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Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes
Open accessAbstract
Background Habitual red meat consumption was consistently related to a higher risk of type 2 diabetes in observational studies. Potentially underlying mechanisms are unclear.Objective This study aimed to identify blood metabolites that possibly relate red meat consumption to the occurrence of type 2 diabetes.Design Analyses were conducted in the prospective European Prospective Investigation into Cancer and Nutrition-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2681, including 688 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Total red meat consumption was defined as energy-standardized summed intake of unprocessed and processed red meats. Concentrations of 14 amino acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and ferritin were determined in serum samples from baseline. These biomarkers were considered potential mediators of the relation between total red meat consumption and diabetes risk in Cox models. The proportion of diabetes risk explainable by biomarker adjustment was estimated in a bootstrapping procedure with 1000 replicates.Results After adjustment for age, sex, lifestyle, diet, and body mass index, total red meat consumption was directly related to diabetes risk [HR for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57]. Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk. The red meat-associated diabetes risk was significantly (P < 0.001) attenuated after simultaneous adjustment for these biomarkers [biomarker-adjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38]. The proportion of diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%).Conclusion In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk. The red meat-associated diabetes risk was largely attenuated after adjustment for selected biomarkers, which is consistent with the presumed mediation hypothesis.
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TL;DR
In the EPIC-Potsdam prospective cohort, higher total red meat consumption was associated with higher type 2 diabetes risk, and this association was largely attenuated after adjustment for selected serum biomarkers. Ferritin, glycine, and specific lipid metabolites were identified as potential mediators linking red meat intake to diabetes risk.
Key findings
- After adjustment for age, sex, lifestyle, diet, and BMI, total red meat consumption was directly related to diabetes risk: HR for 2 SD (11 g/MJ) = 1.26 (95% CI: 1.01, 1.57).
- Six biomarkers were associated with both red meat consumption and diabetes risk: ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1.
- Simultaneous adjustment for selected biomarkers attenuated the red meat–diabetes association to HR 1.09 (95% CI: 0.86, 1.38); the proportion of diabetes risk explainable by biomarkers was 69% (IQR: 49%, 106%) in the BMI-adjusted model.
- In sensitivity analyses, the explainable proportion was 49% (IQR: 29%, 89%) for unprocessed red meat and 71% (IQR: 45%, 115%) for processed meat.
Methods
- Prospective EPIC-Potsdam cohort (n = 27,548) with a nested case-cohort design (n = 2681, including 688 incident type 2 diabetes cases; mean follow-up 7.0 y).
- Habitual diet was assessed by validated semiquantitative food-frequency questionnaires; total red meat was energy-standardized summed intake of unprocessed and processed red meat.
- Serum concentrations of 14 amino acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and ferritin were measured; Cox models with Prentice weighting and a bootstrapping procedure with 1000 replicates estimated mediation/attenuation.
Limitations
- The paper states that residual confounding cannot be ruled out because of the observational design, and that the results cannot prove causality.
- The paper notes dietary information relied on FFQ estimates and metabolites were measured at a single time point; the targeted metabolite set was not exhaustive, and selection was somewhat sensitive for lysophosphatidylcholine 17:0 and hydroxy-sphingomyelin 14:1.
- Evident from the text: the study population was middle-aged adults from Potsdam, Germany, so generalizability to other populations is not established.
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36 Not checked yet · 21 Own result · 10 Own interpretation · 9 Own method
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“The red meat-associated diabetes risk was significantly (P , 0.001) attenuated after simultaneous adjustment for these biomarkers [biomarkeradjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38].”
- Also stated in: § Attenuation of the red meat-associated diabetes risk by selected biomarkers · plain
“After mutually including the 5 other selected biomarkers as covariates, the HR (per 2 SD) of total red meat consumption was significantly attenuated from 1.33 (95% CI: 1.09, 1.62) to 1.04 (0.83, 1.30) for the non-BMI-adjusted model 2 and from 1.26 (95% CI: 1.01, 1.57) to 1.09 (0.86, 1.38) for the BMI-adjusted model 3.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
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- Also stated in: § Attenuation of the red meat-associated diabetes risk by selected biomarkers · plain
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In the paper
“After adjustment for age, sex, lifestyle, diet, and body mass index, total red meat consumption was directly related to diabetes risk [HR for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57].”
- Also stated in: § Attenuation of the red meat-associated diabetes risk by selected biomarkers · plain
“This association was further attenuated after also adjusting for BMI and again remained significant (HR for 2 SD: 1.26; 95% CI: 1.01, 1.57).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
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In the paper
“If the non-BMI-adjusted model 2 was defined as reference, the red meat-associated diabetes risk was attenuated by 89% (IQR: 69%, 121%) after simultaneous adjustment for the selected biomarkers (Figure 1A).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
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“Additional adjustment for lifestyle, medication, and diet (model 2) attenuated the relation (HR: 1.33; 95% CI: 1.09, 1.62).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
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“The proportion of diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%).”
- Also stated in: § Attenuation of the red meat-associated diabetes risk by selected biomarkers · plain
“If the BMIadjusted model 3 was defined as reference, the red meatassociated diabetes risk was attenuated by 69% (IQR: 49%, 106%) after simultaneous adjustment for selected biomarkers (Figure 1B).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
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In the paper
“The explainable proportion ranged between 8% and 33% for single biomarker adjustments.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
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In the paper
“A higher total red meat consumption was related to a higher risk of developing type 2 diabetes [HR for 2 SD (11 g/MJ): 1.47; 95% CI: 1.24, 1.75] in the minimally adjusted model 1 (Table 4).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
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In the paper
“Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk.”
- Also stated in: § Biomarker selection · plain
“For 6 of these 13 biomarkers-namely, ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxysphingomyelin 14:1-the associations with total red meat consumption and with diabetes risk were consistent with the mediation hypothesis (Table 2 and Table 3); that is, both associations were in the same direction.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
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“Regarding lipid profiles, we found strong sex-consistent associations with total red meat consumption for 19 lipid metabolites from 4 classes.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“The marked attenuation of red meat-associated diabetes risk after adjustment for selected biomarkers suggests that these biomarkers reflect metabolic processes that link habitual red meat consumption to diabetes risk.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“Directions of the associations were largely accordant with the direction of the relations of the selected mediators with the risk of type 2 diabetes.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Relation of selected biomarkers with other diabetes risk markers
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“Among amino acids, glycine fulfilled predefined selection criteria.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“We observed a direct association of total red meat consumption with plasma ferritin levels.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“Our sensitivity analyses in subcategories of exposure (unprocessed and processed meat, respectively) suggest that the mutual set of selected biomarkers is relevant across subtypes of red meat.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“Furthermore, iron status, as reflected in circulating ferritin, was shown to be related to the risk of diabetes in EPIC-Potsdam (13).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [13] Montonen, 2012, Body iron stores and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, Diabetologia source
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In the paper
“Red meat consumption has consistently been associated with a higher risk of type 2 diabetes mellitus in several large cohort studies and summarized by several meta-analyses (1-3).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [1] Feskens, 2013, Meat consumption, diabetes, and its complications, Curr Diab Rep source
- Not checked yetcites [2] Pan, 2011, Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis, Am J Clin Nutr source
- Not checked yetcites [3] Benedinelli, 2013, Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study, Diabetologia source
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In the paper
“We have previously reported from the European Prospective Investigation into Cancer and Nutrition (EPIC) 5 -Potsdam study that with regard to type 2 diabetes risk assessment, a 150-g/d portion of red meat had a predictive value similar to smoking .20 cigarettes/d, having a 7.6-cm higher waist circumference, or having one parent with diabetes (5).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [5] Mühlenbruch, 2014, Update of the German Diabetes Risk Score and external validation in the German MONICA/KORA study, Diabetes Res Clin Pract source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, available evidence from prospective cohorts indicates red meat consumption as a risk factor for the development of type 2 diabetes (6).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [6] Ley, 2014, Prevention and management of type 2 diabetes: dietary components and nutritional strategies, Lancet source
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“In a randomized controlled feeding trial, glycine concentrations were slightly lower in response to a meat protein-based diet compared with a plant protein-based diet, whereas the amount of glycine provided by the meat diet was about 50% higher (39).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [39] Altorf-van der Kuil, 2013, Identification of biomarkers for intake of protein from meat, dairy products and grains: a controlled dietary intervention study, Br J Nutr source
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“Heme iron intake from red meats was shown to induce higher ferritin levels in feeding trials (43).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [43] Wells, 2003, Comparisons of vegetarian and beef-containing diets on hematological indexes and iron stores during a period of resistive training in older men, J Am Diet Assoc source
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“A Mendelian randomization study, however, did not provide evidence for a causal role of glycine in diabetes-related traits (42).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [42] Xie, 2013, Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes, Diabetes source
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In the paper
“Glycine is related to insulin resistance and oxidative stress by its essential role in gluconeogenesis and the formation of glutathione (40).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [40] Wang, 2013, Glycine metabolism in animals and humans: implications for nutrition and health, Amino Acids source
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In the paper
“The marked attenuation of red meat-associated diabetes risk after adjustment for selected biomarkers suggests that these biomarkers reflect metabolic processes that link habitual red meat consumption to diabetes risk.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Circulating lipid metabolites reflect synthesis activity of lipid classes as well as availability and metabolism of specific fatty acids in the liver.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, available evidence suggests elevated glycine utilization in response to red meat intake.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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In the paper
“Consistent with other studies (44), elevated iron status as assessed by ferritin was directly related to the risk of diabetes in EPIC-Potsdam (13).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutual adjustment for selected biomarkers revealed that the red meat-associated diabetes risk was largely dependent on the serum concentrations of ferritin, a small set of glycerophospholipids, and glycine.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: Lipid metabolites, amino acids, and ferritin are likely influenced by total red meat consumption in a relatively direct manner based on its nutrient composition.
In the paper
“Interestingly, heme biosynthesis, which is triggered by high iron availability, is an important glycine-using pathway, and high expression of heme-synthesizing enzymes was associated with low circulating glycine concentrations in humans (41).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [41] Wang-Sattler, 2012, Novel biomarkers for pre-diabetes identified by metabolomics, Mol Syst Biol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Still, an elevated diabetes risk was consistently observed for both unprocessed and processed red meat (1-3).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [1] Feskens, 2013, Meat consumption, diabetes, and its complications, Curr Diab Rep source
- Not checked yetcites [2] Pan, 2011, Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis, Am J Clin Nutr source
- Not checked yetcites [3] Benedinelli, 2013, Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study, Diabetologia source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Several studies found an inverse relation between red meat intake and the glycine concentration in biofluids (37,38).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [37] Xu, 2010, Identification of biochemical changes in lactovegetarian urine using 1H NMR spectroscopy and pattern recognition, Anal Bioanal Chem source
- Not checked yetcites [38] O’Sullivan, 2011, Dietary intake patterns are reflected in metabolomic profiles: potential role in dietary assessment studies, Am J Clin Nutr source
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In the paper
“Interestingly, heme biosynthesis, which is triggered by high iron availability, is an important glycine-using pathway, and high expression of heme-synthesizing enzymes was associated with low circulating glycine concentrations in humans (41).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [41] Wang-Sattler, 2012, Novel biomarkers for pre-diabetes identified by metabolomics, Mol Syst Biol source
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In the paper
“Because of the observational nature of our study, however, the possibility of residual confounding cannot be ruled out.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“For these 2 metabolites, therefore, a nonneglectable probability of type I error might have remained even after P value adjustment.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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“The prospective design of our study should have minimized various sources of bias (selection bias, reverse causation), and we controlled for a large set of potentially confounding factors in our analyses, including lifestyle, medication, dietary factors, and BMI.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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In the paper
“The large attenuation of the red meat-associated diabetes risk after adjustment for these potential mediators is consistent with the hypothesis that metabolic processes reflected in the circulating concentrations of these biomarkers take part in linking red meat consumption to type 2 diabetes incidence.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The prospective design of our study should have minimized various sources of bias (selection bias, reverse causation), and we controlled for a large set of potentially confounding factors in our analyses, including lifestyle, medication, dietary factors, and BMI.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In this study, however, we only selected biomarkers that were associated with red meat in both sexes to avoid spurious findings.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 15
- Probably not a substantial claim. 28
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our sensitivity analysis evaluating different subtypes of exposure revealed that the attenuation of the associated diabetes risk after mutual adjustment for all selected biomarkers was also significant if only unprocessed red meat (P = 0.007) or processed meat (P = 0.002) consumption was considered the exposure variable (reference: model 3).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When using the BMI-adjusted model 3 as reference, the attenuation was significant after adjustment for diacyl phosphatidylcholine 36:4, hydroxy-sphingomyelin 14:1, and glycine and borderline significant after adjustment for diacyl phosphatidylcholine 38:4 (P = 0.05) and ferritin (P = 0.06).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diacyl phosphatidylcholines 36:4 and 38:4 were highly correlated, and adjustment for diacyl phosphatidylcholine 36:4 did not further attenuate the association between total red meat consumption and type 2 diabetes risk if diacyl phosphatidylcholine 38:4 was also included in the same model (data not shown).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the fully adjusted model 3, the proportion of associated diabetes risk explainable by simultaneous biomarker adjustment (median and IQR from 1000 bootstrap replicates) was 49% (IQR: 29%, 89%) for unprocessed red meat consumption, whereas it was 71% (IQR: 45%, 115%) for processed meat consumption (Supplemental Figure 8).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, results were robust to the choice of selection strategy and P value adjustment method for glycine, ferritin, and phosphatidylcholines 36:4 and 38:4 and were somewhat sensitive to that choice for lysophosphatidylcholine 17:0 and hydroxy-sphingomyelin 14:1.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Biomarker selection
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our sensitivity analysis applying different P value adjustments and differently defined selection criteria showed that selection was very robust for most potential mediators but was somewhat sensitive to these choices for lysophosphatidylcholine 17:0 and hydroxy-sphingomyelin 14:1.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, high ferritin, low glycine, and altered hepaticderived lipids in the circulation were associated with both total red meat consumption and diabetes risk.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Components of red meat that were proposed to affect diabetogenic pathways include heme iron, cholesterol, fatty acids (FAs), amino acids, and advanced glycation and lipoxidation end products (1), among others.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [1] Feskens, 2013, Meat consumption, diabetes, and its complications, Curr Diab Rep source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Habitual diet was assessed with validated semiquantitative food-frequency questionnaires.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
What the sources say
- Not checked yetcites [16] Kroke, 1999, Am J Clin Nutr source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To reduce the probability of spurious associations, we selected biomarkers only if they were associated with total red meat consumption in both sexes in stratified analyses.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Statistical analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“In EPIC-Potsdam, metabolomic data were used to identify lipid metabolites and amino acids as biomarkers of diabetes risk (12).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [12] Floegel, 2013, Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach, Diabetes source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Reported associations of red meat consumption with biomarkers of inflammation, glucose metabolism, and hepatocellular and oxidative stress were mostly explainable by differences in BMI (7,8).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [7] Montonen, 2013, Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress, Eur J Nutr source
- Not checked yetcites [8] Ley, 2014, Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women, Am J Clin Nutr source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Recently, change in red meat consumption was observed to be related to a change in diabetes risk among 3 large US cohorts (4), suggesting a dose-response relation.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [4] Pan, 2013, Changes in red meat consumption and subsequent risk of type 2 diabetes mellitus: three cohorts of US men and women, JAMA Intern Med source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“On the basis of a previous evaluation of the reliability of measurements (23), we excluded metabolites below the limit of detection (n = 30) and those with very high analytic variance (n = 6).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Quantification of biomarkers
What the sources say
- Not checked yetcites [23] Floegel, 2011, Reliability of serum metabolite concentrations over a 4-month period using a targeted metabolomic approach, PLoS ONE source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“We selected mediators of the red meat-diabetes association according to 4 predefined mediation criteria (25) (see Supplemental Figure 1A).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Statistical analysis
What the sources say
- Not checked yetcites [25] Baron, 1986, The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations, J Pers Soc Psychol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The case-cohort design was accounted for by Prentice weighting (26).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Assessment of the red meat association with type 2 diabetes
What the sources say
- Not checked yetcites [26] Prentice, 1988, Aspects of the use of relative risk models in the design and analysis of cohort studies and prevention trials, Stat Med source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Furthermore, the red meat-associated diabetes risk was also observed in models in which red meat was substituted by foods with a similar macronutrient content (2), suggesting the relation to be independent of macronutrient composition of the diet.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [2] Pan, 2011, Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis, Am J Clin Nutr source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The P values were controlled for false discovery rate (FDR) within metabolite class by using the linear step-up method by Benjamini and Hochberg (30).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Biomarker selection
What the sources say
- Not checked yetcites [30] Benjamini, 1995, Controlling the false discovery rate—a practical and powerful approach to multiple testing, J R Stat Soc B source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Potential confounders to be included as covariates were a priori selected based on the literature on the association between red meat intake and diabetes risk (2, 3) and prior investigations in EPIC-Potsdam regarding risk factors of type 2 diabetes (5), dietary patterns (27), and determinants of metabolic profiles (28,29).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Assessment of the red meat association with type 2 diabetes
What the sources say
- Not checked yetcites [2] Pan, 2011, Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis, Am J Clin Nutr source
- Not checked yetcites [3] Benedinelli, 2013, Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study, Diabetologia source
- Not checked yetcites [5] Mühlenbruch, 2014, Update of the German Diabetes Risk Score and external validation in the German MONICA/KORA study, Diabetes Res Clin Pract source
- Not checked yetcites [27] Schulze, 2001, Dietary patterns and their association with food and nutrient intake in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study, Br J Nutr source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The red meat-associated diabetes risk was largely attenuated after adjustment for selected biomarkers, which is consistent with the presumed mediation hypothesis.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: Lipid metabolites, amino acids, and ferritin are likely influenced by total red meat consumption in a relatively direct manner based on its nutrient composition.
None of the sources cited for this claim have been checked yet.
In the paper
“In the literature, several lines of experimental evidence relate lipid metabolism to the pathogenesis of type 2 diabetes, among them a challenged mitochondrial metabolism, altered cellular signaling processes at the membrane, and modulation of gene expression (34,35).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Given that an observational study is generally prone to confounding and other sources of bias, interpretation of our findings with regard to biological paths is rather hypothesis generating than able to proof their causal nature (45).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [45] Hafeman, 2009, “Proportion explained”: a causal interpretation for standard measures of indirect effect?, Am J Epidemiol source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Thus, our results generate and underline experimentally testable hypotheses that can inform future dietary interventions in terms of design and biomarker assessment (46).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [46] Pearl, 2010, Causal Inference, Int J Biostat source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
None of the sources cited for this claim have been checked yet.
In the paper
“described by us and others (12,41).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Consistently, endogenous FA composition in several lipid compartments has been related to the risk of type 2 diabetes in several prospective cohorts, including EPIC-Potsdam (36).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [36] Kröger, 2011, Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study, Am J Clin Nutr source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Underlying mechanisms seem to be manifold and likely include oxidative stress and modulation of intracellular signaling cascades (44).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [44] Simcox, 2013, Iron and diabetes risk, Cell Metab source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This should have reduced the likelihood of false discoveries.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, estrogen is a modulator of mitochondrial function, and associations of red meat consumption with acylcarnitines might be sex specific.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Estrogen is a modulator of mitochondrial function.
In the paper
“For example, advanced glycation end products, trans FA, nitrites and nitrates, and methylamines are discussed as meat type-specific mediators (1).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [1] Feskens, 2013, Meat consumption, diabetes, and its complications, Curr Diab Rep source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, we evaluated the robustness of our results in a bootstrapping procedure.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Still, random measurement error may have masked some associations.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, there is the possibility that cases remained undiagnosed during follow-up.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, this misclassification should not bias the associations between red meat consumption and diabetes given that false-positive case definitions should have been rare due to the strict verification procedures in EPIC-Potsdam (49).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [49] Rothman, 2008
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This effect, however, may reflect mitochondrial metabolism under acute dietary challenge (48) rather than effects of long-term habitual diet as assessed in our study.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [48] Krug, 2012, The dynamic range of the human metabolome revealed by challenges, FASEB J source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, FFQs showed good reliability and relative validity to assess meat intake, and investigated metabolites showed good reliability in validation studies (23).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [23] Floegel, 2011, Reliability of serum metabolite concentrations over a 4-month period using a targeted metabolomic approach, PLoS ONE source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Still, the a priori design of our search strategy included arbitrary decisions, and P values lose their straightforward interpretability with regard to the probability of type I errors in a step-by-step selection procedure such as ours (47).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [47] Gelman, 2014, The statistical crisis in science, Am Sci source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Albeit large, the set of targeted metabolites was not exhaustive with regard to potential mediating mechanisms.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, acylcarnitines have previously been linked to red meat intake (38).”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [38] O’Sullivan, 2011, Dietary intake patterns are reflected in metabolomic profiles: potential role in dietary assessment studies, Am J Clin Nutr source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results, however, cannot prove causality of the observed associations and, where possible, the suggested single relations should inform the design and the biomarker assessment of interventional studies.”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
Mechanisms underlying the relation of red meat consumption with diabetes risk remain largely unknown.
“Yet, mechanisms underlying the relation of red meat consumption with diabetes risk remain largely unknown.”
The authors state this as an assumption.
Lipid metabolites, amino acids, and ferritin are likely influenced by total red meat consumption in a relatively direct manner based on its nutrient composition.
“Lipid metabolites, amino acids, and ferritin were included as potential mediators of the red meat-associated diabetes risk because these biomarkers were assumed to be likely influenced by total red meat consumption in a relatively direct manner based on its nutrient composition (Supplemental Figure 1B).”
The paper relies on this without support.
Circulating lipid metabolites reflect synthesis activity of lipid classes as well as availability and metabolism of specific fatty acids in the liver.
“Circulating lipid metabolites reflect synthesis activity of lipid classes as well as availability and metabolism of specific FAs in the liver.”
The paper relies on this without support.
Total red meat as defined in the study is a large and heterogeneous food group.
“Total red meat as defined in our study is a large and heterogeneous food group.”
The paper relies on this without support.
Estrogen is a modulator of mitochondrial function.
“Furthermore, estrogen is a modulator of mitochondrial function, and associations of red meat consumption with acylcarnitines might be sex specific.”
The paper relies on this without support.
This is the first study evaluating a large set of metabolites as potential mediators of the association between red meat intake and diabetes risk, including several lipid metabolites, amino acids, and ferritin.
“To our knowledge, this is the first study evaluating a large set of metabolites as potential mediators of the association between red meat intake and diabetes risk, including several lipid metabolites, amino acids, and ferritin.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Mechanisms require further study, but risk for diabetes may be linked to iron content179, 180 as well as possibly lipid and amino acid metabolites, advanced glycation end products, trimethylamine N-oxide, and nitrates/nitrites.181, 182”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [181]
In the citing paper
“For example, intake of yogurt, but not milk, is consistently associated with lower incidence of diabetes; while intake of cheese, which has high calorie, fat, and saturated fat content, also associates with lower diabetes risk in several although not all studies.57, 179-184, 224, 226-228”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [181]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > DISCUSSION
“| Energy, MJ/d | 7369 6 1845 | 7428 6 1664 | 7455 6 1709 | 10,539 6 2651 | 10,574 6 2386 | 10,911 6 2703 |”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Study population
“implausible self-reported energy intake (,3.35 MJ/d or .25.12 MJ/d)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Abstract
“Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk.The red meat-associated diabetes risk was significantly (P , 0.001) attenuated after simultaneous adjustment for these biomarkers”
§ Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes 1-4 > Attenuation of the red meat-associated diabetes risk by selected biomarkers
“Therefore, mutual biomarker-adjusted models did not include diacyl phosphatidylcholine 36:4.”
Citations
Cites
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Epidemiology: Beyond the Basics
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Self-citationThe Statistical Crisis in Science
Gelman, A., & Loken, E. (2014) · American Scientist · doi:10.1511/2014.111.460 · Cited by 963
Glycine metabolism in animals and humans: implications for nutrition and health
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Cited by
Sorted by citations
Mozaffarian, D. (2016) · Circulation · doi:10.1161/circulationaha.115.018585 · Cited by 2,216
“lipid and amino acid metabolites, advanced glycation end products, trimethylamine N-oxide, and nitrates/nitrites.(181,182) In sum, these findings provide little support for conven-”
Impact of Dietary Fiber Consumption on Insulin Resistance and the Prevention of Type 2 Diabetes
Weickert, M. O., & Pfeiffer, A. F. H. (2018) · Journal of Nutrition · doi:10.1093/jn/nxx008 · Cited by 568
Best (but oft-forgotten) practices: mediation analysis ,
Fairchild, A. J., & McDaniel, H. L. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.152546 · Cited by 548
“Indeed, the impetus behind mediation by design analyses aligns well with the defined scope of this Journal that seeks, in part, to “describe scientific mechanisms [emphasis added] . of dietary interventions in the context of disease prevention.””
Influentialde Mello, V. D., Paananen, J., Lindström, J., Lankinen, M. A., Shi, L. S., Kuusisto, J., Pihlajamäki, J., Auriola, S. O. K., Lehtonen, M., Rolandsson, O., et al. (2017) · Scientific Reports · doi:10.1038/srep46337 · Cited by 395
Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases
Alves, A., Bassot, A., Bulteau, A., Pirola, L., & Morio, B. (2019) · Nutrients · doi:10.3390/nu11061356 · Cited by 385
“An investigation conducted on 2681 individuals of the sub-cohort European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam [95] showed that total consumption of red meat was significantly associated with the risk of T2DM, after adjustment for age, sex, lifestyle, diet, and body mass index.”
MethodResult
Metadata
- Authors
- Wittenbecher, C., Mühlenbruch, K., Kröger, J., Jacobs, S., Kuxhaus, O., Floegel, A., Fritsche, A., Pischon, T., Prehn, C., Adamski, J., Joost, H.-G., Boeing, H., & Schulze, M. B.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Schulze, Matthias B
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 101
- Issue
- 6
- Pages
- 1241-1250
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2128199390
- Semantic Scholar
- 787e907852c477230bad79180e71e6df48f3d1d4
- Cited by
- 120
- References
- 54
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 15 · 2021: 10 · 2020: 14 · 2019: 15 · 2018: 12 · 2017: 11 · 2016: 11 · 2015: 6
- FWCI
- 14.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Federal Ministry of Science and Research (01 EA 9401)
- European Union (SOC 95201408 05 F02)
- EPIC–Potsdam Study
- German Cancer Aid (70-2488-Ha I)
- European Community (SOC 98200769 05 F02)
- German Federal Ministry of Education and Research (BMBF)
- German Center for Diabetes Research
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- consumption, type 2 diabetes, amino acids, glycine, lipid metabolites, acylcarnitines, glycerophospholipids, sphingomyelin, ferritin, processed meat, hepatic lipid metabolism, blood metabolites, EPIC-Potsdam cohort, biomarkers of diabetes risk, saturated fatty acids, lysophosphatidylcholine
- MeSH terms
- Adult, Amino Acids, Energy Intake, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diet, Female, Ferritins, Follow-Up Studies, Humans, Life Style, Male, Meat, Middle Aged, Prospective Studies, Risk Factors, Reproducibility of Results, Multicenter Studies as Topic, Biomarkers, Body Mass Index, Incidence, Linear Models, Proportional Hazards Models, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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