Serum biomarkers combined with ultrasonography for early diagnosis of non-alcoholic fatty liver disease confirmed by magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized ß = 0.185, P < 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816-0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice.

Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia.

There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (ß = 0.151, P = 0.035) and HOMA-IR (ß = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes.

Predicted secreted protein analysis reveals synaptogenic function of Clstn3 during WAT browning and BAT activation in mice.

Promoting white adipose tissue (WAT) browning and enhancing brown adipose tissue (BAT) activity are attractive therapeutic strategies for obesity and its metabolic complications. Targeting sympathetic innervation in WAT and BAT represents a promising therapeutic concept. However, there are few reports on extracellular microenvironment remodeling, especially changes in nerve terminal connections. Identifying the key molecules mediating the neuro-adipose synaptic junctions is a key point. In this study, we used bioinformatics methods to identify the differentially expressed predicted secreted genes (DEPSGs) during WAT browning and BAT activation. These DEPSGs largely reflect changes of cytokines, extracellular matrix remodeling, vascularization, and adipocyte-neuronal cross-talk. We then performed functional enrichment and cellular distribution specificity analyses. The upregulated and downregulated DEPDGs during WAT browning displayed a distinctive biological pattern and cellular distribution. We listed a cluster of adipocyte-enriched DEPSGs, which might participate in the cross-talk between mature adipocytes and other cells; then identified a synaptogenic adhesion molecule, Clstn3, as the top gene expressed enriched in both mature white and brown adipocytes. Using Q-PCR and immunohistochemistry, we found significantly increased Clstn3 expression level during WAT browning and BAT activation in mice subjected to cold exposure (4 °C). We further demonstrated that treatment with isoproterenol significantly increased Clstn3 and UCP1 expression in differentiated white and beige adipocytes in vitro. In conclusion, our study demonstrates that the secretion pattern was somewhat different between WAT browning and BAT activation. We reveal that Clstn3 may be a key gene mediating the neuro-adipose junction formation or remodeling in WAT browning and BAT activation process.

Inhibition of mitochondrial complex I improves glucose metabolism independently of AMPK activation.

Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes. Glucose output was measured in primary hepatocytes. Compound C and adenoviruses expressing dominant negative AMP-activated protein kinase (AMPK) α1/2 were exploited to inactivate AMPK pathway. Cellular NAD+ /NADH ratio was assayed to evaluate energy transforming and redox state. Rotenone ameliorated hyperglycaemia and insulin resistance in db/db mice. It induced glucose consumption and glycolysis and reduced hepatic glucose output. Rotenone also activated AMPK. Furthermore, it remained effective with AMPK inactivation. The enhanced glycolysis and repressed gluconeogenesis correlated with a reduction in cellular NAD+ /NADH ratio, which resulted from complex I suppression. Amobarbital, another representative complex I inhibitor, stimulated glucose consumption and decreased hepatic glucose output in vitro, too. Similar changes were observed while expression of NDUFA13, a subunit of complex I, was knocked down with gene silencing. These findings reveal mitochondrial complex I emerges as a key drug target for diabetes treatment. Inhibition of complex I improves glucose homoeostasis via non-AMPK pathway, which may relate to the suppression of the cellular NAD+ /NADH ratio.

Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population.

Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. The levels of serum uric acid and bone turnover markers (BTMs) were detected along with other biochemical traits. In addition, the fat distribution was calculated through MRI and image analysis software, and bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. For postmenopausal females, the prevalence of osteoporosis was significantly lower in the hyperuricemia group compared with the normouricemic group (P=4.65E-06). In females, serum uric acid level was significantly associated with osteoporosis, with odds ratio (OR) and 95% confidence interval (95% CI) of 0.844 [0.763; 0.933] (P=0.0009) after adjusting for age, body mass index, HbA1c, lean mass, visceral and subcutaneous fat areas, albumin, 25-hydroxyvitamin D3 [25(OH)D3], and parathyroid hormone (PTH). In females, serum uric acid level was positively correlated with the BMD of the femoral neck (ß±SE: 0.0463±0.0161; P=0.0042), total hip (ß±SE: 0.0433±0.0149; P=0.0038) and L1-4 (ß±SE: 0.0628±0.0165; P=0.0001) after further adjusting for age, BMI, HbA1c, lean mass, VFA, SFA, albumin, 25(OH)D3 and PTH. Regarding BTMs, serum uric acid level was negatively correlated with N-terminal procollagen of type I collagen (PINP) in females (ß±SE: -0.1311±0.0508; P=0.0100). In summary, our results suggest that uric acid has a protective effect on bone metabolism independent of body composition in Chinese postmenopausal females.

Association of bone turnover markers with glucose metabolism in Chinese population.

The association between type 2 diabetes (T2DM) and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Participants were classified according to their glucose tolerance as normal glucose tolerance (NGT), impaired glucose regulation (IGR) or T2DM. Males and females were analyzed separately, and then associations between bone turnover markers (BTMs) and glucose metabolism were evaluated. The results showed that in females, the serum levels of N-terminal osteocalcin (N-MID), N-terminal procollagen of type I collagen (PINP) and ß-cross-linked C-telopeptide of type I collagen (ß-CTX) were significantly decreased in the T2DM group compared to the NGT group (P<0.01). When age, body mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat area, anti-diabetic medicines, PINP, N-MID and ß-CTX were included in one logistic model, N-MID (OR [95% CI]: 0.954 [0.932; 0.976]; P=0.0001) was significantly associated with T2DM in females. In females, N-MID was associated with insulin sensitivity and HOMA-ß. PINP was significantly associated with HOMA-ß, GUTT-ISI, Stumvoll first-phase insulin secretion index (STU-1) and Stumvoll second-phase insulin secretion index (STU-2), but ß-CTX was associated only with HOMA-ß (ß±SE: 0.1331±0.0311; P=1.95×10-5) and GUTT-ISI (ß±SE: 0.0727±0.0229; P=0.0015). In males, N-MID was significantly correlated with HOMA-ß (ß±SE: 0.3439±0.0633; P=7.75×10-8), GUTT-ISI (ß±SE: 0.1601±0.0531; P=0.0027) and STU-1 (ß±SE: 0.2529±0.1033; P=0.0146). Significant associations were also detected between ß-CTX and HOMA-ß (ß±SE: 0.2736±0.0812; P=0.0009). This study reveals that BTMs are highly associated with T2DM, insulin sensitivity and beta cell function in both Chinese males and postmenopausal females.

Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes.

KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study. The anthropometric parameters were determined at baseline and at the final visit, while clinical laboratory tests were performed at baseline and on weeks 2, 4, 6, 12, 16. Two SNPs, rs2237892 and rs2237895, in the region of the KCNQ1 gene were genotyped in all the participants. All calculations and statistical analyses were conducted using SPSS. The rs2237892 TT homozygotes exhibited significantly higher 2-h glucose levels at baseline (P<0.05) and a lower cumulative attainment rate of the target 2-h glucose level (Plog-rank=0.020) than the C allele carriers. Patients with greater numbers of rs2237892 T alleles exhibited larger augmentations (Δ) in the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype exhibited a higher Δ homeostasis model assessment of ß-cell function (HOMA-ß) than CC and CT genotype carriers (P=0.021 and P=0.043, respectively). Moreover, the rs2237895 C allele was associated with a greater decrement in Δ glycated hemoglobin (HbA1c) (P=0.024); and patients with the CC genotype exhibited greater variance than those with the AA and AC genotypes (P=0.005 and 0.021, respectively). Compared with the C allele, the odds ratio for treatment success among carriers of the rs2237892 T allele was 2.533 (P=0.007); and the rs2237895 C allele was associated with a 2.360-fold decrease in HbA1c compared with the A allele (P=0.009). KCNQ1 polymorphisms are associated with gliclazide MR efficacy in Chinese patients with type 2 diabetes.

The coexistence of carotid and lower extremity atherosclerosis further increases cardio-cerebrovascular risk in type 2 diabetes.

BACKGROUND: Both carotid and lower limb atherosclerosis are associated with increased cardiovascular and cerebrovascular risks. However, it is still unclear whether the concomitant presence of carotid and lower extremity atherosclerosis further increases the cardiovascular and cerebrovascular risks. Therefore, our aim is to investigate whether the coexistence of carotid and lower extremity atherosclerosis was associated with higher cardiovascular and cerebrovascular risks in patients with type 2 diabetes. METHODS: This cross-sectional study was performed in 2830 hospitalized patients with type 2 diabetes. Based on carotid and lower limb Doppler ultrasound results, the patients were divided into three groups including 711 subjects without atherosclerosis, 999 subjects with either carotid or lower limb atherosclerosis, and 1120 subjects with both carotid and lower limb atherosclerosis. And we compared the clinical characteristics and prevalence of both cardio-cerebrovascular events (CCBVEs) and self-reported cardio- cerebrovascular diseases (CCBVDs) among the three groups. RESULTS: After adjusting for age, sex, and duration of diabetes, there were significant increases in the prevalence of both CCBVEs (3.8 vs. 11.8 vs. 26.4 %, p < 0.001 for trend) and self-reported CCBVDs (6.9 vs. 19.9 vs. 36.5 %, p < 0.001 for trend) across the three groups (diabetics without atherosclerosis, diabetics with either carotid or lower limb atherosclerosis, and diabetics with both carotid and lower extremity atherosclerosis). A fully adjusted logistic regression analysis also revealed that compared with those without atherosclerosis, those with either carotid or lower limb atherosclerosis had higher risk of CCBVEs (OR 1.724, 95 % CI 1.001-2.966) and self-reported CCBVDs (OR 1.705, 95 % CI 1.115-2.605), and those with concomitant presence of carotid and lower extremity atherosclerosis had the highest risk of CCBVEs (OR 2.869, 95 % CI 1.660-4.960) and self-reported CCBVDs (2.147, 95 % CI 1.388-3.320)(p < 0.001 for trend in CCBVEs and p = 0.002 for trend in CCBVDs, respectively). CONCLUSIONS: Either carotid or lower limb atherosclerosis was obviously related to increased cardio-cerebrovascular risk in type 2 diabetes. The concomitant presence of carotid and lower extremity atherosclerosis further increased cardio-cerebrovascular risk in patients with type 2 diabetes. The combined application of carotid and lower extremity ultrasonography may help identify type 2 diabetics with higher cardio-cerebrovascular risk.

BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis.

Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.

Fibroblast growth factor 21 is regulated by the IRE1α-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis.

Endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR) and represents a critical mechanism that underlies metabolic dysfunctions. Fibroblast growth factor 21 (FGF21), a hormone that is predominantly secreted by the liver, exerts a broad range of effects upon the metabolism of carbohydrates and lipids. Although increased circulating levels of FGF21 have been documented in animal models and human subjects with obesity and nonalcoholic fatty liver disease, the functional interconnections between metabolic ER stress and FGF21 are incompletely understood. Here, we report that increased ER stress along with the simultaneous elevation of FGF21 expression were associated with the occurrence of nonalcoholic fatty liver disease both in diet-induced obese mice and human patients. Intraperitoneal administration of the ER stressor tunicamycin in mice resulted in hepatic steatosis, accompanied by activation of the three canonical UPR branches and increased the expression of FGF21. Furthermore, the IRE1α-XBP1 pathway of the UPR could directly activate the transcriptional expression of Fgf21. Administration of recombinant FGF21 in mice alleviated tunicamycin-induced liver steatosis, in parallel with reduced eIF2α-ATF4-CHOP signaling. Taken together, these results suggest that FGF21 is an integral physiological component of the cellular UPR program, which exerts beneficial feedback effects upon lipid metabolism through counteracting ER stress.

Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice.

It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. But, it is unclear exactly how the two pathways coordinate to regulate insulin sensitivity upon hyperinsulinism stress of type 2 diabetes mellitus (T2DM). Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation.

Decreased urine uric acid excretion is an independent risk factor for chronic kidney disease but not for carotid atherosclerosis in hospital-based patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: The associations between urine uric acid excretion (UUAE) and chronic kidney disease (CKD)/atherosclerosis have not been investigated. Our aims were to investigate the relationships between UUAE and CKD and carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. METHODS: This was a cross-sectional study that was conducted with 2627 Chinese inpatients with type 2 diabetes. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartiles according to their UUAE levels. Carotid atherosclerotic lesions, including carotid intima-media thickness (CIMT), plaque and stenosis, were assessed by Doppler ultrasound. Both CKD and carotid atherosclerotic lesions were compared between the UUAE quartile groups. RESULTS: After adjustment for confounding factors, there was a significant decrease in the prevalence of CKD in the patients with type 2 diabetes across the UUAE quartiles (16.9%, 8.5%, 5.9%, and 4.9%; p < 0.001). Multiple logistic regression analyses revealed that the UUAE quartiles were significantly and inversely associated with the presence of CKD (p < 0.001). Compared with the diabetics in the highest UUAE quartile, those in the lowest quartile exhibited a nearly 4.2-fold increase in the risk of CKD (95% CI: 2.272-7.568; p < 0.001). The CIMT value (0.91 ± 0.22 mm for the diabetics with CKD and 0.82 ± 0.20 mm for the diabetics without CKD, p = 0.001) and the prevalence of carotid plaques (62.1% for the diabetics with CKD and 41.8% for the diabetics without CKD, p = 0.025) were significantly higher in the diabetics with CKD than in those without CKD. However, there was no obvious difference in carotid atherosclerotic lesions across the UUAE quartiles after controlling for the confounding factors. CONCLUSIONS: Decreased UUAE was closely associated with the presence of CKD but not with carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. Our results suggest that UUAE is an independent risk factor for CKD in type 2 diabetes. In selected populations, such as patient with type 2 diabetes, the role of uric acid in atherosclerosis might be the result of other concomitant atherosclerotic risk factors, such as CKD.

Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels.

AIM: Osteocalcin is involved in the progression of nonalcoholic fatty liver disease (NAFLD) in animal models and humans. In this study we investigated the relationship between serum osteocalcin levels and NAFLD in postmenopausal Chinese women. METHODS: A total of 733 postmenopausal women (age range: 41-78 years) with normal blood glucose levels were enrolled in this cross-sectional study. Women taking lipid-lowering or anti-hypertensive drugs were excluded. Serum osteocalcin levels were assessed using an electrochemiluminescence immunoassay. The degree of NAFLD progression for each subject was assessed through ultrasonography. The fatty liver index (FLI) of each subject was calculated to quantify the degree of liver steatosis. RESULTS: The median level of serum osteocalcin for all subjects enrolled was 21.99 ng/mL (interquartile range: 17.84-26.55 ng/mL). Subjects with NAFLD had significantly lower serum osteocalcin levels (18.39 ng/mL; range: 16.03-23.64 ng/mL) compared with those without NAFLD (22.31 ng/mL; range: 18.55-27.06 ng/mL; P<0.01). Serum osteocalcin levels decreased with incremental changes in the FLI value divided by the quartile (P-value for trend<0.01). The serum osteocalcin levels showed a negative correlation with the FLI values, even after adjusting for confounding factors (standardized ß=-0.124; P<0.01). Binary logistic regression analysis identified an individual's serum osteocalcin level as an independent risk factor for NAFLD (odds ratio: 0.951; 95% confidence interval: 0.911-0.992; P=0.02). CONCLUSION: Serum osteocalcin levels are inversely correlated with NAFLD in postmenopausal Chinese women with normal blood glucose levels.

Effect of Dietary Resistant Starch on Prevention and Treatment of Obesity-related Diseases and Its Possible Mechanisms.

Overweight or obesity has become a serious public health problem in the world, scientists are concentrating their efforts on exploring novel ways to treat obesity. Nowadays, the availabilities of bariatric surgery and pharmacotherapy have enhanced obesity treatment, but it should has support from diet, physical exercise and lifestyle modification, especially the functional food. Resistant starch, an indigestible starch, has been studied for years for its beneficial effects on regulating blood glucose level and lipid metabolism. The aim of this review is to summarize the effect of resistant starch on weight loss and the possible mechanisms. According to numerous previous studies it could be concluded that resistant starch can reduce fat accumulation, enhance insulin sensitivity, regulate blood glucose level and lipid metabolism. Recent investigations have focused on the possible associations between resistant starch and incretins as well as gut microbiota. Resistant starch seems to be a promising dietary fiber for the prevention or treatment of obesity and its related diseases.

Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population.

AIM: Genome-wide association studies have identified several novel loci associated with serum uric acid concentrations in individuals of European descent. In the current study, we aimed to evaluate the associations between these loci and serum uric acid concentrations in a Chinese population. METHODS: Fourteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped in 2329 Chinese subjects in Shanghai. Serum biochemical parameters including uric acid concentrations were determined. All the variants were analyzed for gender differences since uric acid metabolism differed between genders. RESULTS: In males after adjustments for age and BMI, GCKR rs780094, SLC2A9 rs11722228 and SF1 rs606458 were associated with the uric acid concentrations, which were statistically significant (P=0.016, 0.001 and 0.03, respectively), whereas SLC2A9 rs3775948 was marginally associated with the uric acid concentrations (P=0.071). In females, SLC22A12 rs506338 was also marginally associated with the uric acid concentrations (P=0.057). The meta-analysis for combined data from both males and females revealed that rs3775948 and rs606458 were associated with the uric acid concentrations (P=0.036 and 0.043, respectively). Furthermore, the gender significantly affected the association of rs11722228 with serum uric acid levels (P=0.012). CONCLUSION: The SLC2A9 rs11722228, SF1 rs606458 and GCKR rs780094 variants modulate uric acid concentrations in Chinese males, while SF1 rs606458 and SLC2A9 rs3775948 are associated with the uric acid concentrations in both Chinese males and females.

Serum vitamin D is associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes.

AIM: Considering the characterization of vitamin D deficiency as a risk factor of ectopic fat deposition, the association of serum 25-hydroxy vitamin D3 [25(OH)D3] levels with non-alcoholic fatty liver disease (NAFLD) was evaluated in Chinese men with normal body mass index (BMI) and enzyme markers of liver function. METHODS: A total of 514 participants (22 to 79 years old) with normal BMI and liver enzymes were identified for analysis. Abdominal ultrasound was performed to diagnose NAFLD, and the fatty liver index (FLI) was calculated to quantify liver steatosis. Serum 25(OH)D3 levels were determined by an electrochemiluminescence immunoassay. RESULTS: Among the entire study population, the mean levels of serum 25(OH)D3 were 15.32±5.77 ng/mL. However, when serum 25(OH)D3 levels were compared between non-NAFLD subjects (n=438) and NAFLD subjects (n=76), the latter showed significantly lower levels (15.65±5.89 ng/mL vs 13.46±4.65 ng/mL, P=0.002). In addition, serum 25(OH)D3 levels were found to be significantly correlated with FLI after adjustment for age and BMI (r=-0.108, P=0.014). Logistic regression showed that serum 25(OH)D3 levels were independently correlated with NAFLD (OR: 0.937, 95% CI: 0.884-0.993, P=0.028). Furthermore, stepwise regression analysis revealed that serum 25(OH)D3 levels were inversely associated with FLI (ß=-0.055, P=0.040). CONCLUSION: The present study demonstrated that serum 25(OH)D3 levels were inversely associated with NAFLD, even in subjects with normal total body fat, suggesting a potential role of lower levels of vitamin D in the occurrence and development of NAFLD.

Prevalence of unruptured cerebral aneurysms in Chinese adults aged 35 to 75 years: a cross-sectional study.

BACKGROUND: The reported prevalence of unruptured cerebral aneurysms (UCAs) varies widely. OBJECTIVE: To measure the prevalence of UCAs by using 3-dimensional time-of-flight magnetic resonance angiography in adults aged 35 to 75 years. DESIGN: Cross-sectional study done between June 2007 and June 2011. SETTING: Two communities chosen at random from 2 districts (1 urban and 1 suburban) in Shanghai, China. PARTICIPANTS: 4813 adults aged 35 to 75 years. MEASUREMENTS: Three-dimensional time-of-flight magnetic resonance angiography, interpreted by 3 observers blinded to the participants' information, was used to identify the location and size of UCAs and to estimate the overall, age-specific, and sex-specific prevalence. RESULTS: 369 UCAs were found in 336 participants (130 men and 206 women); 4477 participants had no evidence of UCAs. The prevalence was 7.0% overall (95% CI, 6.3% to 7.7%), with 5.5% for men (CI, 4.6% to 6.4%) and 8.4% for women (CI, 7.3% to 9.5%). The overall prevalence of UCAs was higher in women than in men (P < 0.001) and peaked at ages 55 to 64 years in men and women. The UCAs were mostly located in the internal carotid artery (81%), and 90.2% had a maximum diameter less than 5 mm. Mean diameter was larger in women than in men (3.7 mm vs. 3.2 mm; P < 0.009). LIMITATION: Participants were from 2 communities selected from 2 districts in Shanghai, and adults older than 75 years were not studied. CONCLUSION: The overall prevalence of UCAs was 7.0% in Chinese adults aged 35 to 75 years, and most lesions had a diameter less than 5 mm. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Relationship between waist circumference and elevation of carotid intima-media thickness in newly-diagnosed diabetic patients.

OBJECTIVE: Waist circumference, as a brief indicator of visceral obesity, is associated with multi-metabolic disorders and cardiovascular diseases. The present study was aimed to find out the relationship between waist circumference and carotid intima media thickness (C-IMT), as well as the best waist circumference cutoff for identifying C-IMT elevation in Chinese male patients with newly-diagnosed diabetes. METHODS: Five hundred and seventy-eight patients from Department of Endocrinology and Metabolism in Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University were enrolled. Both physical examination (for measurement of waist circumference) and carotid ultrasonography (for measurement of C-IMT) were performed. RESULTS: After grouping according to the quartiles of C-IMT, the waist circumference increased across all its quartiles. The waist circumference in 3rd and 4th quartiles (90.7±9.8 cm and 90.8±9.6 cm) was significant higher than in 1st and 2nd quartiles (P<0.05). When subjects were divided into 4 groups according to waist circumference, the C-IMT of subjects with waist circumference 90-95 cm was significant higher than that of subjects with waist circumference 85-90 cm and less than 85 cm respectively (P<0.05). Both spearman and partial correlation analysis showed that C-IMT was positively correlated with waist circumference (P<0.01). C-IMT was found significantly elevated with the increase of waist circumference. Multiple stepwise regression analysis showed that waist circumference was one of the independent risk factors of C-IMT. After an average of 2.23±0.85 years follow up, there was a significant elevation of C-IMT in the group with baseline waist circumference over 90 cm P<0.05), while no significant difference was detected in the group with baseline waist circumference less than 90 cm (P=0.27). Logistic regression showed that baseline waist circumference over 90 cm was associated with a relative risk to C-IMT elevation of 1.132 (95% CI 1.043-1.431, P<0.05). CONCLUSION: Among newly-diagnosed diabetic male patients, waist circumference over 90 cm not only reflects sub-clinical atherosclerosis in early stage, but also predicts the progression of atherosclerosis.

Effectiveness of different waist circumference cut-off values in predicting metabolic syndrome prevalence and risk factors in adults in China.

OBJECTIVE: To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China. METHODS: A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria. RESULTS: The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions. CONCLUSION: Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. METHODS: In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. RESULTS: The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, p<0.001), but no significant difference was found compared with the non-ketotic type 2 diabetics (0.73±0.19 mm, p=0.582) after controlling for differences in age and sex. In both the ketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both p<0.001) after controlling for sex, but no sex difference was observed (p=0.479 and p=0.707, respectively) after controlling for age. In the ketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. CONCLUSIONS: The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2 diabetics. The characteristics of carotid atherosclerotic lesions in the ketosis-onset diabetics resembled those in the non-ketotic type 2 diabetics. Our findings support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes.