Weight management using meal replacements and cardiometabolic risk reduction in individuals with pre-diabetes and features of metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

This review synthesized the evidence from randomized controlled trials comparing the effect of meal replacements (MRs) as part of a weight loss intervention with conventional food-based weight loss diets on cardiometabolic risk in individuals with pre-diabetes and features of metabolic syndrome. MEDLINE, EMBASE, and Cochrane Library were searched through January 16, 2024. Data were pooled using the generic inverse variance method and expressed as mean difference [95% confidence intervals]. The overall certainty of the evidence was assessed using GRADE. Ten trials (n = 1254) met the eligibility criteria. MRs led to greater reductions in body weight (-1.38 kg [-1.81, -0.95]), body mass index (BMI, -0.56 kg/m2 [-0.78, -0.34]), waist circumference (-1.17 cm [-1.93, -0.41]), HbA1c (-0.11% [-0.22, 0.00]), LDL-c (-0.18 mmol/L [-0.28, -0.08]), non-HDL-c (-0.17 mmol/L [-0.33, -0.01]), and systolic blood pressure (-2.22 mmHg [-4.20, -0.23]). The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. The available evidence suggests that incorporating MRs into a weight loss intervention leads to small important reductions in body weight, BMI, LDL-c, non-HDL-c, and systolic blood pressure, and trivial reductions in waist circumference and HbA1c, beyond that seen with conventional food-based weight loss diets.

Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.

Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies.

BACKGROUND: The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke. METHODS: We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol. RESULTS: During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; Ptrend<0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; Ptrend=0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; Ptrend=0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile. CONCLUSIONS: The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts.

Fructose-containing food sources and blood pressure: A systematic review and meta-analysis of controlled feeding trials.

Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

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

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

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.

Nuts and Cardiovascular Disease Outcomes: A Review of the Evidence and Future Directions.

Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been less consistent. This narrative review summarizes recommendations for nuts by clinical practice guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes, nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future research directions, such as the use of biomarkers to help better assess nut intake. Although there are still some uncertainties around nuts and CVD prevention which require further research, as summarized in this review, there is a substantial amount of evidence that supports that consuming nuts will have a positive impact on primary and secondary prevention of CVD.

The Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis.

Background: There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Results: Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). Conclusions: The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.

Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

OBJECTIVE: Combined 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 METHODS: A 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). RESULTS: Thirty 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. CONCLUSIONS: There 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.

Effect of honey on cardiometabolic risk factors: a systematic review and meta-analysis.

CONTEXT: Excess calories from free sugars are implicated in the epidemics of obesity and type 2 diabetes. Honey is a free sugar but is generally regarded as healthy. OBJECTIVE: The effect of honey on cardiometabolic risk factors was assessed via a systematic review and meta-analysis of controlled trials using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library databases were searched up to January 4, 2021, for controlled trials ≥1 week in duration that assessed the effect of oral honey intake on adiposity, glycemic control, lipids, blood pressure, uric acid, inflammatory markers, and markers of nonalcoholic fatty liver disease. DATA EXTRACTION: Independent reviewers extracted data and assessed risk of bias. Data were pooled using the inverse variance method and expressed as mean differences (MDs) with 95%CIs. Certainty of evidence was assessed using GRADE. DATA ANALYSIS: A total of 18 controlled trials (33 trial comparisons, N = 1105 participants) were included. Overall, honey reduced fasting glucose (MD = -0.20 mmol/L, 95%CI, -0.37 to -0.04 mmol/L; low certainty of evidence), total cholesterol (MD = -0.18 mmol/L, 95%CI, -0.33 to -0.04 mmol/L; low certainty), low-density lipoprotein cholesterol (MD = -0.16 mmol/L, 95%CI, -0.30 to -0.02 mmol/L; low certainty), fasting triglycerides (MD = -0.13 mmol/L, 95%CI, -0.20 to -0.07 mmol/L; low certainty), and alanine aminotransferase (MD = -9.75 U/L, 95%CI, -18.29 to -1.21 U/L; low certainty) and increased high-density lipoprotein cholesterol (MD = 0.07 mmol/L, 95%CI, 0.04-0.10 mmol/L; high certainty). There were significant subgroup differences by floral source and by honey processing, with robinia honey, clover honey, and raw honey showing beneficial effects on fasting glucose and total cholesterol. CONCLUSION: Honey, especially robinia, clover, and unprocessed raw honey, may improve glycemic control and lipid levels when consumed within a healthy dietary pattern. More studies focusing on the floral source and the processing of honey are required to increase certainty of the evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42015023580.

The Portfolio Diet and Incident Type 2 Diabetes: Findings From the Women's Health Initiative Prospective Cohort Study.

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.

Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.

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.

Effect of Important Food Sources of Fructose-Containing Sugars on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence. RESULTS: We identified 64 controlled trials (91 trial comparisons, n = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses. CONCLUSIONS: Food source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control. CLINICALTRIALS: gov: (NCT02716870).

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.

Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies.

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.

Systematic review and meta-analysis examining the relationship between postprandial hypotension, cardiovascular events, and all-cause mortality.

BACKGROUND: Postprandial hypotension (PPH) has been reported to be associated with syncope, falls, adverse cardiovascular outcomes, and increased all-cause mortality. It has been reported to have an incidence as high as 30% in the elderly and persons with diabetes. We therefore performed a meta-analysis to determine the relation of PPH with cardiovascular disease (CVD) events and all-cause mortality. OBJECTIVES: Our objective was to conduct a systematic review and meta-analysis of cohort and cross-sectional studies to determine the association of PPH with CVD and all-cause mortality. METHODS: We searched the databases MEDLINE, EMBASE, and Cochrane library up to 13 April 2022 for prospective cohort and cross-sectional studies that examined the association of PPH with CVD outcomes and all-cause mortality. Data were analyzed using the generic inverse variance method with a random-effects model. Grading of Recommendations, Assessment, Development, and Evaluation approach assessed the certainty of evidence. RESULTS: Seven studies that included 2389 participants met our inclusion criteria. PPH was associated with each outcome individually, including increased all-cause mortality, total CVD, CVD mortality, and stroke. CVD outcomes and all-cause mortality combined were also associated with PPH (RR: 1.52; 95% CI: 1.05, 2.18; P = 0.03; I2 = 77%). The certainty of evidence was graded as very low due to significant heterogeneity and the limited number of studies. CONCLUSIONS: This assessment indicates an association of PPH with CVD and all-cause mortality. Further studies are required to improve CVD and mortality estimates, but the potential seriousness of CVD and all-cause mortality as outcomes of PPH justifies more screening, diagnosis, and research.