Changes in Plasma Metabolome Profiles Following Oral Glucose Challenge among Adult Chinese.

Little is known about changes in plasma metabolome profiles during the oral glucose tolerance test (OGTT) in Chinese. We aimed to characterize plasma metabolomic profiles at 0 and 2 h of OGTT and their changes in individuals of different glycemic statuses. A total of 544 metabolites were detected at 0 and 2 h of OGTT by a nontarget strategy in subjects with normal glucose (n = 234), prediabetes (n = 281), and newly diagnosed type 2 diabetes (T2D) (n = 66). Regression model, mixed model, and partial least squares discrimination analysis were applied. Compared with subjects of normal glucose, T2D cases had significantly higher levels of glycerone at 0 h and 22 metabolites at 2 h of OGTT (false discovery rate (FDR) < 0.05, variable importance in projection (VIP) > 1). Seven of the twenty-two metabolites were also significantly higher in T2D than in prediabetes subjects at 2 h of OGTT (FDR < 0.05, VIP > 1). Two hours after glucose challenge, concentrations of 35 metabolites (normal: 18; prediabetes: 23; T2D: 13) significantly increased (FDR < 0.05, VIP > 1, fold change (FC) > 1.2), whereas those of 45 metabolites (normal: 36; prediabetes: 29; T2D: 18) significantly decreased (FDR < 0.05, VIP > 1, FC < 0.8). Distinct responses between cases and noncases were detected in metabolites including 4-imidazolone-5-acetate and 4-methylene-L-glutamine. More varieties of distinct metabolites across glycemic statuses were observed at 2 h of OGTT compared with fasting state. Whether the different patterns and responsiveness of certain metabolites in T2D reflect a poor resilience of specific metabolic pathways in regaining glucose homeostasis merits further study.

Genetic susceptibility, dietary cholesterol intake, and plasma cholesterol levels in a Chinese population.

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRSTC, 57 SNPs), LDL-C (GRSLDL-C, 45 SNPs), and HDL-C (GRSHDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRSTC (effect sizes: -0.29, 0.34, 2.45, and 6.47; Pinteraction = 0.002) and GRSLDL-C (effect sizes: -1.35, 0.17, 5.45, and 6.07; Pinteraction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRSTC (Pinteraction = 0.001) and GRSLDL-C (Pinteraction = 0.004). The adverse effects of GRSTC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; Pinteraction = 0.023) and GRSLDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; Pinteraction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.

Erythrocyte PUFAs, circulating acylcarnitines, and metabolic syndrome risk: a prospective study in Chinese.

The effects of PUFAs on metabolic syndrome (MetS) remain to be characterized, particularly in Asians. We aimed to investigate the prospective associations of PUFAs with MetS and the role of acylcarnitines in these associations in Chinese individuals. Among 1,245 Chinese men and women aged 50-70 years who completed a 6 year follow-up, baseline erythrocyte FAs and plasma acylcarnitines were profiled using gas chromatography coupled with positive chemical ionization and liquid chromatography-tandem mass spectrometry, respectively. Total n-6 PUFAs and three 22-carbon n-6 PUFAs were significantly associated with lower MetS risk comparing extreme quartiles: relative risks (RRs) (95% CIs) were 0.75 (0.57, 0.97) for total n-6 PUFAs, 0.69 (0.56, 0.85) for 22:2n-6, 0.76 (0.59, 0.99) for 22:4n-6, and 0.74 (0.58, 0.94) for 22:5n-6, while 18:3n-3 and 18:3n-6 were positively associated with MetS risk. In a network analysis, a module mostly consisting of long-chain n-6 PUFAs and very-long-chain saturated FAs was inversely associated with incident MetS (RR per SD: 0.84; 95% CI: 0.76, 0.92), and this module was more strongly associated with lower MetS risk when a short- to medium-chain acylcarnitine (C5-C10) module score was lower (Pinteraction = 0.03). Our data suggested inverse associations of total n-6 and certain long-chain n-6 PUFAs with cardiometabolic disorders, and this association might be modified by certain acy-l-carnitines.

Effects of Genetic and Nongenetic Factors on Total and Bioavailable 25(OH)D Responses to Vitamin D Supplementation.

Context: Little is known about how genetic and nongenetic factors modify responses of vitamin D supplementation in nonwhite populations. Objective: To investigate factors modifying 25-hydroxyvitamin D [25(OH)D] and bioavailable 25(OH)D [25(OH)DBio] responses after vitamin D3 supplementation. Design, Setting, Participants, and Intervention: In this 20-week, randomized, double-blinded, placebo-controlled trial, 448 Chinese with vitamin D deficiency received 2000 IU/d vitamin D3 or placebo. Main Outcome Measures: Serum 25(OH)D, vitamin D-binding protein (VDBP), parathyroid hormone (PTH) and calcium were measured, and 25(OH)DBio was calculated based on VDBP levels. Six common polymorphisms in vitamin D metabolism genes were genotyped. Results: Between-arm net changes were +30.6 ± 1.7 nmol/L for 25(OH)D, +2.7 ± 0.2 nmol/L for 25(OH)DBio, and -5.2 ± 1.2 pg/mL for PTH, corresponding to 70% [95% confidence interval (CI), 62.8% to 77.2%] net reversion rate for vitamin D deficiency at week 20 (P < 0.001). Only 25(OH)DBio change was positively associated with calcium change (P < 0.001). Genetic factors (GC-rs4588/GC-rs7041, VDR-rs2228570, and CYP2R1-rs10741657; P ≤ 0.04) showed stronger influences on 25(OH)D or 25(OH)DBio responses than nongenetic factors, including baseline value, body mass index, and sex. An inverse association of PTH-25(OH)D was demonstrated only at 25(OH)D of <50.8 (95% CI, 43.6 to 59.0) nmol/L. Conclusions: Supplemented 2000 IU/d vitamin D3 raised 25(OH)D and 25(OH)DBio but was unable to correct deficiency in 25% of Chinese participants, which might be partially attributed to the effect of genetic modification. More studies are needed to elucidate appropriate vitamin D recommendations for Asians and the potential clinical implications of 25(OH)DBio.

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study.

OBJECTIVE: Acylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODS: A population-based prospective study was conducted among 2,103 community-living Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTS: Over the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONS: A panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.

Poor vitamin D status is prospectively associated with greater muscle mass loss in middle-aged and elderly Chinese individuals.

BACKGROUND: Poor vitamin D status can increase age-related muscle mass loss. However, existing prospective evidence is limited and controversial. OBJECTIVE: This study aimed to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D] with muscle mass loss in middle-aged and elderly Chinese individuals over 6 years. DESIGN: We conducted a prospective cohort study. PARTICIPANTS/SETTING: This community-based study included 568 men and women aged 50 to 70 years at baseline. MAIN OUTCOMES MEASURES: Baseline plasma concentrations of 25(OH)D and biomarkers of liver and kidney functions and inflammation were measured. Body composition was assessed at baseline and 6-year follow-up by dual-energy x-ray absorptiometry. Appendicular skeletal muscle mass (ASMM) and trunk lean mass were calculated and total body lean mass was defined as an overall measure of total nonfat and nonbone tissues. STATISTICAL ANALYSES PERFORMED: Descriptive statistics and multiple linear regression were applied. RESULTS: The 6-year loss of ASMM was 1.14 kg (5.3%) in men and 0.47 kg (3.1%) in women (all P values <0.001). Compared with the highest 25(OH)D tertile, participants in the lowest tertile had significantly more absolute loss of ASMM (-1.21 vs -1.00 kg; P for trend=0.024) after multivariate adjustments for conventional confounders, as well as protein intake. The association persisted after additional adjustment of bone mineral density and inflammatory markers (P for trend=0.017). No significant associations were detected between 25(OH)D and absolute loss of trunk lean mass or total body lean mass. CONCLUSIONS: Lower 25(OH)D concentrations were prospectively associated with greater ASMM loss in middle-aged and elderly Chinese individuals independent of bone mineral density, inflammation, diet, and other risk factors.

Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese.

AIMS/HYPOTHESIS: Although microbiota-derived endotoxaemia has previously been shown to induce metabolic disorders, data from population-based longitudinal studies are scarce. This study therefore investigated the associations between lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic syndrome (MetS), as well as the potentially modifying effects of obesity status in middle-aged and older Chinese men and women. METHODS: A total of 2,529 men and women aged 50-70 years from Beijing and Shanghai, China, were followed for 6 years. Those free of MetS at baseline (1,312) were included in the analyses for the risk of developing MetS. Baseline plasma LBP was measured using an ELISA kit. RESULTS: During the 6 year follow-up, 449 (34.2%) participants developed MetS. Baseline LBP was significantly associated with BMI, waist circumference, blood lipid profile and C-reactive protein (CRP) both at baseline and during follow-up (all p < 0.05). The RR for incident MetS comparing extreme quartiles of LBP was 1.28 (95% CI 1.04, 1.58), after multivariate adjustment including BMI and CRP. In stratified analysis, LBP was positively associated with incident MetS only in normal-weight participants (RR, comparing extreme tertiles, 1.59; 95% CI 1.18, 2.15; p(trend)= 0.002), but not in their overweight/obese counterparts (RR, comparing extreme tertiles, 0.99; 95% CI 0.80, 1.22; p(trend) = 0.880). A significant interaction was observed between LBP and obesity status (p(interaction) = 0.013). CONCLUSIONS/INTERPRETATION: Our study suggested that elevated plasma LBP was associated with an increased risk of developing MetS among middle-aged and older Chinese, especially in normal-weight individuals.

Dairy consumption, type 2 diabetes, and changes in cardiometabolic traits: a prospective cohort study of middle-aged and older Chinese in Beijing and Shanghai.

OBJECTIVE To prospectively investigate associations of dairy consumption with risk of type 2 diabetes and changes of cardiometabolic traits. RESEARCH DESIGN AND METHODS In 2005, 2,091 middle-aged and older Chinese men and women were recruited and followed for 6 years. Baseline dairy consumption was assessed by a 74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by gas chromatography coupled with flame ion detector. Cardiometabolic traits were measured at both baseline and follow-up visits. RESULTS Only 1,202 (57.5%) participants reported any dairy consumption, with a median intake of 0.89 (interquartile range 0.19-1.03) serving/day. Compared with nonconsumers, the relative risks (RRs) of type 2 diabetes among those having 0.5-1 serving/day and >1 serving/day were 0.70 (95% CI 0.55-0.88) and 0.65 (0.49-0.85), respectively, after multivariate adjustment (Ptrend < 0.001), which were attenuated by further adjusting for changes in glucose during follow-up (Ptrend = 0.07). Total dairy consumption was associated with favorable changes in glucose, waist circumference, BMI, diastolic blood pressure (all Ptrend < 0.05), and systolic blood pressure (Ptrend = 0.05) after multivariate adjustment, including baseline values of dependent variables. Erythrocyte trans-18:1 isomers were significantly correlated with total dairy consumption (rs = 0.37, Ptrend < 0.001), and these dairy food biomarkers were associated with a lower risk of type 2 diabetes. The RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82 (0.65-1.04, Ptrend = 0.02), which was attenuated after adjustment for dairy consumption (Ptrend = 0.15). CONCLUSIONS Dairy consumption was associated with a significantly lower risk of type 2 diabetes and favorable changes of cardiometabolic traits in Chinese.

Elevated plasma ferritin is associated with increased incidence of type 2 diabetes in middle-aged and elderly Chinese adults.

Epidemiological studies suggest that elevated circulating ferritin is associated with heightened incident diabetes in mainly Western populations, although the results were not entirely consistent. We aimed to prospectively investigate the ferritin-diabetes association in an Asian population for the first time, to our knowledge, and also to examine this association with an updated meta-analysis. Our prospective study included 2198 community-living Chinese between 50 and 70 y of age in 2005. All individuals participated in a 6-y follow-up survey in 2011. Fasting plasma ferritin, high-sensitivity C-reactive protein (hsCRP), adiponectin, and γ-glutamyltransferase (GGT) were measured at baseline. A total of 538 incident diabetes cases were documented by self-reports and/or fasting glucose ≥7.0 mmol/L at the follow-up survey. After multiple adjustments, the RR of type 2 diabetes was 1.90 (95% CI: 1.37, 2.65) when comparing the highest with the lowest sex-specific ferritin quintile. The association remained significant after further controlling for BMI, hsCRP, adiponectin, and GGT. To update the evidence reported in previous meta-analyses, we searched all prospective studies evaluating the association between blood ferritin and incident diabetes on PubMed prior to October 24, 2012. Besides our prospective study, 9 additional studies were also included. The pooled RR was 1.60 (95% CI: 1.25, 2.04) when comparing the highest with the lowest category of ferritin with a moderate heterogeneity (I(2) = 49.0%; P = 0.03). A significant linear dose-response relationship was detected in this meta-analysis. Overall, our results indicate an independent and significant positive association between higher plasma ferritin, a marker of elevated body iron stores, and increased risk of developing type 2 diabetes in middle-aged and elderly Chinese adults, which is similar to Western populations.

Associations of erythrocyte fatty acids in the de novo lipogenesis pathway with risk of metabolic syndrome in a cohort study of middle-aged and older Chinese.

BACKGROUND: Experimental studies suggest that elevated de novo lipogenesis (DNL) might be involved in the pathogenesis of metabolic disorders. Few prospective studies have been conducted, especially among populations with a high carbohydrate intake, to determine whether DNL fatty acids are associated with the risk of the metabolic syndrome (MetS). OBJECTIVE: We aimed to investigate associations of erythrocyte fatty acids in the DNL pathway-including myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1n-7), hexadecenoic acid (16:1n-9), stearic acid (18:0), vaccenic acid (18:1n-7), and oleic acid (18:1n-9)-with the risk of MetS in a Chinese population with an average carbohydrate intake of >60% of energy. DESIGN: A total of 1176 free-living Chinese men and women aged 50-70 y from Beijing and Shanghai were included in our analysis, giving rise to 412 incident MetS cases during 6 y of follow-up. Erythrocyte fatty acids and metabolic traits were measured in these participants. RESULTS: Erythrocyte fatty acids in the DNL pathway were correlated with a high ratio of carbohydrate-to-fat intake, less favorable lipid profiles, and elevated liver enzymes at baseline. In comparison with the lowest quartile, RRs (95% CIs) of MetS in the highest quartile were 1.30 (1.04, 1.62; P-trend = 0.007) for 16:1n-7, 1.48 (1.17, 1.86; P-trend < 0.001) for 16:1n-9, 1.26 (1.01, 1.56; P-trend = 0.06) for 18:1n-7, and 1.51 (1.19, 1.92; P-trend < 0.001) for 18:1n-9 after multivariate adjustment for lifestyle factors and body mass index. Moreover, 16:0 and 16:1n-7 were associated with an elevated risk of diabetes. CONCLUSION: Our findings suggest that fatty acids in the DNL pathway are independently associated with an elevated risk of metabolic disorders.