Huaixing（黎怀星） Li

Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals.

OBJECTIVE To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome in the Chinese population. RESEARCH DESIGN AND METHODS Plasma 25(OH)D was measured in a cross-sectional sample of 1,443 men and 1,819 women aged 50–70 years from Beijing and Shanghai. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Fasting plasma glucose, insulin, lipid profile, A1C, and inflammatory markers were measured. RESULTS The geometric mean of plasma 25(OH)D was 40.4 nmol/l, and percentages of vitamin D deficiency [25(OH)D <50 nmol/l] and insufficiency [50 ≤ 25(OH)D <75 nmol/l] were 69.2 and 24.4%, respectively. Compared with the highest 25(OH)D quintile (≥57.7 nmol/l), the odds ratio for metabolic syndrome in the lowest quintile (≤28.7 nmol/l) was 1.52 (95% CI 1.17–1.98, Ptrend = 0.0002) after multiple adjustment. Significant inverse associations also existed between 25(OH)D and individual metabolic syndrome components plus A1C. Moreover, we observed significant inverse associations of 25(OH)D with fasting insulin and the insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) in overweight and obese individuals (BMI ≥24 kg/m2) but not in their normal-weight counterparts (test for interaction: P = 0.0363 and 0.0187 for insulin and HOMA-IR, respectively). CONCLUSIONS Vitamin D deficiency is common in the middle-aged and elderly Chinese population, and a low 25(OH)D level is significantly associated with an increased risk of having metabolic syndrome and insulin resistance. Prospective studies and randomized clinical trials are warranted to determine the role of 25(OH)D in the development of metabolic syndrome and related metabolic diseases.

Variants in the Fat Mass–and Obesity-Associated ( FTO ) Gene Are Not Associated With Obesity in a Chinese Han Population

OBJECTIVE— Recently, genome-wide association studies have provided evidence that several common variants within the fat mass–and obesity-associated (FTO) gene were significantly associated with obesity in populations of European origin. However, their effects in other ethnic populations remain to be elucidated. RESEARCH DESIGN AND METHODS— In this study, we examined the association between three FTO variants (rs8050136, rs9939609, and rs9930506) and obesity and related traits in a population-based study of 3,210 unrelated Chinese Han subjects from Shanghai and Beijing. In secondary analyses, we also tested for association with type 2 diabetes and related traits. Logistics regression and generalized linear models were used to test for additive and dominant effects of the risk alleles. RESULTS— The minor allele frequencies of rs8050136, rs9939609, and rs9930506 in our population (0.12, 0.12, and 0.20, respectively) were substantially lower than those observed for populations of European descent (e.g., for CEU population of HapMap: 0.45, 0.48, and 0.45, respectively). Despite our study being sufficiently powered to detect effects similar to those previously reported, none of the FTO SNPs were found to be associated with obesity, overweight, BMI, waist circumference, or body fat percentage. In addition, none of the SNPs exhibited significant associations with fasting levels of plasma glucose, A1C, insulin, or β-cell function (estimated via homeostasis model assessment) under either an additive or a dominant model in the quantitative trait analyses. Analyses stratified by sex or geographical region did not change these observations. CONCLUSIONS— Our data do not support that the FTO common variants are major contributors of obesity or type 2 diabetes in the Chinese Han population.

Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population

OBJECTIVE— Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and examine the associations of these variants with type 2 diabetes and diabetes-related phenotypes. RESEARCH DESIGN AND METHODS— We genotyped 17 single nucleotide polymorhisms (SNPs) in 3,210 unrelated Chinese Hans, including 424 participants with type 2 diabetes, 878 with impaired fasting glucose (IFG), and 1,908 with normal fasting glucose. RESULTS— We confirmed the associations between type 2 diabetes and variants near CDKAL1 (odds ratio 1.49 [95% CI 1.27–1.75]; P = 8.91 × 10−7) and CDKN2A/B (1.31 [1.12–1.54]; P = 1.0 × 10−3). We observed significant association of SNPs in IGF2BP2 (1.17 [1.03–1.32]; P = 0.014) and SLC30A8 (1.12 [1.01–1.25]; P = 0.033) with combined IFG/type 2 diabetes. The SNPs in CDKAL1, IGF2BP2, and SLC30A8 were also associated with impaired β-cell function estimated by homeostasis model assessment of β-cell function. When combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960, and SLC30A8-rs13266634 increased the risk for type 2 diabetes by 1.24-fold (P = 2.85 × 10−7) or for combined IFG/type 2 diabetes by 1.21-fold (P = 6.31 × 10−11). None of the SNPs in EXT2 or LOC387761 exhibited significant association with type 2 diabetes or IFG. Significant association was observed between the HHEX/IDE SNPs and type 2 diabetes in individuals from Shanghai only (P < 0.013) but not in those from Beijing (P > 0.33). CONCLUSIONS— Our results indicate that in Chinese Hans, common variants in CDKAL1, CDKN2A/B, IGF2BP2, and SLC30A8 loci independently or additively contribute to type 2 diabetes risk, likely mediated through β-cell dysfunction.

A Marker of Endotoxemia Is Associated With Obesity and Related Metabolic Disorders in Apparently Healthy Chinese

OBJECTIVE Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese. RESEARCH DESIGN AND METHODS A population-based study including 559 overweight/obese (BMI ≥24.0 kg/m2) and 500 normal-weight (18.0 ≤ BMI <24.0 kg/m2) subjects aged 35–54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW) adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. RESULTS LBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] vs. 10.0 [9.1–11.1] μg/ml; P < 0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05–6.09) and 5.53 (95% CI 2.64–11.59) for metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results. CONCLUSIONS Elevated circulating LBP was associated with obesity, metabolic syndrome, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders. Prospective studies are needed to confirm these results.

Ferritin Concentrations, Metabolic Syndrome, and Type 2 Diabetes in Middle-Aged and Elderly Chinese

CONTEXT Elevated ferritin concentrations frequently cluster with well-established risk factors of diabetes including obesity, metabolic syndrome, chronic inflammation, and altered circulating adipokines. Few studies, however, have systematically evaluated the effect of these risk factors on ferritin-diabetes association, particularly in Chinese populations. OBJECTIVE We aimed to investigate, in a middle-aged and elderly Chinese population, whether elevated ferritin concentrations are associated with higher risk of metabolic syndrome and type 2 diabetes and to what extent the associations were influenced by obesity, inflammation, and adipokines. DESIGN AND METHODS We conducted a population-based, cross-sectional survey of 3,289 participants aged 50-70 yr in Beijing and Shanghai in 2005. Fasting plasma ferritin, glucose, insulin, lipid profile, glycohemoglobin, inflammatory markers, adipokines, and dietary profile were measured. RESULTS Median ferritin concentrations were 155.7 ng/ml for men and 111.9 ng/ml for women. After multiple adjustment, the odds ratios (ORs) were substantially higher for type 2 diabetes (OR 3.26, 95% confidence interval 2.36-4.51) and metabolic syndrome [OR 2.80 (95% confidence interval 2.24-3.49)] in the highest ferritin quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for dietary factors, body mass index, inflammatory markers, and adipokines. CONCLUSIONS Elevated circulating ferritin concentrations were associated with higher risk of type 2 diabetes and metabolic syndrome in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors. Our data support the crucial role of iron overload for metabolic diseases, even in a country with relatively high prevalence of iron deficiency.

Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese

BACKGROUND Vitamin D deficiency is recently speculated to play a role in the development of depression. Nevertheless, few studies have explored the association between blood 25-hydroxyvitamin D [25(OH)D] concentrations and depression in the general population. Therefore, we aimed to determine this association in middle-aged and elderly Chinese. METHODS We conducted a population-based cross-sectional study in 2005 in Beijing and Shanghai, China. Participants included 3262 community residents aged 50-70. Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale (CES-D) score of 16 or higher. Circulating 25(OH)D concentrations were measured by radioimmunoassay. RESULTS The prevalence of depressive symptoms was lower in the top tertile of 25(OH)D concentrations compared to the lowest tertile (7.2% vs. 11.1%) in the study population (odds ratio, 0.62; 95% confidence interval, 0.46-0.83; P for trend=0.002). This association was substantially attenuated after controlling for various confounding factors, and disappeared after including geographic location in the model. Stratified analysis by location did not find any association between depressive symptoms and 25(OH)D levels among participants from either Beijing or Shanghai. LIMITATIONS Due to the cross-sectional study design, causal relation remains unknown. CONCLUSIONS Depressive symptoms are not associated with 25(OH)D concentrations in middle-aged and elderly Chinese. Further prospective studies are required to determine whether they are correlated.

Associations of Physical Activity With Inflammatory Factors, Adipocytokines, and Metabolic Syndrome in Middle-Aged and Older Chinese People

Background— Inflammatory factors, adipocytokines, and the metabolic syndrome are important determinants of cardiometabolic disease. It remains unclear how physical activity is related to these risk factors. Our objective was to investigate single and joint associations of physical activity with inflammatory factors, adipocytokines, and the metabolic syndrome among middle-aged and older Chinese people. Methods and Results— A total of 3289 individuals (1458 men, 1831 women) 50 to 70 years of age participated in a population-based cross-sectional survey in Beijing and Shanghai, China. Levels of total physical activity were assessed with the International Physical Activity Questionnaire. High-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-&agr; receptor 2, adiponectin, and retinol-binding protein 4 were measured. The metabolic syndrome was defined using the updated National Cholesterol Education Program/Adult Treatment Panel III criteria for Asian Americans. Plasma concentrations of high-sensitivity C-reactive protein were 1.58, 1.74, and 1.27 mg/L (P=0.0138) and of adiponectin were 16.12, 16.20, and 17.21 mg/L (P=0.0078) among individuals with low, medium, and high levels of total physical activity, respectively, with adjustment for potential confounders. In the multivariable-adjusted logistic regression analyses, participants with higher levels of total physical activity had a lower risk of having the metabolic syndrome (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.85; P for trend=0.001) compared with those with lower levels. Conclusions— Being physically active is associated with a better profile of inflammatory factors and adipocytokines and a reduced risk of having the metabolic syndrome among Chinese people.

Lifestyle Counseling and Supplementation with Flaxseed or Walnuts Influence the Management of Metabolic Syndrome

A healthy lifestyle may ameliorate metabolic syndrome (MetS); however, it remains unclear if incorporating nuts or seeds into lifestyle counseling (LC) has additional benefit. A 3-arm, randomized, controlled trial was conducted among 283 participants screened for MetS using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Participants were assigned to a LC on the AHA guidelines, LC + flaxseed (30 g/d) (LCF), or LC + walnuts (30 g/d) (LCW) group. After the 12-wk intervention, the prevalence of MetS decreased significantly in all groups: -16.9% (LC), -20.2% (LCF), and -16.0% (LCW). The reversion rate of MetS, i.e. those no longer meeting the MetS criteria at 12 wk, was not significantly different among groups (LC group, 21.1%; LCF group, 26.6%; and LCW group, 25.5%). However, the reversion rate of central obesity was higher in the LCF (19.2%; P = 0.008) and LCW (16.0%; P = 0.04) groups than in the LC group (6.3%). Most of the metabolic variables (weight, waist circumference, serum glucose, total cholesterol, LDL cholesterol, apolipoprotein (Apo) B, ApoE, and blood pressure) were significantly reduced from baseline in all 3 groups. However, the severity of MetS, presented as the mean count of MetS components, was significantly reduced in the LCW group compared with the LC group among participants with confirmed MetS at baseline (P = 0.045). Our results suggest that a low-intensity lifestyle education program is effective in MetS management. Flaxseed and walnut supplementation may ameliorate central obesity. Further studies with larger sample sizes and of longer duration are needed to examine the role of these foods in the prevention and management of MetS.

Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans

Objectives Recent genome-wide association studies have identified a number of variants influencing blood pressure. We aimed to examine whether these associations can be replicated in Chinese. Methods We genotyped eight of these variants (in or near FGF5, CYP17A1, MTHFR, ZNF652, PLCD3, ATP2B1, c10orf107) in a population-based cohort of Chinese Hans (N = 3210). Logistics regression and generalized linear analyses were applied to test for association of each variant with hypertension risk and blood pressure (BP), BMI, waistline and high-sensitivity C-reactive protein (hsCRP), respectively. Results Six variants showed directionally consistent association with blood pressure and risk of hypertension, of which four (FGF5, two in CYP17A1, MTHFR) reached significance. The associations were most pronounced for FGF5-rs16998073 [SBP: β = 1.97 mmHg/allele, P = 0.0006; DBP: β = 0.95 mmHg/allele, P = 0.0008, hypertension: odds ratio (OR) 1.36/allele, P = 0.0001]. Effect size of FGF5-rs16998073 on SBP and hypertension were significantly more pronounced in Han Chinese compared to white Europeans. None of these variants was associated with BMI, waistline or hsCRP that are the well established risk factors for hypertension. The genetic risk score, calculated as the sum of BP-increasing alleles of FGF5-rs16998073, CYP17A1-rs11191548, CYP17A1-rs1004467 and MTHFR-rs17367504, was significantly associated with increased SBP (1.16 mmHg/allele, P = 9.01E–5), DBP (0.51 mmHg/allele, P = 4.40E–4) and hypertension risk (OR = 1.22/allele, P = 2.74E–7). Conclusion Variants in or near FGF5, CYP17A1 and MTHFR contributed to variation in BP and hypertension risk. Effect sizes of these three loci tended to be larger in Chinese than in white Europeans, but more studies with larger sample size are required for a definitive conclusion.