1.
Impact of dietary interventions on pre-diabetic oral and gut microbiome, metabolites and cytokines.
Shoer, S, Shilo, S, Godneva, A, Ben-Yacov, O, Rein, M, Wolf, BC, Lotan-Pompan, M, Bar, N, Weiss, EI, Houri-Haddad, Y, et al
Nature communications. 2023;14(1):5384
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Pre-diabetes, a condition characterized by elevated blood glucose levels but below diabetes thresholds, is a significant risk factor for the development of type 2 diabetes, as well as other comorbidities including cardiovascular and kidney diseases. Diet plays a critical role in the development of hyperglycaemia and the onset of pre-diabetes. The aim of this study was to assess the impact of a personalized postprandial glucose-targeting diet (PPT), as well as the standard of care Mediterranean diet (MED), on the oral and gut microbiome, metabolites and cytokines in 200 pre-diabetic individuals. This study was a biphasic, randomised, controlled, single-blind dietary intervention. Phase one included a six-month intervention that compared two diets targeting glycaemic control, while phase two included a six-month follow-up period. Participants (n = 225) were randomly assigned in a 1:1 ratio to a PPT (n = 113) or a MED (n = 112). Results showed that participants assigned to the PPT diet had significant changes in 19 gut microbial species, 14 gut and one oral microbial pathway, 86 serum metabolites and four cytokines. Participants assigned to the MED diet showed significant changes in five gut and one oral microbial species, 18 gut microbial pathways, 27 serum metabolites and four cytokines. Authors conclude that dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host. Thus, diets such as the PPT used in this study, which takes into account microbiome features, could be designed to affect the microbiome and inflict desired metabolic outcomes.
Abstract
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
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Effects of personalized diets by prediction of glycemic responses on glycemic control and metabolic health in newly diagnosed T2DM: a randomized dietary intervention pilot trial.
Rein, M, Ben-Yacov, O, Godneva, A, Shilo, S, Zmora, N, Kolobkov, D, Cohen-Dolev, N, Wolf, BC, Kosower, N, Lotan-Pompan, M, et al
BMC medicine. 2022;20(1):56
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Type 2 diabetes mellitus (T2DM) affects around 10% of the global population. The primary goal in its management is to improve glycemic control. Modifying the diet can help, but many patients fail to achieve improvements with diet alone. The aim of the randomized dietary intervention pilot trial is to evaluate the effects of a personalized postprandial-targeting (PPT) diet on glycemic control and metabolic health in 23 adults with newly diagnosed T2DM, as compared to the commonly recommended Mediterranean-style (MED) diet. The PPT diet led to significant lower levels of continuous-glucose-monitoring (CGM)-based measures as compared to the MED diet. In the additional 6-months intervention, metabolic parameters were further improved and 61% of the participants exhibited diabetes remission. Improvements in clinical outcomes were also accompanied by changes in the gut microbiome. These findings may be useful for the design of larger studies in the future that may have implications for dietary advice in clinical practice.
Abstract
BACKGROUND Dietary modifications are crucial for managing newly diagnosed type 2 diabetes mellitus (T2DM) and preventing its health complications, but many patients fail to achieve clinical goals with diet alone. We sought to evaluate the clinical effects of a personalized postprandial-targeting (PPT) diet on glycemic control and metabolic health in individuals with newly diagnosed T2DM as compared to the commonly recommended Mediterranean-style (MED) diet. METHODS We enrolled 23 adults with newly diagnosed T2DM (aged 53.5 ± 8.9 years, 48% males) for a randomized crossover trial of two 2-week-long dietary interventions. Participants were blinded to their assignment to one of the two sequence groups: either PPT-MED or MED-PPT diets. The PPT diet relies on a machine learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses (PPGR). We further evaluated the long-term effects of PPT diet on glycemic control and metabolic health by an additional 6-month PPT intervention (n = 16). Participants were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using a smartphone application. RESULTS In the crossover intervention, the PPT diet lead to significant lower levels of CGM-based measures as compared to the MED diet, including average PPGR (mean difference between diets, - 19.8 ± 16.3 mg/dl × h, p < 0.001), mean glucose (mean difference between diets, - 7.8 ± 5.5 mg/dl, p < 0.001), and daily time of glucose levels > 140 mg/dl (mean difference between diets, - 2.42 ± 1.7 h/day, p < 0.001). Blood fructosamine also decreased significantly more during PPT compared to MED intervention (mean change difference between diets, - 16.4 ± 37 μmol/dl, p < 0.0001). At the end of 6 months, the PPT intervention leads to significant improvements in multiple metabolic health parameters, among them HbA1c (mean ± SD, - 0.39 ± 0.48%, p < 0.001), fasting glucose (- 16.4 ± 24.2 mg/dl, p = 0.02) and triglycerides (- 49 ± 46 mg/dl, p < 0.001). Importantly, 61% of the participants exhibited diabetes remission, as measured by HbA1c < 6.5%. Finally, some clinical improvements were significantly associated with gut microbiome changes per person. CONCLUSION In this crossover trial in subjects with newly diagnosed T2DM, a PPT diet improved CGM-based glycemic measures significantly more than a Mediterranean-style MED diet. Additional 6-month PPT intervention further improved glycemic control and metabolic health parameters, supporting the clinical efficacy of this approach. TRIAL REGISTRATION ClinicalTrials.gov number, NCT01892956.
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Personalized Postprandial Glucose Response-Targeting Diet Versus Mediterranean Diet for Glycemic Control in Prediabetes.
Ben-Yacov, O, Godneva, A, Rein, M, Shilo, S, Kolobkov, D, Koren, N, Cohen Dolev, N, Travinsky Shmul, T, Wolf, BC, Kosower, N, et al
Diabetes care. 2021;(9):1980-1991
Abstract
OBJECTIVE To compare the clinical effects of a personalized postprandial-targeting (PPT) diet versus a Mediterranean (MED) diet on glycemic control and metabolic health in prediabetes. RESEARCH DESIGN AND METHODS We randomly assigned adults with prediabetes (n = 225) to follow a MED diet or a PPT diet for a 6-month dietary intervention and additional 6-month follow-up. The PPT diet relies on a machine learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses. During the intervention, all participants were connected to continuous glucose monitoring (CGM) and self-reported dietary intake using a smartphone application. RESULTS Among 225 participants randomized (58.7% women, mean ± SD age 50 ± 7 years, BMI 31.3 ± 5.8 kg/m2, HbA1c, 5.9 ± 0.2% [41 ± 2.4 mmol/mol], fasting plasma glucose 114 ± 12 mg/dL [6.33 ± 0.67 mmol/L]), 200 (89%) completed the 6-month intervention. A total of 177 participants also contributed 12-month follow-up data. Both interventions reduced the daily time with glucose levels >140 mg/dL (7.8 mmol/L) and HbA1c levels, but reductions were significantly greater in PPT compared with MED. The mean 6-month change in "time above 140" was -0.3 ± 0.8 h/day and -1.3 ± 1.5 h/day for MED and PPT, respectively (95% CI between-group difference -1.29 to -0.66, P < 0.001). The mean 6-month change in HbA1c was -0.08 ± 0.19% (-0.9 ± 2.1 mmol/mol) and -0.16 ± 0.24% (-1.7 ± 2.6 mmol/mol) for MED and PPT, respectively (95% CI between-group difference -0.14 to -0.02, P = 0.007). The significant between-group differences were maintained at 12-month follow-up. No significant differences were noted between the groups in a CGM-measured oral glucose tolerance test. CONCLUSIONS In this clinical trial in prediabetes, a PPT diet improved glycemic control significantly more than a MED diet as measured by daily time of glucose levels >140 mg/dL (7.8 mmol/L) and HbA1c. These findings may have implications for dietary advice in clinical practice.
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Phase II study of etoposide (VP-16) in patients with thyroid cancer with no prior chemotherapy: an Eastern Cooperative Oncology Group Study (E1385).
Leaf, AN, Wolf, BC, Kirkwood, JM, Haselow, RE
Medical oncology (Northwood, London, England). 2000;(1):47-51
Abstract
This study of etoposide in thyroid cancer was designed to determine the activity and toxicity of etoposide in a variety of inoperable, thyroid hormone insensitive, and radio-iodine resistant primary cancers of the thyroid. The patients were required to have an ECOG performance status of at least 3 and no previous exposure to chemotherapy. The etoposide was given at a dose of 140 mg/m2 daily for 3 days and every 3 weeks until progression. The study was closed after 18 months because of poor accrual. There were no responses seen among the 10 patients accrued. The toxicity was primarily hematologic. There was no evidence of activity of etoposide in thyroid carcinoma, although this study lacked significant power because of the poor accrual.