Efficacy and Safety of Intermittent Fasting in People With Insulin-Treated Type 2 Diabetes (INTERFAST-2)—A Randomized Controlled Trial

Obermayer, Anna; Tripolt, Norbert J.; Pferschy, Peter N.; Kojzar, Harald; Aziz, Faisal; Müller, Alexander; Schauer, Markus; Oulhaj, Abderrahim; Aberer, Felix; Sourij, Caren; Habisch, Hansjörg; Pieber, Thomas R.; Obermayer-Pietsch, B.; Stadlbauer, Vanessa; Sourij, Harald

doi:10.2337/dc22-1622

Cited by 43 publications

(50 citation statements)

References 17 publications

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“…A decline in resting metabolic rate (RMR) is described for most caloric restriction interventions [ 31 , 32 ]; however, interestingly we did not observe a significant change in RMR in people following an intermittent fasting regimen, neither in healthy, normal-weight people [ 20 ] nor patients with type 2 diabetes [ 33 ]. Dietary interventions without reducing RMR are crucial, in particular with regard to weight regain following the intervention.…”

Section: Discussionmentioning

confidence: 87%

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People—A Cohort Trial

et al. 2023

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Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p < 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 ± 31 mg/dL vs. 79 ± 18 mg/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 ± 34.1 mU/L after 36 h vs. 56.1 ± 29.7 mU/L; p < 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only.

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Section: Discussionmentioning

confidence: 87%

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People—A Cohort Trial

et al. 2023

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“…Thus, larger RCTs should further explore the clinical effectiveness of fasting programs in metabolic syndrome patients [ 31 ]. In another study, Obermayer et al assessed the efficacy of IF in individuals with type 2 diabetes [ 32 ]. This study found that after 12 weeks of intervention, the IF group exhibited a significant reduction in total daily insulin dose of 9 ± 10 IU as opposed to the control group, with an increase of 4 ± 10 IU.…”

Section: Resultsmentioning

confidence: 99%

Chrononutrition in the Prevention and Management of Metabolic Disorders: A Literature Review

Mentzelou,

Papadopoulou,

Psara

et al. 2024

Nutrients

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Background: The concept of time-restricted eating (TRE) or time-restricted feeding (TRF) promotes daily periods of feeding and fasting to determine whole-body physiology. Chronic misalignment of circadian rhythms or chrono-disruption is related to an increased risk of diverse metabolic disorders. The progression of non-communicable diseases seems to be affected by the timing of meals. As a result, intermittent fasting is a promising approach for their management. The aim of the present literature review is to examine and scrutinize the TRE protocols in the fields of prevention and management of metabolic disorders. Methods: This is a thorough literature review of the reported associations among circadian rhythm, metabolic disorders, diabetes mellitus, obesity, TRE, TRF, dietary habits, circadian disruption, cardiovascular diseases, atherosclerosis, and non-alcoholic fatty liver to find the already existing clinical studies from the last decade (2014–2024) in the most precise scientific online databases, using relevant specific keywords. Several inclusion and exclusion criteria were applied to scrutinize only longitudinal, cross-sectional, descriptive, and prospective clinical human studies. Results: The currently available clinical findings remain scarce and suggest that chrononutrition behaviors such as TRE or TRF may promote several metabolic benefits, mainly in body weight control and fat loss. Improvements in glucose levels and lipid profiles are currently quite controversial since some clinical studies show little or no effect. As far as liver diseases are concerned, the efficacy of intermittent fasting seems to be stronger in the management of non-alcoholic fatty liver disease due to body weight decline and fat loss. Conclusions: Even if there has been a gradual increase in clinical studies in the last few years, providing promising perspectives, currently, there is no conclusive evidence for the role of chrononutrition in metabolic disorders. Future studies should be well-designed with longer duration and larger sample sizes. Moreover, it is important to examine the best timing of the eating window and its feasibility.

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“…Therefore, a CR murine model called meal feeding (MF) was established by feeding mice twice daily to reduce the fasting interval as a more appropriate reference for IF to distinguish CR from diet patterns. Every-other-day feeding (EODF) is the most commonly used research model for IF and has been applied in many clinical studies, even in individuals with diabetes, without serious adverse effects ( 17–21 ). Therefore, we used the MF model, where food intake was calculated based on the total consumption of the EODF group, distributed equally at 10:00 a.m. and 6:00 p.m. , effectively reducing the fasting duration to ∼12 h. This strategy guaranteed precise management of the intake variable and minimized extended fasting periods, which is a novel aspect of our experimental design.…”

Section: Introductionmentioning

confidence: 99%

Intermittent Fasting–Improved Glucose Homeostasis Is Not Entirely Dependent on Caloric Restriction in db/db Male Mice

Zheng,

Hong,

et al. 2024

Diabetes

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Intermittent fasting (IF), which involves prolonged fasting intervals accompanied by caloric restriction, is an effective dietary treatment for obesity and diabetes. Although IF offers many benefits, it is difficult to determine whether these benefits are the consequences of caloric restriction. Every-other-day feeding (EODF) is a commonly used IF research model. This study was designed to identify other effectors of EODF, in addition to caloric restriction, and the possible underlying mechanisms. Diabetic db/db mice were divided into three groups: ad libitum (AL), meal-feeding (MF) and EODF. The MF model was employed to attain a level of caloric restriction comparable to EODF, with food distribution evenly divided between 10 AM and 6 PM, thereby minimizing the fasting interval. EODF yielded greater improvements in glucose homeostasis than MF in db/db mice by reducing fasting glucose levels and enhancing glucose tolerance. However, these effects on glucose metabolism were less pronounced in lean mice. Furthermore, ubiquitination of the liverspecific glucocorticoid receptor (GR) facilitated its degradation, and downregulating Kruppel-like factor 9 (KLF9), which ultimately suppressed liver gluconeogenesis in diabetic EODF mice. Although GR and KLF9 might mediate the metabolic benefits of EODF, the potential benefits of EODF might be limited by elevated serum glucocorticoid (GC) levels in diabetic EODF mice. Overall, this study suggests that the metabolic benefits of EODF in improving glucose homeostasis are independent of caloric restriction, possibly due to the downstream effects of liver-specific GR degradation.

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Efficacy and Safety of Intermittent Fasting in People With Insulin-Treated Type 2 Diabetes (INTERFAST-2)—A Randomized Controlled Trial

Cited by 43 publications

References 17 publications

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People—A Cohort Trial

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People—A Cohort Trial

Chrononutrition in the Prevention and Management of Metabolic Disorders: A Literature Review

Intermittent Fasting–Improved Glucose Homeostasis Is Not Entirely Dependent on Caloric Restriction in db/db Male Mice

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