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The association of glucose metabolism measures and diabetes status with Alzheimer's disease biomarkers of amyloid and tau: A systematic review and meta-analysis.
van Gils, V, Rizzo, M, Côté, J, Viechtbauer, W, Fanelli, G, Salas-Salvadó, J, Wimberley, T, Bulló, M, Fernandez-Aranda, F, Dalsgaard, S, et al
Neuroscience and biobehavioral reviews. 2024;:105604
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Abstract
Conflicting evidence exists on the relationship between diabetes mellitus (DM) and Alzheimer's disease (AD) biomarkers. Therefore, we conducted a random-effects meta-analysis to evaluate the correlation of glucose metabolism measures (glycated hemoglobin, fasting blood glucose, insulin resistance indices) and DM status with AD biomarkers of amyloid-β and tau measured by positron emission tomography or cerebrospinal fluid. We selected 37 studies from PubMed and Embase, including 11,694 individuals. More impaired glucose metabolism and DM status were associated with higher tau biomarkers (r=0.11[0.03-0.18], p=0.008; I2=68%), but were not associated with amyloid-β biomarkers (r=-0.06[-0.13-0.01], p=0.08; I2=81%). Meta-regression revealed that glucose metabolism and DM were specifically associated with tau biomarkers in population settings (p=0.001). Furthermore, more impaired glucose metabolism and DM status were associated with lower amyloid-β biomarkers in memory clinic settings (p=0.004), and in studies with a higher prevalence of dementia (p<0.001) or lower cognitive scores (p=0.04). These findings indicate that DM is associated with biomarkers of tau but not with amyloid-β. This knowledge is valuable for improving dementia and DM diagnostics and treatment.
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Is telomere length a biomarker of sperm quality? A systematic review and meta-analysis of observational studies.
Fernández de la Puente, M, Salas-Huetos, A, Valle-Hita, C, Babio, N, Murphy, MM, Canudas, S, Salas-Salvadó, J
Andrology. 2024;(2):277-288
Abstract
BACKGROUND Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility. OBJECTIVES To conduct a systematic review and meta-analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions. MATERIAL AND METHODS A systematic review and meta-analysis was conducted with studies from Medline-PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross-sectional and case-control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes. RESULTS Twenty-three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta-analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference [95% confidence interval]: -1.43 [-1.66 to -1.21], p-value <0.001 and -1.67 [-2.02 to -1.31], p-value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (-0.97 [-1.32, -0.61], p-value <0.001). CONCLUSION The current systematic review and meta-analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis.
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Vegetable and Fruit Intake Variety and Cardiovascular Health and Mortality: A Systematic Review and Meta-Analysis of Observational Studies.
Nishi, SK, Khoury, N, Valle Hita, C, Zurbau, A, Salas-Salvadó, J, Babio, N
Nutrients. 2023;(23)
Abstract
INTRODUCTION A multitude of evidence supports the consumption of a higher quantity of vegetables and fruits for their cardiovascular benefits. Nonetheless, the extent to which variety is associated with cardiovascular health remains unclear. OBJECTIVE To conduct a systematic review and meta-analysis of observational studies (prospective cohort and cross-sectional studies) assessing the role of a variety of vegetable and fruit consumption in cardiovascular morbidity and mortality in adults. DATA SOURCES MEDLINE-PubMed, Cochrane databases, and reference lists were searched through March 2023. DATA EXTRACTION Two independent reviewers extracted data and assessed the risk of bias (National Heart, Lung, and Blood Institute Tool and Newcastle-Ottawa Scale). DATA ANALYSIS Data were pooled (fixed and random [DerSimonian and Laird] effects for <5 and ≥5 study comparisons, respectively), and heterogeneity was assessed using the Cochran Q statistic and quantified (I2 statistic). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the overall certainty of the evidence. Five cross-sectional (n = 45,761) and seven prospective studies (n = 253,422) met the eligibility criteria. Greater variety of vegetable and fruit consumption was prospectively related to decreased all-cause mortality (risk ratio, 0.89 [95% CI, 0.82-0.97], seven study comparisons, n = 196,925), while no significant associations were observed with assessed cardiovascular-related mortality or morbidity. For all outcomes, the certainty of the evidence was graded as "low" or "very low" owing to inconsistency and/or imprecision. CONCLUSIONS Overall, this study shows that greater variety in vegetable and fruit consumption may reduce all-cause mortality and highlights the need for additional studies with a higher degree of evidence to better understand its role in cardiovascular health.
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Circulating vitamin D levels and colorectal cancer risk: A meta-analysis and systematic review of case-control and prospective cohort studies.
Hernández-Alonso, P, Boughanem, H, Canudas, S, Becerra-Tomás, N, Fernández de la Puente, M, Babio, N, Macias-Gonzalez, M, Salas-Salvadó, J
Critical reviews in food science and nutrition. 2023;(1):1-17
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The associations between circulating vitamin D concentrations and total and site-specific colorectal cancer (CRC) incidence have been examined in several epidemiological studies with overall inconclusive findings. The aim of this systematic review and meta-analysis of both case-control and prospective cohort studies was to evaluate the association between CRC and circulating levels of vitamin D. The main exposure and outcome were circulating total 25(OH)D and CRC, respectively, in the overall population (i.e., all subjects). Two reviewers, working independently, screened all the literature available to identify studies that met the inclusion criteria (e.g., case-control or prospective cohort studies, published in English, and excluding non-original papers). Data were pooled by the generic inverse variance method using a random or fixed effect model, as approriate. Heterogeneity was identified using the Cochran's Q-test and quantified by the I2 statistic. Results were stratified by study design, sex, and metabolite of vitamin D. Sensitivity and subgroup analyses were also performed. A total of 28 original studies were included for the quantitative meta-analysis. Meta-analyses comparing the highest vs lowest categories, showed a 39% lower risk between levels of total 25(OH)D and CRC risk (OR (95% CI): 0.61 (0.52; 0.71); 11 studies) in case-control studies; whereas a 20% reduced CRC risk in prospective cohort studies (HR (95% CI): 0.80 (0.66; 0.97); 6 studies). Results in women mirrored main results, whereas results in men were non-significant in both analyses. Our findings support an inverse association between circulating vitamin D levels and CRC risk.
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Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.
Khan, TA, Field, D, Chen, V, Ahmad, S, Mejia, SB, Kahleová, H, Rahelić, D, Salas-Salvadó, J, Leiter, LA, Uusitupa, M, et al
Diabetes care. 2023;(3):643-656
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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.
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Lack of association between endocrine disrupting chemicals and male fertility: A systematic review and meta-analysis.
Martínez, MÁ, Marquès, M, Salas-Huetos, A, Babio, N, Domingo, JL, Salas-Salvadó, J
Environmental research. 2023;217:114942
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Exposure to natural or synthetic chemicals is directly related to environmental conditions, dietary and other lifestyle factors. Some of these chemicals are named endocrine disrupting chemicals (EDCs) because of their capability to interfere with the endocrine system. The aim of this study was to summarise and explore the association between exposure to EDCs and human male fertility indicators. This study is a systematic review and meta-analysis of seven studies; 4 assessed bisphenol A (BPA) in urine and sperm quality parameters, while 3 articles evaluated PCB153 [polychlorinated biphenyls] in serum and sperm quality parameters. Results show that there weren’t any positive or inverse associations between BPA or PCB153 and the sperm parameters analysed. Authors conclude that the systematic review showed a high disparity between studies, making difficult a consensus on the possible detrimental effect of the 12 groups of EDCs on male fertility. Thus, no conclusive statements can be drawn. Further studies are needed in order to provide more robust data.
Abstract
The incidence of infertility currently affects about 15% of the world's population. Male factors are estimated to be responsible for up to 40-50% of these cases. While the cause of these reproductive disorders is still unclear, the exposure to a family of ubiquitous compounds in our daily life, named endocrine disrupting chemicals (EDCs) could be involved. This paper was aimed at performing a systematic review and meta-analysis of population studies exploring whether human male exposure to EDCs affects male fertility. Clinical and observational studies assessing the exposure to EDCs along with sperm quality, the most common reproductive disorders, sperm DNA damage, sperm oxidative stress, fertilization rate, implantation rate, clinical pregnancy rate, live birth rate, and miscarriage rate were included. The quality assessment tool from the NHLBI-NIH was used to assure that studies met standardized quality criteria. Sensitivity analysis and heterogeneity among studies was assessed. Overall, the 32 selected articles, including 7825 individuals in the systematic review, explored 12 families of EDCs. The results revealed a high heterogeneity among studies in relation to the association between exposure to EDCs and the endpoints analyzed. Meta-analyses were performed with data from 7 articles including 479 individuals, 4 articles assessing the association between BPA in urine and sperm quality, and 3 articles evaluating PCB153 in serum and sperm quality. In the meta-analysis, we identified an unpredicted significant positive association between PCB153 exposure and sperm concentration. However, it would not be clinically relevant. No positive or inverse associations were found neither for BPA, nor for PCB153 and the rest of sperm parameters analyzed. The high disparity between studies made difficult to draw conclusions on the potential harmful effects of EDCs on male fertility. Consequently, to delineate the potential relationship that EDCs can have on male fertility, an important condition stressing the health system, further investigations are required.
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Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis.
McGlynn, ND, Khan, TA, Wang, L, Zhang, R, Chiavaroli, L, Au-Yeung, F, Lee, JJ, Noronha, JC, Comelli, EM, Blanco Mejia, S, et al
JAMA network open. 2022;(3):e222092
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IMPORTANCE There are concerns that low- and no-calorie sweetened beverages (LNCSBs) do not have established benefits, with major dietary guidelines recommending the use of water and not LNCSBs to replace sugar-sweetened beverages (SSBs). Whether LNCSB as a substitute can yield similar improvements in cardiometabolic risk factors vs water in their intended substitution for SSBs is unclear. OBJECTIVE To assess the association of LNCSBs (using 3 prespecified substitutions of LNCSBs for SSBs, water for SSBs, and LNCSBs for water) with body weight and cardiometabolic risk factors in adults with and without diabetes. DATA SOURCES Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 26, 2021. STUDY SELECTION Randomized clinical trials (RCTs) with at least 2 weeks of interventions comparing LNCSBs, SSBs, and/or water were included. DATA EXTRACTION AND SYNTHESIS Data were extracted and risk of bias was assessed by 2 independent reviewers. A network meta-analysis was performed with data expressed as mean difference (MD) or standardized mean difference (SMD) with 95% CIs. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the certainty of the evidence. MAIN OUTCOMES AND MEASURES The primary outcome was body weight. Secondary outcomes were other measures of adiposity, glycemic control, blood lipids, blood pressure, measures of nonalcoholic fatty liver disease, and uric acid. RESULTS A total of 17 RCTs with 24 trial comparisons were included, involving 1733 adults (mean [SD] age, 33.1 [6.6] years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes. Overall, LNCSBs were a substitute for SSBs in 12 RCTs (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTs (n = 974). Substitution of LNCSBs for SSBs was associated with reduced body weight (MD, -1.06 kg; 95% CI, -1.71 to -0.41 kg), body mass index (MD, -0.32; 95% CI, -0.58 to -0.07), percentage of body fat (MD, -0.60%; 95% CI, -1.03% to -0.18%), and intrahepatocellular lipid (SMD, -0.42; 95% CI, -0.70 to -0.14). Substituting water for SSBs was not associated with any outcome. There was also no association found between substituting LNCSBs for water with any outcome except glycated hemoglobin A1c (MD, 0.21%; 95% CI, 0.02% to 0.40%) and systolic blood pressure (MD, -2.63 mm Hg; 95% CI, -4.71 to -0.55 mm Hg). The certainty of the evidence was moderate (substitution of LNCSBs for SSBs) and low (substitutions of water for SSBs and LNCSBs for water) for body weight and was generally moderate for all other outcomes across all substitutions. CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis found that using LNCSBs as an intended substitute for SSBs was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm and had a similar direction of benefit as water substitution. The evidence supports the use of LNCSBs as an alternative replacement strategy for SSBs over the moderate term in adults with overweight or obesity who are at risk for or have diabetes.
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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.
Lee, JJ, Khan, TA, McGlynn, N, Malik, VS, Hill, JO, Leiter, LA, Jeppesen, PB, Rahelić, D, Kahleová, H, Salas-Salvadó, J, et al
Diabetes care. 2022;(8):1917-1930
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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.
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Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials.
Massara, P, Zurbau, A, Glenn, AJ, Chiavaroli, L, Khan, TA, Viguiliouk, E, Mejia, SB, Comelli, EM, Chen, V, Schwab, U, et al
Diabetologia. 2022;65(12):2011-2031
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Dietary patterns high in plant foods such as the Mediterranean diet, Dietary Approaches for Stopping Hypertension (DASH), Portfolio and healthy vegetarian are associated with a lower risk of cardio vascular disease (CVD) and certain cardiometabolic risk factors in adults with and without diabetes. In Northern European countries it may be more difficult to apply these dietary principals due to availability and cost of specific foods. Nordic dietary patterns include foods such as rye, oats and barley, berries and temperate fruits like apples and pears, vegetables (especially root and cruciferous vegetables), legumes, fish/shellfish, nuts and canola oil/rapeseed oil and low-fat dairy foods. The benefits of Nordic dietary patterns have been recognised but to update the clinical practice guidelines for the European Association for the Study of Diabetes (EASD), a systematic review and meta-analysis was commissioned. 15 cohort studies and 6 RCTs were included. Adopting Nordic dietary patterns is associated with small important reductions in the risk of major CVD outcomes and diabetes. These are supported by similar reductions in LDL-cholesterol and other 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.
Abstract
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.
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Nut consumption and type 2 diabetes risk: a systematic review and meta-analysis of observational studies.
Becerra-Tomás, N, Paz-Graniel, I, Hernández-Alonso, P, Jenkins, DJA, Kendall, CWC, Sievenpiper, JL, Salas-Salvadó, J
The American journal of clinical nutrition. 2021;(4):960-971
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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.