Diet-Related Lipidomic Signatures and Changed Type 2 Diabetes Risk in a Randomized Controlled Feeding Study With Mediterranean Diet and Traditional Chinese or Transitional Diets.

OBJECTIVE: Few trials studied the links of food components in different diets with their induced lipidomic changes and related metabolic outcomes. Thus, we investigated specific lipidomic signatures with habitual diets and modified diabetes risk by using a trial and a cohort. RESEARCH DESIGN AND METHODS: We included 231 Chinese with overweight and prediabetes in a randomized feeding trial with Mediterranean, traditional, or transitional diets (control diet) from February to September 2019. Plasma lipidomic profiles were measured at baseline, third month, and sixth month by high-throughput targeted liquid chromatography-mass spectrometry. Associations of the identified lipids with habitual dietary intakes were examined in another lipidomic database of a Chinese cohort (n = 1,117). The relationships between diet-induced changes of lipidomic species and diabetes risk factors were further investigated through both individual lipids and relevant modules in the trial. RESULTS: Out of 364 lipidomic species, 26 altered across groups, including 12 triglyceride (TAG) fractions, nine plasmalogens, four phosphatidylcholines (PCs), and one phosphatidylethanolamine. TAG fractions and PCs were associated with habitual fish intake while plasmalogens were associated with red meat intake in the cohort. Of the diet-related lipidomic metabolites, 10 TAG fractions and PC(16:0/22:6) were associated with improved Matsuda index (ß = 0.12 to 0.42; PFDR < 0.030). Two plasmalogens were associated with deteriorated fasting glucose (ß = 0.29 to 0.31; PFDR < 0.014). Similar results were observed for TAG and plasmalogen related modules. CONCLUSIONS: These fish- and red meat-related lipidomic signatures sensitively reflected different diets and modified type 2 diabetes risk factors, critical for optimizing dietary patterns.

Isocaloric-restricted Mediterranean Diet and Chinese Diets High or Low in Plants in Adults With Prediabetes.

CONTEXT: Calorie restriction plus dietary advice is suggested as a preventive strategy for individuals with obesity and prediabetes; however, optimal diet is still debatable. We aimed to compare the effects of Mediterranean diet (MD) and Chinese diets high or low in plants on body weight and glucose homeostasis among high-risk Chinese. SUBJECTS AND METHODS: In this parallel-arm randomized controlled trial, 253 Chinese adults aged 25 to 60 years with a body mass index ≥ 24.0 kg/m2 and fasting blood glucose ≥ 5.6 mmol/L were randomly assigned to 3 isocaloric-restricted diets: MD (n = 84), a traditional Jiangnan diet high in plants (TJD, n = 85), or a control diet low in plants (CD, n = 84). During the 6-month trial, a 5-weekday full-feeding regimen was followed, along with mobile app-based monitoring. Abdominal fat measurement (magnetic resonance imaging), oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM) were conducted at baseline and 3 and 6 months. RESULTS: With a 25% calorie restriction for 6 months, weight deduction was 5.72 kg (95% confidence interval, 5.03-6.40) for MD, 5.05 kg (4.38-5.73) for TJD, and 5.38 kg (4.70-6.06) for CD (Ptime < 0.0001). No between-group differences were found for fasting glucose, insulin, and the Matsuda index from OGTT. Notably, CD had significantly longer time below range (glucose < 3.9 mmol/L) than MD (0.81% [0.21-1.40], P = 0.024) and marginally longer time than TJD (0.56% [-0.03 to 1.15], P = 0.065), as measured by CGM. CONCLUSIONS: With the 6-month isocaloric-restricted feeding, TJD and MD achieved comparable weight deduction and improved glucose homeostasis, whereas CD showed a higher risk for hypoglycemia.

Lipidomic Signatures of Dairy Consumption and Associated Changes in Blood Pressure and Other Cardiovascular Risk Factors Among Chinese Adults.

BACKGROUND: Omics data may provide a unique opportunity to discover dairy-related biomarkers and their linked cardiovascular health. METHODS: Dairy-related lipidomic signatures were discovered in baseline data from a Chinese cohort study (n=2140) and replicated in another Chinese study (n=212). Dairy intake was estimated by a validated food-frequency questionnaire. Lipidomics was profiled by high-coverage liquid chromatography-tandem mass spectrometry. Associations of dairy-related lipids with 6-year changes in cardiovascular risk factors were examined in the discovery cohort, and their causalities were analyzed by 2-sample Mendelian randomization using available genome-wide summary data. RESULTS: Of 350 lipid metabolites, 4 sphingomyelins, namely sphingomyelin (OH) C32:2, sphingomyelin C32:1, sphingomyelin (2OH) C30:2, and sphingomyelin (OH) C38:2, were identified and replicated to be positively associated with total dairy consumption (ß=0.130 to 0.148; P<1.43×10-4), but not or weakly with nondairy food items. The score of 4 sphingomyelins showed inverse associations with 6-year changes in systolic (-2.68 [95% CI, -4.92 to -0.43]; P=0.019), diastolic blood pressures (-1.86 [95% CI, -3.12 to -0.61]; P=0.004), and fasting glucose (-0.25 [95% CI, -0.41 to -0.08]; P=0.003). Mendelian randomization analyses further revealed that genetically inferred sphingomyelin (OH) C32:2 was inversely associated with systolic (-0.57 [95% CI, -0.85 to -0.28]; P=9.16×10-5) and diastolic blood pressures (-0.39 [95% CI, -0.59 to -0.20]; P=7.09×10-5). CONCLUSIONS: The beneficial effects of dairy products on cardiovascular health might be mediated through specific sphingomyelins among Chinese with overall low dairy consumption.

Studies on Gas Seepage Characteristics in Different Stress Zones of Bottom Coal in Steeply Inclined and Extra-Thick Coal Seams under Mining Action.

The gas released from the bottom coal of the horizontal slicing mining face in steeply inclined and extra-thick coal seams seriously threatens the safety of the upper slicing mining face. To explore the seepage characteristics of bottom coal gas, the coal deformation and gas permeability evolution law of four coal samples in different stress zones of bottom coal in the working face were analyzed through true triaxial fluid-solid coupling seepage experiments. At the same time, the seepage capacity of bottom coal gas was partitioned according to the field test. The results show the following: (1) The gas permeability of the bottom coal stress concentration zone first decreased and then increased with axial pressure loading and confining pressure unloading. The gas permeability of the bottom coal stress relief zone increased rapidly with decreasing axial pressure and confining pressure. The gas permeability of the bottom coal stress recovery zone gradually decreased with the cyclic loading and unloading of axial pressure and tended to be stabilized. (2) The evolution law of gas permeability in the bottom coal was closely related to the damage and deformation of coal. (3) From the original stress zone to the stress recovery zone, the gas seepage capacity of bottom coal can be divided into four zones, namely, the original seepage zone, the seepage reduction zone, the seepage sharp increase zone, and the seepage reduction zone. The gas seepage capacity in the stress concentration zone was more substantial than that of the stress recovery zone. The results of this study are of great significance for strengthening the dynamic disaster prevention and control of bottom coal gas in the horizontal slicing mining face of steeply inclined and extra-thick coal seams.

Change Law of Lower Limit of Gas Explosion at Ultra-High Temperatures.

During coal seam mining, a large amount of low-concentration mine gas will be produced, and it is the main utilization way to pass it into a thermal storage oxidation device to obtain heat energy. The thermal storage oxidation process is carried out in an ultra-high temperature environment. The excessive gas concentration not only reduces the production efficiency but also presents an explosion hazard. To solve the abovementioned problems, the lower explosion limit of a low-concentration gas at ultra-high temperatures (900-1200 °C) was studied through a self-developed high-temperature explosion experimental device. Fluent software was used to simulate the reaction of a low-concentration gas in a high-temperature environment, and the experimental results were verified according to the maximum explosion pressure. Through analysis and discussion, the following are found: (1) the relationship between the instantaneous explosion pressure of the low-concentration gas and the gas concentration as well as the relationship between the maximum explosion pressure near the lower explosion limit and the gas concentration are in accordance with the Boltzmann function. (2) When the temperature rises from 900 to 1200 °C, the lower limit of gas explosion obtained from experiments is reduced from 2.33 to 1.36%. (3) The lower limit of gas explosion decreases with increasing temperature at ultra-high temperatures and the downward trend slows down, this is similar to the change rule of the lower limit of gas explosion at temperatures below 200 °C. These findings have certain practical significance for improving the utilization efficiency of the low-concentration gas in heat storage oxidation.

Plasma Sphingolipid Profile in Association with Incident Metabolic Syndrome in a Chinese Population-Based Cohort Study.

Although bioactive sphingolipids have been shown to regulate cardiometabolic homeostasis and inflammatory signaling pathways in rodents, population-based longitudinal studies of relationships between sphingolipids and onset of metabolic syndrome (MetS) are sparse. We aimed to determine associations of circulating sphingolipids with inflammatory markers, adipokines, and incidence of MetS. Among 1242 Chinese people aged 50-70 years who completed the 6-year resurvey, 76 baseline plasma sphingolipids were quantified by high-throughput liquid chromatography-tandem mass spectrometry. There were 431 incident MetS cases at 6-year revisit. After multivariable adjustment including lifestyle characteristics and BMI, 21 sphingolipids mainly from ceramide and hydroxysphingomyelin subclasses were significantly associated with incident MetS. Meanwhile, the baseline ceramide score was positively associated (RRQ4 versus Q1 = 1.31; 95% CI 1.05, 1.63; ptrend = 0.010) and the hydroxysphingomyelin score was inversely associated (RRQ4 versus Q1 = 0.60; 95% CI 0.45, 0.79; ptrend < 0.001) with incident MetS. When further controlling for clinical lipids, both associations were attenuated but remained significant. Comparing extreme quartiles, RRs (95% CIs) of MetS risk were 1.34 (95% CI 1.06, 1.70; ptrend = 0.010) for ceramide score and 0.71 (95% CI 0.51, 0.97; ptrend = 0.018) for hydroxysphingomyelin score, respectively. Furthermore, a stronger association between ceramide score and incidence of MetS was evidenced in those having higher inflammation levels (RRQ4 versus Q1 1.57; 95% CI 1.16, 2.12; pinteraction = 0.004). Our data suggested that elevated ceramide concentrations were associated with a higher MetS risk, whereas raised hydroxysphingomyelin levels were associated with a lower MetS risk beyond traditional clinical lipids.

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.

Plasma glycerophospholipid profile, erythrocyte n-3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women.

BACKGROUND: Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce. OBJECTIVES: We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort. METHODS: A total of 1243 community-dwelling Chinese aged 50-70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. RESULTS: After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16-1.30 per SD change; Bonferroni-corrected P < 0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P < 0.05]. This association was more pronounced in participants with lower erythrocyte total n-3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)< 0.05]. CONCLUSIONS: Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.

Circulating Glycerolipids, Fatty Liver Index, and Incidence of Type 2 Diabetes: A Prospective Study Among Chinese.

CONTEXT: Few lipidomic studies have specifically investigated the association of circulating glycerolipids and type 2 diabetes (T2D) risk, especially among Asian populations. It remains unknown whether or to what degree fatty liver could explain the associations between glycerolipids and T2D. OBJECTIVE: We aimed to assess associations between plasma glycerolipids and incident T2D and to explore a potential role of liver fat accumulation in the associations. METHODS: This was a prospective cohort study with 6 years of follow-up. The study population included 1781 Chinese participants aged 50 to 70 years. The main outcome measure was incident T2D. RESULTS: At the 6-year resurvey, 463 participants had developed T2D. At the false discovery rate (FDR) of 5%, 43 of 104 glycerolipids were significantly associated with incident T2D risk after multivariate adjustment for conventional risk factors. After further controlling for glycated hemoglobin (HbA1c), 9 of the 43 glycerolipids remained significant, including 2 diacylglycerols (DAGs) (16:1/20:4, 18:2/20:5) and 7 triacylglycerols (TAGs) (46:1, 48:0, 48:1, 50:0, 50:1, 50:2, and 52:2), with relative risks (RRs) (95% CIs) ranging from 1.16 (1.05-1.27) to 1.23 (1.11-1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index largely attenuated these findings (RR [95% CI] 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the fatty liver index explained 12% to 28% of the glycerolipids-T2D associations (all P < 0.01). CONCLUSION: Higher plasma levels of DAGs and TAGs were associated with increased incident T2D risk in this Chinese population, which might be partially explained by liver fat accumulation.

Fatty acids and cardiometabolic health: a review of studies in Chinese populations.

Rapid nutrition transition from plant-based traditional diet to westernized diet has led to dramatically heightening burdens of cardiometabolic diseases in China in past decades. Recently, national surveys reported that poor dietary quality including low marine n-3 fatty acids and high intakes of red meat and processed meat was associated with considerably elevated cardiometabolic deaths. Previous studies mainly from Western population-based cohorts have indicated that not only fat quantity but also quality linked with different cardiometabolic outcomes. Compared with Western peoples, Asian peoples, including Chinese, are known to have different dietary patterns and lifestyle, as well as genetic heterogeneities, which may modify fatty acid metabolism and disease susceptibility in certain degree. To date, there were limited prospective studies investigating the relationships between fatty acids and cardiometabolic disease outcomes in Chinese, and most existing studies were cross-sectional nature and within one or two region(s). Notably, shifting dietary patterns could change not only amount, types, and ratio of fatty acids accounting for overall energy intake, but also their food sources and ratio to other macronutrients. Moreover, large geographic and urban-rural variations in prevalence of cardiometabolic diseases among Chinese may also reflect the effects of socioeconomic development and local diets on health status. Therefore, current review will summarize available literatures with more focus on the Chinese-based studies which may extend current knowledge about the roles of fatty acids in pathogenesis of cardiometabolic diseases for Asian populations and also provide useful information for trans-ethnic comparisons with other populations.

Replacing white rice bars with peanuts as snacks in the habitual diet improves metabolic syndrome risk among Chinese adults: a randomized controlled trial.

BACKGROUND: Observational studies have suggested that intake of nuts is associated with lower risk of cardiometabolic diseases, whereas refined grain consumption has been linked to higher risk. Little is known about whether substituting white rice, a refined grain, with nuts may confer benefit among adults at high risk of cardiometabolic diseases. OBJECTIVES: We aimed to evaluate isocaloric substitution of peanuts for white rice bars as snacks on changes in fasting glucose, lipid profile, body weight, as well as changes in metabolic syndrome (MetS) status among participants with MetS or at risk of MetS. METHODS: This parallel-arm randomized controlled trial included 224 participants either with MetS (according to the International Diabetes Federation criteria for Chinese adults, n = 163) or at risk of MetS (central obesity plus 1 additional MetS risk factor, n = 61). Participants were randomly assigned to either the peanut arm (56 g/d as snacks, n = 113) or the control arm (isocaloric white rice bars, n = 111) for 12 wk. RESULTS: A total of 209 participants (93.3%) completed the 12-wk intervention with a compliance rate > 85% among all participants. No between-group differences were found for improvements in fasting glucose, HDL cholesterol, waist circumference, and body weight. Participants in the peanut group had a significantly higher MetS reversion rate (no longer meeting MetS criteria after the 12-wk trial) than those in the control group (RR: 2.33; 95% CI: 1.10, 4.89; P = 0.026). CONCLUSIONS: Including peanuts as a snack in the habitual diet in place of a refined-grain snack did not significantly change glycemic or lipid parameters, but improved overall MetS risk without promoting weight gain among Chinese adults at high risk of cardiometabolic diseases. Further larger-scale trials are needed to confirm these findings and elucidate underlying biological mechanisms.This trial was registered at clinicaltrials.gov as NCT03194152.

Associations among circulating sphingolipids, ß-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China.

BACKGROUND: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, ß-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms. METHODS AND FINDINGS: The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through ß-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05-1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication. CONCLUSIONS: In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through ß-cell dysfunction, in Chinese individuals.

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.

Linking of metabolomic biomarkers with cardiometabolic health in Chinese population.

Due to rapid nutrition transitions, the prevalence of cardiometabolic diseases, such as metabolic syndrome, type 2 diabetes, and cardiovascular diseases, has been increasing at an alarming rate in the Chinese population. Moreover, Asians, including Chinese, have been hypothesized to have a higher susceptibility to cardiometabolic diseases than Caucasians. Early prediction and prevention are key to controlling this epidemic trend; to this end, the identification of novel biomarkers is critical to reflect environmental exposure, as well as to reveal endogenous metabolic and pathophysiologic mechanisms. The emerging "omics" technologies, especially metabolomics, offer a unique opportunity to provide novel signatures or fingerprints to understand the effects of genetic and non-genetic factors on cardiometabolic health. During the past two decades, metabolomic approaches have been increasingly used in various epidemiological studies, primarily in Western populations. Although the field is still in its early stages, some studies have tried to identify novel compounds or confirm their metabolites and associations with cardiometabolic diseases in Chinese populations, including amino acids, fatty acids, acylcarnitines and other metabolites. Despite major efforts to discover novel biomarkers for disease prediction or intervention, the limits in current study design, analytical platforms, and data processing approaches are challenges in metabolomic research worldwide. Therefore, future research with more advanced technologies, rigorous study designs, standardized detection and analytic approaches, and integrated data from multiomics approaches are essential to evaluate the feasibility of using metabolomics in clinical settings. Finally, the functional roles and underlying biological mechanisms of metabolomic biomarkers should be elucidated by future mechanistic research.

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.

Interethnic analyses of blood pressure loci in populations of East Asian and European descent.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

Cholecalciferol Supplementation Promotes Bone Turnover in Chinese Adults with Vitamin D Deficiency.

BACKGROUND: Bone turnover markers (BTMs) are proposed as alternative indicators for bone mineral density in diagnosis and management of osteoporosis. However, little is known about the effects of vitamin D supplementation on BTMs in nonwhite populations. OBJECTIVE: We aimed to investigate the responses in BTMs after vitamin D supplementation in Asians. METHODS: In this secondary data analysis of a randomized, double-blind, placebo-controlled trial, 448 Chinese adults [mean ± SD age: 31.9 ± 8.0 y; mean ± SD body mass index (kg/m2): 22.1 ± 2.6; 69% were women] with vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) received 2000 IU/d cholecalciferol or placebo for 20 wk. Serum concentrations of 25(OH)D, parathyroid hormone (PTH), calcium, and markers of bone formation and resorption were measured at weeks 0 and 20. Intention-to-treat analysis was applied, and between-group differences were compared by general linear models with adjustments. RESULTS: Cholecalciferol supplementation increased the serum bone alkaline phosphatase (BALP) concentration (+1.7 ± 1.9 µg/L) significantly more than placebo (+1.1 ± 1.7 µg/L; P = 0.004), but not circulating concentrations of procollagen type I N-terminal propeptide (PINP), ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX), or tartrate-resistant acid phosphatase 5b (TRAP5b) (P ≥ 0.53). Notably, a pooled analysis indicated that changes in serum 25(OH)D were positively associated with changes in serum BALP, PINP, and TRAP5b (r = 0.07-0.16, P ≤ 0.02), but inversely with changes in PTH (r = -0.15, P < 0.001). Among cholecalciferol-treated participants, individuals who achieved serum 25(OH)D ≥75 nmol/L had greater increases in serum ß-CTX (224% compared with 146%; P = 0.02) and TRAP5b (22.2% compared with 9.1%; P = 0.007), but smaller decreases in serum calcium (-1.3% compared with -1.9%; P = 0.005) and calcium-phosphorus product (-2.6% compared with -3.3%; P = 0.02) compared with those with serum 25(OH)D <75 nmol/L. CONCLUSIONS: Daily supplementation with 2000 IU cholecalciferol for 20 wk may promote bone formation in Chinese adults with vitamin D deficiency. More studies are needed to elucidate the potential clinical implications of BTMs.This trial was registered at clinicaltrials.gov as NCT01998763.

Associations of Plasma Amino Acid and Acylcarnitine Profiles with Incident Reduced Glomerular Filtration Rate.

BACKGROUND AND OBJECTIVES: Metabolomics is instrumental in identifying novel biomarkers of kidney function to aid in the prevention and management of CKD. However, data linking the metabolome to incident eGFR are sparse, particularly in Asian populations with different genetic backgrounds and environmental exposures. Therefore, we aimed to investigate the associations of amino acid and acylcarnitine profiles with change in eGFR in a Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 1765 community-living Chinese adults aged 50-70 years with baseline eGFR≥60 ml/min per 1.73 m2. At baseline, 22 amino acids and 34 acylcarnitines in plasma were quantified by gas or liquid chromatography coupled with mass spectrometry. Annual rate of change in eGFR was calculated, and incident eGFR decline was defined as eGFR<60 ml/min per 1.73 m2 by the end of 6 years of follow-up. RESULTS: The mean (SD) unadjusted annual change in eGFR was 2.2±2.0 ml/min per 1.73 m2 and the incidence of reduced eGFR was 16%. After Bonferroni correction, 13 of 56 metabolites were significantly associated with annual eGFR change. After multivariable adjustment of baseline covariates, including baseline eGFR, seven of the 13 metabolites, including cysteine, long-chain acylcarnitines (C14:1OH, C18, C18:2, and C20:4), and other acylcarnitines (C3DC and C10), were significantly associated with incident reduced eGFR (relative risks ranged from 1.16 to 1.25 per SD increment of metabolites; P<3.8E-03 after Bonferroni correction of multiple testing of the 13 metabolites). Moreover, principal component analysis identified two factors, consisting of cysteine and long-chain acylcarnitines, respectively, that were associated with incident reduced eGFR. CONCLUSIONS: Elevated plasma levels of cysteine and a panel of acylcarnitines were associated with a higher incidence of reduced eGFR in Chinese adults, independent of baseline eGFR and other conventional risk factors.

Correction to: Age at menarche and age at natural menopause in East Asian women: a genome-wide association study.

The original version of this article unfortunately contained a mistake.

Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease.

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.