Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

Razquín, Cristina; Ruiz‐Canela, Miguel; Clish, Clary B.; Li, Jun; Toledo, Estefanía; Dennis, Courtney; Liang, Liming; Salas‐Huetos, Albert; Pierce, Kerry A.; Guasch‐Ferré, Marta; Corella, Dolores; Ros, Emilio; Estruch, Ramón; Gómez‐Gracia, Enrique; Fitó, Montserrat; Lapetra, José; Romaguera, Dora; Alonso‐Gómez, Ángel M.; Serra‐Majem, Lluís; Salas‐Salvadó, Jordi; Hu, Frank B.

doi:10.1186/s12933-019-0958-2

Cited by 40 publications

(35 citation statements)

References 24 publications

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“…Furthermore, the different associations between animal or plant proteins and mortality risk could be due to the differences in amino acid composition. Plant proteins contain lower amounts of lysine and histidine amino acids than animal proteins; high intake of these amino acids has been shown to increase secretion of lipoproteins containing apo B 88. Therefore, intake of plant proteins could be associated with protection against cardiovascular diseases through this mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Plant proteins contain lower amounts of lysine and histidine amino acids than animal proteins; high intake of these amino acids has been shown to increase secretion of lipoproteins containing apo B. 88 Therefore, intake of plant proteins could be associated with protection against cardiovascular diseases through this mechanism. In addition to amino acids, plant proteins are rich in non-essential amino acids such as arginine and pyruvate precursors, which in turn can lead to upregulation of glucagon and downregulation of insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

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Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies

Naghshi

Sadeghi

Willett

et al. 2020

BMJ

202

134

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ObjectiveTo examine and quantify the potential dose-response relation between intake of total, animal, and plant protein and the risk of mortality from all causes, cardiovascular disease, and cancer.DesignSystematic review and meta-analysis of prospective cohort studies.Data sourcesPubMed, Scopus, and ISI Web of Science until December 2019, and references of retrieved relevant articles.Study selectionProspective cohort studies that reported the risk estimates for all cause, cardiovascular, and cancer mortality in adults aged 18 or older.Data synthesisRandom effects models were used to calculate pooled effect sizes and 95% confidence intervals for the highest versus lowest categories of protein intake and to incorporate variation between studies. Linear and non-linear dose-response analyses were done to evaluate the dose-response relations between protein intake and mortality.Results32 prospective cohort studies were included in the systematic review and 31 in the meta-analysis. During the follow-up period of 3.5 to 32 years, 113 039 deaths (16 429‬ from cardiovascular disease and 22 303‬ from cancer) occurred among 715 128 participants. Intake of total protein was associated with a lower risk of all cause mortality (pooled effect size 0.94, 95% confidence interval 0.89 to 0.99, I2=58.4%, P<0.001). Intake of plant protein was significantly associated with a lower risk of all cause mortality (pooled effect size 0.92, 95% confidence interval 0.87 to 0.97, I2=57.5%, P=0.003) and cardiovascular disease mortality (pooled hazard ratio 0.88, 95% confidence interval 0.80 to 0.96, I2=63.7%, P=0.001), but not with cancer mortality. Intake of total and animal protein was not significantly associated with risk of cardiovascular disease and cancer mortality. A dose-response analysis showed a significant inverse dose-response association between intake of plant protein and all cause mortality (P=0.05 for non-linearity). An additional 3% energy from plant proteins a day was associated with a 5% lower risk of death from all causes.ConclusionsHigher intake of total protein was associated with a lower risk of all cause mortality, and intake of plant protein was associated with a lower risk of all cause and cardiovascular disease mortality. Replacement of foods high in animal protein with plant protein sources could be associated with longevity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies

Naghshi

Sadeghi

Willett

et al. 2020

BMJ

202

134

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“…Betaine, for instance, which was previously found to have a protective role in T2DM 53 , appears to have a causal effect on glucose. Alterations of lysine levels were also already associated to T2DM risk 63 . Another interesting metabolite, which shows bidirectional causal effect on T2DM in our study, is mannose, a hexose with essential function for glycoprotein synthesis.…”

Section: Discussionmentioning

confidence: 94%

Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes

Porcu

Gilardi

Darrous

et al. 2021

Sci Rep

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The number of people affected by Type 2 diabetes mellitus (T2DM) is close to half a billion and is on a sharp rise, representing a major and growing public health burden. Given its mild initial symptoms, T2DM is often diagnosed several years after its onset, leaving half of diabetic individuals undiagnosed. While several classical clinical and genetic biomarkers have been identified, improving early diagnosis by exploring other kinds of omics data remains crucial. In this study, we have combined longitudinal data from two population-based cohorts CoLaus and DESIR (comprising in total 493 incident cases vs. 1360 controls) to identify new or confirm previously implicated metabolomic biomarkers predicting T2DM incidence more than 5 years ahead of clinical diagnosis. Our longitudinal data have shown robust evidence for valine, leucine, carnitine and glutamic acid being predictive of future conversion to T2DM. We confirmed the causality of such association for leucine by 2-sample Mendelian randomisation (MR) based on independent data. Our MR approach further identified new metabolites potentially playing a causal role on T2D, including betaine, lysine and mannose. Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. In addition, our study revealed a reverse causal effect of metabolites such as glutamic acid and alanine. Collectively, these findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.

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“…As stated by Sell et al [ 10 ], α-AA is, unlike its precursor, allysine, a stable final product from lysine, and this is actually corroborated by our present results. Recent studies emphasized the role of α-AA as an early indicator of type 2 diabetes [ 8 , 30 ]. The results from the present study underline the molecular connection between elevated glucose concentrations and the formation of α-AA in HSA.…”

Section: Resultsmentioning

confidence: 99%

Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations

et al. 2021

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Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed.

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Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

Cited by 40 publications

References 24 publications

Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies

Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies

Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes

Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations

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