Ultra-processed food consumption and human health: an umbrella review of systematic reviews with meta-analyses.

Recently, ultra-processed foods received a lot of attention, but also criticism. Our aim was to provide an overview of the existing evidence of ultra-processed food consumption on human health. We conducted a systematic search in four databases until January 5th, 2024. Systematic reviews with meta-analyses on ultra-processed food consumption as defined by the NOVA classification system were included. The certainty of evidence was evaluated by the GRADE approach. We identified 16 publications. Moderate certainty of evidence was found for all-cause mortality (Summary Risk Ratio per 50 g: 1.02; 95% confidence Interval (CI): 1.01, 1.03), cardiovascular disease incidence and mortality (per 50 g/d: 1.04; 95% CI: 1.02, 1.06, and 1.05; 95% CI: 1.01, 1.08), type 2 diabetes incidence (per 10%: 1.12; 95% CI: 1.10, 1.13) and colorectal cancer (per 10%: 1.04; 95% CI: 1.01, 1.07). For several outcomes such as inflammatory bowel diseases, obesity, metabolic syndrome, nonalcoholic fatty liver disease, mental health as well as nutrient quality, similar estimates were observed, but certainty of evidence was limited. Discussing the NOVA concept, it remains unclear whether the processing of foods leads to increased health risks or if ultra-processed food consumption is only a measure for poor diet quality.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower visceral and hepatic lipid content in recent-onset type 1 diabetes and type 2 diabetes.

AIM: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes. METHODS: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis. RESULTS: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm3). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm3) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes. CONCLUSIONS: A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR.

Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis.

AIMS/HYPOTHESIS: To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death. METHODS: This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach. RESULTS: A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n=21 studies), HbA1c (53-75 mmol/mol [7-9%]: 1.18 [1.06, 1.32], n=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n=9), pre-existing heart failure (1.33 [1.21, 1.47], n=14), pre-existing liver disease (1.40 [1.17, 1.67], n=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n=2), high levels of C-reactive protein (per 5 mg/l increase: 1.07 [1.02, 1.12], n=10), aspartate aminotransferase level (per 5 U/l increase: 1.28 [1.06, 1.54], n=5), eGFR (per 10 ml/min per 1.73 m2 increase: 0.80 [0.71, 0.90], n=6), lactate dehydrogenase level (per 10 U/l increase: 1.03 [1.01, 1.04], n=7) and lymphocyte count (per 1×109/l increase: 0.59 [0.40, 0.86], n=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing COVID-19  vaccination status (0.32 [0.26, 0.38], n=3), pre-existing hypertension (1.23 [1.14, 1.33], n=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out. CONCLUSIONS/INTERPRETATION: Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease. REGISTRATION: PROSPERO registration no. CRD42020193692. PREVIOUS VERSION: This is a living systematic review and meta-analysis. The previous version can be found at https://link.springer.com/article/10.1007/s00125-021-05458-8 FUNDING: The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD).

Evidence of a vegan diet for health benefits and risks - an umbrella review of meta-analyses of observational and clinical studies.

To summarize and evaluate the evidence on the health impact of a vegan diet, we conducted an umbrella review of systematic reviews and meta-analyses. PubMed, Cochrane Library, Web of Science and Epistemonikos were searched up to September 2021. Meta-analyses were recalculated by using a random effects model. The certainty of evidence (CoE) was evaluated by the GRADE approach. For the general healthy population, a vegan diet was effective for reducing body weight [MD (95% CI): -2.52 kg (-3.06, -1.98), n = 8 RCTs; moderate CoE] and was associated with further health benefits (with low CoE), including a lower risk of cancer incidence [SRR (95% CI): 0.84 (0.75, 0.95), n = 2] and a trend for lower risk of all-cause mortality [SRR (95% CI): 0.87 (0.75, 1.01), n = 2], as well as lower ApoB levels [MD (95% CI): -0.19 µmol/L (-0.23, -0.15), n = 7 RCTs). The findings suggested adverse associations for a vegan diet with risk of fractures [SRR (95% CI): 1.46 (1.03, 2.07), n = 3; low CoE]. For persons with diabetes or at high CVD risk, a vegan diet reduced measures of adiposity, total cholesterol, LDL and improved glycemic control (CoE moderate to low). A vegan diet may have the potential for the prevention of cardiometabolic health, but it may also impair bone health. More well-conducted primary studies are warranted.

Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies.

AIMS/HYPOTHESIS: The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA1c levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic 'diabetes-related' complications. This umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between prediabetes and incident diabetes-related complications in adults and to evaluate their strength and certainty. METHODS: For this umbrella review, systematic reviews with meta-analyses reporting summary risk estimates for the associations between prediabetes (based on fasting or 2 h postload glucose or on HbA1c) and incidence of diabetes-related complications, comorbidities and mortality risk were included. PubMed, Web of Science, the Cochrane Library and Epistemonikos were searched up to 17 June 2021. Summary risk estimates were recalculated using a random effects model. The certainty of evidence was evaluated by applying the GRADE tool. This study is registered with PROSPERO, CRD42020153227. RESULTS: Ninety-five meta-analyses from 16 publications were identified. In the general population, prediabetes was associated with a 6-101% increased risk for all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, heart failure, atrial fibrillation and chronic kidney disease, as well as total cancer, total liver cancer, hepatocellular carcinoma, breast cancer and all-cause dementia with moderate certainty of evidence. No associations between prediabetes and incident depressive symptoms and cognitive impairment were observed (with low or very low certainty of evidence). The association with all-cause mortality was stronger for prediabetes defined by impaired glucose tolerance than for prediabetes defined by HbA1c. CONCLUSIONS/INTERPRETATION: Prediabetes was positively associated with risk of all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, chronic kidney disease, cancer and dementia. Further high-quality studies, particularly on HbA1c-defined prediabetes and other relevant health outcomes (e. g. neuropathy) are required to support the evidence.

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

Intake of dietary fats and fatty acids and the incidence of type 2 diabetes: A systematic review and dose-response meta-analysis of prospective observational studies.

BACKGROUND: The role of fat quantity and quality in type 2 diabetes (T2D) prevention is controversial. Thus, this systematic review and meta-analysis aimed to investigate the associations between intake of dietary fat and fatty acids and T2D, and to evaluate the certainty of evidence. METHODS AND FINDINGS: We systematically searched PubMed and Web of Science through 28 October 2019 for prospective observational studies in adults on the associations between intake of dietary fat and fatty acids and T2D incidence. The systematic literature search and data extraction were conducted independently by 2 researchers. We conducted linear and nonlinear random effects dose-response meta-analyses, calculated summary relative risks (SRRs) with their corresponding 95% confidence intervals (95% CIs), and assessed the certainty of evidence. In total, 15,070 publications were identified in the literature search after the removal of duplicates. Out of the 180 articles screened in full text, 23 studies (19 cohorts) met our inclusion criteria, with 11 studies (6 cohorts) conducted in the US, 7 studies (7 cohorts) in Europe, 4 studies (5 cohorts) in Asia, and 1 study (1 cohort) in Australia. We mainly observed no or weak linear associations between dietary fats and fatty acids and T2D incidence. In nonlinear dose-response meta-analyses, the protective association for vegetable fat and T2D was steeper at lower levels up to 13 g/d (SRR [95% CI]: 0.81 [0.76; 0.88], pnonlinearity = 0.012, n = 5 studies) than at higher levels. Saturated fatty acids showed an apparent protective association above intakes around 17 g/d with T2D (SRR [95% CI]: 0.95 [0.90; 1.00], pnonlinearity = 0.028, n = 11). There was a nonsignificant association of a decrease in T2D incidence for polyunsaturated fatty acid intakes up to 5 g/d (SRR [95% CI]: 0.96 [0.91; 1.01], pnonlinearity = 0.023, n = 8), and for alpha-linolenic acid consumption up to 560 mg/d (SRR [95% CI]: 0.95 [0.90; 1.00], pnonlinearity = 0.014, n = 11), after which the curve rose slightly, remaining close to no association. The association for long-chain omega-3 fatty acids and T2D was approximately linear for intakes up to 270 mg/d (SRR [95% CI]: 1.10 [1.06; 1.15], pnonlinearity < 0.001, n = 16), with a flattening curve thereafter. Certainty of evidence was very low to moderate. Limitations of the study are the high unexplained inconsistency between studies, the measurement of intake of dietary fats and fatty acids via self-report on a food group level, which is likely to lead to measurement errors, and the possible influence of unmeasured confounders on the findings. CONCLUSIONS: There was no association between total fat intake and the incidence of T2D. However, for specific fats and fatty acids, dose-response curves provided insights for significant associations with T2D. In particular, a high intake of vegetable fat was inversely associated with T2D incidence. Thus, a diet including vegetable fat rather than animal fat might be beneficial regarding T2D prevention.

Dietary patterns associated with inflammatory biomarkers in a Northern German population.

PURPOSE: The aim of the present study was to derive overall and sex-specific dietary patterns associated with inflammatory biomarkers in a general population sample from Northern Germany. METHODS: The present analysis included 1158 participants (477 men, 681 women, mean age: 53.1 years; mean body mass index: 26.2 kg/m2) of the Food Chain Plus (FoCus) cohort in Kiel, Germany. Participants completed a semi-quantitative food frequency questionnaire and provided blood samples. Reduced rank regression with C-reactive protein (CRP) and Interleukin 6 (IL-6) as response variables was used to derive dietary patterns. After a mean follow-up of 1.7 years, a second blood sample was obtained in a subsample of 112 individuals. Multiple regression models were used to examine the association between dietary patterns at baseline and inflammatory biomarkers at follow-up. RESULTS: The overall pattern characterised by high intakes of soft drinks, meat, potatoes and sauce, and low intakes of other cereals (except pasta/rice), wine, nuts, seeds, vegetarian dishes, vegetable oil, and fish was positively associated with CRP (OR 2.20; 95% CI 1.12, 4.35) and IL-6 (OR 3.14; 95% CI 1.26, 7.87) at follow-up. In men, the dietary pattern was higher in soft drinks, processed meat and low in cereals and plant-based fats. In women, the pattern was characterised by soft drinks, meat, vegetables and low in other cereals, wine, nuts, and seeds. The association between sex-specific patterns with inflammatory biomarkers was weaker for CRP. CONCLUSION: We identified dietary patterns positively associated with established biomarkers of chronic low-grade inflammation.

Joint Data Analysis in Nutritional Epidemiology: Identification of Observational Studies and Minimal Requirements.

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration. Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, the minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition.

Comparison of two exploratory dietary patterns in association with the metabolic syndrome in a Northern German population.

Diet is related to many chronic disease conditions such as the metabolic syndrome (MetS). We set out to compare behaviour-related with disease-related patterns and their association with the MetS in a German cross-sectional study. A total of 905 participants of a Northern German cohort (aged 25-82 years) completed a FFQ, underwent anthropometric assessments and provided a blood sample. Dietary patterns were derived by principal component analysis (PCA) and reduced-rank regression (RRR) from forty-two food groups. Components of the MetS were used as response variables for the RRR analysis. Simplified patterns comprising ten food groups were generated. Logistic regression analysis was performed to evaluate the likelihood of having the MetS across the quartiles of simplified pattern scores. We identified two similar dietary patterns derived by PCA and RRR characterised by high intakes of potatoes, various vegetables, red and processed meat, fats, sauce and bouillon. Comparing simplified patterns, an increased RRR pattern score was associated with a higher OR (2·18, 95% CI 1·25, 3·81) of having the MetS than an increased PCA pattern score (OR 1·92, 95% CI 1·21, 3·03). Comparing concordant food groups by both dietary pattern methods, a diet high in legumes, beef, processed meat and bouillon was also positively associated with the prevalence of the MetS after adjustment for potential confounders (OR 1·71, 95% CI 1·04, 2·79). We identified a behaviour-related pattern that was positively associated with the MetS. The application of both dietary pattern methods may be advantageous to obtain information for designing and realising dietary guidelines. Prospective studies are needed to confirm the results.

Effects of carotenoid supplementation on glycemic control: a systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effects of carotenoid supplementation on glycemic indices, and the certainty of evidence. METHODS: A systematic literature search in PubMed, SCOPUS, ISI-Web of Science, and Cochrane Library was conducted from inception up to Jun 17, 2024. Randomized controlled trials (RCTs) investigating the effect of carotenoid supplementation on circulating glycemic parameters were included. Records were excluded when studies reported the effect of co-interventions with other nutrients, did not provide mean differences (MDs) and standard deviations (SD) for outcomes, or administered whole food rather than supplements of carotenoids. Summary mean differences (MDs) and 95% CI between intervention and control groups were estimated using a random-effects model. The risk of bias of the included studies was assessed using the Risk of Bias 2.0 (RoB 2.0) tool. RESULTS: Overall, 36 publications with 45 estimated effect sizes were included in the meta-analyses. The overall findings showed an improvement in fasting blood glucose (FBG) (MD = -4.54 mg/dl; 95% CI: -5.9, -3.2; n = 45), and hemoglobin A1C (HbA1C) (MD = -0.25% (95% CI: -0.4, -0.11; n = 22) in the intervention group in comparison with the control group. Moreover, in individuals with type 2 diabetes (T2D), interventions with astaxanthin and fucoxanthin led to a reduction in FBG by 4.36 mg/dl (95% CI: -6.13, -2.6; n = 10). The findings also showed that the intervention with crocin reduced FBG levels by 13.5 mg/dl (95% CI: -15.5, -7.8; n = 5), and HbA1C by 0.55% (95% CI: -0.77, -0.34; n = 5) in individuals with T2D. However, the certainty of evidence was very low. CONCLUSION: Carotenoid's supplementation improved glycemic parameters especially in people with T2D. However. the certainty of evidence was very low, mainly due to small sample size, and indirectness. Therefore, no specific recommendations can be provided at present and well-designed RCTs are required. REGISTRY URL: https://www.crd.york.ac.uk/PROSPERO/ REGISTRY NUMBER: CRD42021285084 REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: PROSPERO ID: CRD42021285084.

Association between substituting macronutrients and all-cause mortality: a network meta-analysis of prospective observational studies.

Background: Suboptimal diet quality is a key risk factor for premature death. Assuming relatively stable energy intake among individuals, changes in nutrient intakes occur by exchanging different nutrients. Therefore we aimed to examine the association of isocaloric substitution of dietary (macro)nutrients with all-cause mortality using network meta-analysis (NMA). Methods: For this systematic review and NMA of prospective observational studies MEDLINE, Embase, and Scopus were searched from inception to February 13th, 2024. Eligible studies reported substitution analyses for quantity and/or quality of macronutrients, including carbohydrates, proteins, and fatty acids on all-cause mortality. Random-effects NMA were used in order to evaluate the pooled hazard ratios (HR) and 95% confidence intervals (CI) of substituting each included nutrient with another. We assessed risk of bias with the ROBINS-E tool, and the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach. This study is registered with PROSPERO (CRD42023450706). Findings: Thirty-nine studies with 1,737,644 participants, 395,491 deaths, 297 direct comparisons, and seven nutrient-specific networks were included. Moderate CoE was found for an association with lower mortality risk when replacing 5% of energy intake from carbohydrates with polyunsaturated fatty acids (PUFA; HR: 0.90; 95%CI: 0.84, 0.95), n-6 PUFA (0.85; 0.77, 0.94), n-3 PUFA (0.72; 0.59, 0.86), and plant monounsaturated fatty acids (MUFA; 0.90; 0.85, 0.95), and when replacing 5% of energy from saturated fatty acids (SFA) and trans-fatty acids (TFA), with PUFA, MUFA, and plant-MUFA (HRrange: 0.75 to 0.91). A lower mortality risk was additionally found when 5% of animal-MUFA was replaced with plant-MUFA, and when replacing animal protein, and SFA with plant protein (HRrange: 0.81 to 0.87, moderate CoE). Interpretation: Our results provide practical knowledge for public health professionals and can inform upcoming dietary guidelines. The beneficial association of increasing PUFA (both n-3 and n-6) and (plant-) MUFA intake while reducing carbohydrates, SFA and TFA, along with replacing animal protein and animal-MUFA with plant-based sources of protein and fat (MUFA) on the all-cause mortality risk, underscores the importance of plant-based dietary recommendations. Funding: None.

Dietary Factors and All-Cause Mortality in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Prospective Observational Studies.

BACKGROUND: Type 2 diabetes is a major health concern associated with mortality. Diet may influence the progression of diabetes; however, systematic reviews are lacking. PURPOSE: This study systematically summarized the evidence on diet and all-cause mortality in individuals with type 2 diabetes. DATA SOURCES: PubMed and Web of Science were searched until June 2022. STUDY SELECTION: Prospective observational studies investigating dietary factors in association with all-cause mortality in individuals with type 2 diabetes were selected. DATA SYNTHESIS: We identified 107 studies. Moderate certainty of evidence was found for inverse associations of higher intakes of fish (summary risk ratios per serving/week: 0.95; 95% CI 0.92, 0.99; n = 6 studies), whole grain (per 20 g/day: 0.84; 95% CI 0.71, 0.99; n = 2), fiber (per 5 g/day: 0.86; 95% CI 0.81, 0.91; n = 3), and n-3 polyunsaturated fatty acids (per 0.1 g/day: 0.87; 95% CI 0.82, 0.92; n = 2) and mortality. There was low certainty of evidence for inverse associations of vegetable consumption (per 100 g/day: 0.88; 95% CI 0.82, 0.94; n = 2), plant protein (per 10 g/day: 0.91; 95% CI 0.87, 0.96; n = 3), and for positive associations of egg consumption (per 10 g/day: 1.05; 95% CI 1.03, 1.08; n = 7) and cholesterol intake (per 300 mg/day: 1.19; 95% CI 1.13, 1.26; n = 2). For other dietary factors, evidence was uncertain or no association was observed. CONCLUSIONS: Higher intake of fish, whole grain, fiber, and n-3 polyunsaturated fatty acids were inversely associated with all-cause mortality in individuals with type 2 diabetes. There is limited evidence for other dietary factors, and, thus, more research is needed.

Diet in the management of type 2 diabetes: umbrella review of systematic reviews with meta-analyses of randomised controlled trials.

Objective: To systematically summarise and evaluate the existing evidence on the effect of diet on the management of type 2 diabetes and prevention of complications. Design: Umbrella review of systematic reviews with meta-analyses of randomised controlled trials. Data sources: PubMed, Embase, Epistemonikos, and Cochrane, from inception up to 5 June 2022. Eligibility criteria for selecting studies: Systematic reviews with meta-analyses of randomised controlled trials reporting summary effect estimates on the effect of diet on any health outcome in populations with type 2 diabetes were included in the review. Only meta-analyses with randomised controlled trials with the duration of at least 12 weeks were eligible for inclusion. Summary data were extracted by two investigators independently. Summary effect estimates with 95% confidence intervals were recalculated with a random effects model if the information provided was insufficient. Methodological quality was assessed with the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool and the certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach. Results: 88 publications with 312 meta-analyses of randomised controlled trials were included. Methodological quality was high to moderate in 23% and low to very low in 77% of the included publications. A high certainty of evidence was found for the beneficial effects of liquid meal replacement on reducing body weight (mean difference -2.37 kg, 95% confidence interval -3.30 to -1.44; n=9 randomised controlled trials included in the meta-analysis) and body mass index (-0.87, -1.32 to -0.43; n=8 randomised controlled trials), and of a low carbohydrate diet (<26% of total energy) on levels of haemoglobin A1c (-0.47%, -0.60% to -0.34%; n=17 randomised controlled trials) and triglycerides (-0.30 mmol/L, -0.43 to -0.17; n=19 randomised controlled trials). A moderate certainty of evidence was found for the beneficial effects of liquid meal replacement, plant based, Mediterranean, high protein, low glycaemic index, and low carbohydrate diets (<26% total energy) on various cardiometabolic measures. The remaining results had low to very low certainty of evidence. Conclusions: The evidence indicated that diet has a multifaceted role in the management of type 2 diabetes. An energy restricted diet can reduce body weight and improve cardiometabolic health. Beyond energy restriction, dietary approaches such as plant based, Mediterranean, low carbohydrate (<26% total energy), or high protein diets, and a higher intake of omega 3 fatty acids can be beneficial for cardiometabolic health in individuals with type 2 diabetes. Systematic review registration: PROSPERO CRD42021252309.

Physical Activity and Risk of Major Diabetes-Related Complications in Individuals With Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Physical activity is a cornerstone in diabetes management; however, evidence synthesis on the association between physical activity and long-term diabetes-related complications is scarce. PURPOSE: To summarize and evaluate findings on physical activity and diabetes-related complications, we conducted a systematic review and meta-analysis. DATA SOURCES: We searched PubMed, Web of Science, and the Cochrane Library for articles published up to 6 July 2021. STUDY SELECTION: We included prospective studies investigating the association between physical activity and incidence of and mortality from diabetes-related complications, i.e., cardiovascular disease (CVD), coronary heart disease, cerebrovascular events, heart failure, major adverse cardiovascular events, and microvascular complications such as retinopathy and nephropathy, in individuals with diabetes. DATA EXTRACTION: Study characteristics and risk ratios with 95% CIs were extracted. Random-effects meta-analyses were performed, and the certainty of evidence and risk of bias were evaluated with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools. DATA SYNTHESIS: Overall, 31 studies were included. There was moderate certainty of evidence that high versus low levels of physical activity were inversely associated with CVD incidence, CVD mortality (summary risk ratio 0.84 [95% CI 0.77, 0.92], n = 7, and 0.62 [0.55, 0.69], n = 11), and microvascular complications (0.76 [0.67, 0.86], n = 8). Dose-response meta-analyses showed that physical activity was associated with lower risk of diabetes-related complications even at lower levels. For other outcomes, similar associations were observed but certainty of evidence was low or very low. LIMITATIONS: Limitations include residual confounding and misclassification of exposure. CONCLUSIONS: Physical activity, even below recommended amounts, was associated with reduced incidence of diabetes-related complications.

Bidirectional association between periodontal disease and diabetes mellitus: a systematic review and meta-analysis of cohort studies.

Periodontal disease has been reported to be associated with diabetes mellitus. However, the direction of the association and the influence of bias are not clear. Thus, the aim of this systematic review and meta-analysis was to summarize the existing evidence on the bidirectional prospective association between periodontal disease and diabetes mellitus by accounting for the risk of bias of the original studies. The literature search was conducted on the electronic data sources PubMed and Web of Science up to February 9th, 2021. We included observational studies, which investigated the prospective association between diabetes mellitus and periodontal disease or vice versa. The risk of bias of the primary studies was evaluated by applying the Quality in Prognosis Studies (QUIPS) tool. Random effects models were used to calculate summary relative risk (SRR) with 95% CI. Subgroup analyses were applied to investigate heterogeneity and the robustness of the finding. In total, 15 studies were included . The SRR for incident diabetes mellitus was 1.26 (95% CI 1.12, 1.41; I2: 71%, n = 10; participants = 427,620; identified cases = 114,361), when comparing individuals with periodontitis to individuals without periodontitis. The SRR for incident periodontitis was 1.24 (95% CI 1.13, 1.37; I2: 92%, n = 7; participants = 295,804; identified cases: > 22,500), comparing individuals with diabetes to individuals without diabetes. There were no significant differences between subgroups after stratification for risk of bias. The findings show a positive bidirectional association between periodontal disease and diabetes mellitus, and thus, underline the need for screening of patients with periodontitis regarding diabetes mellitus and vice versa. The main limitation of the study is the high unexplained heterogeneity between the studies including the different assessment methods of the disease diagnosis.

Adherence to healthy lifestyles and incidence of diabetes and mortality among individuals with diabetes: a systematic review and meta-analysis of prospective studies.

INTRODUCTION: Lifestyle factors in combination have been hypothesised to be associated with the prevention of type 2 diabetes (T2D) and mortality among individuals with T2D. The aim was to conduct a systematic review and meta-analysis to quantify the association between lifestyle indices and incident T2D as well as mortality in individuals with T2D. METHODS: PubMed and Web of Science were searched up to September 2019. We included prospective cohort studies investigating at least three lifestyle factors in association with T2D, or all-cause mortality in individuals with diabetes. We conducted pairwise and dose-response meta-analyses to calculate summary relative risks (SRR) by using random effects model. RESULTS: In total, 19 studies were included. Adhering to a healthy lifestyle (mostly favourable diet, physical activity, non-smoking, moderate alcohol intake and normal weight) was associated with a reduced SRR of 78% for T2D (SRR: 0.22; 95% CI: 0.16 to 0.32; n=14) and 57% for mortality (SRR: 0.43; 95% CI: 0.31 to 0.58; n=5) compared with low adherence to a healthy lifestyle. In dose-response analyses, the adherence to every additional healthy lifestyle factor was associated with a reduced relative risk of 32% (95% CI: 28% to 36%) for T2D and 21% (95% CI: 15% to 26%) for mortality. CONCLUSIONS: Our findings underline the importance of the joint adherence to healthy lifestyle factors to prevent T2D and improve survival among individuals with diabetes. Adherence to every additional health lifestyle factor play a role in the T2D prevention and progression. PROSPERO REGISTRATION NUMBER: CRD42018091409.

Dietary Factors and Neurodegenerative Disorders: An Umbrella Review of Meta-Analyses of Prospective Studies.

Diet has been hypothesized to be associated with neurodegenerative disorders. The aim was to conduct an umbrella review to summarize and evaluate the current evidence of prospective associations between any dietary factors and the incidence of neurodegenerative disorders. We conducted a systematic search in PubMed, Embase, and the Cochrane library up to November 2019 to identify systematic reviews with meta-analyses of prospective studies investigating the association between dietary factors (dietary patterns, foods and beverages, nutrients, and phytochemicals) and neurodegenerative disorders (cognitive decline, cognitive impairment, Alzheimer disease, all-cause dementia, and Parkinson disease). Summary risk ratios (SRRs) and 95% CIs were recalculated using a random effects model. We evaluated the risk of bias of identified meta-analyses and the quality of evidence for all associations. In total, 20 meta-analyses including 98 SRRs were identified. All original meta-analyses were rated as being at high risk of bias. Methodological concerns related mainly to the inappropriate synthesis, assessment, and discussion of the risk of bias of primary studies. For the recalculated meta-analyses, quality of evidence was moderate for inverse associations between higher adherence to the Mediterranean diet (SRR: 0.63; 95% CI: 0.48, 0.82; n = 4 primary studies) and higher fish intake (SRR: 0.72; 95% CI: 0.59, 0.89; n = 6) and Alzheimer disease, as well as for tea consumption and all-cause dementia (SRR: 0.74; 95% CI: 0.63, 0.88; n = 2) and Parkinson disease (SRR per 2 cups/d: 0.69; 95% CI: 0.54, 0.87; n = 5). This umbrella review provides a comprehensive overview of the available evidence on dietary factors and neurodegenerative disorders. The results indicate that the Mediterranean diet, fish, and tea could be inversely associated with neurodegenerative disorders. However, the quality of evidence was generally low, suggesting that further studies are likely to change the overall estimates. Thus, more well-conducted research, also investigating other dietary factors in association with neurodegenerative disorders, is warranted.