Nuts in the Prevention and Management of Type 2 Diabetes.

Diabetes is a continuously growing global concern affecting >10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D.

Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials.

AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQ<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQ<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION: Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION: ClinicalTrials.gov NCT04094194. FUNDING: Diabetes and Nutrition Study Group of the EASD Clinical Practice.

Physical Activity and Sedentary Behavior Patterns Across Weekdays and Weekend Days in Youth With Multiple Sclerosis and Controls.

Background: This study quantified and compared weekday and weekend patterns of device-measured physical activity (PA) and sedentary behavior between youth with pediatric multiple sclerosis (MS) and controls for the purpose of informing future PA behavior change interventions. Methods: Participant data were obtained from 3 ongoing observational studies, and the sample included 40 participants with pediatric MS and 41 controls. Light PA (LPA), moderate to vigorous PA (MVPA), and sedentary behavior data were collected using activity monitors (ActiGraph LLC) over 1 week. The main analysis involved a 2-way mixed factor analysis of variance with group as a between-subjects factor (pediatric MS vs control) and day as a within-subjects factor (weekday vs weekend day). Results: There was no group by day interaction from the analysis of variance for percentage of activity monitor wear time spent in LPA, MVPA, or sedentary behavior. There was no effect of group for LPA, MVPA, or sedentary behavior. There was an effect of day of week on percentage of day spent in LPA, MVPA, and sedentary behavior. Conclusions: These results suggest that youth with pediatric MS and controls were less physically active and more sedentary on weekends than on weekdays, but there were no differences between groups in PA and sedentary behavior overall or by day of the week. Physical activity interventions may be more successful by initially targeting weekend day activity.

Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose-response meta-regression of prospective cohorts and randomized controlled trials.

Nuts are recommended for cardiovascular health, yet concerns remain that nuts may contribute to weight gain due to their high energy density. A systematic review and meta-analysis of prospective cohorts and randomized controlled trials (RCTs) was conducted to update the evidence, provide a dose-response analysis, and assess differences in nut type, comparator and more in subgroup analyses. MEDLINE, EMBASE, and Cochrane were searched, along with manual searches. Data from eligible studies were pooled using meta-analysis methods. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Certainty of the evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six prospective cohort studies (7 unique cohorts, n = 569,910) and 86 RCTs (114 comparisons, n = 5873) met eligibility criteria. Nuts were associated with lower incidence of overweight/obesity (RR 0.93 [95% CI 0.88 to 0.98] P < 0.001, "moderate" certainty of evidence) in prospective cohorts. RCTs presented no adverse effect of nuts on body weight (MD 0.09 kg, [95% CI -0.09 to 0.27 kg] P < 0.001, "high" certainty of evidence). Meta-regression showed that higher nut intake was associated with reductions in body weight and body fat. Current evidence demonstrates the concern that nut consumption contributes to increased adiposity appears unwarranted.

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.

Mediterranean diet, cardiovascular disease and mortality in diabetes: A systematic review and meta-analysis of prospective cohort studies and randomized clinical trials.

To update the clinical practice guidelines for nutrition therapy of the European Association for the Study of Diabetes, we conducted a systematic review and meta-analysis of prospective cohort studies and randomized clinical trials (RCTs) to evaluate the effect of the Mediterranean diet (MedDiet) on the prevention of cardiovascular disease (CVD) incidence and mortality. We searched Medline, EMBASE (through April 20, 2018) and Cochrane (through May 7, 2018) databases. Pooled relative risks (RRs) and 95% confidence interval (CI) were calculated by the generic inverse variance method. A total of 41 reports (3 RCTs and 38 cohorts) were included. Meta-analyses of RCTs revealed a beneficial effect of the MedDiet on total CVD incidence (RR: 0.62; 95% CI: 0.50, 0.78) and total myocardial infarction (MI) incidence (RR: 0.65; 95% CI: 0.49, 0.88). Meta-analyses of prospective cohort studies, which compared the highest versus lowest categories of MedDiet adherence, revealed an inverse association with total CVD mortality (RR: 0.79; 95% CI: 0.77, 0.82), coronary heart disease (CHD) incidence (RR: 0.73; 95% CI: 0.62, 0.86), CHD mortality (RR: 0.83; 95% CI: 0.75, 0.92), stroke incidence (RR: 0.80; 95% CI: 0.71, 0.90), stroke mortality (RR: 0.87; 95% CI: 0.80, 0.96) and MI incidence (RR: 0.73; 95% CI: 0.61, 0.88). The present study suggests that MedDiet has a beneficial role on CVD prevention in populations inclusive of individuals with diabetes.

Associations between Dietary Pulses Alone or with Other Legumes and Cardiometabolic Disease Outcomes: An Umbrella Review and Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.

To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted an umbrella review and updated systematic review and meta-analysis (SRMA) of prospective cohort studies of the association between dietary pulses with or without other legumes and cardiometabolic disease outcomes. We searched the PubMed, MEDLINE, EMBASE, and Cochrane databases through March 2019. We included the most recent SRMAs of prospective cohort studies and new prospective cohort studies published after the census dates of the included SRMAs assessing the relation between dietary pulses with or without other legumes and incidence and mortality of cardiovascular diseases (CVDs) [including coronary heart disease (CHD), myocardial infarction (MI), and stroke], diabetes, hypertension, and/or obesity. Two independent reviewers extracted data and assessed risk of bias. Risk estimates were pooled using the generic inverse variance method and expressed as risk ratios (RRs) with 95% CIs. The overall certainty of the evidence was assessed using the GRADE approach. Six SRMAs were identified and updated to include 28 unique prospective cohort studies with the following number of cases for each outcome: CVD incidence, 10,261; CVD mortality, 16,168; CHD incidence, 7786; CHD mortality, 3331; MI incidence, 2585; stroke incidence, 8570; stroke mortality, 2384; diabetes incidence, 10,457; hypertension incidence, 83,284; obesity incidence, 8125. Comparing the highest with the lowest level of intake, dietary pulses with or without other legumes were associated with significant decreases in CVD (RR: 0.92; 95% CI: 0.85, 0.99), CHD (RR: 0.90; 95% CI: 0.83, 0.99), hypertension (RR: 0.91; 95% CI: 0.86, 0.97), and obesity (RR: 0.87; 95% CI: 0.81, 0.94) incidence. There was no association with MI, stroke, and diabetes incidence or CVD, CHD, and stroke mortality. The overall certainty of the evidence was graded as "low" for CVD incidence and "very low" for all other outcomes. Current evidence shows that dietary pulses with or without other legumes are associated with reduced CVD incidence with low certainty and reduced CHD, hypertension, and obesity incidence with very low certainty. More research is needed to improve our estimates. This trial was registered at clinicaltrials.gov as NCT03555734.

Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis.

Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.

Relation of Vegetarian Dietary Patterns With Major Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Background: Vegetarian dietary patterns are recommended for cardiovascular disease (CVD) prevention and management due to their favorable effects on cardiometabolic risk factors, however, the role of vegetarian dietary patterns in CVD incidence and mortality remains unclear. Objective: To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we undertook a systematic review and meta-analysis of the association of vegetarian dietary patterns with major cardiovascular outcomes in prospective cohort studies that included individuals with and without diabetes using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Methods: MEDLINE, EMBASE, and Cochrane databases were searched through September 6th, 2018. We included prospective cohort studies ≥1 year of follow-up including individuals with or without diabetes reporting the relation of vegetarian and non-vegetarian dietary patterns with at least one cardiovascular outcome. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). The pre-specified outcomes included CVD incidence and mortality (total CVD, coronary heart disease (CHD) and stroke). Risk ratios for associations were pooled using inverse variance random effects model and expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I 2-statistic). The overall certainty of the evidence was assessed using GRADE. Results: Seven prospective cohort studies (197,737 participants, 8,430 events) were included. A vegetarian dietary pattern was associated with reduced CHD mortality [RR, 0.78 (CI, 0.69, 0.88)] and incidence [0.72 (0.61, 0.85)] but were not associated with CVD mortality [0.92 (0.84, 1.02)] and stroke mortality [0.92 (0.77, 1.10)]. The overall certainty of the evidence was graded as "very low" for all outcomes, owing to downgrades for indirectness and imprecision. Conclusions: Very low-quality evidence indicates that vegetarian dietary patterns are associated with reductions in CHD mortality and incidence but not with CVD and stroke mortality in individuals with and without diabetes. More research, particularly in different populations, is needed to improve the certainty in our estimates. Clinical Trial Registration: Clinicaltrials.gov, identifier: NCT03610828.

Cumulative Meta-Analysis of the Soy Effect Over Time.

Background Soy protein foods have attracted attention as useful plant protein foods with mild cholesterol-lowering effects that are suitable for inclusion in therapeutic diets. But on the basis of the lack of consistency in significant cholesterol reduction by soy in 46 randomized controlled trials, the US Food and Drug Administration (FDA) is reassessing whether the 1999 heart health claim for soy protein should be revoked. Methods and Results We have, therefore, performed a cumulative meta-analysis on the 46 soy trials identified by the FDA to determine if at any time, since the 1999 FDA final rule that established the soy heart health claim, the soy effect on serum cholesterol lost significance. The cumulative meta-analysis for both total cholesterol and low-density lipoprotein cholesterol demonstrated preservation of the small, but significant, reductions seen both before and during the subsequent 14 years since the health claim was originally approved. For low-density lipoprotein cholesterol, the mean reduction in 1999 was -6.3 mg/dL (95% CI, -8.7 to -3.9 mg/dL; P=0.00001) and remained in the range of -4.2 to -6.7 mg/dL ( P=0.0006 to P=0.0002, respectively) in the years after 1999. At no time point did the total cholesterol or low-density lipoprotein cholesterol reductions lose significance or were the differences at individual time points in the cumulative meta-analysis significantly different from those seen in 1999 when the health claim was approved. Conclusions A cumulative meta-analysis of the data selected by the FDA indicates continued significance of total cholesterol and low-density lipoprotein cholesterol reduction after soy consumption and supports the rationale behind the original soy FDA heart health claim.

A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults.

BACKGROUND: Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. OBJECTIVE: We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. METHODS: We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. RESULTS: Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant. CONCLUSIONS: Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. This trial was registered at clinicaltrials.gov as NCT03468127.

DASH Dietary Pattern and Cardiometabolic Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern, which emphasizes fruit, vegetables, fat-free/low-fat dairy, whole grains, nuts and legumes, and limits saturated fat, cholesterol, red and processed meats, sweets, added sugars, salt and sugar-sweetened beverages, is widely recommended by international diabetes and heart association guidelines. OBJECTIVE: To summarize the available evidence for the update of the European Association of the Study of Diabetes (EASD) guidelines, we conducted an umbrella review of existing systematic reviews and meta-analyses using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach of the relation of the DASH dietary pattern with cardiovascular disease and other cardiometabolic outcomes in prospective cohort studies and its effect on blood pressure and other cardiometabolic risk factors in controlled trials in individuals with and without diabetes. METHODS: MEDLINE and EMBASE were searched through 3 January 2019. We included systematic reviews and meta-analyses assessing the relation of the DASH dietary pattern with cardiometabolic disease outcomes in prospective cohort studies and the effect on cardiometabolic risk factors in randomized and non-randomized controlled trials. Two independent reviewers extracted relevant data and assessed the risk of bias of individual studies. The primary outcome was incident cardiovascular disease (CVD) in the prospective cohort studies and systolic blood pressure in the controlled trials. Secondary outcomes included incident coronary heart disease, stroke, and diabetes in prospective cohort studies and other established cardiometabolic risk factors in controlled trials. If the search did not identify an existing systematic review and meta-analysis on a pre-specified outcome, then we conducted our own systematic review and meta-analysis. The evidence was summarized as risk ratios (RR) for disease incidence outcomes and mean differences (MDs) for risk factor outcomes with 95% confidence intervals (95% CIs). The certainty of the evidence was assessed using GRADE. RESULTS: We identified three systematic reviews and meta-analyses of 15 unique prospective cohort studies (n = 942,140) and four systematic reviews and meta-analyses of 31 unique controlled trials (n = 4,414) across outcomes. We conducted our own systematic review and meta-analysis of 2 controlled trials (n = 65) for HbA1c. The DASH dietary pattern was associated with decreased incident cardiovascular disease (RR, 0.80 (0.76⁻0.85)), coronary heart disease (0.79 (0.71⁻0.88)), stroke (0.81 (0.72⁻0.92)), and diabetes (0.82 (0.74⁻0.92)) in prospective cohort studies and decreased systolic (MD, -5.2 mmHg (95% CI, -7.0 to -3.4)) and diastolic (-2.60 mmHg (-3.50 to -1.70)) blood pressure, Total-C (-0.20 mmol/L (-0.31 to -0.10)), LDL-C (-0.10 mmol/L (-0.20 to -0.01)), HbA1c (-0.53% (-0.62, -0.43)), fasting blood insulin (-0.15 µU/mL (-0.22 to -0.08)), and body weight (-1.42 kg (-2.03 to -0.82)) in controlled trials. There was no effect on HDL-C, triglycerides, fasting blood glucose, HOMA-IR, or CRP. The certainty of the evidence was moderate for SBP and low for CVD incidence and ranged from very low to moderate for the secondary outcomes. CONCLUSIONS: Current evidence allows for the conclusion that the DASH dietary pattern is associated with decreased incidence of cardiovascular disease and improves blood pressure with evidence of other cardiometabolic advantages in people with and without diabetes. More research is needed to improve the certainty of the estimates.

Effect of vegetarian dietary patterns on cardiometabolic risk factors in diabetes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of randomized controlled trials to summarize the evidence for the effect of vegetarian dietary patterns on glycemic control and other established cardiometabolic risk factors in individuals with diabetes. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through February 26, 2018 for randomized controlled trials ≥3 weeks assessing the effect of vegetarian dietary patterns in individuals with diabetes. The primary outcome was HbA1c. Secondary outcomes included other markers of glycemic control, blood lipids, body weight/adiposity, and blood pressure. Two independent reviewers extracted data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Nine trials (n = 664 participants) met the eligibility criteria. Vegetarian dietary patterns significantly lowered HbA1c (MD = -0.29% [95% CI: -0.45, -0.12%]), fasting glucose (MD = -0.56 mmol/L [95% CI: -0.99, -0.13 mmol/L]), LDL-C (MD = -0.12 mmol/L [95% CI: -0.20, -0.04 mmol/L]), non-HDL-C (MD = -0.13 mmol/L [95% CI: -0.26, -0.01 mmol/L]), body weight (MD = -2.15 kg [95% CI: -2.95, -1.34 kg]), BMI (MD = -0.74 kg/m2 [95% CI: -1.09, -0.39 kg/m2]) and waist circumference (MD = -2.86 cm [95% CI: -3.76, -1.96 cm]). There was no significant effect on fasting insulin, HDL-C, triglycerides or blood pressure. The overall certainty of evidence was moderate but was low for fasting insulin, triglycerides and waist circumference. CONCLUSION: Vegetarian dietary patterns improve glycemic control, LDL-C, non-HDL-C, and body weight/adiposity in individuals with diabetes, supporting their inclusion for diabetes management. More research is needed to improve our confidence in the estimates. CLINICALTRIALS. GOV IDENTIFIER: NCT02600377.

Effect of dried fruit on postprandial glycemia: a randomized acute-feeding trial.

BACKGROUND/OBJECTIVES: To investigate the effect of dried fruit in modifying postprandial glycemia, we assessed the ability of 4 dried fruits (dates, apricots, raisins, sultanas) to decrease postprandial glycemia through three mechanisms: a glycemic index (GI) effect, displacement effect, or 'catalytic' fructose effect. SUBJECTS/METHODS: We conducted an acute randomized, multiple-crossover trial in an outpatient setting in 10 healthy adults. Participants received 3 white bread control meals and 12 dried fruit test meals in random order. The test meals included each of 4 dried fruits (dates, apricots, raisins, sultanas) alone (GI effect), 4 of the dried fruits displacing half the available carbohydrate in white bread (displacement effect), or 4 of the dried fruits providing a small 'catalytic' dose (7.5 g) of fructose added to white bread ('catalytic' fructose effect). The protocol followed the ISO method for the determination of GI (ISO 26642:2010). The primary outcome was mean ± SEM GI (glucose scale) for ease of comparison across the three mechanisms. RESULTS: Ten healthy participants (7 men, 3 women; mean ± SD age and BMI: 39 ± 12 years and 25 ± 2 kg/m2) were recruited and completed the trial. All dried fruit had a GI below that of white bread (GI = 71); however, only dried apricots (GI = 42 ± 5), raisins (GI = 55 ± 5), and sultanas (51 ± 4) showed a significant GI effect (P < 0.05). When displacing half the available carbohydrate in white bread, all dried fruit lowered the GI; however, only dried apricots (GI = 57 ± 5) showed a significant displacement effect (P = 0.025). None of the dried fruits showed a beneficial 'catalytic' fructose effect. CONCLUSIONS: In conclusion, dried fruits have a lower GI and reduce the glycemic response of white bread through displacement of half of the available carbohydrate. Longer-term randomized trials are needed to confirm whether dried fruit can contribute to sustainable improvements in glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02960373.

Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies.

OBJECTIVE: To assess the effect of different food sources of fructose-containing sugars on glycaemic control at different levels of energy control. DESIGN: Systematic review and meta-analysis of controlled intervention studies. DATA SOURCES: Medine, Embase, and the Cochrane Library up to 25 April 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Controlled intervention studies of at least seven days' duration and assessing the effect of different food sources of fructose-containing sugars on glycaemic control in people with and without diabetes were included. Four study designs were prespecified on the basis of energy control: substitution studies (sugars in energy matched comparisons with other macronutrients), addition studies (excess energy from sugars added to diets), subtraction studies (energy from sugars subtracted from diets), and ad libitum studies (sugars freely replaced by other macronutrients without control for energy). Outcomes were glycated haemoglobin (HbA1c), fasting blood glucose, and fasting blood glucose insulin. DATA EXTRACTION AND SYNTHESIS: Four independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by random effects models and overall certainty of the evidence assessed by the GRADE approach (grading of recommendations assessment, development, and evaluation). RESULTS: 155 study comparisons (n=5086) were included. Total fructose-containing sugars had no harmful effect on any outcome in substitution or subtraction studies, with a decrease seen in HbA1c in substitution studies (mean difference -0.22% (95% confidence interval to -0.35% to -0.08%), -25.9 mmol/mol (-27.3 to -24.4)), but a harmful effect was seen on fasting insulin in addition studies (4.68 pmol/L (1.40 to 7.96)) and ad libitum studies (7.24 pmol/L (0.47 to 14.00)). There was interaction by food source, with specific food sources showing beneficial effects (fruit and fruit juice) or harmful effects (sweetened milk and mixed sources) in substitution studies and harmful effects (sugars-sweetened beverages and fruit juice) in addition studies on at least one outcome. Most of the evidence was low quality. CONCLUSIONS: Energy control and food source appear to mediate the effect of fructose-containing sugars on glycaemic control. Although most food sources of these sugars (especially fruit) do not have a harmful effect in energy matched substitutions with other macronutrients, several food sources of fructose-containing sugars (especially sugars-sweetened beverages) adding excess energy to diets have harmful effects. However, certainty in these estimates is low, and more high quality randomised controlled trials are needed. STUDY REGISTRATION: Clinicaltrials.gov (NCT02716870).

A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial.

Recent literature suggests that catalytic doses (≤10 g/meal or 36 g/day) of D-fructose and D-allulose may reduce postprandial blood glucose responses to carbohydrate loads in people with and without type 2 diabetes by inducing glycogen synthesis. To assess the effect of small single doses of fructose and allulose on postprandial blood glucose regulation in response to a 75 g-oral glucose tolerance test (75 g-OGTT) in healthy individuals, we conducted an acute randomized, crossover, equivalence trial in healthy adults. Each participant randomly received six treatments, separated by a minimum one-week washout. Treatments consisted of a 75 g-OGTT with the addition of fructose or allulose at 0 g (control), 5 g or 10 g. A standard 75 g-OGTT protocol was followed with blood samples at −30, 0, 30, 60, 90, 120 min. The primary outcome was the difference in plasma glucose incremental area under the curve (iAUC). A total of 27 participants underwent randomization with data available from 25 participants. Small doses of fructose or allulose did not show a significant effect on plasma glucose iAUC or other secondary markers of postprandial blood glucose regulation in response to a 75 g-OGTT in healthy individuals. These results were limited by the low power to detect a significant difference, owing to greater than expected intra-individual coefficient of variation (CV) in plasma glucose iAUC. Overall, we failed to confirm the catalytic effects of small doses of fructose and allulose in healthy individuals. Future trials may consider recruiting larger sample sizes of healthy individuals. TRIAL REGISTRATION: clinicaltrials.gov identifier, NCT02459834.

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.

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial.

AIM: To assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes. METHODS: A double-blind, multiple-crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by >1-week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75-g glucose solution. A standard 75-g oral glucose tolerance test protocol was followed with blood samples at -30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC). RESULTS: Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax ], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre-specified equivalence margins of ±20%. CONCLUSION: Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long-term randomized trials to confirm the sustainability of these improvements.

Effect of Plant Protein on Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is a heightened interest in plant-based diets for cardiovascular disease prevention. Although plant protein is thought to mediate such prevention through modifying blood lipids, the effect of plant protein in specific substitution for animal protein on blood lipids remains unclear. To assess the effect of this substitution on established lipid targets for cardiovascular risk reduction, we conducted a systematic review and meta-analysis of randomized controlled trials using the Grading of Recommendations Assessment, Development, and Evaluation system. METHODS AND RESULTS: MEDLINE, EMBASE, and the Cochrane Registry were searched through September 9, 2017. We included randomized controlled trials of ≥3 weeks comparing the effect of plant protein in substitution for animal protein on low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences with 95% confidence intervals. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality (certainty) of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. One-hundred twelve randomized controlled trials met the eligibility criteria. Plant protein in substitution for animal protein decreased low-density lipoprotein cholesterol by 0.16 mmol/L (95% confidence interval, -0.20 to -0.12 mmol/L; P<0.00001; I2=55%; moderate-quality evidence), non-high-density lipoprotein cholesterol by 0.18 mmol/L (95% confidence interval, -0.22 to -0.14 mmol/L; P<0.00001; I2=52%; moderate-quality evidence), and apolipoprotein B by 0.05 g/L (95% confidence interval, -0.06 to -0.03 g/L; P<0.00001; I2=30%; moderate-quality evidence). CONCLUSIONS: Substitution of plant protein for animal protein decreases the established lipid targets low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. More high-quality randomized trials are needed to improve our estimates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02037321.