Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D).
The aim of this study was to test whether baseline metabolites can additionally improve the ...prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D.
We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography–tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR–related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models.
We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline 0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73) and during a 1-y period 0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62). The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors.
The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Few studies have analyzed the associations between impulsivity and dietary patterns. Some of them have shown a cross-sectional inverse relationship between impulsivity and healthy diet scores, ...whereas others reported a positive association with unhealthy dietary assessments. We aimed to examine longitudinal associations of impulsivity trait with adherence to healthy and unhealthy dietary patterns in older participants at high risk of cardiovascular disease over 3 years of follow-up. A 3-year prospective cohort analysis within the PREDIMED-Plus-Cognition study conducted in 4 PREDIMED-Plus study centers was performed. The PREDIMED-Plus study aimed to test the beneficial effect of a lifestyle intervention on the primary prevention of cardiovascular disease. The participants with overweight or obesity and metabolic syndrome included in the present study (n = 462; mean age of 65.3 years; 51.5% female) completed both the UPPS-P Impulsive Behavior Scale (range: 0-236 points) and the 143-item Food Frequency Questionnaire at baseline, 1-year and 3-years of follow-up. Ten diet scores assessing healthy and unhealthy dietary patterns were evaluated. Linear mixed models were performed adjusting by several confounders to study the longitudinal associations between impulsivity trait and adherence to dietary pattern scores over 3 years of follow-up (also assessing interactions by sex, age, and intervention group). Impulsivity were negatively associated with adherence to the Healthy Plant-Based beta = -0.92 (95%CI -1.67, -0.16), Mediterranean beta = -0.43 (95%CI -0.79, -0.07), Energy-Restricted Mediterranean beta = -0.76 (95%CI -1.16, -0.37), Alternative Healthy Eating Index beta = -0.88 (95%CI -1.52, -0.23), Portfolio beta = -0.57 (95%CI -0.91, -0.22), and DASH beta = -0.50 (95%CI -0.79, -0.22) diet scores over 3 years of follow-up, whereas impulsivity was positively related with adherence to the unhealthy Western diet beta = 1.59 (95%CI 0.59, 2.58) over time. An interaction by intervention group was found, with those participants in the intervention group with high impulsivity levels having lower adherence to several healthy dietary patterns. Heightened impulsivity was longitudinally associated with lower adherence to healthy dietary patterns and higher adherence to the Western diet over 3 years of follow-up. Furthermore, nutritional intervention programs should consider impulsivity as a relevant factor for the intervention success.
BACKGROUND:Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL ...lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively.
METHODS:We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched (1:2) to control patients by sex, age, intervention group, body mass index, and follow-up time. We investigated 2 individual manifestations (myocardial infarction, unstable angina) as secondary outcomes. We measured the following functional characteristicsHDL cholesterol concentration (in plasma); cholesterol efflux capacity; antioxidant ability, measured by the HDL oxidative-inflammatory index; phospholipase A2 activity; and sphingosine-1-phosphate, apolipoproteins A-I and A-IV, serum amyloid A, and complement 3 protein (in apolipoprotein B–depleted plasma). We used conditional logistic regression models adjusted for HDL cholesterol levels and cardiovascular risk factors to estimate odds ratios (ORs) between 1-SD increments in HDL functional characteristics and clinical outcomes.
RESULTS:Low values of cholesterol efflux capacity (OR1SD, 0.58; 95% CI, 0.40–0.83) and low levels of sphingosine-1-phosphate (OR1SD, 0.70; 95% CI, 0.52–0.92) and apolipoprotein A-I (OR1SD, 0.58; 95% CI, 0.42–0.79) were associated with higher odds of acute coronary syndrome. Higher HDL oxidative inflammatory index values were marginally linked to acute coronary syndrome risk (OR1SD, 1.27; 95% CI, 0.99–1.63). Low values of cholesterol efflux capacity (OR1SD, 0.33; 95% CI, 0.18–0.61), sphingosine-1-phosphate (OR1SD0.60; 95% CI0.40–0.89), and apolipoprotein A-I (OR1SD, 0.59; 95% CI, 0.37–0.93) were particularly linked to myocardial infarction, whereas high HDL oxidative-inflammatory index values (OR1SD, 1.53; 95% CI, 1.01–2.33) and low apolipoprotein A-I levels (OR1SD, 0.52; 95% CI, 0.31–0.88) were associated with unstable angina.
CONCLUSIONS:Low cholesterol efflux capacity values, pro-oxidant/proinflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were associated with increased odds of acute coronary syndrome and its manifestations in individuals at high cardiovascular risk.
CLINICAL TRIAL REGISTRATION:URLhttps://www.controlled-trials.com/ISRCTN35739639. Unique identifierISRCTN35739639.
Ultra-processed food and drink products (UPF) consumption has been associated with obesity and its-related comorbidities. Excess of visceral fat, which appears with increasing age, has been ...considered as the culprit contributing to adiposity-associated adverse health outcomes. However, none of previous studies elucidated the link between UPF and directly quantified adiposity and its distribution. We aimed to prospectively investigate the association between concurrent changes in UPF consumption and objectively assessed adiposity distribution.
A subsample of 1485 PREDIMED-Plus participants (Spanish men and women aged 55–75 years with overweight/obesity and metabolic syndrome) underwent body composition measurements. Consumption of UPF at baseline, 6 and 12 months was evaluated using a validated 143-item semi-quantitative Food Frequency Questionnaire. Food items (g/day) were categorized according to their degree of processing using NOVA system. Regional adiposity (visceral fat (in g) and android-to-gynoid fat ratio) and total fat mass (in g) at three time points were measured with dual-energy X-ray absorptiometry (DXA) and were normalized using sex-specific z-scores. The association of changes in UPF consumption, expressed as the percentage of total daily intake (daily g of UPF/total daily g of food and beverage intake∗100), with adiposity changes was evaluated using linear mixed-effects models.
On average, the consumption of UPF accounted for 8.11% (SD 7.41%) of total daily intake (in grams) at baseline. In multivariable-adjusted model, 10% daily increment in consumption of UPF was associated with significantly (all p-values <0.05) greater accumulation of visceral fat (β 0.09 z-scores, 95% CI 0.05; 0.13), android-to-gynoid fat ratio (0.05, 0.00; 0.09) and total fat (0.09, 0.06; 0.13).
A higher consumption of UPF was associated with greater age-related visceral and overall adiposity accumulation. Further studies are warranted to confirm these results in other populations and settings.
The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
Short dietary assessment tools can be useful to estimate food intake and diet quality in large-scale epidemiological studies with time constraints.
To determine the concurrent validity of the 17-item ...energy-restricted Mediterranean Adherence Screener (er-MEDAS) used in the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial and to analyse its capacity to detect 1-year changes in diet and cardiometabolic risk factors.
Validation study nested in the PREDIMED-Plus (n = 6760, 55–75 years). Dietary data were collected by the 17-item er-MEDAS and a 143-item validated semiquantitative food frequency questionnaire (FFQ) at baseline and after 1-year intervention. Cardiometabolic risk markers were measured at both time points. A Mediterranean diet (MedDiet) score was derived from both instruments. Concurrent validity was evaluated by Pearson and intra-class correlation coefficients (ICC) and Bland and Altman limits of agreement. Construct validity was evaluated by assessing 1-year changes in FFQ-reported dietary intake and cardiometabolic profile changes in relation to changes in er-MEDAS.
A moderate to good correlation between the MedDiet score calculated by both measurement instruments was found: r = 0.61 and ICC = 0.60 (both p < 0.001). Agreement of each of the er-MEDAS items ranged from 55.4% to 85.0% with a moderate mean concordance (kappa = 0.41). Between baseline and 1-year follow-up, energy intake measured by the FFQ decreased by 242 kcal, while Mediterranean food consumption increased in participants with the highest increase in the er-MEDAS MedDiet score. An increase in the er-MEDAS MedDiet score ratings was associated with a decrease in BMI, waist circumference, triglycerides, fasting glucose, diastolic blood pressure, and triglycerides/HDL-cholesterol ratio (p < 0.001 for all), and with an increase in HDL-cholesterol (p = 0.006).
The er-MEDAS shows a modest to good concurrent validity compared with FFQ data. It shows acceptable construct validity, as a greater er-MEDAS score was associated with more favourable dietary and cardiometabolic profiles over time.
ISRCTN89898870; registration date, 24 July 2014. https://www.isrctn.com/ISRCTN89898870.
Background: Osteocalcin has been related to insulin secretion in experimental models. Few prospective studies have evaluated the association between circulating osteocalcin concentrations and insulin ...secretion and sensitivity in humans.Objective: The objective was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin and insulin secretion and sensitivity in elderly men at high cardiovascular risk.Design: We examined cross-sectional and longitudinal associations between serum measurements of total osteocalcin and undercarboxylated osteocalcin (ucOC) with fasting glucose, fasting insulin, HOMA–IR, and HOMA β cell function (HOMA-BCF) in 79 elderly men. We also examined the association between 2-y changes in osteocalcin and changes in fasting glucose, insulin, HOMA-IR, and HOMA-BCF.Results: In an adjusted multivariable linear regression analysis, increases in serum osteocalcin were significantly associated with an increase in HOMA-BCF (β coefficient: 2.87; 95% CI: 0.23, 5.52; P = 0.033), and changes in ucOC were linked to a decrease in HOMA-IR (β coefficient: -0.31; 95% CI: -0.60, 0.03; P = 0.032). Moreover, in subjects not taking oral antidiabetic drugs, baseline osteocalcin concentrations were positively associated with higher fasting insulin concentrations and HOMA-BCF even after adjustment for BMI, physical activity, intervention group, presence of type 2 diabetes mellitus, and baseline values of each dependent variable.Conclusions: Changes in serum osteocalcin and ucOC are associated with an improvement in insulin secretion and sensitivity, which suggests a possible role of bone in the development of type 2 diabetes. This trial is registered at clinicaltrials.gov as ISRCTN35739639.
Several epidemiological studies have shown an inverse association between the consumption of polyphenol-rich foods and risk of cardiovascular diseases. However, accuracy and reliability of these ...studies may be increased using urinary total polyphenol excretion (TPE) as a biomarker for total polyphenol intake. Our aim was to assess if antioxidant activity, measured by a Folin-Ciocalteu assay in urine, is correlated with an improvement in cardiovascular risk factors (blood pressure and serum glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations) in an elderly population at high risk. A longitudinal study was performed with 573 participants (aged 67.3 ± 5.9) from the PREDIMED study (ISRCTN35739639). We used Folin-Ciocalteu method to determine TPE in urine samples, assisting with solid phase extraction. Participants were categorized into three groups according to changes in TPE. Multiple linear regression models were used to assess relationships between TPE and clinical cardiovascular risk factors, adjusting for potential confounders. After a 5-year follow-up, significant inverse correlations were observed between changes in TPE and plasma triglyceride concentration ( β = - 8.563 ; P = 0.007 ), glucose concentration ( β = - 4.164 ; P = 0.036 ), and diastolic blood pressure ( β = - 1.316 ; P = 0.013 ). Our results suggest that the consumption of more polyphenols, measured as TPE in urine, could exert a protective effect against some cardiovascular risk factors.
Abstract
Context
The potential associations between acylcarnitine profiles and incidence of type 2 diabetes (T2D) and whether acylcarnitines can be used to improve diabetes prediction remain unclear.
...Objective
To evaluate the associations between baseline and 1-year changes in acylcarnitines and their diabetes predictive ability beyond traditional risk factors.
Design, Setting, and Participants
We designed a case-cohort study within the PREDIMED Study including all incident cases of T2D (n = 251) and 694 randomly selected participants at baseline (follow-up, 3.8 years). Plasma acylcarnitines were measured using a targeted approach by liquid chromatography–tandem mass spectrometry. We tested the associations between baseline and 1-year changes in individual acylcarnitines and T2D risk using weighted Cox regression models. We used elastic net regressions to select acylcarnitines for T2D prediction and compute a weighted score using a cross-validation approach.
Results
An acylcarnitine profile, especially including short- and long-chain acylcarnitines, was significantly associated with a higher risk of T2D independent of traditional risk factors. The relative risks of T2D per SD increment of the predictive model scores were 4.03 (95% CI, 3.00 to 5.42; P < 0.001) for the conventional model and 4.85 (95% CI, 3.65 to 6.45; P < 0.001) for the model including acylcarnitines, with a hazard ratio of 1.33 (95% CI, 1.08 to 1.63; P < 0.001) attributed to the acylcarnitines. Including the acylcarnitines into the model did not significantly improve the area under the receiver operator characteristic curve (0.86 to 0.88, P = 0.61). A 1-year increase in C4OH-carnitine was associated with higher risk of T2D per SD increment, 1.44 (1.03 to 2.01).
Conclusions
An acylcarnitine profile, mainly including short- and long-chain acylcarnitines, was significantly associated with higher T2D risk in participants at high cardiovascular risk. The inclusion of acylcarnitines into the model did not significantly improve the T2D prediction C-statistics beyond traditional risk factors, including fasting glucose.
A panel of acylcarnitines, especially those with a short chain and long chain, was significantly associated with the incidence of T2D in individuals at high cardiovascular risk.
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