The potential causal association between systemic lupus erythematosus and endocrine and metabolic disorders in the East Asian population: A bidirectional two-sample Mendelian randomization study.

OBJECTIVES: Observational studies indicate a significant correlation between systemic lupus erythematosus (SLE) and endocrine and metabolic disorders, but the causal association between SLE and endocrine and metabolic disorders remains unclear due to the reverse causality and confounding biases commonly presented in conventional observational research. This study endeavors to uncover the causal association between SLE and three common endocrine and metabolic disorders, including Graves' disease (GD), type 2 diabetes mellitus (T2DM), and osteoporosis (OP). METHODS: We used genome-wide association study data for SLE and three endocrine and metabolic disorders in an East Asian population, employing bidirectional two-sample Mendelian randomization (MR) analysis and sensitivity analysis to ascertain the causal association between SLE and endocrine and metabolic disorders. RESULTS: A multiplicative random-effect inverse-variance weighted approach revealed a significant positive correlation between SLE and an elevated risk of GD with an odds ratio (OR) of 1.12 (95% CI: 1.04-1.22, p < .01), and inverse-variance weighted (IVW) analysis also indicated that SLE increased the risk of OP with an OR of 1.035 (95% CI: 1.003-1.068, p < .05). Additionally, GD causally affected SLE in an IVW analysis after Bonferroni correction, with an OR of 1.33 (95% CI: 1.19-1.49, p < .05/3), but the application of multivariable MR analysis resulted in the absence of a causal association of GD on SLE (OR 1.047, 95% CI: 0.952-1.151, p > .05). Lastly, the robustness and validity of the findings were verified through a sensitivity analysis. CONCLUSIONS: We confirmed that SLE has a causal effect on GD as well as OP, but no evidence exists to substantiate a causal link between SLE and T2DM. Our study offers valuable contributions for uncovering the etiology of SLE and endocrine and metabolic disorders and furthering disease risk research while providing potential targets for disease monitoring and therapeutic intervention.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Rare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review.

BACKGROUND: Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy. CASE PRESENTATION: A patient with primary aldosteronism (PA) associated with severe Cushing's syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings. CONCLUSION: Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis.

Background Type 2 Diabetes Mellitus (T2DM) frequently coexists with osteoporosis and reduced bone mineral density (BMD). Dipeptidyl peptidase-4 inhibitors (DPP-4i), a class of antihyperglycemic agents, are commonly employed in T2DM treatment. However, the influence of DPP-4i on bone health remains unclear and debated. This meta-analysis is conducted to explore the relationship between the use of DPP-4i and changes in BMD, as well as the prevalence of osteoporosis among T2DM patients. Methods We conducted a comprehensive search in PubMed, Embase, and Cochrane Library and Web of Science databases for relevant studies published up until June 2023. Studies included in the meta-analysis were those investigating T2DM patients under DPP-4i treatment, and examining the effects on BMD and osteoporosis. Random-effects models and fixed-effect models were utilized to compute the pooled effects. Heterogeneity among the included studies was evaluated using I² statistics. Results This meta-analysis incorporated a total of 10 studies, encompassing a combined population of 214,541 individuals. The results from this meta-analysis indicated an increase in BMD following DPP-4i usage (SMD 0.15, 95 % confidence interval 0.03-0.26). Additionally, the risk of osteoporosis was significantly reduced (OR 0.90, 95 % confidence interval 0.86-0.94) with very low heterogeneity, recorded at 0 % and 53.0 % respectively. No publication bias was detected in the funnel plot, and sensitivity analyses affirmed the stability of the study's conclusions. Conclusion Our results offer valuable insights into the positive impact of DPP-4i on bone health in T2DM patients, contributing to informed clinical decision-making. These findings may inform the development of more comprehensive T2DM management strategies that account for bone health.

TSAb Modulates Microglia M1 Polarization via Activation of the TSHR-Mediated NF-κB Signaling Pathway.

INTRODUCTION: Thyrotropin receptor-stimulating antibody (TSAb) is a pathogenic antibody in the serum of patients with Graves' disease. The binding of TSAb to thyroid-stimulating hormone receptor (TSHR) in non-thyroid tissue may be associated with the occurrence and development of Graves' disease-related complications. However, only few studies have been conducted on the effects of TSAb on the brain, and the pathogenesis of acute hyperthyroidism myopathy (ATM) is unclear. Therefore, this study aimed to explore the effect of TSAb on the polarization of BV-2 cells in the brain and its possible mechanism and provide a basic experimental basis for ATM. METHODS: BV-2 cells were treated with different concentrations of TSAb. The relative survival rate of BV-2 cells was determined using the CCK-8 assay; the migration ability of BV-2 cells was detected using the Transwell migration assay; and the expression levels of M1/M2 polarization markers (CD86, inducible nitric oxide synthase [iNOS], CD206, and arginase 1 [Arg-1]), TSHR, tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein in BV-2 cells were measured using WB. RESULTS: Compared with the negative control group, the proliferative activity of BV-2 cells was significantly increased in the 20, 50, and 100 ng/mL TSAb groups, and the migration ability of BV-2 cells was significantly enhanced in the 50 and 100 ng/mL TSAb groups. The expression levels of M1 polarization markers (CD86 and iNOS), TSHR, TNF-α, and NF-κB protein in BV-2 cells treated with 50 and 100 ng/mL TSAb for 24 h were significantly upregulated, whereas those of M2 polarization markers (CD206 and Arg-1) significantly decreased. CONCLUSIONS: TSAb can induce abnormal activation of microglia, polarize to the M1 phenotype, and promote the inflammatory cascade reaction, in which TSHR plays a key role in NF-κB activation and proinflammatory cytokine release.

Thyrotropin receptor autoantibody (TRAb) enhance the expression of thyrotropin receptor on mouse brain vascular endothelial cells: in vivo and in vitro.

The possibility that thyrotropin receptor (TSHR) expression in non-thyroid tissue is well-documented. However, there is insufficient data on the expression of TSHR in medulla oblongata regions, particularly when focusing on the background of encephalopathy associated with hyperthyroidism. In this study, we explored the expression of the functional TSHR in Graves' disease (GD) mouse cerebral vascular endothelial cells and the effects of thyrotropin receptor autoantibody (TRAb) on its expression. A mouse model of GD was constructed with an adenovirus overexpressing TSHR289. The location and expression of the TSHR gene and protein in vivo were determined via RT-qPCR, Western blot, and immunofluorescence techniques. The effect of TRAb on the expression of functional TSHR in vitro was investigated using bEnd.3 cells. Our results show that medulla oblongata vascular endothelial cells from GD mice expressed higher levels of TSHR compared to control mice. In an in vitro experiment, novel results demonstrated that after treatment with a monoclonal TSHR-specific agonistic antibody (M22), the expression of TSHR on the bEnd.3 cells increased at both the protein and mRNA levels. Furthermore, compared with bEnd.3 cells were treated with IBMX only, those treated with M22 showed increased cAMP production. This study suggested that TSHR is expressed and functionally active in the mouse medulla oblongata and in vitro-cultured bEnd.3 cells and TRAb (M22) increased the expression of TSHR on bEnd.3 cells.

Correlation between plasma long non-coding RNA MEG-3 and inflammatory cytokines in patients with diabetic nephropathy.

To identify the correlation between the plasma long non-coding RNA maternally expressed gene 3 (lncRNA MEG-3) and inflammatory cytokines in patients with diabetic nephropathy (DN) and search for a potential index for the diagnosis of DN. Quantitative real-time PCR (qPCR) was used to assess lncRNA MEG-3 expression. The levels of plasma cytokines were detected via enzyme-linked immunosorbent assay (-ELISA). 20 patients with type 2 diabetes (T2DM) and DN (DM+DN+ group), 19 patients with T2DM (DM+DN- group), and 17 healthy subjects (DM-DN- group) were finally enrolled. The expression of lncRNA MEG-3 was significantly upregulated in the DM+DN+ group compared to the DM+DN- group (p < 0.05) and the DM-DN- group (p < 0.001). Pearson's correlation analysis showed a positive correlation of lncRNA MEG-3 levels with cystatin C (Cys-C) (r = 0.468, p < 0.05), albumin-creatinine ratio (ACR) (r = 0.532, p < 0.05), and creatinine (Cr) (r = 0.468, p < 0.05), and a negative correlation with estimated glomerular filtration rate (eGFR) (r = -0.674, p < 0.01). Furthermore, the expression level of plasma lncRNA MEG-3 had a significantly positive correlation with the level of interleukin 1ß (IL-1ß) (r = 0.524, p < 0.05) and interleukin 18 (IL-18) (r = 0.230, p < 0.05). Binary regression analysis showed that lncRNA MEG-3 was a risk factor for DN with odds ration (OR) value of 1.71 (p < 0.05). The area under receiver operation characteristic (ROC) curve (AUC) of DN identified by lncRNA MEG-3 was 0.724. LncRNA MEG-3 was highly expressed in DN patients and showed a positive correlation with IL-1ß, IL-18, ACR, Cys-C, and Cr.

U-shaped association between triglyceride and risk of incident diabetes in normoglycemic males with NAFLD: A population-base cohort study.

Background: Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. Methods: A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. Results: During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). Conclusions: A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.

Metabolomics study reveals systematic metabolic dysregulation and early detection markers associated with incident pancreatic cancer.

Biomarkers for early detection of pancreatic cancer are in urgent need. To explore systematic circulating metabolites unbalance and identify potential biomarkers for pancreatic cancer in prospective Chinese cohorts, we conducted an untargeted metabolomics study in subjects with incident pancreatic cancer and matched controls (n = 192) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We characterized 998 metabolites in baseline serum and calculated 156 product-to-precursor ratios based on the KEGG database. The identified metabolic profiling revealed systematic metabolic network disorders before pancreatic cancer diagnosis. Forty-Five metabolites or product-to-precursor ratios showed significant associations with pancreatic cancer (P < .05 and FDR < 0.1), revealing abnormal metabolism of amino acids (especially alanine, aspartate and glutamate), lipids (especially steroid hormones), vitamins, nucleotides and peptides. A novel metabolite panel containing aspartate/alanine (OR [95% CI]: 1.97 [1.31-2.94]), androstenediol monosulfate (0.69 [0.49-0.97]) and glycylvaline (1.68 [1.04-2.70]) was significantly associated with risk of pancreatic cancer. Area under the receiver operating characteristic curves (AUCs) was improved from 0.573 (reference model of CA 19-9) to 0.721. The novel metabolite panel was validated in an independent cohort with AUC improved from 0.529 to 0.661. These biomarkers may have a potential value in early detection of pancreatic cancer.

Interaction between smoking and diabetes in relation to subsequent risk of cardiovascular events.

BACKGROUND: Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. METHODS: This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011-2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. RESULTS: Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17-1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01-1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71-1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77-2.14) or former smokers (HR, 1.22; 95% CI, 0.66-2.28). CONCLUSIONS: Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.

Isotemporal substitution of different behaviour patterns with the presence of MAFLD in Chinese adults.

BACKGROUND: Lack of physical activity and excessive sitting time contributed to ectopic fat accumulation, especially in the liver. Previous studies have illustrated the harm of sedentary behaviour and the benefits of physical activity on fatty liver disease. We aimed to explore the association between the behaviour patterns and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) using isotemporal substitution model to examine the effect of replacing one behaviour to another while keeping the total time and other behaviours fixed among Chinese middle-aged and elderly population. METHODS: This study included 161 147 participants aged ≥40 years old from the nationwide, population-based cohort of the REACTION study. The International Physical Activity Questionnaire was used to measure self-reported time for sleeping, sitting, walking and moderate-to-vigorous physical activity (MVPA). MAFLD was defined by evidence of fatty liver index (FLI) ≥ 60 in addition to one of the following three patterns, namely overweight/obesity, presence of diabetes, or evidence of metabolic dysregulation. Isotemporal substitution models using logistic regression models to evaluate the association of replacement of different behaviour patterns with each other and the risk of MAFLD. RESULTS: Substitution of 60 minutes per day of sleeping, walking or total MVPA for sitting was associated with a 2%-8% reduction of MAFLD risk in overall participants. In employed individuals, replacing sitting time with occupational MVPA or nonoccupational MVPA both could bring benefits to liver steatosis. Stratified analysis found that replacing 60 minutes of sitting time with an equivalent time of other behaviour pattern could reduce approximately 8% of the risk among MAFLD participants with metabolic abnormalities. Such a relationship might be explained by the important mediated role of metabolic elements, such as waist circumference, body mass index, triglycerides and homoeostasis model assessment of insulin resistance. Furthermore, replacing sitting with MVPA showed a stronger association among participants who got enough sleep (sleep duration ≥7 hours per day). CONCLUSION: Replacing sitting with other behaviour patterns could reduce the prevalence of MAFLD, and such substitution effect was much remarkably in individuals with abnormal metabolic status. Observably, obese individuals were more likely to benefit from appropriate changes in behaviour patterns. Moreover, the analysis of sleep duration stratification appealed that the adequacy of individual sleep duration also had a significant impact on the substitution effect. It is worth noting that adjusting the time allocation of behaviour patterns might have a beneficial impact on liver-metabolic health, and these findings might help us better recognize the importance of reasonable arrangement of behaviour patterns according to the individual's situation.

Association of soy food with cardiovascular outcomes and all-cause mortality in a Chinese population: a nationwide prospective cohort study.

PURPOSE: This study aimed to clarify the association of soy intake with cardiovascular disease (CVD) and all-cause mortality. METHODS: We conducted a prospective cohort study in a Chinese population composed of 97,930 participants aged ≥ 40 years old without CVD at baseline in 2011. Habitual soy intake over a period of 12 months was evaluated using a food frequency questionnaire. All participants were classified into four groups based on their soy food consumption levels: < 15, 15-29, 30-59, and ≥ 60 g/day, with the lowest category as the reference group. Follow-up was conducted between 2014 and 2016 to assess CVD incidence and all-cause mortality since baseline, which was collected from the local mortality and disease registers of the National Disease Surveillance Point System and National Health Insurance System. The Cox proportional hazards regression models were used to analyze the relationship of soy intake with later CVD events and all-cause mortality. RESULTS: During 350,604 person-years of follow-up (median [interquartile range]: 3.16 [2.98, 4.77] years), 2523 total CVD events and 1473 all-cause mortalities were documented. After controlling for covariates, the hazard ratios (95% confidence intervals) for total CVD events across increasing soy intake levels were 1.03 (0.93-1.14); 0.96 (0.86-1.07); and 0.86 (0.75-0.98; p for trend = 0.0434), while those for all-cause mortality were 0.88 (0.77-1.02); 0.86 (0.74-1.00); and 0.83 (0.69-0.99; p for trend = 0.0084). CONCLUSION: High soy intake was associated with a reduced risk of total CVD events and all-cause mortality among a Chinese population.

Cardiovascular Risk Based on ASCVD and KDIGO Categories in Chinese Adults: A Nationwide, Population-Based, Prospective Cohort Study.

BACKGROUND: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline used eGFR and urinary albumin-creatinine ratio (ACR) to categorize risks for CKD prognosis. The utility of KDIGO's stratification of major CVD risks and predictive ability beyond traditional CVD risk prediction scores are unknown. METHODS: To evaluate CVD risks on the basis of ACR and eGFR (individually, together, and in combination using the KDIGO risk categories) and with the atherosclerotic cardiovascular disease (ASCVD) score, we studied 115,366 participants in the China Cardiometabolic Disease and Cancer Cohort study. Participants (aged ≥40 years and without a history of cardiovascular disease) were examined prospectively for major CVD events, including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. RESULTS: During 415,111 person-years of follow-up, 2866 major CVD events occurred. Incidence rates and multivariable-adjusted hazard ratios of CVD events increased significantly across the KDIGO risk categories in ASCVD risk strata (all P values for log-rank test and most P values for trend in Cox regression analysis <0.01). Increases in c statistic for CVD risk prediction were 0.01 (0.01 to 0.02) in the overall study population and 0.03 (0.01 to 0.04) in participants with diabetes, after adding eGFR and log(ACR) to a model including the ASCVD risk score. In addition, adding eGFR and log(ACR) to a model with the ASCVD score resulted in significantly improved reclassification of CVD risks (net reclassification improvements, 4.78%; 95% confidence interval, 3.03% to 6.41%). CONCLUSIONS: Urinary ACR and eGFR (individually, together, and in combination using KDIGO risk categories) may be important nontraditional risk factors in stratifying and predicting major CVD events in the Chinese population.

Visceral adiposity index is closely associated with urinary albumin-creatinine ratio in the Chinese population with prediabetes.

AIMS: Visceral obesity is a major health issue and is a risk factor for an atherogenic state. Visceral obesity has been reported to be a crucial link between albuminuria and cardiovascular diseases (CVD). This study attempted to explore the association between visceral obesity and albuminuria in prediabetic individuals. METHODS: This cross-sectional study included 24871 prediabetic participants over 40 years of age from seven centres across China (REACTION study). The visceral adiposity index (VAI) was determined based on the measurements of anthropometric indices and lipid parameters. Increased albuminuria was defined as a urinary albumin-creatinine ratio (UACR) ≥30 mg/g, indicating kidney damage. Propensity score matching was used to reduce bias, and a multiple logistic regression model was performed to evaluate the association between visceral obesity and albuminuria in the population with prediabetes. RESULTS: Participants with increased UACR exhibited increased VAI, age, blood pressure, triglycerides, poor glycaemic control, CVD events, and decreased estimated glomerular filtration rate (eGFR). Multiple logistic regression analysis demonstrated that VAI quartiles were positively associated with an increased risk of albuminuria (Q2: odds rate [OR]: 1.10, 95% confidence intervals [CI] 0.96-1.25; Q3: OR: 1.16, 95% CI 1.01-1.32; Q4: OR: 1.26, 95% CI 1.10-1.44, p for trend = 0.001). Stratified analysis revealed that the association of VAI level with increased albuminuria risk also occurred in people who were young, women, overweight or obese, with poor control of blood pressure, and eGFR ≥90 ml/min per 1.73 m2 . CONCLUSIONS: Visceral obesity assessed by VAI is significantly associated with increased UACR in a Chinese population with prediabetes.

High concentrations of triglycerides are associated with diabetic kidney disease in new-onset type 2 diabetes in China: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

AIMS: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. METHODS: In total, 11 142 patients with new-onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011-2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow-up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow-up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high-density lipoprotein cholesterol (HDL-c) was defined by HDL-c <1.0 mmol/L for men or <1.3 mmol/L for women. RESULTS: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL-c at both baseline and follow-up visits. The DKD group also had higher levels of post-load plasma glucose and TG at follow-up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p = .012) and high TG at follow-up (OR = 1.71, p < .001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow-up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p < .001) after adjustment for covariates. CONCLUSIONS: In a large population of patients with new-onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD.

Electron-Dense Deposition Patterns and the Outcomes of Nephrotic Idiopathic Membranous Nephropathy Treated with Tacrolimus in Chinese Adults.

BACKGROUND Tacrolimus may be effective in the short-term treatment of idiopathic membranous nephropathy (IMN). However, it is not clear whether an electron microscopic classification of the homogeneous and heterogeneous types of nephrotic IMN is related to the efficacy of tacrolimus in patients with IMN. This study aimed to explore this question and to provide evidence for individualized patient treatment. MATERIAL AND METHODS This 6-month retrospective study included 61 Chinese patients previously diagnosed with IMN. Patients received treatment was tacrolimus plus glucocorticoid. The patients were divided into a homogeneous group and a heterogeneous group based on the evaluation of electron-dense deposits. The initial clinicopathologic factors in the 2 groups were analyzed, and the difference in efficacy of tacrolimus in the 2 groups was assessed. The factors predicting remission were also studied. RESULTS No significant alteration in the initial clinicopathologic status was found between the 2 groups, except for proteinuria, serum albumin levels, systolic blood pressure, and renal biopsy results (stages I/II/III/IV). After 3 months of treatment, the difference in remission was not significant between the 2 groups. However, after 6 months of treatment, a significant difference in remission rates was observed between the 2 groups. The binary logistic model showed that the homogeneous nephrotic IMN was independently associated with total remission (partial plus complete remission), and was also related to complete remission. CONCLUSIONS The results of our study revealed that the homogeneous type of nephrotic IMN had a higher short-term remission rate and a predictive value for partial or complete remission, and it might be a meaningful marker of the short-term response to tacrolimus.

A high triglyceride glucose index is more closely associated with hypertension than lipid or glycemic parameters in elderly individuals: a cross-sectional survey from the Reaction Study.

BACKGROUND: Both lipid and glucose abnormalities are associated with hypertension (HTN). However, it is unclear whether the triglyceride-glucose (TyG) index is associated with HTN. Therefore the aim of this study is to investigate the association of the TyG index and HTN and to compare the discriminative power of the TyG index, lipid, glycemic parameters for the risk of HTN in elderly individuals. METHODS: The present study was nested in a longitudinal (REACTION) study from May 2011 to December 2011, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. In total, 47,808 participants were recruited in this cross-sectional study. The TyG index was divided into five groups: the < 20% group, the 20-39% group, the 40-59% group, the 60-79% group and the ≥ 80% group, according to quintile division of the subjects. Three multivariate logistic regression models were used to evaluate the association between the TyG vs. lipid parameters, glycemic parameters and HTN. RESULTS: Multivariate logistic regression analysis shows that compared with lipid and glycemic parameters, the TyG index remains significantly associated with HTN in either total subjects or subjects separated into men and women (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.18-1.51, p < 0.0001 in total subjects; OR 1.39, 95% CI 1.11-1.74, p = 0.0042 in men; OR 1.28, 95% CI 1.11-1.49, p = 0.0010 in women). In a stratified analysis, an elevated TyG index is significantly associated with HTN in the subgroup of the oldest age (≥ 65) (OR 1.67, 95% CI 1.30-2.14, p < 0.0001), as well as with obesity (Body mass index (BMI) ≥ 28 kg/m2) (OR 1.85, 95% CI 1.29-2.66, p = 0.0009) or lower estimated glomerular filtration rate (eGFR) (< 90 mL/(min·1.73 m2)) (OR 1.72, 95% CI 1.33-2.21, p < 0.0001). CONCLUSION: The TyG index is significantly associated with HTN and shows the superior discriminative ability for HTN compared with lipid and glycemic parameters in the Chinese elderly population.

Elevated triglycerides rather than other lipid parameters are associated with increased urinary albumin to creatinine ratio in the general population of China: a report from the REACTION study.

BACKGROUND: Dyslipidaemia has always been regarded as the cornerstone of arteriosclerosis and is related to the pathogenesis of renal insufficiency. However, it is unclear which routinely available lipid parameter is related to urinary albumin to creatinine ratio (UACR). The purpose of this study was to examine the lipid abnormalities associated with UACR in the general population in China. METHODS: The present study was nested in an ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: A lONgitudinal (REACTION) study, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. This cross-sectional study included 34, 569 subjects (11, 390 males and 23, 179 females) from 8 different regional community cohorts, with an average age of 57.9 years. The UACR data were divided into the < 25% group, the 25-49% group, the 50-74% group, and the ≥ 75% group according to the quartile division of the centre where the subjects visited. The lipid classes were defined according to the guidelines for the prevention and treatment of dyslipidaemia in Chinese adults. Multiple logistic regression analysis was used to evaluate the association of the lipid parameters and UACR. RESULTS: Multivariable regression analysis revealed that compared with the other lipid parameters, triglycerides (TG) showed an adjusted odds ratio that was significant in model 1-4. This relationship was attenuated after adjusting for Haemoglobin A1c (HbA1c) and blood pressure (BP), but TG ≥ 2.3 mmol/L was still significantly associated with UACR in total subjects and in both men and women (OR: 1.131, 95% CI 1.065-1.203, P < 0.001 in total subjects; OR: 1.134, 95% CI 1.022-1.258, P = 0.017 in men; OR: 1.129, 95% CI 1.046-1.219, P = 0.002 in women). In the stratified analysis, elevated TG was significantly associated with increased urinary albumin in subjects with eGFR ≥ 90 mL/min per 1.73 m2, 5.6 ≤ FBG < 7.0 or 7.8 ≤ PBG < 11.1 mmol/L, 24 ≤ BMI < 28 kg/m2, 120 ≤ SBP < 140 and/or 80 ≤ DBP < 90 mmHg. CONCLUSIONS: We conclude that high TG levels rather than total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol levels are associated with UACR in the general population in China.

EUS-guided lauromacrogol ablation of insulinomas: a novel treatment.

BACKGROUND AND AIMS: EUS-guided ablation with ethanol has been used to treat insulinoma since 2006 as a minimally invasive alternative for those who are unwilling or unsuitable for surgeries. However, pancreatic fistula, pancreatitis and other adverse effects were found after the procedure in these patients. Herein, we aimed to find a novel feasible injection. METHODS: Seven patients with different chief complaints were diagnosed with insulinoma by symptoms, lab results and pathology results from EUS fine needle aspiration. All the patients refused to have surgeries and were treated by EUS-guided ablation with lauromacrogol. The injection volume was calculated by tumor size. All the patients were followed up by at least 1 month to see if there is any adverse effect. Blood glucose (BG), insulin and C-peptide levels were monitored before and after the procedure. RESULTS: Insulinoma size ranged from 0.76 cm ×0.84 cm to 3.39 cm ×1.84 cm. With a mean injection volume of 1.9 ml (range from 0.9 to 3.9 ml), all the patients showed relief in symptoms after the procedure. During the follow up, their BG, insulin and C-peptide levels went back to normal. None of the patients had any adverse effect. CONCLUSIONS: EUS-guided ablation with lauromacrogol showed good treatment results and received no adverse effect after the procedure. Hence, we consider it as an effective and safe method to treat insulinoma.

A predictive model of thyroid malignancy using clinical, biochemical and sonographic parameters for patients in a multi-center setting.

BACKGROUND: Thyroid nodules are highly prevalent, but a robust, feasible method for malignancy differentiation has not yet been well documented. This study aimed to establish a practical model for thyroid nodule discrimination. METHODS: Records for 2984 patients who underwent thyroidectomy were analyzed. Clinical, laboratory, and US variables were assessed retrospectively. Multivariate logistic regression analysis was performed and a mathematical model was established for malignancy prediction. RESULTS: The results showed that the malignant group was younger and had smaller nodules than the benign group (43.5 ± 11.6 vs. 48.5 ± 11.5 y, p < 0.001; 1.96 ± 1.16 vs. 2.75 ± 1.70 cm, p < 0.001, respectively). The serum thyrotropin (TSH) level (median = 1.63 mIU/L, IQR (0.89-2.66) vs. 1.19 (0.59-2.10), p < 0.001) was higher in the malignant group than in the benign group. Patients with malignancies tested positive for anti-thyroglobulin antibody (TGAb) and anti-thyroid peroxidase antibody (TPOAb) more frequently than those with benign nodules (TGAb, 30.3% vs. 15.0%, p < 0.001; TPOAb, 25.6% vs. 18.0%, p = 0.028). The prevalence of ultrasound (US) features (irregular shape, ill-defined margin, solid structure, hypoechogenicity, microcalcifications, macrocalcifications and central intranodular flow) was significantly higher in the malignant group. Multivariate logistic regression analysis confirmed that age (OR = 0.963, 95% CI = 0.934-0.993, p = 0.017), TGAb (OR = 4.435, 95% CI = 1.902-10.345, p = 0.001), hypoechogenicity (OR = 2.830, 95% CI = 1.113-7.195, p = 0.029), microcalcifications (OR = 4.624, 95% CI = 2.008-10.646, p < 0.001), and central intranodular flow (OR = 2.155, 95% CI = 1.011-4.594, p < 0.05) were independent predictors of thyroid malignancy. A predictive model including four variables (age, TGAb, hypoechogenicity and microcalcification) showed an optimal discriminatory accuracy (area under the curve, AUC) of 0.808 (95% CI = 0.761-0.855). The best cut-off value for prediction was 0.52, achieving sensitivity and specificity of 84.6% and 76.3%, respectively. CONCLUSION: A predictive model of malignancy that combines clinical, laboratory and sonographic characteristics would aid clinicians in avoiding unnecessary procedures and making better clinical decisions.