Xu（林旭） Lin

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.

Meta-analysis of the effects of flaxseed interventions on blood lipids

BACKGROUND Several clinical trials have investigated the effects of flaxseed and flaxseed-derived products (flaxseed oil or lignans) on blood lipids; however, the findings have been inconsistent. OBJECTIVE We aimed to identify and quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles. DESIGN A comprehensive literature search was performed on the basis of English reports of randomized controlled trials of flaxseed or its derivatives on lipid profiles in adults, which were published from January 1990 to October 2008. Attempts also were made to access unpublished data. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS Twenty-eight studies were included. Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively; significant reductions were observed with whole flaxseed (-0.21 and -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements but not with flaxseed oil. The cholesterol-lowering effects were more apparent in females (particularly postmenopausal women), individuals with high initial cholesterol concentrations, and studies with higher Jadad scores. No significant changes were found in the concentrations of HDL cholesterol and triglycerides. CONCLUSIONS Flaxseed significantly reduced circulating total and LDL-cholesterol concentrations, but the changes were dependent on the type of intervention, sex, and initial lipid profiles of the subjects. Further studies are needed to determine the efficiency of flaxseed on lipid profiles in men and premenopausal women and to explore its potential benefits on other cardiometabolic risk factors and prevention of cardiovascular disease.

A crucial role for RACK1 in the regulation of glucose-stimulated IRE1alpha activation in pancreatic beta cells.

RACK1 dictates the response of the intracellular stress sensor IRE1α to different extracellular stimuli. Stress Control Obesity and metabolic diseases, such as diabetes, are associated with endoplasmic reticulum (ER) stress and the accumulation of unfolded proteins in the ER, which activates the unfolded protein response (UPR). One of the mediators of the UPR is inositol-requiring enzyme 1α (IRE1α), which is autophosphorylated and activated in response to ER stress. In pancreatic β cells, IRE1α promotes insulin biosynthesis in response to acute glucose stimulation but inhibits this process after chronic glucose stimulation. To determine the mechanisms that mediate these different responses of IRE1α to glucose stimulation, Qiu et al. searched for previously unidentified binding partners of IRE1α. They found that the scaffold protein RACK1 interacted with IRE1α after glucose stimulation. Protein phosphatase 2A (PP2A) remained associated with RACK1 after acute glucose stimulation but dissociated from RACK1 after chronic glucose stimulation or the induction of ER stress. The differential association of PP2A with RACK1 accounted for stimulus-specific alterations in the phosphorylation and activation state of IRE1α. Islets from db/db mice, which are obese and mildly diabetic, showed decreased RACK1 abundance, as well as increased IRE1α phosphorylation and insulin content, and overexpression of RACK1 in these islets partially reversed these increases. Thus, RACK1 differentially modulates the activation of IRE1α in response to the duration of glucose stimulation and to ER stress, and RACK1-mediated regulation of IRE1α may be altered by prolonged metabolic stress. Autophosphorylation of inositol-requiring enzyme 1α (IRE1α) is required for its activation, which elicits the cellular unfolded protein response (UPR) and is functionally connected with insulin biosynthesis in pancreatic β cells. We found that the scaffold protein receptor for activated C-kinase 1 (RACK1) interacted with IRE1α in a glucose-stimulated or endoplasmic reticulum (ER) stress–responsive manner in pancreatic β cells and primary islets. RACK1 mediated the glucose-inducible assembly of a complex containing IRE1α, RACK1, and protein phosphatase 2A (PP2A) to promote dephosphorylation of IRE1α by PP2A, thereby inhibiting glucose-stimulated IRE1α activation and attenuating IRE1α-dependent increases in insulin production. Moreover, IRE1α activation was increased and RACK1 abundance was decreased in a mouse model of diabetes. Thus, our findings demonstrate that RACK1 functions as a key component in regulating the IRE1α signaling pathway in pancreatic β cells.

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.