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.

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.

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.

How amenable is type 2 diabetes treatment for precision diabetology? A meta-regression of glycaemic control data from 174 randomised trials.

AIMS/HYPOTHESIS: There are two prerequisites for the precision medicine approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in the case of treatment heterogeneity, we need to detect clinical predictors to identify people who would benefit from one treatment more than from others. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. Our aim was to apply this approach to the treatment of type 2 diabetes. METHODS: We performed a meta-regression analysis using information from 174 placebo-controlled randomised trials with 178 placebo and 272 verum (i.e. active treatment) arms including 86,940 participants with respect to the variability of glycaemic control as assessed by HbA1c after treatment and its potential predictors. RESULTS: The adjusted difference in log(SD) values between the verum and placebo arms was 0.037 (95% CI: 0.004, 0.069). That is, we found a small increase in the variability of HbA1c values after treatment in the verum arms. In addition, one potentially relevant predictor for explaining this increase, drug class, was observed, and GLP-1 receptor agonists yielded the largest differences in log(SD) values. CONCLUSIONS/INTERPRETATION: The potential of the precision medicine approach in the treatment of type 2 diabetes is modest at best, at least with regard to an improvement in glycaemic control. Our finding of a larger variability after treatment with GLP-1 receptor agonists in individuals with poor glycaemic control should be replicated and/or validated with other clinical outcomes and with different study designs. FUNDING: The research reported here received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. DATA AVAILABILITY: Two datasets (one for the log[SD] and one for the baseline-corrected log[SD]) to reproduce the analyses from this paper are available on https://zenodo.org/record/7956635 .

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).

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.

Coconut Oil and Cardiovascular Disease Risk.

PURPOSE OF REVIEW: This narrative review summarizes the current peer-reviewed literature and mechanisms surrounding the cardiovascular health impact of coconut oil. RECENT FINDINGS: No randomized controlled trials (RCTs) and/or prospective cohort studies have investigated the effect or association of coconut oil with cardiovascular disease. Evidence from RCTs indicated that coconut oil seems to have less detrimental effects on total and LDL-cholesterol compared to butter, but not compared to cis-unsaturated vegetable oils, such as safflower, sunflower, or canola oil. The isocaloric replacement (by 1% of energy intake) of carbohydrates with lauric acid (the predominant fatty acid in coconut oil) increased total cholesterol by 0.029 mmol/L (95% CI: 0.014; 0.045), LDL-cholesterol by 0.017 mmol/L (0.003; 0.031), and HDL-cholesterol by 0.019 mmol/L (0.016; 0.023). The current evidence from shorter term RCTs suggests that replacement of coconut oil with cis-unsaturated oils lowers total and LDL-cholesterol, whereas for the association between coconut oil intake and cardiovascular disease, less evidence is available.

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.

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.

Diabetes mellitus, prediabetes and the risk of Parkinson's disease: a systematic review and meta-analysis of 15 cohort studies with 29.9 million participants and 86,345 cases.

A diagnosis of diabetes mellitus and prediabetes has been associated with increased risk of Parkinson's disease (PD) in several studies, but results have not been entirely consistent. We conducted a systematic review and meta-analysis of cohort studies on diabetes mellitus, prediabetes and the risk of PD to provide an up-to-date assessment of the evidence. PubMed and Embase databases were searched for relevant studies up to 6th of February 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes, prediabetes and Parkinson's disease were included. Summary RRs (95% CIs) were calculated using a random effects model. Fifteen cohort studies (29.9 million participants, 86,345 cases) were included in the meta-analysis. The summary RR (95% CI) of PD for persons with diabetes compared to persons without diabetes was 1.27 (1.20-1.35, I2 = 82%). There was no indication of publication bias, based on Egger's test (p = 0.41), Begg's test (p = 0.99), and inspection of the funnel plot. The association was consistent across geographic regions, by sex, and across several other subgroup and sensitivity analyses. There was some suggestion of a stronger association for diabetes patients reporting diabetes complications than for diabetes patients without complications (RR = 1.54, 1.32-1.80 [n = 3] vs. 1.26, 1.16-1.38 [n = 3]), vs. those without diabetes (pheterogeneity=0.18). The summary RR for prediabetes was 1.04 (95% CI: 1.02-1.07, I2 = 0%, n = 2). Our results suggest that patients with diabetes have a 27% increased relative risk of developing PD compared to persons without diabetes, and persons with prediabetes have a 4% increase in RR compared to persons with normal blood glucose. Further studies are warranted to clarify the specific role age of onset or duration of diabetes, diabetic complications, glycaemic level and its long-term variability and management may play in relation to PD risk.

Soy consumption, cognitive function, and dementia.

PURPOSE OF REVIEW: With the rising number of people living with dementia, the interest in modifiable risk factors including dietary intake for dementia is increasing. Although there is a growing body of evidence investigating soy's health effects, the direction and strength of the association between soy consumption and risk of dementia and cognitive decline are still uncertain. Thus, we aimed to review the evidence linking soy consumption to dementia and cognitive function. RECENT FINDINGS: Some studies showed that higher intake of total soy products was associated with a lower risk or prevalence of cognitive impairment. Some studies pointed to an inverse association between higher tofu consumption and cognitive function, whereas a higher intake of soybean was associated with better cognitive function. SUMMARY: Previous studies are scarce and have provided contradictory results. Soy is a high-protein alternative to red meat and processed meat. Further studies are needed to clarify the safety and potential preventive effects particularly in healthy populations before clinical disease manifestation and irreversible injury have occurred.

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.

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

AIMS/HYPOTHESIS: Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death. METHODS: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Four different databases were searched up to 10 October 2020. We used a random effects meta-analysis to calculate summary relative risks (SRR) with 95% CI. The certainty of evidence was evaluated by the GRADE tool. RESULTS: A total of 22 articles, including 17,687 individuals, met our inclusion criteria. For COVID-19-related death among individuals with diabetes and COVID-19, there was high to moderate certainty of evidence for associations (SRR [95% CI]) between male sex (1.28 [1.02, 1.61], n = 10 studies), older age (>65 years: 3.49 [1.82, 6.69], n = 6 studies), pre-existing comorbidities (cardiovascular disease: 1.56 [1.09, 2.24], n = 8 studies; chronic kidney disease: 1.93 [1.28, 2.90], n = 6 studies; chronic obstructive pulmonary disease: 1.40 [1.21, 1.62], n = 5 studies), diabetes treatment (insulin use: 1.75 [1.01, 3.03], n = 5 studies; metformin use: 0.50 [0.28, 0.90], n = 4 studies) and blood glucose at admission (≥11 mmol/l: 8.60 [2.25, 32.83], n = 2 studies). Similar, but generally weaker and less precise associations were observed between risk phenotypes of diabetes and severity of COVID-19. CONCLUSIONS/INTERPRETATION: Individuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted. REGISTRATION: PROSPERO registration ID CRD42020193692.

Physical activity and the risk of heart failure: a systematic review and dose-response meta-analysis of prospective studies.

Although physical activity is an established protective factor for cardiovascular diseases such as ischemic heart disease and stroke, less is known with regard to the association between specific domains of physical activity and heart failure, as well as the association between cardiorespiratory fitness and heart failure. We conducted a systematic review and meta-analysis of prospective observational studies to clarify the relations of total physical activity, domains of physical activity and cardiorespiratory fitness to risk of heart failure. PubMed and Embase databases were searched up to January 14th, 2020. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine prospective studies (36 publications) were included in the review. The summary RRs for high versus low levels were 0.77 (95% CI 0.70-0.85, I2 = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68-0.81, I2 = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59-0.74, I2 = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69-0.94, I2 = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86-0.95, I2 = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19-0.49, I2 = 96%, n = 6) for cardiorespiratory fitness. In dose-response analyses, the summary RRs were 0.89 (95% CI 0.83-0.95, I2 = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65-0.78, I2 = 85%, n = 11) per 20 MET-hours per week of leisure-time activity. Nonlinear associations were observed in both analyses with a flattening of the dose-response curve at 15-20 MET-hours/week for leisure-time activity. These findings suggest that high levels of total physical activity, leisure-time activity, vigorous activity, occupational activity, walking and bicycling combined and cardiorespiratory fitness are associated with reduced risk of developing heart failure.

Association between per capita sugar consumption and diabetes prevalence mediated by the body mass index: results of a global mediation analysis.

PURPOSE: The aim of this study was to examine the mediation of body mass index (BMI) on the association between per capita sugar consumption and diabetes prevalence using country-related data. RESEARCH DESIGN AND METHODS: In this ecological study, based on 192 countries, data on per capita sugar consumption were obtained from the Food and Agriculture Organization of the United Nations (FAO), on BMI from the World Health Organization and on diabetes prevalence from the International Diabetes Federation. Data on demography and economic factors were obtained from the Central Intelligence Agency, the United Nations and the FAO. Multiple linear regression analysis was performed to investigate the association between per capita sugar consumption and diabetes prevalence, and mediation analysis to detect the mediated percentage of BMI on this association. RESULTS: Each increase of 100 kcal/day per capita sugar consumption was associated with a 1.62% higher diabetes prevalence [adjusted ß-estimator (95% CI): 1.62 (0.71, 2.53)]. Mediation analysis using BMI as the mediator demonstrated an adjusted direct association of 0.55 (95% CI: - 0.22, 1.32) and an adjusted indirect association of 1.07 (95% CI: 0.54, 1.68). Accordingly, the BMI explained 66% (95% CI: 34%, 100%) of the association between per capita sugar consumption on diabetes prevalence. CONCLUSIONS: These findings indicate that the association between dietary sugar intake and the occurrence of diabetes is mediated by BMI to a large proportion. However, it seems that other mechanisms may explain the association between sugar consumption and development of type 2 diabetes.

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.

Dose-response relationship between physical activity and mortality in adults with noncommunicable diseases: a systematic review and meta-analysis of prospective observational studies.

BACKGROUND: This study aims to investigate the relationship between post-diagnosis physical activity and mortality in patients with selected noncommunicable diseases, including breast cancer, lung cancer, type 2 diabetes, ischemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), osteoarthritis, low back pain and major depressive disorder. METHODS: A systematic search was conducted of PubMed, Scopus and the Web of Science from their inception to August 2018. Additionally, the search was updated in August 2019. Eligibility criteria included prospective observational studies examining the relationship between at least three physical activity categories (e.g. low, moderate, high) and all-cause mortality as the primary outcome. RESULTS: In total, 28 studies were included in the meta-analysis: 12 for breast cancer, 6 for type 2 diabetes, 8 for ischemic heart disease and 2 for COPD. The linear meta-analysis revealed that each 10 metabolic equivalent task hours increase of physical activity per week was associated with a 22% lower mortality rate in breast cancer patients (Summary Hazard Ratio [HR], 0.78; 95% CI: 0.71, 0.86; I2: 90.1%), 12% in ischemic heart disease patients (HR, 0.88; 95% CI: 0.83, 0.93; I2: 86.5%), 30% in COPD patients (HR, 0.70; 95% CI: 0.45, 1.09; I2: 94%) and 4% in type 2 diabetes patients (HR, 0.96; 95% CI: 0.93, 0.99; I2: 71.8%). There was indication of a non-linear association with mortality risk reductions even for low levels of activity, as well as a flattening of the curve at higher levels of activity. The certainty of evidence was low for breast cancer, type 2 diabetes and ischemic heart disease but only very low for COPD. CONCLUSION: Higher levels of post-diagnosis physical activity are associated with lower mortality rates in breast cancer, type 2 diabetes, ischemic heart disease and COPD patients, with indication of a no-threshold and non-linear dose-response pattern.

Physical activity and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies.

BACKGROUND: Physical activity has been associated with a significant reduction in risk of sudden cardiac death in epidemiological studies, however, the strength of the association needs clarification. We conducted a systematic review and meta-analysis to summarize the available data from population-based prospective studies. METHODS: PubMed and Embase databases were searched for studies of physical activity and sudden cardiac death from inception to March 26th 2019. Prospective studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of sudden cardiac death associated with physical activity were included. A random effects model was used to estimate summary RRs (95% CIs). RESULTS: Thirteen prospective studies were included in the systematic review. Eight prospective studies with 1193 sudden cardiac deaths among 136,298 participants were included in the meta-analysis of physical activity and sudden cardiac death and the summary RR for highest vs. lowest level of physical activity was 0.52 (95% CI: 0.45-0.60, I2 = 0%, pheterogeneity = 0.72). The association was similar in men and women and among American and European studies. In the dose-response analysis the summary RR was 0.68 (95% CI: 0.55-0.86, I2 = 44%, n = 3) per 20 MET-hours/week. Although the test for nonlinearity was not significant, pnonlinearity = 0.18, there was no further reduction in risk beyond 20-25 MET-hours/week. The summary RR was 0.58 (95% CI: 0.41-0.81, I2 = 0%, pheterogeneity = 0.65, n = 2) for the highest vs. the lowest level of cardiorespiratory fitness. CONCLUSION: This meta-analysis suggest that a high compared to a low level of physical activity may reduce the risk of sudden cardiac death in the general population. Further studies are needed to clarify the dose-response relationship between specific subtypes and intensities of physical activity in relation to sudden cardiac death.

Dietary fat and risk of type 2 diabetes.

PURPOSE OF REVIEW: Nutrition recommendations emphasize that not only dietary fat quantity but also fat quality plays a role in the prevention of type 2 diabetes (T2D). The aim of this review is to summarize the evidence for dietary fat and risk of T2D, to highlight recent findings and point out future research directions. RECENT FINDINGS: Total fat intake was not associated with risk of T2D, whereas the findings on fatty acids (FAs) and risk of T2D were controversial. Recent findings suggested that FAs from the same classes (e.g. omega-6 FAs) but different sources might be differently associated with the risk of T2D, with indication for an association with lower risk of T2D for plant-based and higher risk/no association for animal-based FAs. In addition, differences between populations from different geographic areas might exist, but no interaction effects for fat intake and genetic predisposition were observed regarding T2D risk. The simultaneous investigation of different fats and dietary patterns can provide important and meaningful insights into these associations. SUMMARY: The evidence for the association between dietary fat intake and risk of T2D is not conclusive yet. To strengthen the evidence, the complexity of the different associations of dietary fats should be considered in well conducted future studies.