Dataset Information

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

ABSTRACT: The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year changes in arginine (adjusted hazard ratio [HR] per SD 0.68, 95% confidence interval [CI] 0.49, 0.95; Q4 vs. Q1 0.46, 95% CI 0.21, 1.04; P trend = 0.02) and arginine/ADMA ratio (adjusted HR per SD 0.73, 95% CI 0.51, 1.04; Q4 vs. Q1 0.52, 95% CI 0.22, 1.25; P trend = 0.04) were associated with a lower risk of T2D. Positive changes of citrulline and ornithine, and negative changes in SDMA and arginine/(ornithine + citrulline) were associated with concurrent 1-year changes in homeostatic model assessment of insulin resistance. Individuals in the low-fat-diet group had a higher risk of T2D for 1-year changes in NMMA than individuals in Mediterranean-diet groups (P interaction = 0.02). We conclude that arginine bioavailability is important in T2D pathophysiology.

SUBMITTER: Yu E

PROVIDER: S-EPMC6329637 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

Yu Edward E Ruiz-Canela Miguel M Razquin Cristina C Guasch-Ferré Marta M Toledo Estefania E Wang Dong D DD Papandreou Christopher C Dennis Courtney C Clish Clary C Liang Liming L Bullo Monica M Corella Dolores D Fitó Montserrat M Gutiérrez-Bedmar Mario M Lapetra José J Estruch Ramón R Ros Emilio E Cofán Montserrat M Arós Fernando F Romaguera Dora D Serra-Majem Lluis L Sorlí Jose V JV Salas-Salvadó Jordi J Hu Frank B FB Martínez-González Miguel A MA

Diabetes, obesity & metabolism 20181002 2

The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year ch ...[more]

PMID: 30146690

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Project description:AIMS/HYPOTHESIS:Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial. METHODS:We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n?=?273), a MedDiet+nuts (n?=?324) or a control diet (n?=?295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial. RESULTS:Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend?=?0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD?=?1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p?= 0.005 vs the control group). CONCLUSIONS/INTERPRETATION:Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence. Clinical trial number: SRCTN35739639 ( www.controlled-trials.com ).

Project description:Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes.We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations.We observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model.In agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.

Project description:BackgroundDiet quality has been linked to obesity, but this relationship remains unclear in individuals with type 2 diabetes (T2D). The aim of this study is to examine the association between diet quality and obesity in Chinese adults with T2D.MethodsBetween April and November 2016, a total of 211 Chinese T2D adults who underwent assessment of diabetes-related treatment goals and metabolic control were recruited into two groups based on their body mass index (BMI): obese group (BMI ≥30 kg/m2) and non-obese group (BMI = 18.5-24.9 kg/m2). Diet quality indices including Alternate Healthy Eating Index-2010 (AHEI-2010), Diet Quality Index-International (DQI-I), and Dietary Approach to Stop Hypertension (DASH) score, were derived from a validated food frequency questionnaire.ResultsObese T2D patients had significantly lower AHEI-2010 (P < 0.001), DQI-I (P < 0.001), and DASH total scores (P = 0.044) than their non-obese counterparts, independent of age and sex. They also had higher total energy (P < 0.001), protein percentage of energy (P = 0.023), and meat, poultry and organ meat (P < 0.001), but lower vegetable (P = 0.014) intakes. Our multivariate logistic regression analyses demonstrated that the AHEI-2010, but not DQI-I and DASH, total score had an inverse association with obesity, independent of sociodemographics, anti-diabetic medication use, physical activity level and total energy intake (odds ratio [OR] per standard deviation (1-SD) increase: 0.95, 95% confidence interval [CI]: 0.91-0.99, P = 0.020). This association remained significant after further adjustment for glycemic control. Inverse associations were also found between obesity and multivariate-adjusted component scores, including AHEI-2010 red/processed meat (OR per 1-SD: 0.71, 95% CI: 0.51-0.99, P = 0.044), DQI-I variety (OR per 1-SD: 0.63, 95% CI: 0.46-0.86, P = 0.004), and DASH red/processed meat (OR per 1-SD: 0.57, 95% CI: 0.38-0.84, P = 0.005).ConclusionsBetter diet quality, as characterized by higher AHEI-2010 scores, was associated with lower odds of obesity in Chinese adults with T2D. Dietary patterns reflecting high consumption of plant-based foods and low consumption of animal-based, high-fat, and processed foods may be imperative to optimize nutritional guidance for obesity management in this population.

Dataset Information

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

Publications

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

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