FGF21/adiponectin ratio predicts deterioration in glycemia: a 4.6-year prospective study in China.

BACKGROUND: The fibroblast growth factor (FGF) 21-adiponectin pathway is involved in the regulation of insulin resistance. However, the relationship between the FGF21-adiponectin pathway and type 2 diabetes in humans is unclear. Here, we investigated the association of FGF21/adiponectin ratio with deterioration in glycemia in a prospective cohort study. METHODS: We studied 6361 subjects recruited from the prospective Shanghai Nicheng Cohort Study in China. The association between baseline FGF21/adiponectin ratio and new-onset diabetes and incident prediabetes was evaluated using multiple logistic regression analysis. RESULTS: At baseline, FGF21/adiponectin ratio levels increased progressively with the deterioration in glycemic control from normal glucose tolerance to prediabetes and diabetes (p for trend < 0.001). Over a median follow-up of 4.6 years, 195 subjects developed new-onset diabetes and 351 subjects developed incident prediabetes. Elevated baseline FGF21/adiponectin ratio was a significant predictor of new-onset diabetes independent of traditional risk factors, especially in subjects with prediabetes (odds ratio, 1.367; p = 0.001). Moreover, FGF21/adiponectin ratio predicted incident prediabetes (odds ratio, 1.185; p = 0.021) while neither FGF21 nor adiponectin were independent predictors of incident prediabetes (both p > 0.05). Furthermore, net reclassification improvement and integrated discrimination improvement analyses showed that FGF21/adiponectin ratio provided a better performance in diabetes risk prediction than the use of FGF21 or adiponectin alone. CONCLUSIONS: FGF21/adiponectin ratio independently predicted the onset of prediabetes and diabetes, with the potential to be a useful biomarker of deterioration in glycemia.

Serum Glycated Albumin Levels Are Affected by Alcohol in Men of the Jinuo Ethnic Group in China.

AIM: To investigate the effects of alcohol on serum glycated albumin (GA) levels in Chinese men. METHODS: A total of 2314 male subjects from the Jinuo ethnic group in China were enrolled. Of these, 986 subjects drank alcohol frequently and 404 subjects did not. Lifestyle information was gathered by using a questionnaire, and measurements of blood pressure, body mass index, blood glucose level, liver function, and kidney function were collected. GA was measured by using an enzymatic method. Frequent drinking was defined as a history of drinking ethanol > 80 g/d within the past two weeks. Nondrinking was defined as no alcohol consumption in the past three months. Subjects with an alcohol intake between 0 and 80 g/d in the past two weeks were included in the drinking-occasionally group. Analysis of variance (ANOVA), correlation analysis, and linear regression were used to evaluate the effects of drinking on serum GA levels. Decision tree regression (DTR) algorithm was used to evaluate the effect of features (variables) on GA levels. RESULTS: We found that male subjects who drank frequently had significantly lower serum GA levels than subjects who did not drink (13.0 ± 1.7 vs. 14.1 ± 3.7, p < 0.05). Spearman's correlation analysis calculated a coefficient of -0.152 between drinking and GA (p < 0.005). Linear regression established that drinking was an independent predictor for GA levels with a standardized regression coefficient of -0.144 (p < 0.05). Decision tree regression showed that the effect of drinking on GA levels (0.0283) is five times higher than that of smoking (0.0057). CONCLUSIONS: Frequent alcohol consumption could result in decreased GA levels in men of the Jinuo ethnic group in China.

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.

Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women.

BACKGROUND: The association between nonalcoholic fatty liver disease (NAFLD) and free triiodothyronine (FT3) in euthyroid subjects was in dispute. We aimed to investigate this issue in a population-based cohort study. MATERIALS AND METHODS: A total of 3144 euthyroid subjects at baseline from the Shanghai Nicheng Atherosclerosis Study were selected for the cross-sectional analysis, and 2089 subjects being followed up after 2.2 years were selected for the longitudinal analysis. NAFLD was diagnosed by ultrasound. The cut-off point of elevated alanine aminotransferase (ALT) level was 40 U/L. The FIB-4 index was used to assess the risk of advanced liver fibrosis. RESULTS: Age-adjusted mean levels of FT3 and FT3/free thyroxine (FT4) ratio were higher in subjects with NAFLD than those without NAFLD and linearly increased with a higher risk of NAFLD progression (assessed by levels of ALT and FIB-4 index) in euthyroid women but not in men. After adjustment for confounding variables, FT3 levels significantly increased with the presence of NAFLD (ß = 0.1, P < 0.001) and linearly increased with a higher risk of NAFLD progression in euthyroid women. After a 2.2-year follow-up, FT3 levels increased with the occurrence of NAFLD (mean change percentage: 1.4%) and decreased with the remission of NAFLD (mean change percentage: -2.7%) in euthyroid women. CONCLUSIONS: There are positive associations of FT3 levels with NAFLD and the risk of NAFLD progression in euthyroid women. The changes in FT3 levels with the alteration of NAFLD status may be an adaptive response to maintain energy and metabolic homeostasis.

Development and validation of a non-invasive assessment tool for screening prevalent undiagnosed diabetes in middle-aged and elderly Chinese.

To develop a non-invasive assessment tool and compare it to other assessment tools among middle-aged and elderly Shanghainese, 15,309 individuals, who were 45-70 years old, not previously diagnosed with diabetes, and from a cross-sectional survey conducted between April 2013 and August 2014 in Shanghai, were selected into this study. The participants were randomly assigned to either the exploratory group or the validation group. Undiagnosed diabetes was defined according to the American Diabetes Association diagnostic criteria, and score points were generated according to the logistic regression coefficients. Age, family history of diabetes, hypertension, overweight/obesity, and central obesity all contributed to the constructed model, the Shanghai Nicheng diabetes screening score, with the area under the receiver-operating characteristic curve (AUC) being 0.654 (95% CI 0.637-0.670) in the exploratory group and 0.669 (95% CI 0.653-0.686) in the validation group. The score value of 6 was the optimal cut-point with the largest Youden's index. When applied to the validation group, our model had a similar discriminative ability to the New Chinese Diabetes Risk Score (AUC: 0.669 vs. 0.662, p = 0.187), and performed better than other screening scores for Chinese. However, our model was inferior to fasting plasma glucose, 2-hour plasma glucose, and glycosylated hemoglobin in detecting prevalent undiagnosed diabetes (AUC: 0.669 (0.653-0.686) vs. 0.881 (0.868-0.894), 0.934 (0.923-0.944), and 0.834 (0.819-0.848), all p < 0.001). Although non-invasive models, based on demographic and clinical information, are advisable in resource-scarce developing areas, regular blood glucose screening is still necessary among those aged 45 or older.

Abdominal subcutaneous adipose tissue: a favorable adipose depot for diabetes?

BACKGROUND: Previous studies have documented that visceral adipose tissue is positively associated with the risk of diabetes. However, the association of subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to assess the associations between different adipose distributions and the risk of newly diagnosed diabetes in Chinese adults. METHODS: The Shanghai Nicheng Cohort Study was conducted among Chinese adults aged 45-70 years. The baseline data of 12,137 participants were analyzed. Subcutaneous and visceral fat area (SFA and VFA) were measured by magnetic resonance imaging. Diabetes was newly diagnosed using a 75 g oral glucose tolerance test. RESULTS: The multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of newly diagnosed diabetes per 1-standard deviation increase in SFA and VFA were 1.29 (1.19-1.39) and 1.61 (1.49-1.74) in men, and 1.10 (1.03-1.18) and 1.56 (1.45-1.67) in women, respectively. However, the association between SFA and newly diagnosed diabetes disappeared in men and was reversed in women (OR 0.86 [95% CI, 0.78-0.94]) after additional adjustment for body mass index (BMI) and VFA. The positive association between VFA and newly diagnosed diabetes remained significant in both sexes after further adjustment for BMI and SFA. Areas under the receiver operating characteristic curve of newly diagnosed diabetes predicted by VFA (0.679 [95% CI, 0.659-0.699] for men and 0.707 [95% CI, 0.690-0.723] for women) were significantly larger than by the other adiposity indicators. CONCLUSIONS: SFA was beneficial for lower risk of newly diagnosed diabetes in women but was not associated with newly diagnosed diabetes in men after taking general obesity and visceral obesity into account. VFA, however, was associated with likelihood of newly diagnosed diabetes in both Chinese men and women.

Distribution and related factors of cardiometabolic disease stage based on body mass index level in Chinese adults-The National Diabetes and Metabolic Disorders Survey.

BACKGROUND: It is important to characterize distribution of cardiometabolic disease (CMD) based on different body mass index (BMI) levels in a population. This information remains scarce in China, so we investigated the proportions and related factors of cardiometabolic disease stages based on different BMI levels in Chinese adults. METHODS: We included 45 093 participants aged ≥20 years from the National Diabetes and Metabolic Disorders Survey. Cardiometabolic disease (central obesity, elevated triglycerides, elevated blood pressure, elevated plasma glucose, reduced high-density lipoprotein cholesterol, and cardiovascular disease) was classified as stage 0 (no CMD), stage 1 (mild-to-moderate CMD), or stage 2 (severe CMD). Overweight/obesity was defined as BMI ≥25 kg/m2 . RESULTS: The standardized proportions of stage 0, stage 1, and stage 2 were 32.6%, 36.4%, and 30.9% in normal-weight men, 29.9%, 42.5%, and 27.7% in normal-weight women, 4.9%, 31.7%, and 63.4% in overweight/obese men, and 6.9%, 31.4%, and 61.7% in overweight/obese women, respectively. Multinomial regression showed that regardless of gender or region, the probability of severe cardiometabolic disease rapidly increased with increasing BMI. Severe cardiometabolic disease risk was positively associated with ageing, family history of diabetes, hypertension, or cardiovascular disease, but was inversely associated with higher levels of education and increased physical activity. CONCLUSIONS: Of Chinese men and women with normal weight, more than one third had mild-to-moderate cardiometabolic disease, and less than one third had severe cardiometabolic disease, while of these with overweight or obesity, nearly one third had mild-to-moderate cardiometabolic disease, and nearly two thirds had severe cardiometabolic disease.

Computer-Assisted Decision Support System in Pulmonary Cancer detection and stage classification on CT images.

Pulmonary cancer is considered as one of the major causes of death worldwide. For the detection of lung cancer, computer-assisted diagnosis (CADx) systems have been designed. Internet-of-Things (IoT) has enabled ubiquitous internet access to biomedical datasets and techniques; in result, the progress in CADx is significant. Unlike the conventional CADx, deep learning techniques have the basic advantage of an automatic exploitation feature as they have the ability to learn mid and high level image representations. We proposed a Computer-Assisted Decision Support System in Pulmonary Cancer by using the novel deep learning based model and metastasis information obtained from MBAN (Medical Body Area Network). The proposed model, DFCNet, is based on the deep fully convolutional neural network (FCNN) which is used for classification of each detected pulmonary nodule into four lung cancer stages. The performance of proposed work is evaluated on different datasets with varying scan conditions. Comparison of proposed classifier is done with the existing CNN techniques. Overall accuracy of CNN and DFCNet was 77.6% and 84.58%, respectively. Experimental results illustrate the effectiveness of proposed method for the detection and classification of lung cancer nodules. These results demonstrate the potential for the proposed technique in helping the radiologists in improving nodule detection accuracy with efficiency.

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.

Impaired pancreatic beta cell compensatory function is the main cause of type 2 diabetes in individuals with high genetic risk: a 9 year prospective cohort study in the Chinese population.

AIMS/HYPOTHESIS: We aimed to evaluate the combined effects of type 2 diabetes risk variants on predicting deterioration of blood glucose and progression of beta cell function and insulin sensitivity in a 9 year prospective cohort from the Chinese population. METHODS: We constructed a weighted genetic risk score (GRS) model based on 40 variants associated with type 2 diabetes validated in an established cross-sectional Chinese population (n = 6,822). The weighted scores were categorised into tertiles to assess the predictive capacity for incidence of type 2 diabetes and impaired glucose regulation (IGR), as well as for changes in Stumvoll first- and second-phase insulin secretion indices and Gutt's insulin sensitivity index (ISI) in a community-based 9 year prospective cohort (n = 2,495), including 2,192 individuals with normal glucose tolerance and 303 with IGR at baseline, through logistic, Cox and multiple linear regression tests. RESULTS: Weighted GRS predicted the incidence of type 2 diabetes and IGR in logistic regression (OR 1.236, 95% CI 1.100, 1.389, p = 0.0004) as well as in the Cox model (HR 1.129, 95% CI 1.026, 1.242, p = 0.0128) after adjusting for age, sex, BMI, smoking and alcohol status at baseline. Moreover, we observed that weighted GRS was able to predict deterioration in beta cell function (ß = -0.0480, p = 9.66 × 10(-5) and ß = -0.0303, p = 3.32 × 10(-5) for first- and second-phase insulin secretion, respectively), but not insulin sensitivity (p = 0.3815), during the 9 year follow-up period. CONCLUSIONS/INTERPRETATION: The weighted GRS predicted blood glucose deterioration arising from change in beta cell function in the Chinese population. Individuals in the intermediate- or high-weighted GRS group exhibited progressive deterioration of beta cell function.

Association between uric acid, cancer incidence and mortality in patients with type 2 diabetes: Shanghai diabetes registry study.

BACKGROUND: An elevated serum uric acid level has often been observed with type 2 diabetes or cancer progression. This study aimed to investigate the association between the serum uric acid, cancer incidence, and mortality in Chinese patients with type 2 diabetes. METHODS: A total of 8274 patients with type 2 diabetes from the Shanghai Diabetes Registry (SDR) participated. The follow-up rate was 85.4%. All subjects were divided into four groups according to the serum uric acid concentration: group 1 (1.0 mg/dL ≤ SUA < 3.0 mg/dL), group 2 (3.0 mg/dL ≤ SUA <5.0 mg/dL), group 3 (5.0 mg/dL ≤ SUA < 7.0 mg/dL), and group 4 (SUA ≥ 7.0 mg/dL). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. A Cox proportional hazards model was used to estimate the relative risks of cancer and death. RESULTS: One hundred thirty-seven men and 115 women had cancer by the end of the study. In women, group 1 had the lowest incidence rate of cancer at 30.3 cases per 10 000 person-years, followed by group 2 (48.2). The cancer incidence rates in groups 3 (80.4) and 4 (100.8) were significantly higher than in group 2 (p < 0.05). No significant differences were observed in the incidence of cancer in men (p = 0.76). The risks of overall mortality and death from cancer were not significantly different among the different serum uric acid groups in either sex (Pmale = 0.480, Pfemale = 0.075). CONCLUSION: In Chinese female diabetic patients, the incidence of cancer increased with serum uric acid levels.

Pancreatic volume is reduced in patients with latent autoimmune diabetes in adults.

AIMS: This study aimed to compare pancreatic volume and its clinical significance among patients with type 2 diabetes mellitus (DM), adult-onset type 1 DM and latent autoimmune diabetes in adults (LADA). METHODS: This is a cross-sectional study. One hundred twenty-six outpatients (68 with LADA and 58 with type 1 DM) and 158 inpatients (71 with type 2 DM and 87 non-diabetic controls) were recruited during May-July 2013 in Shanghai Jiao Tong University Affiliated Sixth People's Hospital. All the patients underwent abdominal computerized tomography; pancreatic volume was then calculated. RESULTS: The mean pancreatic volume was highest in the controls, followed by those in patients with type 2 DM, LADA and type 1 DM. The pancreatic volume in LADA was comparable with that in type 2 DM but significantly greater than that in type 1 DM (p < 0.05). The pancreatic volume in patients with LADA was significantly correlated with sex, waist circumference, body surface area, body mass index, diastolic blood pressure and high-density lipoprotein cholesterol (all p < 0.05). The correlation between pancreatic volume and fasting C-peptide was high in patients with LADA (r = 0.643, p < 0.001) and moderate in patients with type 2 DM (r = 0.467, p < 0.001). The area under the receiver operating characteristic curve for pancreatic volume predictive of absolute insulin deficiency (FCP < 0.9 ng/mL) was 0.85 (0.76-0.94) in LADA. CONCLUSIONS: Pancreatic atrophy in LADA was less marked than in type 1 DM. Pancreatic atrophy may suggest reduced level of fasting C-peptide in patients with LADA. Copyright © 2016 John Wiley & Sons, Ltd.

Associations between clinical characteristics and chronic complications in latent autoimmune diabetes in adults and type 2 diabetes.

BACKGROUND: This study aimed to assess the associations between clinical characteristics and chronic complications in latent autoimmune diabetes in adults (LADA) and type 2 diabetes. METHODS: This is a retrospective study. Our diabetes registry included 6975 patients aged 30-75 years old with phenotypic type 2 diabetes who underwent islet autoantibody screening between 2003 and 2012; 384 patients were identified to have LADA. Rates of chronic complications for LADA and type 2 diabetes were compared using a 1 : 2 matched design. Logistic models were fitted to identify the presence of chronic diabetic complications using clinical characteristics including gender, age, duration of diabetes, glycemic control and metabolic syndrome. RESULTS: When duration of diabetes is <5 years, the prevalence of diabetic nephropathy (nephropathy; 12.2% versus 21.8%, p = 0.018) and diabetic retinopathy (retinopathy; 8.1% versus 15.9%, p = 0.011) were significantly lower in patients with LADA than in patients with type 2 diabetes; the prevalence of nephropathy and retinopathy were comparable between both groups when duration is ≥5 years. There was no significant difference in the prevalence of macrovascular complications between groups. The areas under the receiver operating characteristic curves based on the nephropathy and retinopathy models were larger for LADA than for type 2 diabetes (0.72 versus 0.61, p = 0.013; 0.76 versus 0.68, p = 0.056). CONCLUSIONS: Patients with LADA had a lower prevalence of microvascular complications than patients with type 2 diabetes when the duration of diabetes was <5 years. Regression equation fitted by clinical characteristics can better predict the risk of microvascular complications in LADA than in type 2 diabetes.

Elevated circulating lipocalin-2 levels independently predict incident cardiovascular events in men in a population-based cohort.

OBJECTIVE: Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of cardiovascular diseases (CVD). Lipocalin-2 (LCN2), mainly released from adipocytes, has been shown to be positively associated with CVD in cross-sectional studies. We aimed to evaluate the association of LCN2 with CVD involving a population-based cohort recruited from the Shanghai Diabetes Study. APPROACH AND RESULTS: Serum LCN2 levels were measured using ELISA. Independent predictors of CVD development were identified using Cox proportion hazards regression. The predictive performances of the various models were assessed by Kaplan-Meier analysis. At baseline, circulating LCN2 was significantly associated with a cluster of traditional cardiovascular risk factors. Baseline LCN2 levels in male subjects who developed CVD events during follow-up were significantly higher than those who did not develop CVD events (P=0.012). However, such difference was not significant in female subjects. LCN2 was a predictor of CVD in men, which remained statistically significant after adjustment for traditional cardiovascular risk factors (hazard ratio, 1.038 [95% confidence interval, 1.017-1.060]). LCN2 remained significantly associated with incident CVD even after adjustment for renal function, adiponectin, and high-sensitivity C-reactive protein levels. Kaplan-Meier analysis suggested combination of LCN2 and high-sensitivity C-reactive protein might improve the prediction of CVD events in male subjects. CONCLUSIONS: Elevated circulating LCN2 level is an independent predictor of CVD events in men in a population-based cohort and adds to the prognostic value of high-sensitivity C-reactive protein, which is currently the most extensively studied biomarker of CVD. Measurement of serum LCN2 might be useful for early detection and intervention of CVD.

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.

A deep learning system for predicting time to progression of diabetic retinopathy.

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.

High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: a 3-year prospective study in China.

BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21), a hormone predominantly secreted by the liver, has been shown to be positively associated with the severity of non-alcoholic fatty liver disease (NAFLD) in cross-sectional studies. We investigated the prospective association of FGF21 with NAFLD development in a 3-year prospective study involving a population-based cohort comprising 808 Chinese subjects. METHODS: Serum FGF21 levels at baseline and follow-up were measured using an enzyme-linked immunosorbent assay. Independent predictors of NAFLD development were identified using multiple logistic regressions. The predicting accuracy of the models was evaluated using area under the receiver-operating characteristic (ROC) curves (AUCs). RESULTS: In subjects who had progressed to NAFLD, the baseline FGF21 concentration (319.12 pg/ml [172.65, 518.78]) was significantly higher than that in subjects who did not develop NAFLD (199.10 pg/ml [123.56, 322.80]) (p <0.001). At follow-up, significant increase of FGF21 level was observed in those subjects who developed NAFLD (p <0.05). Baseline FGF21 was an independent predictor of NAFLD (OR: 7.102 [95% CI 2.488-20.270]; p <0.001), together with body mass index (BMI) (OR: 1.489 [95% CI 1.310-1.691]; p <0.001). The ROC-AUC was 0.816 (95% CI 0.766-0.867) for the FGF21 Model, which was calculated with FGF21 and BMI. FGF21 Model <0.13 can be used to rule out (sensitivity=85.71%, negative likelihood ratio=0.23) and ≥0.30 can be rule in (specificity=86.34%, positive likelihood ratio=3.66) ultrasonography-diagnosed NAFLD after 3 years. CONCLUSIONS: High serum FGF21 concentration was an independent predictor of NAFLD in humans. The FGF21 Model and its cut-offs may be useful for early diagnosis and intervention of NAFLD.

Serum electrolyte levels in relation to macrovascular complications in Chinese patients with diabetes mellitus.

BACKGROUND: The prevalence of diabetes in China is increasing rapidly. However, scarce data are available on serum electrolyte levels in Chinese adults with diabetes, especially in those with cardiovascular complications. This study measured serum electrolyte levels and examined their relationship with macrovascular complications in Chinese adults with diabetes. METHODS: The three gender- and age-matched groups were enrolled into this analysis, which were 1,170 subjects with normal glucose regulation (NGR), 389 with impaired glucose regulation (IGR) and 343 with diabetes. Fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG), glycosylated hemoglobin A1c (HbA1c) and serum electrolyte levels were measured. Data collection included ankle brachial index results. RESULTS: Serum sodium and magnesium levels in the diabetes group were significantly decreased compared to the NGR group (sodium: 141.0 ± 2.4 vs. 142.1 ± 2.0 mmol/l; magnesium: 0.88 ± 0.08 vs. 0.91 ± 0.07 mmol/l, all P < 0.01), while the serum calcium level was significantly increased (2.36 ± 0.11 vs. 2.33 ± 0.09 mmol/l, P < 0.01). Multiple linear regression showed that serum sodium and magnesium levels in the diabetes group were negatively correlated with FPG, 2hPG and HbA1c (sodium: Std ß = -0.35, -0.19, -0.25; magnesium: Std ß = -0.29, -0.17, -0.34, all P < 0.01), while the serum calcium level was positively correlated with HbA1c (Std ß = 0.17, P < 0.05). In diabetic subjects, serum sodium, magnesium and potassium levels were decreased in the subjects with the elevation of estimated glomerular filtration rates (P < 0.05). ANCOVA analysis suggested that serum magnesium level in subjects with diabetic macrovascular complications was significantly decreased compared with diabetic subjects without macrovascular complications after the effect of some possible confounding being removed (P < 0.05). CONCLUSIONS: Serum sodium and magnesium levels were decreased in Chinese subjects with diabetes, while the observed increase in calcium level correlated with increasing glucose level. Diabetic patients with macrovascular complications had lower serum magnesium level than those with no macrovascular complications.

Ten-year changes in the prevalence of overweight, obesity and central obesity among the Chinese adults in urban Shanghai, 1998-2007 - comparison of two cross-sectional surveys.

BACKGROUND: In China, obesity is expected to increase rapidly in both urban and rural areas. However, there have been no comprehensive reports on secular trends in obesity prevalence among Chinese adults in urban Shanghai, which is the largest city in southern China. METHODS: In 1998-2001 and again in 2007-2008, two independent population-based cross-sectional surveys were conducted in Shanghai to investigate the prevalence of metabolic disorders. These surveys obtained height, waist circumference (WC), and weight measurements for Chinese adults aged between 20 and 74 years who lived in urban communities. From the 1998-2001 survey, 4,894 participants (2,081 men and 2,813 women, mean age: 48.9 years) were recruited, and 4,395 participants (1,599 men and 2,796 women, mean age: 49.8 years) were recruited from the 2007-2008 survey. Using the World Health Organization criteria, overweight was defined as 25 kg/m² ≤ BMI < 30 kg/m² and obesity as BMI ≥ 30 kg/m². Central obesity was defined as WC ≥ 90 cm in men or ≥85 cm in women. The differences in prevalence of obesity, central obesity and overweight between the two surveys were tested using multivariable logistic regression analyses. RESULTS: Compared to the 1998-2001 survey, in the 2007-2008 survey the BMI distribution for men and the WC distribution for both genders is shifted significantly to the right along the x-axis (all p < 0.001). Over the ten years, the prevalence of combined overweight and obesity increased 24% (from 31.5% to 39.1%, p < 0.001) in men, but decreased 8% (from 27.3% to 25.0%; p < 0.01) in women. The prevalence of central obesity increased 40% in men (from 19.5% to 27.3%; p < 0.01), but the increase was not significant in women (15.0% to 17.1%; p = 0.051). In the total population, only central obesity showed a significant change between the populations in the two surveys, increasing 29% (from 17.3% to 22.4%; p < 0.001). CONCLUSIONS: Over this 10 year period, central obesity increased significantly in the Shanghai adult population. However, the prevalence of combined overweight and obesity was significantly increased in men but not in women.