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.

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.

A Bayesian Reanalysis of the CULPRIT-SHOCK Trial.

BACKGROUND: The optimal revascularization strategy for patients with acute myocardial infarction (AMI), cardiogenic shock (CS), and multivessel disease remains controversial. The CULPRIT-SHOCK trial compared culprit-lesion-only versus immediate multivessel percutaneous coronary intervention (PCI), providing important data but leaving efficacy questions unresolved. To address lingering uncertainties and gain deeper insights, we performed a Bayesian reanalysis of the CULPRIT-SHOCK trial data. METHODS: We conducted a Bayesian re-analysis of the CULPRIT-SHOCK trial data using non-informative, skeptical, and enthusiastic priors. Relative risks (RR) with 95% highest posterior density intervals were calculated. We defined the Minimally Clinically Important Difference (MCID) as RR <0.84. We performed subgroup analyses for key patient characteristics and assessed secondary outcomes and safety endpoints. Probabilities of benefit, achieving MCID, and harm were computed. Results are presented as median RR with probabilities of effect sizes. RESULTS: Bayesian re-analysis showed a median relative risk of 0.82 (95% HPD: 0.66-1.04) with a non-informative prior, indicating a 95% probability of benefit and 59% probability of achieving MCID. Subgroup analyses revealed potentially stronger effects in males (RR: 0.78, 73% probability of MCID), patients without diabetes (RR: 0.76, 79% probability of MCID), and those with non-anterior STEMI (RR: 0.74, 76% probability of MCID). Secondary outcomes suggested potential benefits in mortality (RR: 0.85) and need for renal replacement therapy (RR: 0.72), but increased risks of recurrent MI (RR: 2.84) and urgent revascularization (RR: 2.88). CONCLUSION: Our Bayesian reanalysis provides intuitive insights by quantifying probabilities of treatment effect sizes, offering further evidence favoring the culprit-lesion-only PCI strategy in AMI patients with cardiogenic shock and multivessel disease. The analysis demonstrates a high probability of overall benefit, with a notable chance of achieving a minimally clinically important difference, particularly in specific subgroups. These findings not only support the consideration of culprit-lesion-only PCI in certain patient populations but also underscore the need for careful risk-benefit assessment. Furthermore, our hypothesis-generating subgroup analyses, which show varying probabilities of achieving MCID, illuminate promising avenues for future targeted investigations in this critical patient population.

Diabetes as a risk factor for tuberculosis disease.

BACKGROUND: Tuberculosis (TB) is amongst the leading causes of death from an infectious disease, with an estimated 1.3 million deaths from TB in 2022. Approximately 25% of the global population is estimated to be infected with the TB bacterium, giving rise to 10.6 million episodes of TB disease in 2022. The prevalence of diabetes influences TB incidence and TB mortality. It is associated not only with an increased risk of TB disease but also death during TB treatment, TB relapse after treatment completion and multidrug-resistant TB. Since 2011, the World Health Organization (WHO) has recommended collaborative TB and diabetes activities as outlined in the Collaborative Framework for Care and Control of TB and Diabetes. OBJECTIVES: To determine the prognostic value of diabetes mellitus (DM) in the general population of adults, adolescents and children for predicting tuberculosis disease. SEARCH METHODS: We searched the literature databases MEDLINE (via PubMed) and WHO Global Index Medicus, and the WHO International Clinical Trials Registry Platform (ICTRP) on 3 May 2023 (date of last search for all databases); we placed no restrictions on the language of publication. SELECTION CRITERIA: We included retrospective and prospective cohort studies, irrespective of publication status or language. The target population comprised adults, adolescents and children from diverse settings, encompassing outpatient and inpatient cohorts, with varying comorbidities and risk of exposure to tuberculosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and the Quality In Prognosis Studies (QUIPS) tool. Prognostic factors assessed at enrolment/baseline included diabetes, as defined by the individual studies, encompassing patient-reported status, abstracted from medical records or claims data, or diagnosed by plasma glucose/glycosylated haemoglobin. The primary outcome was the incidence of tuberculosis disease. The secondary outcome was recurrent TB disease. We performed a random-effects meta-analysis for the adjusted hazard ratios, risk ratios, or odds ratios, employing the restricted maximum likelihood estimation. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 48 cohort studies with over 61 million participants from the six WHO regions. However, the representation was variable as eight population-based studies were from South Korea and 19 from China, with overlapping study periods, and only one from the African region (Ethiopia). All studies included adults, and nine studies also included children and adolescents. Most studies diagnosed DM based on clinical records, including fasting blood glucose levels or glucose-lowering treatments. The studies did not distinguish between type 1 and type 2 DM; only one study focused on type 1 DM. Diagnosis and exclusion of TB were performed using culture or molecular WHO-recommended rapid diagnostic tests (mWRD) in only 12 studies, which could have biassed the effect estimate. The median follow-up time was five years (interquartile range 1.5 to 10, range 1 to 16.9), and the studies primarily reported an adjusted hazard ratio from a multivariable Cox-proportional hazard model. Hazard Ratios (HR) The HR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. We present 95% confidence intervals (CI) and prediction intervals, which show between-study heterogeneity represented in measuring the variability of effect sizes (i.e. the interval within which the effect size of a new study would fall considering the same population of studies included in the meta-analysis). DM may increase the risk of tuberculosis disease (HR 1.90, 95% CI 1.51 to 2.40; prediction interval 0.83 to 4.39; 10 studies; 11,713,023 participants). The certainty of the evidence is low, due to a moderate risk of bias across studies and inconsistency. Considering a risk without diabetes of 129 cases per 100,000 population, this represents 102 more (59 to 153 more) cases per 100,000. When stratified by follow-up time, the results are more consistent across < 10 years follow-up (HR 1.52, 95% CI 1.47 to 1.57; prediction interval 1.45 to 1.59; 7 studies; 10,380,872 participants). This results in a moderate certainty of the evidence due to a moderate risk of bias across studies. However, at 10 or more years of follow-up, the estimates yield a wider CI and a higher HR (HR 2.44, 95% CI 1.22 to 4.88; prediction interval 0.09 to 69.12; 3 studies; 1,332,151 participants). The certainty of the evidence is low due to the moderate risk of bias and inconsistency. Odds Ratio (OR) DM may increase the odds of tuberculosis disease (OR 1.61, 95% CI 1.27 to 2.04; prediction interval 0.96 to 2.70; 4 studies; 167,564 participants). Stratification by follow-up time was not possible as all studies had a follow-up < 10 years. The certainty of the evidence is low due to a moderate risk of bias and inconsistency. Risk Ratio (RR) The RR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. DM probably increases the risk of tuberculosis disease (RR 1.60, 95% CI 1.42 to 1.80; prediction interval 1.38 to 1.85; 6 studies; 44,058,675 participants). Stratification by follow-up time was not possible as all studies had a follow-up < 10 years. The certainty of the evidence is moderate due to a moderate risk of bias. AUTHORS' CONCLUSIONS: Diabetes probably increases the risk of developing TB disease in the short term (< 10 years) and may also increase the risk in the long term (≥ 10 years). As glycaemic control and access to care may be potential effect modifiers of the association between diabetes and the risk of TB disease, the overall estimates should be interpreted with caution when applied locally. Policies targeted at reducing the burden of diabetes are needed to contribute to the aims of ending TB. Large population-based cohorts, including those derived from high-quality national registries of exposures (diabetes) and outcomes (TB disease), are needed to provide estimates with a high certainty of evidence of this risk across different settings and populations, including low- and middle-income countries from different WHO regions. Moreover, studies including children and adolescents and currently recommended methods for diagnosing TB would provide more up-to-date information relevant to practice and policy. FUNDING: World Health Organization (203256442) REGISTRATION: PROSPERO registration: CRD42023408807.

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.

Test accuracy of rapid diagnostic tests and reverse-transcription polymerase chain reaction against virus isolation in cell culture for assessing SARS-CoV-2 infectivity: Systematic review and meta-analysis.

We aimed to assess the performance of Ag-RDT and RT-qPCR with regard to detecting infectious SARS-CoV-2 in cell cultures, as their diagnostic test accuracy (DTA) compared to virus isolation remains largely unknown. We searched three databases up to 15 December 2021 for DTA studies. The bivariate model was used to synthesise the estimates. Risk of bias was assessed using QUADAS-2/C. Twenty studies (2605 respiratory samples) using cell culture and at least one molecular test were identified. All studies were at high or unclear risk of bias in at least one domain. Three comparative DTA studies reported results on Ag-RDT and RT-qPCR against cell culture. Two studies evaluated RT-qPCR against cell culture only. Fifteen studies evaluated Ag-RDT against cell culture as reference standard in RT-qPCR-positive samples. For Ag-RDT, summary sensitivity was 93% (95% CI 78; 98%) and specificity 87% (95% CI 70; 95%). For RT-qPCR, summary sensitivity (continuity-corrected) was 98% (95% CI 95; 99%) and specificity 45% (95% CI 28; 63%). In studies relying on RT-qPCR-positive subsamples (n = 15), the summary sensitivity of Ag-RDT was 93% (95% CI 92; 93%) and specificity 63% (95% CI 63; 63%). Ag-RDT show moderately high sensitivity, detecting most but not all samples demonstrated to be infectious based on virus isolation. Although RT-qPCR exhibits high sensitivity across studies, its low specificity to indicate infectivity raises the question of its general superiority in all clinical settings. Study findings should be interpreted with caution due to the risk of bias, heterogeneity and the imperfect reference standard for infectivity.

Undernutrition as a risk factor for tuberculosis disease.

BACKGROUND: Tuberculosis (TB) is a leading cause of mortality due to an infectious disease, with an estimated 1.6 million deaths due to TB in 2022. Approximately 25% of the global population has TB infection, giving rise to 10.6 million episodes of TB disease in 2022. Undernutrition is a key risk factor for TB and was linked to an estimated 2.2 million TB episodes in 2022, as outlined in the World Health Organization (WHO) Global Tuberculosis Report. OBJECTIVES: To determine the prognostic value of undernutrition in the general population of adults, adolescents, and children for predicting tuberculosis disease over any time period. SEARCH METHODS: We searched the literature databases MEDLINE (via PubMed) and WHO Global Index Medicus, as well as the WHO International Clinical Trials Registry Platform (ICTRP) on 3 May 2023 (date of last search for all databases). We placed no restrictions on the language of publication. SELECTION CRITERIA: We included retrospective and prospective cohort studies, irrespective of publication status or language. The target population comprised adults, adolescents, and children from diverse settings, encompassing outpatient and inpatient cohorts, with varying comorbidities and risk of exposure to tuberculosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and the Quality In Prognosis Studies (QUIPS) tool to assess the risk of bias of the studies. Prognostic factors included undernutrition, defined as wasting, stunting, and underweight, with specific measures such as body mass index (BMI) less than two standard deviations below the median for children and adolescents and low BMI scores (< 18.5) for adults and adolescents. Prognostication occurred at enrolment/baseline. The primary outcome was the incidence of TB disease. The secondary outcome was recurrent TB disease. We performed a random-effects meta-analysis for the adjusted hazard ratios (HR), risk ratios (RR), or odds ratios (OR), employing the restricted maximum likelihood estimation. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 51 cohort studies with over 27 million participants from the six WHO regions. Sixteen large population-based studies were conducted in China, Singapore, South Korea, and the USA, and 25 studies focused on people living with HIV, which were mainly conducted in the African region. Most studies were in adults, four in children, and three in children and adults. Undernutrition as an exposure was usually defined according to standard criteria; however, the diagnosis of TB did not include a confirmatory culture or molecular diagnosis using a WHO-approved rapid diagnostic test in eight studies. The median follow-up time was 3.5 years, and the studies primarily reported an adjusted hazard ratio from a multivariable Cox-proportional hazard model. Hazard ratios (HR) The HR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. We present 95% confidence intervals (CI) and prediction intervals, which present between-study heterogeneity represented in a measurement of the variability of effect sizes (i.e. the interval within which the effect size of a new study would fall considering the same population of studies included in the meta-analysis). Undernutrition may increase the risk of TB disease (HR 2.23, 95% CI 1.83 to 2.72; prediction interval 0.98 to 5.05; 23 studies; 2,883,266 participants). The certainty of the evidence is low due to a moderate risk of bias across studies and inconsistency. When stratified by follow-up time, the results are more consistent across < 10 years follow-up (HR 2.02, 95% CI 1.74 to 2.34; prediction interval 1.20 to 3.39; 22 studies; 2,869,077 participants). This results in a moderate certainty of evidence due to a moderate risk of bias across studies. However, at 10 or more years of follow-up, we found only one study with a wider CI and higher HR (HR 12.43, 95% CI 5.74 to 26.91; 14,189 participants). The certainty of the evidence is low due to the moderate risk of bias and indirectness. Odds ratio (OR) Undernutrition may increase the odds of TB disease, but the results are uncertain (OR 1.56, 95% CI 1.13 to 2.17; prediction interval 0.61 to 3.99; 8 studies; 173,497 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is very low due to the high risk of bias and inconsistency. Contour-enhanced funnel plots were not reported due to the few studies included. Risk ratio (RR) Undernutrition may increase the risk of TB disease (RR 1.95, 95% CI 1.72 to 2.20; prediction interval 1.49 to 2.55; 4 studies; 1,475,867 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is low due to the high risk of bias. Contour-enhanced funnel plots were not reported due to the few studies included. AUTHORS' CONCLUSIONS: Undernutrition probably increases the risk of TB two-fold in the short term (< 10 years) and may also increase the risk in the long term (> 10 years). Policies targeted towards the reduction of the burden of undernutrition are not only needed to alleviate human suffering due to undernutrition and its many adverse consequences, but are also an important part of the critical measures for ending the TB epidemic by 2030. Large population-based cohorts, including those derived from high-quality national registries of exposures (undernutrition) and outcomes (TB disease), are needed to provide high-certainty estimates of this risk across different settings and populations, including low and middle-income countries from different WHO regions. Moreover, studies including children and adolescents and state-of-the-art methods for diagnosing TB would provide more up-to-date information relevant to practice and policy. FUNDING: World Health Organization (203256442). REGISTRATION: PROSPERO registration: CRD42023408807 Protocol: https://doi.org/10.1002/14651858.CD015890.

Development of the VEGANScreener, a Tool for a Quick Diet Quality Assessment among Vegans in Europe.

BACKGROUND: Plant-based diets are not inherently healthy. Similar to omnivorous diets, they may contain excessive amounts of sugar, sodium, and saturated fats, or lack diversity. Moreover, vegans might be at risk of inadequate intake of certain vitamins and minerals commonly found in foods that they avoid. We developed the VEGANScreener, a tool designed to assess the diet quality of vegans in Europe. METHODS: Our approach combined best practices in developing diet quality metrics with scale development approaches and involved the following: (a) narrative literature synthesis, (b) evidence evaluation by an international panel of experts, and (c) translation of evidence into a diet screener. We employed a modified Delphi technique to gather opinions from an international expert panel. RESULTS: Twenty-five experts in the fields of nutrition, epidemiology, preventive medicine, and diet assessment participated in the first round, and nineteen participated in the subsequent round. Initially, these experts provided feedback on a pool of 38 proposed items from the literature review. Consequently, 35 revised items, with 17 having multiple versions, were suggested for further consideration. In the second round, 29 items were retained, and any residual issues were addressed in the final consensus meeting. The ultimate screener draft encompassed 29 questions, with 17 focusing on foods and nutrients to promote, and 12 addressing foods and nutrients to limit. The screener contained 24 food-based and 5 nutrient-based questions. CONCLUSIONS: We elucidated the development process of the VEGANScreener, a novel diet quality screener for vegans. Future endeavors involve contrasting the VEGANScreener against benchmark diet assessment methodologies and nutritional biomarkers and testing its acceptance. Once validated, this instrument holds potential for deployment as a self-assessment application for vegans and as a preliminary dietary screening and counseling tool in healthcare settings.

Substitution of Dairy Products and Risk of Death and Cardiometabolic Diseases: A Systematic Review and Meta-Analysis of Prospective Studies.

Substitution models in epidemiologic studies specifying both substitute and substituted food in relation to disease risk may be useful to inform dietary guidelines. A systematic review of prospective observational studies was performed to quantify the risks of all-cause mortality, cardiovascular disease, and type 2 diabetes (T2D) associated with the substitution of dairy products with other foods and between different dairy products. We systematically searched MEDLINE, Embase, and Web of Science until 28th June, 2023. We calculated summary relative risks (SRRs) and 95% confidence intervals (95% CI) in random-effects meta-analyses. We assessed the risk of bias with the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool and certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach. Fifteen studies (with 34 publications) were included. There was moderate CoE that the substitution of low-fat dairy with red meat was associated with a higher risk of mortality, coronary artery disease, and T2D [SRR (95% CI): 1.11 (1.06, 1.16), 1.13 (1.08, 1.18), and 1.20 (1.16, 1.25)]. A higher risk of mortality and T2D was also observed when substituting low-fat dairy with processed meat [SRR (95% CI): 1.19 (1.11, 1.28) and 1.41 (1.33, 1.49); moderate CoE]. A lower mortality risk was associated with the substitution of dairy and yogurt with whole grains [SRR (95% CI): 0.89 (0.84, 0.93) and 0.91 (0.85, 0.97)], and butter with olive oil [SRR (95% CI): 0.94 (0.92, 0.97); all moderate CoE]. Mainly no associations were observed when substituting dairy products against each other on disease and mortality risk. Our findings indicate associations between substituting dairy with red or processed meat and higher disease risk, whereas its substitution with whole grains was associated with a lower risk. However, there is little robust evidence that substituting whole-fat with low-fat dairy is associated with disease risk. (CRD42022303198).

Assessing the potential for precision medicine in body weight reduction with regard to type 2 diabetes mellitus therapies: A meta-regression analysis of 120 randomized controlled trials.

AIMS: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability. METHODS: We used randomized clinical trials (RCTs) comparing glucose-lowering drugs (including but not limited to sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.e., treatment response heterogeneity) in verum (i.e., treatment) and placebo groups were included. Meta-regression analyses were performed with respect to variability of body weight after treatment and potential predictors. RESULTS: A total of 120 RCTs with a total of 43 663 participants were analysed. A slightly larger treatment response heterogeneity was shown in the verum groups, with a median log(SD) of 2.83 compared to 2.79 from placebo. After full adjustment in the meta-regression model, the difference in body weight log(SD) was -0.026 (95% confidence interval -0.044; 0.008), with greater variability in the placebo groups. Scatterplots did not show any slope divergence (i.e., interaction) between clinical predictors and the respective treatment (verum or placebo). CONCLUSIONS: We found no major treatment response heterogeneity in RCTs of glucose-lowering drugs for body weight reduction in type 2 diabetes. The precision medicine approach may thus be of limited value in this setting.

Association of dietary patterns with diabetes-related comorbidities varies among diabetes endotypes.

BACKGROUND AND AIMS: Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed adherence to pre-specified dietary patterns and their associations with cardiovascular risk factors, kidney function, and neuropathy among diabetes endotypes. METHODS AND RESULTS: The cross-sectional analysis included 765 individuals with recent-onset (67 %) and prevalent diabetes (33 %) from the German Diabetes Study (GDS) allocated into severe autoimmune diabetes (SAID, 35 %), severe insulin-deficient diabetes (SIDD, 3 %), severe insulin-resistant diabetes (SIRD, 5 %), mild obesity-related diabetes (MOD, 28 %), and mild age-related diabetes (MARD, 29 %). Adherence to a Mediterranean diet score (MDS), Dietary Approaches to Stop Hypertension (DASH) score, overall plant-based diet (PDI), healthful (hPDI) and unhealthful plant-based diet index (uPDI) was derived from a food frequency questionnaire and associated with cardiovascular risk factors, kidney function, and neuropathy using multivariable linear regression analysis. Differences in dietary pattern adherence between endotypes were assessed using generalized mixed models. People with MARD showed the highest, those with SIDD and MOD the lowest adherence to the hPDI. Adherence to the MDS, DASH, overall PDI, and hPDI was inversely associated with high-sensitivity C-reactive protein (hsCRP) among people with MARD (ß (95%CI): -9.18 % (-15.61; -2.26); -13.61 % (-24.17; -1.58); -19.15 % (-34.28; -0.53); -16.10 % (-28.81; -1.12), respectively). Adherence to the PDIs was associated with LDL cholesterol among people with SAID, SIRD, and MOD. CONCLUSIONS: Minor differences in dietary pattern adherence (in particular for hPDI) and associations with markers of diabetes-related complications (e.g. hsCRP) were observed between endotypes. So far, evidence is insufficient to derive endotype-specific dietary recommendations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01055093.

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.

Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data.

BACKGROUND: Absolute treatment benefits-expressed as numbers needed to treat-of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome. METHODS: From Kaplan-Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI). RESULTS: Twelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months. CONCLUSION: The present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.

Substitution of animal-based with plant-based foods on cardiometabolic health and all-cause mortality: a systematic review and meta-analysis of prospective studies.

BACKGROUND: There is growing evidence that substituting animal-based with plant-based foods is associated with a lower risk of cardiovascular diseases (CVD), type 2 diabetes (T2D), and all-cause mortality. Our aim was to summarize and evaluate the evidence for the substitution of any animal-based foods with plant-based foods on cardiometabolic health and all-cause mortality in a systematic review and meta-analysis. METHODS: We systematically searched MEDLINE, Embase, and Web of Science to March 2023 for prospective studies investigating the substitution of animal-based with plant-based foods on CVD, T2D, and all-cause mortality. We calculated summary hazard ratios (SHRs) and 95% confidence intervals (95% CI) using random-effects meta-analyses. We assessed the certainty of evidence (CoE) using the GRADE approach. RESULTS: In total, 37 publications based on 24 cohorts were included. There was moderate CoE for a lower risk of CVD when substituting processed meat with nuts [SHR (95% CI): 0.73 (0.59, 0.91), n = 8 cohorts], legumes [0.77 (0.68, 0.87), n = 8], and whole grains [0.64 (0.54, 0.75), n = 7], as well as eggs with nuts [0.83 (0.78, 0.89), n = 8] and butter with olive oil [0.96 (0.95, 0.98), n = 3]. Furthermore, we found moderate CoE for an inverse association with T2D incidence when substituting red meat with whole grains/cereals [0.90 (0.84, 0.96), n = 6] and red meat or processed meat with nuts [0.92 (0.90, 0.94), n = 6 or 0.78 (0.69, 0.88), n = 6], as well as for replacing poultry with whole grains [0.87 (0.83, 0.90), n = 2] and eggs with nuts or whole grains [0.82 (0.79, 0.86), n = 2 or 0.79 (0.76, 0.83), n = 2]. Moreover, replacing red meat for nuts [0.93 (0.91, 0.95), n = 9] and whole grains [0.96 (0.95, 0.98), n = 3], processed meat with nuts [0.79 (0.71, 0.88), n = 9] and legumes [0.91 (0.85, 0.98), n = 9], dairy with nuts [0.94 (0.91, 0.97), n = 3], and eggs with nuts [0.85 (0.82, 0.89), n = 8] and legumes [0.90 (0.89, 0.91), n = 7] was associated with a reduced risk of all-cause mortality. CONCLUSIONS: Our findings indicate that a shift from animal-based (e.g., red and processed meat, eggs, dairy, poultry, butter) to plant-based (e.g., nuts, legumes, whole grains, olive oil) foods is beneficially associated with cardiometabolic health and all-cause mortality.

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.

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.

Health aspects of vegan diets among children and adolescents: a systematic review and meta-analyses.

Health effects of vegan diets among children and adolescents are a controversial public health topic. Thus, the aim of the present systematic review is to evaluate a broad range of health outcomes among vegan children and adolescents aged 0 to 18 years. 18 studies met the inclusion criteria (17 cross-sectional, 1 RCT). Meta-analyses showed lower protein, calcium, vitamin B2, saturated fatty acid, and cholesterol intakes, and lower ferritin, HDL and LDL levels as well as height in vegan compared to omnivorous children/adolescents. Higher intakes of carbohydrates, polyunsaturated fatty acids, fiber, folate, vitamins C and E, magnesium, iron, and potassium were observed in vegans. Blood levels of vitamin B12 were higher among vegan children due to supplement use. Single study results suggested further differences between vegan and non-vegan children, such as lower bone mineral content or urinary iodine among vegan children. Risk of Bias was rated as high or very high in 7 out of 18 studies. The certainty of evidence for the meta-analyses was low (n = 2) or very low (n = 46). Overall, the available evidence points to both risks and benefits associated with a vegan diet among children, although more and better designed studies are needed.

Efficacy of automated insulin delivery (AID) systems in type 1 diabetes: protocol of a systematic review and network meta-analysis of outpatient randomised controlled trials.

INTRODUCTION: Automated insulin delivery (AID), also known as artificial pancreas system or 'closed-loop system', represents a novel option for current treatments for type 1 diabetes (T1D). The objective of this systematic review and meta-analysis is to assess the efficacy of AID systems in comparison with current intensified insulin therapy for glycaemic control and patient-reported outcomes in individuals with T1D. METHODS AND ANALYSIS: Studies will be eligible if they are randomised controlled trials (RCTs) in people with T1D of all ages, and if they compare an AID system for self-administration during the day and night period with any other type of insulin therapy for at least 3 weeks. The primary outcome will be time in the glucose target range of 70-180 mg/dL. A systematic review will be conducted in the MEDLINE, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov registries from their inception dates. Two authors will independently screen all references based on titles and abstracts against the eligibility criteria. For data extraction, standard forms will be developed and tested before extraction. All information will be assessed independently by at least two reviewers. The risk of bias of the included studies will be assessed using the Cochrane Risk of Bias 2 tool. The data synthesis will include a random-effects pairwise and network meta-analysis (NMA) in a frequentist framework. Where applicable and if sufficient RCTs are available, sensitivity analyses will be performed, and heterogeneity and publication bias will be assessed. The certainty of evidence from the NMA will be evaluated following the Grading of Recommendations Assessment, Development, and Evaluation working group guidance. ETHICS AND DISSEMINATION: No ethical approval is needed. The results will be reported to the funder, presented in a peer-reviewed scientific journal and at conferences, and disseminated via press release, social media and public events. PROSPERO REGISTRATION NUMBER: CRD42023395492.

The mediating role of obesity on the prospective association between urinary sucrose and diabetes incidence in a sub-cohort of the EPIC-Norfolk.

BACKGROUND/OBJECTIVES: Findings from epidemiological studies showed controversial findings between dietary sugar intake and the development of diabetes. Most of these studies assessed dietary sugar intake by self-reports which might be prone to bias. Urinary sucrose, an objective biomarker of sucrose intake, might provide better insights into this association. Thus, the aim of this study was to investigate the associations between sucrose intake, measured via self-reports and urinary sucrose, with incident diabetes and to detect the impact of obesity on this association. SUBJECTS/METHODS: Data of a sub-group (n = 2996) from the prospective EPIC-Norfolk cohort were investigated. Sucrose intake was assessed by self-reports (validated food frequency questionnaire (FFQ) and 7-day diet diaries (7DD)) and as an objective urinary sucrose biomarker. Cox proportional hazard models were conducted to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for the associations between urinary and dietary sucrose intake and incident diabetes. Mediation analysis was performed to investigate the mediated percentage of body mass index (BMI) and waist circumference (WC) on this association. RESULTS: The mean age of the participants was 60.6 ± 9.5 years and 53% were women. After a mean follow-up of 11.2 ± 2.9 years, 97 participants developed diabetes. Findings suggested inverse associations regarding incident diabetes for self-reported sucrose intake per 50 g/d via 7DD [HR: 0.63 (95% CI: 0.43, 0.91)], and a tendency via FFQ [HR: 0.81 (95% CI: 0.46, 1.42)]. Urinary sucrose indicated a positive association with incident diabetes for each increase of 100 µM [HR: 1.14 (95% CI: 0.95, 1.36)]. The proportion mediated of BMI and WC for this association was 16 and 22%. CONCLUSIONS: These findings indicate that sucrose measured as objective urinary biomarker points to a positive association with incident diabetes. BMI might partly mediate this association. However, to obtain more precise results, more studies are warranted that consider this objective biomarker.