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Introduction: A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). Objectives: We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. Methods: All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. Results: A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. Conclusion: These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Microbiota , Biomarcadores , Diabetes Mellitus Tipo 2/epidemiologia , Microbioma Gastrointestinal/genética , Humanos , RNA Ribossômico 16S/genéticaRESUMO
PURPOSE: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development. METHODS: We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score. RESULTS: FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04-3.37) in the Training set, and an HR of 2.14 (95% CI 1.50-2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (p < 0.05). CONCLUSION: Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker. CLINICAL TRIALS.GOV. IDENTIFIER: NCT00924937.
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Doença das Coronárias , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Biomarcadores , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Ácidos Graxos , HumanosRESUMO
Pet ownership positively influences clinical outcomes in cardiovascular prevention. Additionally, cardiovascular disease (CVD) has been previously linked to microbiota dysbiosis. We evaluated the influence of owning a pet and its relationship with the intestinal microbiota. We analyzed the gut microbiota from 162 coronary patients from the CORDIOPREV study (NCT00924937) according to whether they owned pets (n = 83) or not (n = 79). The pet-owner group was further divided according to whether they owned dogs only (n = 28) or not (n = 55). A 7-item pet-owners test score was used. Patients who owned pets had less risk of metabolic syndrome (MetS) (OR = 0.462) and obesity (OR = 0.519) and were younger (p < 0.001) than patients who did not own pets. Additionally, patients who owned dogs had less risk of MetS (OR = 0.378) and obesity (OR = 0.418) and were younger (p < 0.001) than patients who did not own pets. A preponderance of the genera Serratia and Coprococcus was found in the group of owners, while the genera Ruminococcus, an unknown genus of Enterobacteriaceae and Anaerotruncus were preponderant in the group of non-owners. In patients who owned dogs, Methanobrevibacter and two more genera, Coprococcus and Oscillospira, were more common. Our study suggests that the prevalence of MetS and obesity in CVD patients is lower in pet owners, and that pet ownership could be a protective factor against MetS through the shaping of the gut microbiota. Thus, owning a pet could be considered as a protective factor against cardiometabolic diseases.
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Diabetes Mellitus Tipo 2/dietoterapia , Microbioma Gastrointestinal , Índice de Massa Corporal , Peso Corporal , Dieta com Restrição de Gorduras , Dieta Mediterrânea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Comportamento de Redução do Risco , Circunferência da CinturaRESUMO
MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group's differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio [HR]low versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease.
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BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.
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Doenças Cardiovasculares/dietoterapia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta com Restrição de Gorduras , Dieta Mediterrânea , MicroRNAs/sangue , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Método Simples-Cego , Adulto JovemRESUMO
SCOPE: It is hypothesized that decreased advanced glycation end products (AGEs) levels could affect type 2 diabetes mellitus (T2DM) remission in newly diagnosed patients through the consumption of two healthy diets. METHODS AND RESULTS: Patients from CORDIOPREV study, all with previous cardiovascular events, with T2DM at the beginning of the study are included. Patients are randomized to a Mediterranean or a low-fat diet for five years. No different diabetes remission rates are found among diets. Serum methylglioxal (MG) and carboximethyllysine (CML), levels dietary AGE, as well as gene expression of AGER1 and RAGE are measured. Serum MG decreases only after the consumption of the Mediterranean diet. Moreover, a COX regression analysis shows that each SD decrease in the MG, occurring after the Mediterranean diet, increases the probability of T2DM remission with HR:2.56(1.02-6.25) and p = 0.046 and each SD increase in disposition index at baseline increases the probability of remission with HR:1.94(1.32-2.87) and p = 0.001. CONCLUSIONS: It is demonstrated that the reduction of serum AGEs levels and the modulation of its metabolism, occurring after the consumption of a Mediterranean diet, might be involved in the molecular mechanism underlying the T2DM remission of newly diagnosed patients with coronary heart disease.
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Doença das Coronárias/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Mediterrânea , Produtos Finais de Glicação Avançada/sangue , Antígenos de Neoplasias/genética , Doença das Coronárias/sangue , Diabetes Mellitus Tipo 2/sangue , Dieta com Restrição de Gorduras , Feminino , Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/genética , Humanos , Resistência à Insulina , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/genética , Aldeído Pirúvico/sangue , Receptor para Produtos Finais de Glicação Avançada/genética , Resultado do TratamentoRESUMO
SCOPE: The differences between the baseline gut microbiota of patients who developed type 2 diabetes (T2D) consuming a low-fat (LF) or a Mediterranean (Med) diet are explored and risk scores are developed to predict the individual risk of developing T2D associated with the consumption of LF or Med diet. METHODS AND RESULTS: All the patients from the CORDIOPREV study without T2D at baseline (n = 462) whose fecal sample are available, are included. Gut microbiota is analyzed by 16S sequencing and the risk of T2D after a median follow-up of 60 months assessed by Cox analysis. Linear discriminant analysis effect size (LEfSe) analysis shows a different baseline gut microbiota in patients who developed T2D consuming LF and Med diets. A higher abundance of Paraprevotella, and lower Gammaproteobacteria and B. uniformis are associated with T2D risk when an LF diet is consumed. In contrast, higher abundances of Saccharibacteria, Betaproteobacteria, and Prevotella are associated with T2D risk when a Med diet is consumed. CONCLUSION: The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of T2D development, which may be used for selecting personalized dietary models to prevent T2D.
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Diabetes (T2DM) is a major global health issue, and developing new approaches to its prevention is of paramount importance. We hypothesized that abnormalities in lipid metabolism are involved in alpha-cell deregulation. We therefore studied the metabolic factors underlying alpha-cell dysfunction in T2DM progression after a dietary intervention (Mediterranean and low-fat). Additionally, we evaluated whether postprandial glucagon levels may be considered as a predictive factor of T2DM in cardiovascular patients. Non-T2DM participants from the CORDIOPREV study were categorized by tertiles of the area under the curve (AUC) for triacylglycerols and also by tertiles of AUC for glucagon. Our results showed that patients with higher triacylglycerols levels presented elevated postprandial glucagon (P = 0.009). Moreover, we observed higher risk of T2DM (hazard ratio: 2.65; 95% confidence interval: 1.56-4.53) in subjects with elevated glucagon. In conclusion, high postprandial lipemia may induce alpha-cell dysfunction in cardiovascular patients. Our results also showed that postprandial glucagon levels could be used to predict T2DM development.
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Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Glucagon/metabolismo , Hiperlipidemias/metabolismo , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Feminino , Glucagon/metabolismo , Humanos , Hiperlipidemias/complicações , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Estudos Prospectivos , Triglicerídeos/metabolismoRESUMO
AIM: Our objective was to investigate the role of two healthy diets in modulating the risk of type 2 diabetes (T2DM) development associated with each prediabetes diagnosis criteria in coronary heart disease patients. Additionally, we explored the pathophysiological characteristics and the risk of developing T2DM in patients with different prediabetes criteria. METHODS: We included 462 patients from the CORDIOPREV study without T2DM at baseline: 213 had prediabetes defined by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (PreDM-IFG/IGT); 180 had prediabetes by isolated hemoglobin glycated plasma levels (PreDM-isolated-HbA1c), and 69 were not prediabetics (non-PreDM), according to the American Diabetes Association criteria. Patients were randomized to consume either a Mediterranean or a low-fat diet. We performed a COX proportional hazards regression analysis to determine the T2DM risk according to diet and the prediabetes criteria after a median follow-up of 60 months. RESULTS: We found higher T2DM risk (HR: 2.98; 95% CI 1.27-6.98) in PreDM-IFG/IGT than in PreDM-isolated-HbA1c (HR: 2.31; 95% CI 0.97-5.49) compared with non-PreDM. Long-term consumption of a low-fat diet was associated with a lower risk of T2DM when compared to the Mediterranean diet in the PreDM-IFG/IGT group (HR: 3.20; 95% CI 0.75-13.69 versus HR: 4.70; 95% CI 1.12-19.67, respectively). Moreover, we found the highest risk of T2DM development associated with patients who had both IFG and IGT (HR: 2.15; 95% CI 1.11-4.16). Patients who had both IFG and IGT and consumed a low-fat diet had a lower T2DM risk than those who consumed a Mediterranean diet (HR: 1.53; 95% CI 0.53-4.39 versus HR: 3.33; 95% CI 1.34-8.30, respectively). CONCLUSION: Our results suggest that the type of diet consumed may modulate the risk of T2DM development according to the prediabetes diagnosis criteria. Specifically, our study showed that the consumption of a low-fat diet was more beneficial than a Mediterranean diet in patients with IFG and IGT. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.govNCT00924937.
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Diabetes Mellitus Tipo 2/prevenção & controle , Dieta com Restrição de Gorduras/estatística & dados numéricos , Dieta Mediterrânea/estatística & dados numéricos , Estado Pré-Diabético/dietoterapia , Estado Pré-Diabético/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Dieta com Restrição de Gorduras/métodos , Feminino , Seguimentos , Intolerância à Glucose/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND AND AIMS: Recent evidence suggests that postprandial hypertriglyceridemia (PPT) is associated with the incidence of CVD. Several non-modifiable factors (genetics, age, gender) and lifestyle factors (physical activity, smoking, regular alcohol) have shown their ability to modulate PPT. We evaluate the influence of regular alcohol intake, physical activity and smoking habit modulating PPT in the CORDIOPREV study (NCT00924937). METHODS: 1002 patients were subject to an oral fat load test meal and serial blood samples were drawn at 0, 1, 2, 3 and 4â¯h during postprandial state. A PPT concentration above 2.5â¯mmol/L (220â¯mg/dL) at any time point has been established as a detrimental response. Alcohol consumption was defined as non-drinkers, moderate and severe intake; regular physical activity exceeding than or lower than 1000 MET/week; smoking habit was classified in current, never, recent ex-smokers and long-term ex-smokers. RESULTS: The prevalence of undesirable PPT response was 68% in current, 58% in recent ex-smokers, 49% in long-term ex-smokers and 48% in never smokers (pâ¯<â¯0.001). Current and recent ex-smokers displayed higher PPT response as well as a greater area under the curve (AUC) and higher incremental (iAUC) of triglycerides (TG) compared with long-term ex-smokers and never smokers (pâ¯<â¯0.05), without differences among these subgroups. No differences were observed in the magnitude of PPT according to regular physical activity or alcohol intake habits. CONCLUSIONS: Smoking is an independent risk factor modulating the magnitude of PPT. However, after tobacco cessation, ex-smokers show a progressive decrease on their PPT to reach levels similar to those of never smokers.
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Doença das Coronárias/epidemiologia , Hipertrigliceridemia/epidemiologia , Estilo de Vida , Período Pós-Prandial , Fumar/efeitos adversos , Triglicerídeos/sangue , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores/sangue , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/prevenção & controle , Ex-Fumantes , Exercício Físico , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , não Fumantes , Prevalência , Estudos Prospectivos , Fatores de Risco , Fumantes , Fumar/epidemiologia , Abandono do Hábito de Fumar , Espanha/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: We try to explore whether long-term consumption of two healthy dietary patterns (low-fat [LF] diet or Mediterranean diet [MedDiet]) interacts with the apolipoprotein E (APOE) single-nucleotide polymorphisms (SNPs: rs439401, rs440446 and rs7412) modulating postprandial hypertriglyceridemia (ppHTG) in coronary heart disease (CHD) patients. METHODS AND RESULTS: We selected patients from the CORDIOPREV study with genotyping and who underwent an oral fat load test (FLT) at baseline and after 3 years follow-up (n = 506). After 3 years of follow-up, we found a gene-diet interaction between the APOE rs439401 SNP and MedDiet. Specifically, T-allele carriers in the MedDiet group showed a more significant decrease in postprandial triglycerides (TG: P = 0.03) and large triacylglycerol-rich lipoproteins (TRLs) TG (large TRLs TG; P = 0.01) compared with CC subjects. Consistently, the area under the curve of TG (AUC-TG; P-interaction = 0.03) and AUC-large TRLs TG (P-interaction = 0.02) were significantly lower in T-allele carriers compared with CC subjects. CONCLUSIONS: The long-term consumption of a MedDiet modulates ppHTG through APOE genetic variants in CHD patients. This gene-diet interaction may contribute to a more precise dietary advice in CHD patients.
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Apolipoproteínas E/genética , Doença das Coronárias/complicações , Dieta Mediterrânea , Hipertrigliceridemia/genética , Hipertrigliceridemia/prevenção & controle , Alelos , Glicemia , Doença das Coronárias/genética , Dieta com Restrição de Gorduras , Feminino , Seguimentos , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Período Pós-Prandial , TriglicerídeosAssuntos
Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Glucagon/fisiologia , Estado Pré-Diabético/dietoterapia , Estado Pré-Diabético/patologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/mortalidade , Dieta Mediterrânea , Intervalo Livre de Doença , Feminino , Glucagon/sangue , Células Secretoras de Glucagon/patologia , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina , Células Secretoras de Insulina/patologia , Células Secretoras de Insulina/fisiologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Aging is an important determinant of the rate of atherosclerosis development, mainly through low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in fasting and postprandial states. OBJECTIVE: We aimed to study the effects of dietary fat on endotoxemia in healthy older adults. MATERIALS AND METHODS: Twenty healthy older adults were randomized to three diets, lasting three-weeks each, using a crossover design: 1. A Mediterranean diet enriched in MUFA with virgin olive oil. 2. An SFA-rich diet. 3. A low-fat high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid of plant origin) (CHO-PUFA diet). At the end of each period, after a 12-h fast, the subjects received a meal with a composition similar to the dietary period just completed. We determined the fasting and the postprandial plasma levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP). RESULTS: In the fasting state, we observed lower LPS plasma levels after the consumption of the CHO-PUFA diet (P=0.046) in comparison with the consumption of the Med and SFA-rich diets. In the postprandial measurements, we observed a statistically significant increase in plasma levels of LPS (P=0.044) and a decrease in LBP (P=0.003) after the intake of the CHO-PUFA meal, whereas no postprandial changes were observed after the ingestion of the Med and SFA-rich meals. CONCLUSION: Our results, together with those obtained in a previous study, support the concept that the consumption of the Med Diet, in contrast to a low-fat PUFA diet, constitutes a more suitable dietary lifestyle for preventing the development of atherosclerosis in a population at risk, such as older adults.