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Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial.
van den Burg, EL, Schoonakker, MP, van Peet, PG, van den Akker-van Marle, EM, Lamb, HJ, Longo, VD, Numans, ME, Pijl, H
Diabetologia. 2024
Abstract
AIMS/HYPOTHESIS The aim of this study was to evaluate the impact on metabolic control of periodic use of a 5-day fasting-mimicking diet (FMD) programme as an adjunct to usual care in people with type 2 diabetes under regular primary care surveillance. METHODS In this randomised, controlled, assessor-blinded trial, people with type 2 diabetes using metformin as the only glucose-lowering drug and/or diet for glycaemic control were randomised to receive 5-day cycles of an FMD monthly as an adjunct to regular care by their general practitioner or to receive regular care only. The primary outcomes were changes in glucose-lowering medication (as reflected by the medication effect score) and HbA1c levels after 12 months. Moreover, changes in use of glucose-lowering medication and/or HbA1c levels in individual participants were combined to yield a clinically relevant outcome measure ('glycaemic management'), which was categorised as improved, stable or deteriorated after 1 year of follow-up. Several secondary outcome measures were also examined, including changes in body weight. RESULTS One hundred individuals with type 2 diabetes, age 18-75 years, BMI ≥27 kg/m2, were randomised to the FMD group (n=51) or the control group (n=49). Eight FMD participants and ten control participants were lost to follow-up. Intention-to-treat analyses, using linear mixed models, revealed adjusted estimated treatment effects for the medication effect score (-0.3; 95% CI -0.4, -0.2; p<0.001), HbA1c (-3.2 mmol/mol; 95% CI -6.2, -0.2 and -0.3%; 95% CI -0.6, -0.0; p=0.04) and body weight (-3.6 kg; 95% CI -5.2, -2.1; p<0.001) at 12 months. Glycaemic management improved in 53% of participants using FMD vs 8% of control participants, remained stable in 23% vs 33%, and deteriorated in 23% vs 59% (p<0.001). CONCLUSIONS/INTERPRETATION Integration of a monthly FMD programme in regular primary care for people with type 2 diabetes who use metformin as the only glucose-lowering drug and/or diet for glycaemic control reduces the need for glucose-lowering medication, improves HbA1c despite the reduction in medication use, and appears to be safe in routine clinical practice. TRIAL REGISTRATION ClinicalTrials.gov NCT03811587 FUNDING The project was co-funded by Health~Holland, Top Sector Life Sciences & Health, the Dutch Diabetes Foundation and L-Nutra.
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Impact of dietary carbohydrate, fat, or protein restriction on the human gut microbiome: a systematic review.
Schoonakker, MP, van Peet, PG, van den Burg, EL, Numans, ME, Ducarmon, QR, Pijl, H, Wiese, M
Nutrition research reviews. 2024;:1-47
Abstract
Restriction of dietary carbohydrates, fat, and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for in-and exclusion criteria, 36 articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, such as Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels, and abundance of some beneficial bacteria, including F. prausnitzii. There was insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveils possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.
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Role of dietary interventions on microvascular health in South-Asian Surinamese people with type 2 diabetes in the Netherlands: A randomized controlled trial.
van der Velden, AIM, IJpelaar, DHT, Chandie Shaw, PK, Pijl, H, Vink, H, van der Vlag, J, Rabelink, TJ, van den Berg, BM
Nutrition & diabetes. 2024;(1):17
Abstract
BACKGROUND/OBJECTIVES We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (EndocalyxTM) could stabilize microvascular function in Surinamese South-Asian patients with type 2 diabetes (SA-T2DM) in the Netherlands, a patient population more prone to develop vascular complications. SUBJECTS/METHODS A randomized, placebo controlled, 3-arm intervention study was conducted in 56 SA-T2DM patients between 18 and 75 years old, for 3 consecutive months, with one additional follow up measurement 3 months after the last intervention. Sublingual microcirculation was assessed with SDF-imaging coupled to the GlycoCheckTM software, detecting red blood cell velocity, capillary density, static and dynamic perfused boundary region (PBR), and the overall microvascular health score (MVHS). Linear mixed models and interaction analysis were used to investigate the effects the interventions had on microvascular function. RESULTS Despite a temporal improvement in BMI and HbA1c after FMD the major treatment effect on microvascular health was worsening for RBC-velocity independent PBRdynamic, especially at follow-up. Glycocalyx supplementation, however, reduced urinary MCP-1 presence and improved both PBRdynamic and MVHSdynamic, which persisted at follow-up. CONCLUSIONS We showed that despite temporal beneficial changes in BMI and HbA1c after FMD, this intervention is not able to preserve microvascular endothelial health in Dutch South-Asian patients with T2DM. In contrast, glycocalyx mimetics preserves the microvascular endothelial health and reduces the inflammatory cytokine MCP-1. CLINICAL STUDY REGISTRATION NCT03889236.
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Metabolic impact of intermittent energy restriction and periodic fasting in patients with type 2 diabetes: a systematic review.
van den Burg, EL, van Peet, PG, Schoonakker, MP, van de Haar, DE, Numans, ME, Pijl, H
Nutrition reviews. 2023;(10):1329-1350
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CONTEXT The effectiveness of intermittent energy restriction (IER) and periodic fasting (PF) in the management of type 2 diabetes (T2D) remains a subject of discussion. OBJECTIVE The aim of this systematic review is to summarize current knowledge of the effects of IER and PF in patients with T2D on markers of metabolic control and the need for glucose-lowering medication. DATA SOURCES PubMed, Embase, Emcare, Web of Science, Cochrane Library, CENTRAL, Academic Search Premier, Science Direct, Google Scholar, Wiley Online Library, and LWW Health Library were searched for eligible articles on March 20, 2018 (last update performed November 11, 2022). Studies that evaluated the effects of IER or PF diets in adult patients with T2D were included. DATA EXTRACTION This systematic review is reported according to PRISMA guidelines. Risk of bias was assessed through the Cochrane risk of bias tool. The search identified 692 unique records. Thirteen original studies were included. DATA ANALYSIS A qualitative synthesis of the results was constructed because the studies differed widely in terms of dietary interventions, study design, and study duration. Glycated hemoglobin (HbA1c) declined in response to IER or PF in 5 of 10 studies, and fasting glucose declined in 5 of 7 studies. In 4 studies, the dosage of glucose-lowering medication could be reduced during IER or PF. Two studies evaluated long-term effects (≥1 year after ending the intervention). The benefits to HbA1c or fasting glucose were generally not sustained over the long term. There are a limited number of studies on IER and PF interventions in patients with T2D. Most were judged to have at least some risk of bias. CONCLUSION The results of this systematic review suggest that IER and PF can improve glucose regulation in patients with T2D, at least in the short term. Moreover, these diets may allow for dosage reduction of glucose-lowering medication. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42018104627.
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Omega-3 fatty acids in heart disease-why accurately measured levels matter.
von Schacky, C, Kuipers, RS, Pijl, H, Muskiet, FAJ, Grobbee, DE
Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2023;(11):415-423
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Current guidelines barely support marine omega‑3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in cardiology, mainly because results of large trials were equivocal. Most large trials have tested EPA alone or EPA + DHA combined as a drug, thereby disregarding the relevance of their blood levels. These levels are frequently assessed with the Omega‑3 Index (percentage of EPA + DHA in erythrocytes), which is determined using a specific standardised analytical procedure. EPA and DHA are present in every human being at unpredictable levels (even in the absence of intake), and their bioavailability is complex. Both facts need to be incorporated into trial design and should direct clinical use of EPA and DHA. An Omega‑3 Index in the target range of 8-11% is associated with lower total mortality, fewer major adverse cardiac and other cardiovascular events. Moreover, functions of organs such as the brain benefit from an Omega‑3 Index in the target range, while untoward effects, such as bleeding or atrial fibrillation, are minimised. In pertinent intervention trials, several organ functions were improved, with improvements correlating with the Omega‑3 Index. Thus, the Omega‑3 Index is relevant in trial design and clinical medicine, which calls for a widely available standardised analytical procedure and a discussion on possible reimbursement of this test.
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Short-Term Fasting Synergizes with Solid Cancer Therapy by Boosting Antitumor Immunity.
de Gruil, N, Pijl, H, van der Burg, SH, Kroep, JR
Cancers. 2022;(6)
Abstract
Short-term fasting (STF), using a low caloric, low protein fasting mimicking diet (FMD), appears to be a promising strategy to enhance chemotherapy-based cancer efficacy, while potentially alleviating toxicity. Preclinical results suggest that enhanced tumor immunity and decreased growth signaling, via lowering of circulating insulin and insulin growth factor 1 (IGF-1) levels form the potential underlying mechanisms. STF may boost anti-tumor responses by promoting tumor immunogenicity and decreasing local immunosuppression. These findings warrant further studies focused on the combination of STF, not only with chemotherapy, but also with immunotherapy to evaluate the full range of benefits of STF in cancer treatment. Here, we delineate the underlying anticancer mechanisms of fasting. We summarize preclinical evidence of STF boosting antitumor immunity and alleviating immunosuppression, as well as the clinical findings reporting the immunomodulatory effects of STF during various cancer treatments, including immunotherapy.
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Observational study on dietary changes of participants following a multicomponent lifestyle program (Reverse Diabetes2 Now).
Pot, GK, de Jong, HBT, Battjes-Fries, MCE, Patijn, ON, Pijl, H, Voshol, PJ
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2022;(5):791-803
Abstract
BACKGROUND Lifestyle intervention studies to treat type 2 diabetes (T2D) are on the rise. However, in-depth research is lacking into the dietary changes that participants make. METHODS The present study aimed to observe the dietary intake of participants following the group program 'Reverse Diabetes2 Now' (RD2N) over 12 months. The web-based 24-h dietary recall-tool Compl-eat was used to collect dietary intake data. RESULTS In total, 147 T2D patients were included in a cross-sectional study (n = 37 at baseline, n = 58 at 6 months, n = 52 at 12 months). A lower intake of total energy, carbohydrates and iodine was found for the groups at 6 and 12 months compared to the baseline group. The absolute consumption of total fat and saturated fat did not differ between the groups; only the percentage as total calorie consumption decreased. Consumption of vegetables and full-fat yoghurt was higher in groups at 6 and 12 months compared to the group at baseline. Consumption of bread, cakes and sweet biscuits, pasta/rice/tortillas, artificially sweetened soft drinks, and crisps were lower in the groups at 6 and 12 months compared to the group at baseline. Similar results were observed in a separate prospective study in 22 participants over 12 months following the same lifestyle-intervention. CONCLUSIONS Overall, participants shifted their dietary intake somewhat towards a healthier dietary pattern with overall lower energy and carbohydrates and more vegetables. Moreover, participants largely maintained this healthier pattern over 12 months. There were some concerns regarding iodine intake. These promising results need to be confirmed in a fully-scaled study, as well in a comparison with controls.
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Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners.
Van Opstal, AM, Hafkemeijer, A, van den Berg-Huysmans, AA, Hoeksma, M, Mulder, TPJ, Pijl, H, Rombouts, SARB, van der Grond, J
Nutritional neuroscience. 2021;(5):395-405
Abstract
INTRODUCTION The brain plays an important regulatory role in directing energy homeostasis and eating behavior. The increased ingestion of sugars and sweeteners over the last decades makes investigating the effects of these substances on the regulatory function of the brain of particular interest. We investigated whole brain functional response to the ingestion of nutrient shakes sweetened with either the nutritive natural sugars glucose and fructose, the low- nutritive natural sugar replacement allulose or the non-nutritive artificial sweetener sucralose. METHODS Twenty healthy, normal weight, adult males underwent functional MRI on four separate visits. In a double-blind randomized study setup, participants received shakes sweetened with glucose, fructose, allulose or sucralose. Resting state functional MRI was performed before and after ingestion. Changes in Blood Oxygen Level Dependent (BOLD) signal, functional network connectivity and voxel based connectivity by Eigenvector Centrality Mapping (ECM) were measured. RESULTS Glucose and fructose led to significant decreased BOLD signal in the cingulate cortex, insula and the basal ganglia. Glucose led to a significant increase in eigen vector centrality throughout the brain and a significant decrease in eigen vector centrality in the midbrain. Sucralose and allulose had no effect on BOLD signal or network connectivity but sucralose did lead to a significant increase in eigen vector centrality values in the cingulate cortex, central gyri and temporal lobe. DISCUSSION Taken together our findings show that even in a shake containing fat and protein, the type of sweetener can affect brain responses and might thus affect reward and satiety responses and feeding behavior. The sweet taste without the corresponding energy content of the non-nutritive sweeteners appeared to have only small effects on the brain. Indicating that the while ingestion of nutritive sugars could have a strong effect on feeding behavior, both in a satiety aspect as well as rewarding aspects, non-nutritive sweeteners appear to not have these effects. TRIAL REGISTRATION This study is registered at clinicaltrials.gov under number NCT02745730.
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Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial.
Lugtenberg, RT, de Groot, S, Kaptein, AA, Fischer, MJ, Kranenbarg, EM, Carpentier, MD, Cohen, D, de Graaf, H, Heijns, JB, Portielje, JEA, et al
Breast cancer research and treatment. 2021;(3):741-758
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PURPOSE In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. METHODS 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. RESULTS Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients' perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. CONCLUSIONS FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449.
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Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic.
Ruissen, MM, Regeer, H, Landstra, CP, Schroijen, M, Jazet, I, Nijhoff, MF, Pijl, H, Ballieux, BEPB, Dekkers, O, Huisman, SD, et al
BMJ open diabetes research & care. 2021;(1)
Abstract
INTRODUCTION Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS We performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown. RESULTS In total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: -0.39% (-4.3 mmol/mol) (p<0.0001 and type 2 diabetes: -0.62% (-6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001). CONCLUSIONS An increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.