The Portfolio Diet and HbA1c in Adults Living with Type 2 Diabetes Mellitus: A Patient-Level Pooled Analysis of Two Randomized Dietary Trials.

(1) Background: The Portfolio Diet, a dietary pattern of cholesterol-lowering foods, is also rich in low glycemic index (GI) foods. While strong evidence supports clinically meaningful reductions in cholesterol, evidence on the relationship between the Portfolio Diet and diabetes management is lacking. (2) Objective: To evaluate the relationship between the Portfolio Diet and glycated hemoglobin (HbA1c) as a determinant of glycemic control among adults living with type 2 diabetes mellitus (T2DM). (3) Methods: Patient-level data was pooled from two randomized dietary trials of low glycemic index interventions compared to high cereal fibre control diets in adults living with T2DM where HbA1c was collected (clinicaltrials.gov identifiers: NCT00438698, NCT00438698). Dietary exposure was assessed using weighed 7-day diet records. Adherence to the Portfolio Diet and its pillars (nuts and seeds, plant protein, viscous fibre, plant sterols, monounsaturated fatty acid [MUFA] oils) was determined using the validated clinical Portfolio Diet Score (c-PDS). Multiple linear regression was used to assess the association between change in the c-PDS and change in HbA1c over 6-months with covariate adjustments. (4) Results: A total of 267 participants, predominantly White (67%) and male (63%), were included, with a mean ± standard error age of 62 ± 0.5 years, baseline BMI of 30.2 ± 0.3 kg/m2, HbA1c of 7.08 ± 0.03%, and a c-PDS of 4.1 ± 0.3 points out of 25. Change in the c-PDS was significantly associated with a change in HbA1c (ß: -0.04% per point, 95% CI: -0.07, -0.02, p = 0.001). A 7.5-point (30%) increase in the c-PDS was associated with a 0.3% reduction in HbA1c. Of the individual pillars, a 1-point change in nut and seeds intake (ß: -0.07%, 95% CI: -0.12, -0.02, p = 0.009) or in plant protein intake (ß: -0.11%, 95% CI: -0.18, -0.03, p = 0.009) was associated with a change in HbA1c. Further analysis of plant protein intake revealed that an increase in dietary pulse intake, a particularly low-GI food, was significantly associated with a reduction in HbA1c (ß: -0.24% per 1-cup points cooked pulses (226 g) or 2 c-PDS points, 95% CI: -0.45, -0.03, p = 0.028). (5) Conclusions: Among adults living with T2DM, the Portfolio Diet was associated with lower HbA1c over a 6-month period, predominantly driven by two pillars: nuts and seeds and plant protein, particularly dietary pulses. These data have implications for including the Portfolio Diet in dietary recommendations for glycemic control in T2DM. A trial demonstrating the direct causal effect of the Portfolio Diet in a diverse group is warranted.

Simulation model to assess the validity of the clinical portfolio diet score used in the PortfolioDiet.app for dietary self-tracking: a secondary analysis of a randomized controlled trial in hyperlipidemic adults.

Introduction: The Portfolio Diet combines cholesterol-lowering plant foods for the management of cardiovascular disease risk. However, the translation of this dietary approach into clinical practice necessitates a user-friendly method for patients to autonomously monitor their adherence. Objective: This study aimed to develop and validate the clinical-Portfolio Diet Score (c-PDS) as a food-based metric to facilitate self-tracking of the Portfolio Diet. Methods: Using a simulation model to estimate the c-PDS, the validity was assessed in a secondary analysis of a completed trial of the Portfolio Diet in 98 participants with hyperlipidemia over 6 months. Concurrent and predictive validity of the estimated c-PDS were assessed against the reference measure (weighed 7-day diet records) and concomitant changes in LDL-C from baseline to 6 months. Bland-Altman analysis was used to assess the limits of agreement between the two methods. Results: The c-PDS was positively correlated with dietary adherence as measured using the 7-day diet records (r = 0.94, p < 0.001). The c-PDS was negatively correlated with change in LDL-C (r = -0.43, p < 0.001) with a 1-point increase in the c-PDS being associated with a - 0.04 mmol/L (CI:-0.06,-0.03; p < 0.001) or a 1.09% reduction in LDL-C. Visual evaluation of the Bland-Altman plots showed reasonable agreement. Conclusion: These findings indicate good validity of the c-PDS for primary prevention in adults with hyperlipidemia. The predictive validity findings have informed the goals and messaging within the PortfolioDiet.app, a digital health application for delivering the Portfolio Diet. Future research will assess the effectiveness of the intended combination of the c-PDS and the PortfolioDiet.app in supporting behavior change.

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study.

BACKGROUND: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the "intended substitution") versus water (the "standard of care substitution") for SSBs on glucose tolerance and microbiota diversity. DESIGN AND METHODS: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, "head-to-head", open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. BASELINE RESULTS: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). CONCLUSIONS: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03543644.

Low-carbohydrate vegan diets in diabetes for weight loss and sustainability: a randomized controlled trial.

BACKGROUND: Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option. OBJECTIVES: We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes. METHODS: One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants. RESULTS: Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (-5.9 kg; 95% CI: -6.5, -5.28 kg; and -5.23 kg; 95% CI: -5.84, -4.62 kg), glycated hemoglobin (-0.99%; 95% CI: -1.07, -0.9%; and -0.88%; 95% CI: -0.97, -0.8%), systolic blood pressure (-4 mmHg; 95% CI: -7, -2 mmHg; and -6 mmHg; 95% CI: -8, -3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of -0.63 kgCO2/d (95% CI: -0.99, -0.27 kgCO2/d) favoring the low-carbohydrate vegan diet. CONCLUSIONS: Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions. TRIAL REGISTRATION NUMBER: clinicaltrials.gov identifier NCT02245399.

A Web-Based Health Application to Translate Nutrition Therapy for Cardiovascular Risk Reduction in Primary Care (PortfolioDiet.app): Quality Improvement and Usability Testing Study.

BACKGROUND: The Portfolio Diet, or Dietary Portfolio, is a therapeutic dietary pattern that combines cholesterol-lowering foods to manage dyslipidemia for the prevention of cardiovascular disease. To translate the Portfolio Diet for primary care, we developed the PortfolioDiet.app as a patient and physician educational and engagement tool for PCs and smartphones. The PortfolioDiet.app is currently being used as an add-on therapy to the standard of care (usual care) for the prevention of cardiovascular disease in primary care. To enhance the adoption of this tool, it is important to ensure that the PortfolioDiet.app meets the needs of its target end users. OBJECTIVE: The main objective of this project is to undertake user testing to inform modifications to the PortfolioDiet.app as part of ongoing engagement in quality improvement (QI). METHODS: We undertook a 2-phase QI project from February 2021 to September 2021. We recruited users by convenience sampling. Users included patients, family physicians, and dietitians, as well as nutrition and medical students. For both phases, users were asked to use the PortfolioDiet.app daily for 7 days. In phase 1, a mixed-form questionnaire was administered to evaluate the users' perceived acceptability, knowledge acquisition, and engagement with the PortfolioDiet.app. The questionnaire collected both quantitative and qualitative data, including 2 open-ended questions. The responses were used to inform modifications to the PortfolioDiet.app. In phase 2, the System Usability Scale was used to assess the usability of the updated PortfolioDiet.app, with a score higher than 70 being considered acceptable. RESULTS: A total of 30 and 19 users were recruited for phase 1 and phase 2, respectively. In phase 1, the PortfolioDiet.app increased users' perceived knowledge of the Portfolio Diet and influenced their perceived food choices. Limitations identified by users included challenges navigating to resources and profile settings, limited information on plant sterols, inaccuracies in points, timed-logout frustration, request for step-by-step pop-up windows, and request for a mobile app version; when looking at positive feedback, the recipe section was the most commonly praised feature. Between the project phases, 6 modifications were made to the PortfolioDiet.app to incorporate and address user feedback. At phase 2, the average System Usability Scale score was 85.39 (SD 11.47), with 100 being the best possible. CONCLUSIONS: By undertaking user testing of the PortfolioDiet.app, its limitations and strengths were able to be identified, informing modifications to the application, which resulted in a clinical tool that better meets users' needs. The PortfolioDiet.app educates users on the Portfolio Diet and is considered acceptable by users. Although further refinements to the PortfolioDiet.app will continue to be made before its evaluation in a clinical trial, the result of this QI project is an improved clinical tool.

Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.

This is an update of the previous 2018 systematic review and meta-analysis of vitamin and mineral supplementation on cardiovascular disease outcomes and all-cause mortality. New randomized controlled trials and meta-analyses were identified by searching the Cochrane library, Medline, and Embase, and data were analyzed using random effects models and classified by the Grading of Recommendations Assessment Development and Evaluation approach. This updated review shows similar findings to the previous report for preventive benefits from both folic acid and B vitamins for stroke and has been graded with moderate quality. No effect was seen for the commonly used multivitamins, vitamin D, calcium, and vitamin C, and an increased risk was seen with niacin (with statin) for all-cause mortality. Conclusive evidence for the benefit of supplements across different dietary backgrounds, when the nutrient is sufficient, has not been demonstrated.

Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS: We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION: The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.

Apple Flavonols Mitigate Adipocyte Inflammation and Promote Angiogenic Factors in LPS- and Cobalt Chloride-Stimulated Adipocytes, in Part by a Peroxisome Proliferator-Activated Receptor-γ-Dependent Mechanism.

Adipose tissue (AT) expansion induces local hypoxia, a key contributor to the chronic low-grade inflammation that drives obesity-associated disease. Apple flavonols phloretin (PT) and phlorizin (PZ) are suggested anti-inflammatory molecules but their effectiveness in obese AT is inadequately understood. Using in vitro models designed to reproduce the obese AT microenvironment, 3T3-L1 adipocytes were cultured for 24 h with PT or PZ (100 µM) concurrent with the inflammatory stimulus lipopolysaccharide (LPS; 10 ng/mL) and/or the hypoxia mimetic cobalt chloride (CoCl2; 100 µM). Within each condition, PT was more potent than PZ and its effects were partially mediated by peroxisome proliferator-activated receptor (PPAR)-γ (p < 0.05), as tested using the PPAR-γ antagonist bisphenol A diglycidyl ether (BADGE). In LPS-, CoCl2-, or LPS + CoCl2-stimulated adipocytes, PT reduced mRNA expression and/or secreted protein levels of inflammatory and macrophage chemotactic adipokines, and increased that of anti-inflammatory and angiogenic adipokines, which was consistent with reduced mRNA expression of M1 polarization markers and increased M2 markers in RAW 264.7 macrophages cultured in media collected from LPS + CoCl2-simulated adipocytes (p < 0.05). Further, within LPS + CoCl2-stimulated adipocytes, PT reduced reactive oxygen species accumulation, nuclear factor-κB activation, and apoptotic protein expression (p < 0.05). Overall, apple flavonols attenuate critical aspects of the obese AT phenotype.

Supplemental Vitamins and Minerals for CVD Prevention and Treatment.

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, ß-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.