Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

AIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study.

BACKGROUND AND AIM: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. METHODS AND RESULTS: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. CONCLUSION: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. CLINICAL TRIAL NUMBER: ISRCTN35739639.

Healthy dietary patterns and risk of cardiovascular disease in US Hispanics/Latinos: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Multiple dietary patterns have been recommended by the 2015-2020 Dietary Guidelines for Americans for the prevention of cardiovascular disease (CVD). The adherence to these patterns and its relation with risk of CVD remain unclear in the US Hispanic/Latino population. OBJECTIVES: We aimed to evaluate 3 healthy eating patterns measured by 3 dietary pattern scores [the Alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful Plant-based Diet Index (hPDI)] across different Hispanic/Latino backgrounds and generations. We further examined the associations of these dietary scores with incident CVD in US Hispanics/Latinos. METHODS: We included 10,293 adult participants of US Hispanics/Latinos of 6 backgrounds (Mexican, Puerto Rican, Cuban, Dominican, Central American, and South American), free of CVD or cancer at baseline, in the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores were derived at the baseline visit using two 24-h dietary recalls. The primary outcome was major incident CVD (n = 232), comprised of coronary heart disease and stroke, during an average 6-y follow-up. RESULTS: Mean levels of all 3 dietary scores were significantly different across the 6 Hispanic/Latino background groups (all P < 0.001), with the highest (i.e., healthiest) in those of Mexican background and lowest in those of Puerto Rican background. Compared with non-mainland-US-born Hispanics/Latinos, mainland-US-born Hispanics/Latinos had significantly lower dietary scores (P < 0.001). Differences in dietary scores between mainland-US-born and non-mainland-US-born Hispanics/Latinos were majorly driven by differences in dietary intakes of healthy plant-based foods. After adjusting for multiple covariates, significantly lower risk ratios (95% CI) of CVD were observed for 1-SD increments of the dietary scores, with 0.74 (0.60, 0.91) for aMED, 0.80 (0.63, 1.00) for HEI-2015, and 0.74 (0.60, 0.93) for hPDI. CONCLUSIONS: Although adherence to healthy eating patterns varied by Hispanic/Latino backgrounds and generations, greater adherence to these eating patterns was associated with lower risk of CVD across diverse US Hispanics/Latinos.

Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years.

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40-65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (ß = -1.6, p = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (ß = -1.4, p = 0.022; ß = -1.6, p = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (ß = -1.6, p = 0.038; ß = -1.9, p = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period.

Diet Quality and Its Association with Cardiometabolic Risk Factors Vary by Hispanic and Latino Ethnic Background in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Healthful diet quality has been associated with a lower risk of metabolic syndrome (MetS) in several populations, but reports on Hispanic and Latino cohorts, grouped or by ethnic background, have been limited and inconsistent. OBJECTIVE: We aimed to examine diet quality by using the 2010 Alternate Healthy Eating Index [(AHEI) range: 0-110, lowest to highest quality] and its cross-sectional association with MetS and its cardiometabolic components across 6 Hispanic and Latino backgrounds. METHODS: We studied 12,406 US Hispanics and Latinos, aged 18-74 y and free of diabetes, from the multicenter, population-based Hispanic Community Health Study/Study of Latinos cohort. Food and nutrients were assessed from two 24-h recalls. MetS was defined by using the 2009 harmonized guidelines. Complex survey procedures were used in multivariable-adjusted linear regression models to test the association of the AHEI with continuous markers and in logistic regression models with MetS as an outcome. RESULTS: The prevalence of MetS was 24.2%. Overall, Hispanics and Latinos had low scores for intakes of sugar-sweetened beverages and fruit juices, whole grains, and fruit and favorable scores for trans fats and nuts and legumes, according to AHEI criteria. Adjusted mean AHEI and its individual components differed by ethnic background (P < 0.001), ranging from 43.0 for Puerto Ricans to 52.6 for Mexicans. Overall, adjusted odds (95% CIs) of having MetS were 22% (9%, 33%) lower for each 10-unit increase in AHEI. This association was modified by ethnic background (P-interaction = 0.03), with significantly lower odds observed only for Mexicans (30%; 95% CIs: 13%, 44%) and Central Americans (42%; 95% CIs: 9%, 64%) for each 10-unit increase in AHEI. AHEI was inversely associated with waist circumference, blood pressure, and glucose among Mexicans and Puerto Ricans and with triglycerides among Mexicans only, and positively associated with HDL cholesterol among Puerto Ricans and Central Americans (all P < 0.05). CONCLUSIONS: Diet quality differed by Hispanic or Latino background. Although healthier diet quality was associated with lower odds of MetS in the overall Hispanic and Latino cohort, the association of AHEI and cardiometabolic factors varied by ethnic background. Nutrition-related research and interventions among ethnically diverse groups should consider individual ethnic backgrounds to optimally address diet quality and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT02060344.

A novel fatty acid profile index--the lipophilic index--and risk of myocardial infarction.

The lipophilic index (LI), a mean measure of fatty acid melting points, has been proposed to capture overall fatty acid profile and may play an important role in the etiology of coronary heart disease. We aimed to determine the association between LI in diet and in adipose tissue and metabolic risk factors for myocardial infarction (MI) and risk of MI. We used a population-based, matched case-control study of nonfatal first acute MI conducted in Costa Rica between 1994 and 2004, with 1,627 case-control pairs. The LI is defined as the mean of the melting points of specific fatty acids in diet or adipose tissue. LIs in diet and adipose tissue were significantly associated with higher plasma triglyceride concentrations, low-density lipoprotein cholesterol concentrations, and low-density:high-density lipoprotein cholesterol ratio. Comparing extreme quintiles for the LI in diet or adipose tissue, the odds ratios for MI were 1.57 (95% confidence interval: 1.22, 2.02; P for trend < 0.001) for dietary LI and 1.30 (95% confidence interval: 1.00, 1.69; P for trend = 0.02) for adipose tissue LI in the multivariable models. We hypothesize that a higher LI in diet and in adipose tissue represents decreased fatty acid fluidity and could play an important role in the etiology of coronary heart disease.

Substituting homemade fruit juice for sugar-sweetened beverages is associated with lower odds of metabolic syndrome among Hispanic adults.

Consumption of sugar-sweetened beverages (SSB) has been associated with metabolic syndrome (MetS); however, studies conducted on Hispanic adults are scarce. To determine the association between beverages consumed by Hispanic adults and MetS and its components, data were analyzed in 1872 Costa Rican adults who served as controls of a population-based, case-control study of coronary heart disease. Multivariate-adjusted means were calculated for components of MetS by servings (never, ≤ 1/wk; 2-6/wk, ≥ 1/d) of 2 traditional fruit-based beverages ("fresco" and freshly-squeezed homemade fruit juice, separately) and 2 SSB (instant drinks and regular sodas, separately and combined). The prevalence ratio (PR) of MetS was calculated for each beverage and the OR was calculated by substituting one serving of homemade fruit juice or water for one of SSB. Significant positive trends were observed for increasing servings of instant drinks with plasma TG and waist circumference and for regular soda with waist circumference (all P-trend < 0.001). Increasing servings of homemade fruit juice were positively associated with HDL cholesterol (P-trend = 0.033). Consuming ≥1 serving/d of instant drinks was associated with a higher PR of MetS [1.42 (95% CI: 1.11, 1.83)] compared with no consumption. Substituting one serving of homemade fruit juice for instant drink was associated with 29% (95% CI: 7, 47%) lower odds of MetS and for regular soda with 30% (95% CI: 1, 50%) lower odds. Substituting water for combined SSB was marginally significant (OR = 0.86 (95% CI: 0.74, 1.00). In conclusion, reducing the consumption of SSB and substituting them with homemade fruit juices in moderation may be a culturally appropriate approach to lower MetS among Hispanic adults.

A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults.

BACKGROUND: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. OBJECTIVE: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. DESIGN: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. RESULTS: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. CONCLUSION: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.

An 18-mo randomized trial of a low-glycemic-index diet and weight change in Brazilian women.

BACKGROUND: Despite interest in the glycemic index diets as an approach to weight control, few long-term evaluations are available. OBJECTIVE: The objective was to investigate the long-term effect of a low-glycemic-index (LGI) diet compared with that of a high-glycemic-index (HGI) diet; all other dietary components were equal. DESIGN: After a 6-wk run-in, we randomly assigned 203 healthy women [body mass index (in kg/m2): 23-30] aged 25-45 y to an LGI or an HGI diet with a small energy restriction. The primary outcome measure was weight change at 18 mo. Secondary outcomes included hunger and fasting insulin and lipids. RESULTS: Despite requiring a run-in and the use of multiple incentives, only 60% of the subjects completed the study. The difference in glycemic index between the diets was approximately 35-40 units (40 compared with 79) during all 18 mo of follow-up, and the carbohydrate intake from energy remained at approximately 60% in both groups. The LGI group had a slightly greater weight loss in the first 2 mo of follow-up (-0.72 compared with -0.31 kg), but after 12 mo of follow-up both groups began to regain weight. After 18 mo, the weight change was not significantly different (P = 0.93) between groups (LGI: -0.41 kg; HGI: -0.26 kg). A greater reduction was observed in the LGI diet group for triacylglycerol (difference = -16.4 mg/dL; P = 0.11) and VLDL cholesterol (difference = -3.7 mg/dL; P = 0.03). CONCLUSIONS: Long-term weight changes were not significantly different between the HGI and LGI diet groups; therefore, this study does not support a benefit of an LGI diet for weight control. Favorable changes in lipids confirmed previous results.