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OBJECTIVECombined low-risk lifestyle behaviors (LRLBs) have been associated with a reduction in type 2 diabetes risk. This relationship has not been systematically quantified.RESEARCH DESIGN AND METHODSA systematic review and meta-analysis was conducted to assess the association of combined LRLBs with type 2 diabetes. Databases were searched up to September 2022. Prospective cohort studies reporting the association between a minimum of three combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using a random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using a one-stage linear mixed model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).RESULTSThirty cohort comparisons (n = 1,693,753) involving 75,669 incident type 2 diabetes cases were included. LRLBs, with author-defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk [RR] 0.20; 95% CI 0.17–0.23), comparing the highest with lowest adherence. Global DRM for maximum adherence to all five LRLBs reached 85% protection (RR 0.15; 95% CI 0.12–0.18). The overall certainty of the evidence was graded as high.CONCLUSIONSThere is a very good indication that a combination of LRLBs that includes maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption is associated with a lower risk of incident type 2 diabetes.

OBJECTIVE High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI −10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

To investigate the energy and macronutrient bioaccessibility of almonds in individuals with hyperlipidemia.In a previously reported randomized crossover trial, men and postmenopausal women with hyperlipidemia incorporated 3 isoenergetic supplements into a National Cholesterol Education Program Step 2 diet for 1 month each between September 20, 2000, and June 27, 2001. Supplements provided consisted of full-dose almonds (73±5 g/d), half-dose almonds (38±3 g/d) plus half-dose muffins, and full-dose muffins (control). Energy and macronutrients, including individual fatty acids, were measured in the dietary supplements and fecal samples using gas chromatography and Association of Official Analytical Chemists methods. Serum was measured for lipids and fatty acids. Bioaccessibility of energy and macronutrients from almond consumption was assessed from dietary intake (7-day food records) and fecal output.Almond-related energy bioaccessibility was 78.5%±3.1%, with an average energy loss of 21.2%±3.1% (40.6 kcal/d in the full-dose almond phase). Bioaccessibility of energy and fat from the diet as a whole was significantly less with almond consumption (in both half- and full-dose phases) compared with the control. Bioaccessibility of fat was significantly different between treatment phases (P.001) and on average lower by 5.1% and 6.3% in the half- and full-dose almond phases, respectively, compared with the control phase. Energy bioaccessibility was significantly different between the treatment phases (P=.02), decreasing by approximately 2% with the inclusion of the full dose of almonds compared with the control.Energy content of almonds may not be as bioaccessible in individuals with hyperlipidemia as predicted by Atwater factors, as suggested by the increased fat excretion with almond intake compared with the control.ClinicalTrials.gov identifier: NCT00507520.

Background Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. Objectives To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. Methods MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. Results We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL; 95% CI: 0.06-0.27 mg/dL; P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. Conclusions Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

[Background & aims]: The Portfolio and Dietary Approaches to Stop Hypertension (DASH) diets have been shown to lower cardiometabolic risk factors in randomized controlled trials (RCTs). However, the Portfolio diet has only been assessed in RCTs of hyperlipidemic patients. Therefore, to assess the Portfolio diet in a population with metabolic syndrome (MetS), we conducted a longitudinal analysis of one-year data of changes in the Portfolio and DASH diet scores and their association with cardiometabolic risk factors in Prevención con Dieta Mediterránea (PREDIMED)-Plus trial. [Methods]: PREDIMED-Plus is an ongoing clinical trial (Trial registration: ISRCTN89898) conducted in Spain that includes 6874 older participants (mean age 65 y, 48% women) with overweight/obesity fulfilling at least three criteria for MetS. Data for this analysis were collected at baseline, six months and one year. Adherence to the Portfolio and DASH diet scores were derived from a validated 143-item food frequency questionnaire. We used linear mixed models to examine the associations of 1-SD increase and quartile changes in the diet scores with concomitant changes in cardiometabolic risk factors. [Results]: After adjusting for several potential confounders, a 1-SD increase in the Portfolio diet score was significantly associated with lower HbA1c (β [95% CI]: −0.02% [−0.02, −0.01], P < 0.001), fasting glucose (−0.47 mg/dL [−0.83, −0.11], P = 0.01), triglycerides (−1.29 mg/dL [−2.31, −0.28], P = 0.01), waist circumference (WC) (−0.51 cm [−0.59, −0.43], P < 0.001), and body mass index (BMI) (−0.17 kg/m2 [−0.19, −0.15], P < 0.001). A 1-SD increase in the DASH diet score was significantly associated with lower HbA1c (−0.03% [−0.04, −0.02], P < 0.001), glucose (−0.84 mg/dL [−1.18, −0.51], P < 0.001), triglycerides (−3.38 mg/dL [−4.37, −2.38], P < 0.001), non-HDL-cholesterol (−0.47 mg/dL [−0.91, −0.04], P = 0.03), WC (−0.69 cm [−0.76, −0.60 cm], P < 0.001), BMI (−0.25 kg/m2 [−0.28, −0.26 kg/m2], P < 0.001), systolic blood pressure (−0.57 mmHg [−0.81, −0.32 mmHg], P < 0.001), diastolic blood pressure (−0.15 mmHg [−0.29, −0.01 mmHg], P = 0.03), and with higher HDL-cholesterol (0.21 mg/dL [0.09, 0.34 mg/dL, P = 0.001]). Similar associations were seen when both diet scores were assessed as quartiles, comparing extreme categories of adherence. [Conclusions]: Among older adults at high cardiovascular risk with MetS, greater adherence to the Portfolio and DASH diets showed significant favourable prospective associations with several clinically relevant cardiometabolic risk factors. Both diets are likely beneficial for cardiometabolic risk reduction., The PREDIMED-Plus trial was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS) and co-funded by European Union ERDF/ESF, “A way to make Europe”/“Investing in your future” (five coordinated FIS projects led by JS-S and JVid, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183,PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332), the Special Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S, the European Research Council (Advanced Research Grant 2014–2019, 340918) to MÁM-G, the Recercaixa Grant to JS-S (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03). This research was also partially funded by EU-H2020 Grant (EAT2BENICE/H2020-SFS-2016-2; Ref 728018). Study resulting from the SLT006/17/00246 grant, funded by the Department of Health of the Generalitat de Catalunya by the call “Acció instrumental de programes de recerca orientats en l'àmbit de la recerca i la innovació en salut”. We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work is partially supported by ICREA under the ICREA Academia programme. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU 17/01925). MRBL was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. AJG was supported by the Nora Martin Fellowship in Nutritional Sciences, the Banting & Best Diabetes Centre Tamarack Graduate Award in Diabetes Research, the Peterborough K.M. Hunter Charitable Foundation Graduate Award and an Ontario Graduate Scholarship. PH-A was supported by a postdoctoral fellowship (Juan de la Cierva-Formación), FJCI-2017–32205, funded by the Ministry of Science and Innovation. RE group has been supported by the ‘Ajut 2017-2021 SGR 1717 from the Generalitat de Catalunya. DJAJ was funded by the Government of Canada through the Canada Research Chair Endowment. JK was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands). JLS was funded by a Diabetes Canada Clinician Scientist Award.

OBJECTIVE A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes. RESEARCH DESIGN AND METHODS This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021. Adherence to the diet was assessed with a score based on six components (high in plant protein [soy and pulses], nuts, viscous fiber, plant sterols, and monounsaturated fat and low in saturated fat and cholesterol) determined from a validated food-frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association of the Portfolio Diet, alongside the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, with incident type 2 diabetes, with adjustment for potential confounders. RESULTS Over a mean follow-up of 16.0 years, 13,943 cases of incident type 2 diabetes were identified. In comparisons of the highest with the lowest quintiles of adherence, the HRs for risk of incident type 2 diabetes were 0.77 (95% CI 0.72, 0.82) for the Portfolio Diet, 0.69 (0.64, 0.73) for the DASH diet, and 0.78 (0.74, 0.83) for the Mediterranean diet. These findings were attenuated by 10% after additional adjustment for BMI. CONCLUSIONS Greater adherence to the plant-predominant Portfolio, DASH, and Mediterranean diets was prospectively associated with lower risk of type 2 diabetes in postmenopausal women.

Background Previous meta-analyses, with some methodological controversies, have assessed the relation between nut consumption and type 2 diabetes (T2D) risk and pointed to contradictory results, making desirable the performance of an updated meta-analysis. Objectives We aimed to systematically review and meta-analyze all the published studies investigating the relations of total nuts and different types of nuts-i.e., walnuts, peanuts, peanut butter, and total tree nuts-with the prevalence and incidence of T2D. Methods A systematic search was conducted in the PubMed and Cochrane databases through 12 August, 2020. The inverse variance method with fixed-effect models was used to pool data across studies, expressed as risk ratios (RRs) or ORs and 95% CIs for prospective cohort and cross-sectional studies, respectively. The Cochran Q test and I2 statistics were used to test and quantify heterogeneity, respectively. Dose-response meta-analysis was also conducted. Results Eight studies (5 prospective and 3 cross-sectional) were included in the quantitative synthesis. Meta-analyses of cross-sectional studies and prospective cohort studies, comparing the highest with the lowest categories, revealed a nonsignificant association between total nut consumption and T2D. Meta-analyses of prospective cohort studies showed an inverse association between peanut butter consumption and T2D incidence (RR: 0.87; 95% CI: 0.77, 0.98; I2 = 50.6%; Pheterogeneity = 0.16), whereas no association was observed between peanuts or tree nuts and T2D. There was no evidence of a linear dose-response or nonlinear dose-response gradient for total nut and peanut consumption in prospective cohort studies. The certainty of the evidence using NutriGrade was very low for all the exposures. Conclusions Current results do not demonstrate an association of total nut, peanut, or tree nut consumption with T2D. Peanut butter consumption may be inversely associated with this disease.This review protocol was registered at www.crd.york.ac.uk/prospero/ as CRD42020149756.

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.

Summary Background Perhaps, as never before, we need innovators. With our growing population numbers, and with increasing pressures on our education systems, are we in danger of becoming more rigid and formulaic and increasingly inhibiting innovation? When young can we predict who will become the great innovators? For example, in medicine, who will change clinical practice? Aims We therefore determined to assess whether the current academic excellence approach to medical school entrance would have captured previous great innovators in medicine, assuming that they should all have well fulfilled current entrance requirements. Methods The authors assembled a list of 100 great medical innovators which was then approved, rejected or added to by a jury of 12 MD fellows of the Royal Society of Canada. Two reviewers, who had taken both the past and present Medical College Admission Test as part of North American medical school entrance requirements, independently assessed each innovator’s early life educational history in order to predict the innovator’s likely success at medical school entry, assuming excellence in all entrance requirements. Results Thirty-one percent of the great medical innovators possessed no medical degree and 24% would likely be denied entry to medical school by today’s standards (e.g. had a history of poor performance, failure, dropout or expulsion) with only 24% being guaranteed entry. Even if excellence in only one topic was required, the figure would only rise to 41% certain of medical school entry. Conclusion These data show that today’s medical school entry standards would have barred many great innovators and raise questions about whether we are losing medical innovators as a consequence. Our findings have important implications for promoting flexibility and innovation for medical education, and for promoting an environment for innovation in general.

Objective To determine the association of total and added fructose-containing sugars on cardiovascular disease (CVD) incidence and mortality. Methods MEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled. Results Eligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P Conclusion Current evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD. Registration clinicaltrials.gov, NCT01608620

BACKGROUND Adverse associations of low- and no-calorie sweetened beverages (LNCSB) with cardiometabolic outcomes in observational studies may be explained by reverse causality and residual confounding. PURPOSE To address these limitations we used change analyses of repeated measures of intake and substitution analyses to synthesize the association of LNCSB with cardiometabolic outcomes. DATA SOURCES MEDLINE, Embase, and the Cochrane Library were searched up to 10 June 2021 for prospective cohort studies with ≥1 year of follow-up duration in adults. STUDY SELECTION Outcomes included changes in clinical measures of adiposity, risk of overweight/obesity, metabolic syndrome, type 2 diabetes (T2D), cardiovascular disease, and total mortality. DATA EXTRACTION Two independent reviewers extracted data, assessed study quality, and assessed certainty of evidence using GRADE. Data were pooled with a random-effects model and expressed as mean difference (MD) or risk ratio (RR) and 95% CI. DATA SYNTHESIS A total of 14 cohorts (416,830 participants) met the eligibility criteria. Increase in LNCSB intake was associated with lower weight (5 cohorts, 130,020 participants; MD −0.008 kg/year [95% CI −0.014, −0.002]). Substitution of LNCSB for sugar-sweetened beverages (SSB) was associated with lower weight (three cohorts, 165,579 participants; MD, −0.12 [−0.14, −0.10,] kg/y) and lower incidence of obesity (OB) (one cohort, 15,765 participants; RR 0.88 [95% CI 0.88, 0.89]), coronary heart disease (six cohorts, 233,676 participants; 0.89 [0.81, 0.98]), cardiovascular disease mortality (one cohort, 118,363 participants; 0.95 [0.90, 0.99]), and total mortality (one cohort, 118,363 participants; 0.96 [0.94, 0.98]) with no adverse associations across other outcomes. Substitution of water for SSB showed lower weight (three cohorts, 165,579 participants; MD −0.10 kg/year [−0.13, −0.06]), lower waist circumference (one cohort, 173 participants; −2.71 cm/year [−4.27, −1.15]) and percent body fat (one cohort, 173 participants; −1.51% per year [−2.61, −0.42]), and lower incidence of OB (one cohort, 15,765 participants; RR 0.85 [0.75, 0.97]) and T2D (three cohorts, 281,855 participants; 0.96 [0.94, 0.98]). Substitution of LNCSB for water showed no adverse associations. LIMITATIONS The evidence was low to very low certainty owing to downgrades for imprecision, indirectness, and/or inconsistency. CONCLUSIONS LNCSB were not associated with cardiometabolic harm in analyses that model the exposure as change or substitutions. The available evidence provides some indication that LNCSB in their intended substitution for SSB may be associated with cardiometabolic benefit, comparable with the standard of care, water.

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.

Objective To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane Library searched up to 13 May 2021. Eligibility criteria for selecting studies Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. Outcome and measures The primary outcome was glycated haemoglobin (HbA 1c ). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. Results 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA 1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P2 =75%, P1c and for absolute dietary GI and SBP (P1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. Conclusions This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. Study registration ClinicalTrials.gov NCT04045938 .

Background The plant‐based Dietary Portfolio combines established cholesterol‐lowering foods (plant protein, nuts, viscous fiber, and phytosterols), plus monounsaturated fat, and has been shown to improve low‐density lipoprotein cholesterol and other cardiovascular disease (CVD) risk factors. No studies have evaluated the relation of the Dietary Portfolio with incident CVD events. Methods and Results We followed 123 330 postmenopausal women initially free of CVD in the Women's Health Initiative from 1993 through 2017. We used Cox proportional‐hazard models to estimate adjusted hazard ratios (HRs) and 95% CI of the association of adherence to a Portfolio Diet score with CVD outcomes. Primary outcomes were total CVD, coronary heart disease, and stroke. Secondary outcomes were heart failure and atrial fibrillation. Over a mean follow‐up of 15.3 years, 13 365 total CVD, 5640 coronary heart disease, 4440 strokes, 1907 heart failure, and 929 atrial fibrillation events occurred. After multiple adjustments, adherence to the Portfolio Diet score was associated with lower risk of total CVD (HR, 0.89; 95% CI, 0.83–0.94), coronary heart disease (HR, 0.86; 95% CI, 0.78–0.95), and heart failure (HR, 0.83; 95% CI, 0.71–0.99), comparing the highest to lowest quartile of adherence. There was no association with stroke (HR, 0.97; 95% CI, 0.87–1.08) or atrial fibrillation (HR, 1.10; 95% CI, 0.87–1.38). These results remained statistically significant after several sensitivity analyses. Conclusions In this prospective cohort of postmenopausal women in the United States, higher adherence to the Portfolio Diet was associated with a reduction in incident cardiovascular and coronary events, as well as heart failure. These findings warrant further investigation in other populations.

The Portfolio Diet, a plant-based portfolio of cholesterol-lowering foods, has been shown to reduce low-density lipoprotein cholesterol (LDL-C), and other cardiovascular risk factors, in randomized controlled trials (RCTs). It is not known if these beneficial effects translate to a lower incidence cardiovascular disease (CVD) risk. To support examinations between Portfolio Diet adherence and disease, a Portfolio Diet score (PDS) was developed and its predictive and concurrent validity was assessed within the Toronto Healthy Diet Study, a six-month RCT in overweight adults. Predictive validity was assessed using change in the PDS measured by food frequency questionnaire (FFQ) and concomitant change in LDL-C from baseline to six months using multiple linear regression, adjusted for potential confounders (n = 652). Concurrent validity was assessed in a subset of participants (n = 50) who completed the FFQ and a 7-day diet record (7DDR) at baseline. The PDS determined from each diet assessment method was used to derive correlation coefficients and Bland–Altman plots to assess the between-method agreement. The change in PDS was inversely associated with change in LDL-C (β coefficients: −0.01 mmol/L (95% confidence intervals (CIs): −0.02, −0.002, p = 0.02). The correlation between the PDS from the FFQ and 7DDR was 0.69 (95% CIs: 0.48, 0.85). The Bland–Altman plot showed reasonable agreement between the score from the FFQ and 7DDR. These findings indicate predictive validity of the PDS with lower LDL-C, and reasonable concurrent validity of the PDS as assessed by an FFQ against a 7DDR.

OBJECTIVES: Fructose as a source of excess calories increases uric acid. Whether this effect is mediated by the food matrix at different levels of energy is unknown. We aim to conduct a systematic review and meta-analysis of controlled feeding trials on the effect of food sources of fructose-containing sugars at different energy levels on uric acid (NCT02716870). METHODS: MEDLINE, Embase and the Cochrane Library were searched through January 27, 2020 for controlled trials ≥7-days assessing the effect of food sources of fructose-containing sugars on uric acid. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients) trials. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using the GRADE approach. RESULTS: Eligibility was met by 41 trials (72 trial comparisons, N = 2109) assessing the effect of 9 food sources (sugar-sweetened beverages [SSBs], sweetened dairy, fruit drink [lemonade], 100% fruit juice, fruit, dried fruit [raisins], baked goods desserts and sweets, added nutritive [caloric] sweetener and mixed sources) across the 4 energy levels. Total fructose-containing sugars increased uric acid in substitution trials (mean difference, 0.15 mg/dL [95% confidence interval, 0.03 to 0.27 mg/dL], P = 0.012) with no effect in addition, subtraction or ad libitum trials. There was evidence of interaction by food source with SSBs and baked goods, desserts and sweets increasing uric acid in substitution and SSBs increasing and 100% fruit juice decreasing uric acid in addition trials. The overall certainty of evidence was moderate for the increasing effect of SSBs in substitution and addition trials and low to very low for all other comparisons. CONCLUSIONS: Food source more than energy control mediate the effect of fructose-containing sugars on uric acid. SSBs and baked goods, desserts and sweets appear to increase, and 100% fruit juice appear to decrease uric acid. More high-quality trials of different food sources of fructose-containing sugars are needed to improve our estimates. FUNDING SOURCES: Diabetes Canada.

OBJECTIVES: Sugar-sweetened beverages (SSBs) have been linked to weight gain. It is unclear if other food sources of fructose-containing sugars behave similarly. We conducted a systematic review and meta-analysis of controlled feeding trials to assess the effect of different food sources of fructose-containing sugars on body weight and markers of adiposity. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through January 2020 for controlled feeding trials ≥2 weeks on the effect of fructose-containing sugars. Trial designs were prespecified by energy control: substitution (energy matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets). The primary outcome was body weight. Secondary outcomes were body mass index, body fat and waist circumference. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using GRADE. (NCT02558920) RESULTS: We identified 119 controlled trials (368 trial comparisons, N = 5263) assessing the effect of 10 food sources (SSBs, sweetened dairy alternative (soy), fruit juice, fruit drink, fruit, dried fruit, sweetened cereal grains/bars, sweets, added sweeteners and mixed sources). Total fructose-containing sugars increased body weight (mean difference, 0.29 kg [95% confidence interval, 0.05 to 0.53 kg], P = 0.017) and body fat in addition trials with no effect in other analyses or outcomes. There was evidence of interaction by food source in substitution trials with fruit reducing and mixed sources increasing some outcomes and in addition trials with 100% fruit juice reducing and SSBs and mixed sources increasing some outcomes. The overall certainty of evidence was moderate for the decreasing effect of fruit and fruit juice and the increasing effect of SSBs and mixed sources and high-to-very low for other comparisons. CONCLUSIONS: Energy control and food source may mediate the effect of fructose-containing sugars on adiposity. The evidence provides good indication that fruit and 100% fruit juice decrease and SSBs and mixed sources increase markers of adiposity. More high-quality randomized trials of different foods are needed to improve our estimates. FUNDING SOURCES: American Society for Nutrition, Diabetes Canada, CIHR, Mitacs.

OBJECTIVES: Intermittent fasting (IF) is a popular trending diet, yet there is limited evidence-based support considering its clinical impact on cardiometabolic outcomes. In an effort to inform the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a network meta-analysis of randomized controlled trials (RCTs) comparing IF strategies and continuous energy restriction (CER) on cardiometabolic outcomes using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched through Nov 2020. We included RCTs assessing the effect of IF strategies (alternate-day fasting (ADF), whole-day periodic fasting (WDF), time-restricted feeding (TRF)), CER, and ad libitum diet. Outcomes included body weight, fasting glucose and LDL-cholesterol. Two independent researchers extracted data and assessed risk of bias. A network meta-analysis was performed and data were expressed as mean differences (MD) with 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. RESULTS: We identified 19 RCTs (n = 590) including adults of varying health backgrounds. ADF and CER both showed a benefit for body weight reduction compared to ad libitum diet (18 trials, n = 520; MD −3.95 kg [95% CI −6.09, −1.81] and MD −2.85 kg [95% CI −4.99, −0.71], respectively). For fasting glucose (17 trials, n = 590), TRF showed a benefit compared to ad libitum diet (MD −0.39 mmol/L [95% CI −0.59, −0.20]), to CER (MD −0.25 mmol/L [95% CI, −0.45 to −0.06]) and to WDF (MD −0.20 mmol/L [95% CI, −0.45, −0.05]). Furthermore, ADF showed a benefit in reducing LDL-cholesterol (17 trials, n = 590) compared to ad libitum diet (MD −0.21 mmol/L [95% CI −0.40, −0.1]), and to CER (MD −0.15 mmol/L [95% CI −0.31, −0.01]). The certainty of the evidence ranged from high to moderate due to variable downgrades for imprecision. CONCLUSIONS: Current evidence provides a good indication that IF strategies have similar benefits to CER for weight loss but may have additional benefits for fasting glucose and LDL-cholesterol. Long-term high quality RCTs are needed to clarify the effect of different IF strategies on cardiometabolic outcomes. FUNDING SOURCES: Diabetes and Nutrition Study Group of the EASD, Canadian Institutes of Health Research (CIHR), Diabetes Canada.

OBJECTIVES: Sugars have been implicated in the epidemic of obesity. It is unclear whether food sources of fructose-containing sugars other than sugar-sweetened beverages (SSBs) are associated with increased risk of obesity. To assess the evidence of the relation of food sources of fructose-containing sugars with incident overweight or obesity, we undertook a systematic review and meta-analysis of prospective cohort studies. METHODS: We searched MEDLINE, EMBASE and Cochrane Library through Aug 2019. We included prospective cohort studies of ≥1 year. Two reviewers extracted data and assessed the risk of bias. The primary outcome was incident overweight/obesity. Data were pooled using generic-inverse variance method (random effects) and expressed as relative risks (RR) for incident outcomes and ß-coefficients for WC with 95% confidence intervals (CI). GRADE assessed the certainty of evidence RESULTS: We included 12 and 8 prospective cohorts involving 181,295 adults and 31,717 children, respectively. Four food sources of fructose-containing sugars were identified: SSBs, 100% fruit juice, fruit and yogurt. There was no data available in children for yogurt or WC. SSBs were associated with increased incident overweight/obesity in children (RR, 1.22 [95% CI, 1.03 to 1.44] but not in adults and increased incident abdominal obesity in both children (3.78 [1.08 to 13.25]) and adults (1.51 [1.11 to 2.06]), but there was no association with change in WC in adults. Fruit juice was associated with increased incident overweight/obesity in children (1.28 [1.07 to 1.53]) but not in adults, and there was no association with incident abdominal obesity in either children or adults or WC in adults. Fruit was associated with decreased incident overweight/obesity (0.87 [0.82 to 0.92]) and decreased WC (ß, −0.23 cm [−0.33 to −0.13]) in adults. Yogurt was associated with decreased incident abdominal obesity (0.65 [0.47 to 0.90]) in adults with no data available on WC. The certainty of the evidence was graded as “very low” to “moderate”. CONCLUSIONS: Current evidence indicates that the relation between fructose-containing sugars and obesity outcomes differs by food sources. More research of more food sources of sugars is needed to improve our certainty in the evidence. (ClinicalTrials.gov, NCT02558920) FUNDING SOURCES: ASN, Diabetes Canada, Banting and Best Diabetes Centre.

Context Previous meta-analyses evaluating the association between nut consumption and the risk of cardiovascular disease (CVD) had substantial methodological limitations and lacked recently published large prospective studies; hence, making an updated meta-analysis highly desirable. Objective To update the clinical guidelines for nutrition therapy in relation to the European Association for the Study of Diabetes (EASD), a systematic review and meta-analysis of prospective studies was conducted using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to summarize the evidence of the association between total nuts, specific types of nuts, and the incidence of, and mortality from, CVD outcomes. Data sources Relevant articles were identified by searching the PubMed and Cochrane databases. Data extraction Two independent researchers screened the articles to identify those that met the inclusion criteria. Data analysis The inverse variance method with fixed-effect or random-effects models was used to pool data across studies (expressed as risk ratio [RR] and 95% confidence interval [CI]). Heterogeneity was tested and quantified using the Cochrane Q test and I2-statistic, respectively. The GRADE system was used to assess the quality of the evidence. Results Nineteen studies were included in the analyses. The results revealed an inverse association between total nut consumption (comparing highest vs lowest categories) and CVD incidence (RR, 0.85; 95%CI, 0.800.91; I2, 0%), CVD mortality (RR, 0.77; 95%CI, 0.72–0.82; I2, 3%), coronary heart disease (CHD) incidence (RR, 0.82; 95%CI, 0.69–0.96; I2, 74%), CHD mortality (RR, 0.76; 95%CI, 0.67–0.86; I2, 46%), stroke mortality (RR, 0.83; 95%CI, 0.75–0.93; I2, 0%), and atrial fibrillation (RR, 0.85; 95%CI, 0.73–0.99; I2, 0%). No association was observed with stroke incidence and heart failure. The certainty of the evidence ranged from moderate to very low. Conclusions This systematic review and meta-analysis revealed a beneficial role of nut consumption in reducing the incidence of, and mortality from, different CVD outcomes.

Summary 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 .

OBJECTIVE The evidence for liquid meal replacements in diabetes has not been summarized. Our objective was to synthesize the evidence of the effect of liquid meal replacements on cardiometabolic risk factors in overweight/obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Data sources included MEDLINE, EMBASE, and the Cochrane Library through 10 December 2018. We included randomized trials of ≥2 weeks assessing the effect of liquid meal replacements in weight loss diets compared with traditional weight loss diets on cardiometabolic risk factors in overweight/obese subjects with type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS Nine trial comparisons (N = 961 [median follow-up 24 weeks]) met eligibility criteria. Mean differences were for body weight −2.37 kg (95% CI −3.30 to −1.44), BMI −0.87 kg/m2 (−1.31 to −0.42), body fat −1.66% (−2.17 to −1.15), waist circumference −2.24 cm (−3.72 to −0.77), HbA1c −0.43% (−0.66 to −0.19) (−4.7 mmol/mol [−7.2 to −2.1]), fasting glucose −0.63 mmol/L (−0.99 to −0.27), fasting insulin −11.83 pmol/L (−23.11 to −0.54), systolic blood pressure −4.97mmHg (−7.32 to −2.62), and diastolic blood pressure −1.98 mmHg (−3.05 to −0.91). There was no effect on blood lipids. The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. CONCLUSIONS Liquid meal replacements in weight loss diets lead to modest reductions in body weight, BMI, and systolic blood pressure, and reductions of marginal clinical significance in body fat, waist circumference, HbA1c, fasting glucose, fasting insulin, and diastolic blood pressure. More high-quality trials are needed to improve the certainty in our estimates.

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.

ContextRare sugars are monosaccharides and disaccharides (found in small quantities in nature) that have slight differences in their chemical structure compared with traditional sugars. Little is known about their unique physiological and cardiometabolic effects in humans.ObjectiveThe objective of this study was to conduct a systematic review and synthesis of controlled intervention studies of rare sugars in humans, using PRISMA guidelines.Data SourcesMEDLINE and EMBASE were searched through October 1, 2020. Studies included both post-prandial (acute) and longer-term (≥1 week duration) human feeding studies that examined the effect of rare sugars (including allulose, arabinose, tagatose, trehalose, and isomaltulose) on cardiometabolic and physiological risk factors.Data extractionIn all, 50 studies in humans focusing on the 5 selected rare sugars were found. A narrative synthesis of the selected literature was conducted, without formal quality assessment or quantitative synthesis.Data synthesisThe narrative summary included the food source of each rare sugar, its effect in humans, and the possible mechanism of effect. Overall, these rare sugars were found to offer both short- and long-term benefits for glycemic control and weight loss, with effects differing between healthy individuals, overweight/obese individuals, and those with type 2 diabetes. Most studies were of small size and there was a lack of large randomized controlled trials that could confirm the beneficial effects of these rare sugars.ConclusionRare sugars could offer an opportunity for commercialization as an alternative sweetener, especially for those who are at high cardiometabolic risk.Systematic Review RegistrationOSF registration no. 10.17605/OSF.IO/FW43D.

Background Public health policies reflect concerns that certain fruit sources may not have the intended benefits and that vegetables should be preferred to fruit. We assessed the relation of fruit and vegetable sources with cardiovascular outcomes using a systematic review and meta‐analysis of prospective cohort studies. Methods and Results MEDLINE, EMBASE, and Cochrane were searched through June 3, 2019. Two independent reviewers extracted data and assessed study quality (Newcastle‐Ottawa Scale). Data were pooled (fixed effects), and heterogeneity (Cochrane‐Q and I 2 ) and certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. Eighty‐one cohorts involving 4 031 896 individuals and 125 112 cardiovascular events were included. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (risk ratio, 0.93 [95% CI, 0.89–0.96]; 0.91 [0.88–0.95]; and 0.94 [0.90–0.97], respectively), coronary heart disease (0.88 [0.83–0.92]; 0.88 [0.84–0.92]; and 0.92 [0.87–0.96], respectively), and stroke (0.82 [0.77–0.88], 0.82 [0.79–0.85]; and 0.88 [0.83–0.93], respectively) incidence. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (0.89 [0.85–0.93]; 0.88 [0.86–0.91]; and 0.87 [0.85–0.90], respectively), coronary heart disease (0.81 [0.72–0.92]; 0.86 [0.82–0.90]; and 0.86 [0.83–0.89], respectively), and stroke (0.73 [0.65–0.81]; 0.87 [0.84–0.91]; and 0.94 [0.90–0.99], respectively) mortality. There were greater benefits for citrus, 100% fruit juice, and pommes among fruit sources and allium, carrots, cruciferous, and green leafy among vegetable sources. No sources showed an adverse association. The certainty of the evidence was “very low” to “moderate,” with the highest for total fruit and/or vegetables, pommes fruit, and green leafy vegetables. Conclusions Fruits and vegetables are associated with cardiovascular benefit, with some sources associated with greater benefit and none showing an adverse association. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT03394339.

International audience; Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.

Dietary carbohydrates are components of healthy foods, but many carbohydrate foods have recently been stigmatized as primary causes of diet-related risk factors for chronic disease. There is an opportunity to enhance efforts within the food landscape to encourage the consumption of higher quality carbohydrate foods. The use of labelling is one strategy that permits consumers to identify healthy carbohydrate foods at the point-of-purchase. This review discusses the regulatory frameworks and examples of associated non-mandatory food labelling claims that are currently employed to highlight healthy carbohydrate foods to consumers. The existing labelling frameworks discussed here align with established measures of carbohydrate quality, such as 1. dietary fibre nutrient content claims and associated dietary fibre-based health claims; 2. the presence of whole carbohydrate foods and ingredients that are intact or reconstituted, such as whole grains; and 3. low glycemic index and glycemic response claims. Standards from Codex Alimentarius, and regulations from Australia and New Zealand, Canada, Europe, and the United States will be used to illustrate the means by which food labelling can be used by consumers to identify quality carbohydrate foods.

OBJECTIVES: Nordic dietary patterns may have a role in diabetes management. To inform the update of the European Association for the Study of Diabetes (EASD) clinical practice guidelines, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched Cochrane, MEDLINE, and EMBASE through Aug 2019. We included cohort studies of ≥1 y and RCTs of ≥3 wk. Two independent reviewers extracted data and assessed risk of bias. The primary outcome was CVD in cohort studies and LDL-C in RCTs. Secondary outcomes included CHD and stroke in cohort studies and markers of glycemic control, lipids, adiposity, BP and inflammation in RCTs. Data were expressed as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). GRADE assessed the certainty of evidence. RESULTS: We identified 10 cohort studies in people inclusive of diabetes and 6 RCTs in people with ≥1 risk factor (overweight/obesity, metabolic syndrome, dyslipidemia). Nordic dietary patterns were associated with lower risk of the primary outcome, total CVD (RR, 0.93 [95% CI, 0.88, 0.99]) and CVD mortality (0.83 [0.73, 0.94]), as well as stroke (0.88 [0.79, 0.98]) in cohort studies. Although Nordic dietary patterns did not reduce the primary outcome, LDL-C, in RCTs, there were reductions in other established lipid targets, non-HDL-C (MD, −0.49 mmol/L [95% CI, −0.67, −0.30]) and apo B (0.15 g/L [−0.19, −0.11]), as well as weight (2.10 kg [−3.58, −0.63]), BMI (−0.90 kg/m(2) [−1.11, −0.69]), waist circumference (2.22 cm [−3.36, −1.09], diastolic BP (1.78 mmHg [−3.21, −0.35]) and insulin (7.23 pmol/L [−11.88, −2.58]). The certainty of evidence was moderate for the reductions in CVD mortality, established lipid targets, adiposity markers, and insulin and low for all other outcomes. CONCLUSIONS: Nordic dietary patterns are associated with decreased CVD and reduce cardiometabolic risk factors in people inclusive of or at risk for diabetes. The available data indicate a benefit for people with diabetes with a moderate likelihood that more studies will alter our estimates. (clinicaltrials.gov identifier, NCT04094194) FUNDING SOURCES: Diabetes and Nutrition Study Group (DNSG) of the EASD, CIHR, Diabetes Canada, Joannah and Brian Lawson Center for Child Nutrition, Connaught Fund, Onassis Foundation.

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.

Introduction: The Dietary Portfolio is a plant-based dietary pattern of a combination of recognized cholesterol-lowering foods and has been shown to lower a number of cardiovascular disease (CVD) risk factors, including low-density lipoprotein cholesterol, blood pressure and C-reactive protein. However, no studies have assessed if following the Portfolio results in fewer CVD events. Hypothesis: Higher adherence to the Portfolio will be associated with fewer CVD events. Methods: We included 125,389 postmenopausal women from the Women’s Health Initiative Observational Study and Clinical Trials (from 1993 to 2017) who were free of CVD at baseline. Adherence to the Portfolio was assessed using an a priori diet index based on 6 food categories (high in plant protein [soy & pulses], nuts, viscous fiber, plant sterols and monounsaturated fat, and low in saturated fat) that were found to lower CVD risk factors in the Portfolio trials. Adjusted hazard ratios (HRs) and 95% confidence intervals [CIs] for CVD were calculated using Cox regressions. We adjusted for CVD risk & lifestyle factors and potential confounders (see Table 1). Results: During 1,826,176 person-years of follow-up, we documented 11,370 total CVD cases, including 5,739 coronary heart disease (CHD) cases, 4,451 stroke cases, 1,946 heart failure (HF) cases and 935 atrial fibrillation (AF) cases. Comparing the highest to the lowest quartile in the fully adjusted model, higher adherence to the Portfolio was associated with a reduced risk of total CVD (HR=0.89 [95% CI 0.84-0.95]), CHD (0.87 [0.79-0.95]) and HF (0.83 [0.70-0.98]). No association was found with stroke (0.97 [0.87-1.08]) and AF (1.09 [0.87-1.38]). Conclusions: In postmenopausal women, higher adherence to the Portfolio was inversely associated with total CVD, CHD and HF but not stroke or AF. These findings suggest that the Portfolio may assist with CVD, CHD and HF prevention and warrants further investigation. Table 1: Association of the Dietary Portfolio and risk of CVD in Postmenopausal Women

The recommended amount and quality of protein in diets of diabetic patients are highly controversial. In order to provide evidence-based information, the Diabetes Nutrition Study Group (DNSG) used a grading procedure used for quality of evidence and strength of recommendations (GRADE). A protein intake of 10% to 20% of energy intake (E%) or about 0.8 to 1.3 g/kg body weight in people below 65 years of age, and 15% to 20% of E% in people above 65 years of age appeared safe in weight-stable conditions. There were no intervention studies addressing metabolic effects, mortality, or cardiovascular events over prolonged periods. Body weight is closely linked to metabolic control and high protein diets are often recommended. Weight-loss diets that include 23% to 32% of E% as protein for up to one year reduced blood pressure and body weight slightly but significantly more than lower protein diets, whereas blood lipids, fasting blood glucose, and HbA1c improved similarly with higher or lower protein intakes in participants with a glomerular filtration rate (GFR) >60 mL/min/1.73 m2. Patients with a GFR 2 did not show a faster decline of GFR or kidney function with protein intakes around 0.8 g/kg body weight as compared with lower intakes, thereby arguing against a restriction. The effects of protein intake on diabetic eye or nerve disease have not been reported. There are a number of studies that have compared different types of animal proteins (milk, chicken, beef, pork, and fish) or compared animal with plant protein in diabetic patients and have reported a greater reduction of serum cholesterol with plant protein. In summary, the suggested range of protein intake appears to be safe and can be adapted according to personal dietary preferences.

Intestinal homeostasis depends on the dynamic interplay among the host, its gut microbiome, and diet. Cohort studies and intervention trials emphasize plant-based diets for chronic disease prevention. Fermentable fiber in these diets is a preferred metabolic fuel for the gut microbiome; prudent diets, encompassing a higher intake of fruits, vegetables, legumes, and rich in fiber, rather than a Western diet, are associated with reduced risk for colorectal cancer (CRC). CRC is characterized by a typical gut microbiome signature, with Fusobacterium nucleatum being an emerging critical species. Remarkably, an inverse association between prudent diets and F. nucleatum–positive CRC risk has been demonstrated, while inflammatory and Western dietary patterns are associated with an increased risk of F. nucleatum–positive CRC tumor subtype. This relationship does not apply to F. nucleatum–negative tumors. The intersection between diet, microbiota composition, and CRC warrants the application of nutritional strategies to prevent the development of CRC.

Background Sugar‐sweetened beverages are associated with hypertension. We assessed the relation of important food sources of fructose‐containing sugars with incident hypertension using a systematic review and meta‐analysis of prospective cohort studies. Methods and Results We searched MEDLINE , EMBASE, and Cochrane (through December week 2, 2018) for eligible studies. For each food source, natural log‐transformed risk ratios (RRs) for incident hypertension were pooled using pair‐wise meta‐analysis and linear and nonlinear dose‐response meta‐analyses. Certainty in our evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. We identified 26 reports, including 15 prospective cohorts (930 677 participants; 363 459 cases). Sugar‐sweetened beverages showed harmful ( RR per‐355‐mL , 1.10 [95% CI , 1.08, 1.12]) whereas fruit ( RR per‐240‐g , 0.94 [95% CI , 0.96, 0.99]) and yogurt showed protective associations ( RR per‐125‐g , 0.95 [95% CI , 0.94, 0.97]) with incident hypertension throughout the dose range. One hundred percent fruit juice showed a protective association only at moderate doses ( RR at‐100‐mL , 0.97 [95% CI , 0.94, 0.99]). The pair‐wise protective association of dairy desserts was not supported by linear dose‐response analysis. Fruit drinks or sweet snacks were not associated with hypertension. Certainty of the evidence was “low” for sugar‐sweetened beverages, 100% fruit juice, fruit, and yogurt and “very low” for fruit drinks, sweet snacks, and dairy desserts. Conclusions The harmful association between sugar‐sweetened beverages and hypertension does not extend to other important food sources of fructose‐containing sugars. Further research is needed to improve our estimates and better understand the dose‐response relationship between food sources of fructose‐containing sugars and hypertension. Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 02702375.

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.

Aims/hypothesis In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors’ request (10.2337/dc16-rt02) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. Methods A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5–8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) ‘full-dose nut diet’ (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) ‘full-dose muffin diet’ (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) ‘half-dose nut diet’ (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. Results A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by −2.0 mmol/mol (95% CI −3.8, −0.3 mmol/mol) (−0.19% [95% CI −0.35%, −0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter

The evidence for the Portfolio dietary pattern, a plant-based dietary pattern that combines recognized cholesterol-lowering foods (nuts, plant protein, viscous fibre, plant sterols), has not been summarized.To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of controlled trials using GRADE of the effect of the Portfolio dietary pattern on the primary therapeutic lipid target for cardiovascular disease prevention, low-density lipoprotein cholesterol (LDL-C), and other established cardiometabolic risk factors.We searched MEDLINE, EMBASE, and The Cochrane Library through April 19, 2018. We included controlled trials ≥ 3-weeks assessing the effect of the Portfolio dietary pattern on cardiometabolic risk factors compared with an energy-matched control diet free of Portfolio dietary pattern components. Two independent reviewers extracted data and assessed risk of bias. The primary outcome was LDL-C. Data were pooled using the generic inverse-variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (IEligibility criteria were met by 7 trial comparisons in 439 participants with hyperlipidemia, in which the Portfolio dietary pattern was given on a background of a National Cholesterol Education Program (NCEP) Step II diet. The combination of a portfolio dietary pattern and NCEP Step II diet significantly reduced the primary outcome LDL-C by ~17% (MD, -0.73 mmol/L, [95% CI, -0.89 to -0.56 mmol/L]) as well as non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, triglycerides, systolic and diastolic blood pressure, C-reactive protein, and estimated 10-year coronary heart disease (CHD) risk, compared with an NCEP Step 2 diet alone (p 0.05). There was no effect on high-density lipoprotein cholesterol or body weight. The certainty of the evidence was high for LDL-cholesterol and most lipid outcomes and moderate for all others outcomes.Current evidence demonstrates that the Portfolio dietary pattern leads to clinically meaningful improvements in LDL-C as well as other established cardiometabolic risk factors and estimated 10-year CHD risk.