differ between iTRE and CR, suggesting that neither regimen was more sustainable when support from the investigators was withdrawn. The increased health benefits in the active intervention groups were also lost by 18 months.

A post hoc subanalysis that divided the iTRE cohort into those that chose to continue versus change the diet plan did not alter outcomes. As an exploratory analysis, we also combined iTRE and CR, and observed sustained reductions in insulin AUC versus standard care.

Future studies should investigate whether intermittent prescription of a longer daily eating window for example, to hours retains the benefit of iTRE versus CR, and if these interventions are more sustainable long-term. Strengths of the study include that it is the largest to date, with a high proportion of men enrolled.

This trial also included assessments of glucose tolerance and aligned meal timing from breakfast during IF. At month 6, we allowed participants in the active groups to choose whether they changed to a weight maintenance plan during the additional month follow-up.

This trial decision has hindered the clinical interpretation of that period because more participants in the iTRE group chose to alter their diet plans.

Whether h post refeeding is sufficient to entirely wash out the acute effect of the h fasting period is not clear, although the washout period is in line with past studies of IF CR and standard care participants were not provided with any instruction on meal timing, and adoption of a shortened daily eating period might have lessened the differences between groups.

The extrapolation of a clinically relevant change in glucose from an oral glucose tolerance test to a mixed-meal tolerance test requires further study. Finally, although we theorized that limiting meals to the morning during iTRE was responsible for the greater health benefits that were observed versus CR, we did not include an iTRE group with a late eating window as a comparator.

In conclusion, iTRE provided modest benefit for postprandial glycemia in response to mixed-meal tolerance test compared with daily CR without timing advice in adults at elevated risk of type 2 diabetes after 6 months.

This study adds to the growing body of evidence to indicate that meal timing and fasting advice might be influential in clinical practice. This open-label, three-arm, parallel group sequential randomized controlled trial was conducted between 26 September and 30 November and involved a 6-month intervention phase followed by a month follow-up.

The primary objective for this study was to assess differences in glucose tolerance in response to a mixed-meal in iTRE versus CR at 6 months.

Because it was expected that weight loss for iTRE and CR would be similar, a standard care group was included to ensure weight losses occurred and to aid quantification of the magnitude of change in the active intervention groups. Secondary aims were to compare iTRE versus CR versus standard care on body weight, body composition, fasting and postprandial markers of glycemia, cardiovascular health and liver health at 6 months, and with a further month follow-up in adults at elevated risk of developing type 2 diabetes.

The detailed study protocol including inclusion and exclusion criteria was reported 49 , 50 , and the statistical analysis plan is available ClinicalTrials.

gov, NCT Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee and participants provided written informed consent. The study was performed at the South Australian Health and Medical Research Institute by researchers from The University of Adelaide and South Australian Health and Medical Research Institute.

An independent data and safety monitoring committee provided oversight. In response to the coronavirus pandemic, a lockdown was in place in South Australia from mid-March to May , which brought a halt to recruiting. The primary outcome visits continued, but the diet consults were shifted from face-to-face to telehealth.

Other than this period, the Australian border force laws in place meant the study visits remained largely unaffected, with the final follow-up visit completing around the time that Adelaide relaxed its border rules.

The prescribed menu included two meal replacements at breakfast approximately hours and lunch approximately hours to aid adherence and to ensure adequate nutrient intake. iTRE participants were instructed to consume their regular prestudy diet during each nonfasting day. The prescribed menu included one meal replacement per day to aid adherence and to ensure adequate nutrient intake.

The standard care group was given current guidelines in a booklet, with no counseling or meal replacements. All participants were instructed to maintain their usual physical activity levels throughout the trial.

At month 6, they were provided with the option to continue with the same weight loss plan or to modify to a weight maintenance plan. The secondary outcomes included changes in body weight, waist circumference, hip circumference, fat mass, fat-free mass, blood pressure, blood lipids cholesterol, low-density lipoprotein LDL , high-density lipoprotein HDL , plasma triglycerides , NEFA, HbA1c, plasma glucose, plasma insulin, serum high-sensitivity C-reactive protein hs-CRP , ALT, AST, β-hexosaminidase activity, physical activity and dietary intake.

During each metabolic visit, body weight, and waist and hip circumference were measured in a gown after voiding. Body weight was measured to the nearest 0. Waist circumference was measured at the mid-axillary line halfway point between lowest rib and the top of iliac crest , and hip circumference was measured at the widest circumference of the buttocks.

Body mass index was calculated as weight in kilograms per height in meters squared. Whole-body composition was measured by dual-energy X-ray absorptiometry DXA Lunar Prodigy; GE Health Care and was analyzed using enCORE software v.

These were assessed in completers who lost at least 3. The mean of the two lowest blood pressure readings was used. Prescribed daily energy requirements were calculated by averaging predicted daily energy expenditure from a published equation that uses gender, age, height and weight variables Participants were asked to self-report all their dietary intake via a smartphone application Easy Diet Diary, Xyris Software before each metabolic testing at baseline, and at months 2, 6 and The energy and macronutrients intakes were calculated by using FoodWorks Professional v.

Perceptions of diet easiness and satisfaction were assessed at months 2 and 6 using visual analog scales. ActiGraph data was downloaded and analyzed by using ActiLife 6 software by the investigators upon collection of the devices. Participants attended the research facility at baseline, month 6 and month 18 for metabolic testing.

Additional fasting samples were obtained following a h fast at month 2. Blood glucose was assayed by the hexokinase method Cobas Integra plus, Roche. Plasma insulin was measured by radioimmunoassay HIK, Millipore. Whole-blood HbA1c, plasma triglycerides, NEFA, hs-CRP, ALT and AST, were measured using commercially available enzymatic kits on an automated clinical analyzer Indiko Plus, Thermo Fisher Scientific.

AUC values were calculated using the trapezoidal rule. The Matsuda index was calculated for insulin sensitivity estimation Insulin secretion was estimated using the insulinogenic index A subset of individuals had additional fasting bloods drawn at baseline, month 2 and month 6 to assess plasma β-hexosaminidase activity as a marker of glycosphingolipid metabolism relevant to liver health.

β-Hexosaminidase activity was measured using a plasma sample as described in Leaback et al. and Whyte et al. Plasma samples were thawed on ice, vortexed and diluted in ice-cold 0. Saline solution 0. M; 2. Fluorescence was read on a GloMax microplate reader Promega. During each clinic visit, participants were asked to report if they had experienced any health-related conditions.

They were also prompted to report any physical symptoms through the use of a check box for example, fatigue, constipation, diarrhea, headache, light-headedness since the proceeding visit. All serious adverse events were immediately reported to the study physician and data safety monitoring committee.

For each assessment period baseline to month 6, and month 7 to month 18 , the number of individuals with at least one event was compared between groups when there were at least four individuals with at least one event across all groups.

The design was changed after the first interim analysis to a single additional final analysis of postprandial glucose AUC owing to slow accrual and the coronavirus pandemic. This change was agreed by the independent data safety monitoring committee 2.

We assume a pre—post intervention correlation of 0. The primary analysis of month 6 postprandial glucose AUC between iTRE and CR was assessed using baseline and stratification factor sex, AUSDRISK adjusted linear regression.

Other analyses also included the standard care and where appropriate the month 2 assessment. The latter were modeled using mixed effects linear regressions with a random intercept per individual and adjusted for assessment month 2 versus month 6 and the pairwise interaction with treatment group as fixed effects.

Residual and random effect distributions were assessed to ensure that the model distributional assumptions were not violated. Fasting triglycerides, hs-CRP, AST, ALT, Matsuda index, insulinogenic index and step counts outcomes were log-transformed.

With three groups and two assessment times there are a number of potential secondary outcome comparisons. We prespecified that pairwise comparisons of secondary analyses would be performed only if the overall effect of treatment group was significant in a likelihood ratio test with the nested submodel excluding treatment.

For these overall tests, mixed effects models did not include the month by group interaction that is, the likelihood ratio test statistic was compared against the chi-squared distribution with two degrees of freedom for all outcomes irrespective of the month 2 assessment.

Month 18 assessments were analyzed separately using linear regressions similarly to secondary outcomes without a month 2 assessment. A post hoc analysis was performed repeating these regressions in which the iTRE group was divided into those who chose to maintain the initial iTRE weight loss plan and those who chose to modify to a weight maintenance plan.

Nonfasting weight assessments were analyzed using linear mixed effects regression assuming piecewise linear effects assumed for the interventions over two periods: months 0—6 and months 7—18, and both random intercepts and slopes for individuals. No multiple test adjustments were performed and as such secondary analyses are considered exploratory.

Statistical analysis was performed using R v. We also report post hoc calculations of the probabilities of benefit—that is, different from zero—both separately and jointly. The analyses were in individuals with both HbA1c and postprandial glucose measures at month 6.

Six individuals had HbA1c data but were missing postprandial glucose change data, and were excluded from this analysis. Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

Anonymized data from this study are available on request from the corresponding author for 36 months from date of publication with a full research plan for academic use only.

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Alteernate-day intermittent fasting seems to be an exception. These plans Alternate-day fasting and diabetes prevention going without caloric foods or drinks for an prevvention period of andd from Alternate-day fasting and diabetes prevention dlabetes to several days—and diabetse have become increasingly Low-carb and satiety. Research has also found them to be effective for weight loss. Doctors often advise people with Type 2 diabetes to lose weight, which can have beneficial effects on blood glucose and insulin sensitivity, as well as on the progression of the disease. For this and other reasons, experts are actively looking at the effects of intermittent fasting among people with Type 2 diabetes. However, there are some safety concerns.