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Background The association between estradiol/testosterone (E2/T) ratio and metabolic dysfunction‐associated steatotic liver disease (MASLD) remains controversial. Moreover, few studies have explored their relationship in men with type 2 diabetes mellitus. We aimed to investigate the association of the E2/T ratio with MASLD in type 2 diabetes mellitus male patients. Methods This real‐world observational study was performed in 1441 male type 2 diabetes mellitus patients. MASLD was determined by abdominal ultrasonography. The clinical characteristics and prevalence of MASLD were compared across the E2/T ratio quartiles. The association of the E2/T ratio and quartiles with MASLD was also evaluated using binary logistic regression. Results After adjusting for age and diabetes duration (DD), MASLD prevalence significantly increased across the E2/T ratio quartiles (37.7%, 42.6%, 53.1%, and 69.3%, respectively, P < 0.001 for trend). Fully adjusted logistic regression showed that both the E2/T ratio (OR: 2.201, 95% CI: 1.380–3.511, P = 0.001) and quartiles (P = 0.001) were positively associated with MASLD in males with type 2 diabetes mellitus. Furthermore, C‐reactive protein (CRP) levels were significantly higher in patients with MASLD compared with those without (P < 0.001), and obviously increased across the E2/T ratio quartiles after controlling for age and DD (P = 0.016 for trend). Conclusions The E2/T ratio was independently and positively associated with the increased risk of MASLD in male type 2 diabetes mellitus patients, which may be attributed to the close association between the E2/T ratio and inflammation. The E2/T ratio may serve as a simple and practical indicator to assess the risk of MASLD in male type 2 diabetes mellitus patients. The E2/T ratio showed an independent and positive association with the risk of MASLD in male patients with type 2 diabetes mellitus, potentially reflecting its link with inflammation. The E2/T ratio may serve as a simple and practical indicator for assessing MASLD risk in this population.

Background: There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM.Methods: This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893).Results: After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P<0.001 for trend; abdominal obesity: 71.5%, 70.5%, 68.2%, 66.4%, and 64.5%, respectively, P=0.001 for trend). After controlling for confounders, there were clearly negative associations of serum magnesium levels and quintiles with obesity and abdominal obesity in T2DM. Moreover, C-reactive protein partly mediates the effect of serum magnesium on obesity and abdominal obesity (P=0.016 and P=0.004, respectively).Conclusion: The significantly negative relationship between serum magnesium and the risk of obesity and abdominal obesity was observed in T2DM. Furthermore, the independently negative association of serum magnesium with obesity may be explained by its anti-inflammatory functions. Serum magnesium levels may be applied to assess the risk of obesity and abdominal obesity in T2DM.

Background Hyperthyroidism-induced hypercalcemia has been reported previously, but hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement in patients with hyperthyroidism is quite rare. We report the coexistence of hypercalcemia, osteoporosis and thymic enlargement in a patient with Graves’ disease. Case presentation A 22-year-old female was diagnosed as Graves’ disease with obviously elevated serum calcium and reduced parathyroid hormone levels. Dual-energy x-ray absorptiometry and chest enhanced computer tomography (CT) revealed severe osteoporosis and a significant enlargement of thymus. After the successful control of hyperthyroidism with methimazole, hypercalcemia was corrected, bone mineral density was improved and thymus also shrank obviously. Conclusion This is a very rare case of hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement induced by Graves’ disease. In clinical practice, examination of thymus and bone density should be considered when a patient with Graves’ disease was present with hypercalcemia.

Background: The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM.Methods: This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed.Results: After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients.Conclusion: Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Background Bilirubin has been found to protect against overt atherosclerotic diseases, but to date, few studies have investigated the effects of bilirubin especially within the normal range on lower limb atherosclerosis. Therefore, we aimed to assess the associations of bilirubin within normal limits including total bilirubin (TB), conjugated bilirubin (CB) and unconjugated bilirubin (UCB) with lower limb atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). Methods 7284 T2DM patients with normal levels of serum bilirubin were included in this cross-sectional, real-world study. Patients were divided into quintiles by TB levels (< 8.7, 8.7-10.19, 10.20-11.99, 12-13.99, > 13.99 µmol/L). Lower limb ultrasonography was conducted to detect lower limb plaque and stenosis. The association between serum bilirubin and lower limb atherosclerosis was explored by multiple logistic regression. Results A remarkable decrease in the prevalence of lower limb plaque (77.5, 75.3, 70.7, 71.7 and 67.9%) and stenosis (21.1, 17.2, 13.3, 13.0 and 12.0%) was observed across the TB quintiles. Multivariable regression analysis showed that serum TB levels were negatively correlated with higher risks of lower limb plaque and stenosis, both as a continuous variable [OR (95%CI): 0.870 (0.784–0.964), p  = 0.008 for plaque; and 0.835 (0.737–0.946), p  = 0.005 for stenosis] and as categorized in quintiles ( p  = 0.015 and 0.016 for plaque and stenosis). Interestingly, serum CB levels were only negatively correlated with lower limb stenosis [OR (95%CI): 0.767 (0.685–0.858), p  < 0.001], whereas serum UCB levels were only negatively associated with lower limb plaque [ OR (95%CI): 0.864 (0.784–0.952), p  = 0.003] after a fully-adjusted analysis. Furthermore, serum CRP was significantly decreased across the TB quintiles and negatively associated with serum TB (r = -0.107, p  < 0.001), CB (r = -0.054, p  < 0.001), and UCB (r = -0.103, p  < 0.001). Conclusions High-normal serum bilirubin levels were independently and significantly related to reduced risks of lower limb atherosclerosis in T2DM patients. Furthermore, serum bilirubin levels including TB, CB and UCB were inversely correlated with CRP. These results suggested that higher-normal serum bilirubin may exhibit an anti-inflammatory and protective effect against lower limb atherosclerotic progression in T2DM subjects.

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.

Background There is still controversy regarding the associations of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Therefore, it is necessary to explore the correlation between them in T2DM patients. Methods We conducted a survey involving 2565 T2DM patients from a single center. The study cohort was classified into three groups based on the levels of albuminuria: normal UAE (UAE < 30 mg/24 h), moderate UAE (UAE between 30 and 299 mg/24 h) and high UAE (UAE ≥ 300 mg/24 h). Additionally, the patients were divided into three separate groups according to eGFR levels, including low eGFR (eGFR < 60 ml/min/1.73 m 2 ), intermediate eGFR (eGFR 60–89 ml/min/1.73 m 2 ) and normal eGFR (eGFR ≥ 90 ml/min/1.73 m 2 ) groups. Atherosclerotic lesions were compared among the three UAE and eGFR groups. Regression analyses were used to assess the associations of atherosclerotic lesions with UAE and eGFR in T2DM. Results After controlling for age, sex and diabetes duration, the prevalence of atherosclerotic plaque and stenosis were significantly increased from the normal to high UAE groups (plaque: 72.2%, 78.6% and 87.3%, respectively, p = 0.016 for trend; stenosis: 14.0%, 25.5% and 37.3%, respectively, p < 0.001 for trend). Likewise, the values of carotid intima-media thickness (CIMT) and femoral intima-media thickness (FIMT) were also obviously increased from the normal to high UAE groups (CIMT: p < 0.001 for trend; FIMT: p = 0.001 for trend). Conversely, only the FIMT value was clearly increased from the low to normal eGFR groups (p = 0.001 for trend). Fully adjusted regression analyses revealed that UAE was closely associated with the presence of atherosclerotic plaque (OR 1.20, 95% CI 1.03–1.40, p = 0.020) and stenosis (OR 1.17, 95% CI 1.01–1.35, p = 0.036), and with the values of CIMT (β 0.05, 95% CI 0.01–0.10, p = 0.029) and FIMT (β 0.07, 95% CI 0.03–0.11, p = 0.001) in T2DM patients. However, there was no significant association between eGFR levels and atherosclerotic lesions in T2DM after adjustment for multiple confounding factors. Conclusions Overall, albuminuria rather than low eGFR is closely associated with atherosclerotic lesions in T2DM patients. Albuminuria is an independent risk factor for carotid and femoral atherosclerotic lesions in T2DM. Therefore, albuminuria may be a potential early marker to predict the development of atherosclerosis in patients with T2DM.

Background It is still debatable whether glycated albumin/glycated hemoglobin A1C (GA/HbA1C) ratio is associated with metabolic dysfunction-associated fatty liver disease (MAFLD), and few studies have been conducted in type 2 diabetes mellitus (T2DM). Therefore, we aimed to investigate the association between GA/HbA1C ratio and MAFLD and to evaluate whether GA/HbA1C ratio can be used an indicator of MAFLD in Chinese patients with T2DM. Methods This cross-sectional study consisted of 7117 T2DM patients including 3296 men and 3821 women from real-world settings. Abdominal ultrasonography was performed to diagnose MAFLD. In addition to comparing the clinical characteristics among the GA/HbA1C ratio quartile groups, we also investigated the associations of GA/HbA1C ratio and quartiles with MAFLD in T2DM subjects. Results There was a significantly decreased trend in the MAFLD prevalence across the GA/HbA1C ratio quartiles (56.3%, 47.4%, 37.8%, and 35.6% for the first, second, third, and fourth quartile, respectively, P < 0.001 for trend) after adjusting for gender, age, and diabetes duration. Fully adjusted Binary logistic regression indicated that both GA/HbA1C ratio (OR: 0.575, 95% CI: 0.471 to 0.702, P < 0.001) and quartiles (P < 0.001 for trend) were inversely associated with the presence of MAFLD among T2DM patients. Additionally, HOMA2-IR values were clearly increased in the T2DM subjects with MAFLD compared with those without MAFLD (P < 0.001), and markedly increased from the highest to the lowest GA/HbA1C ratio quartile (P < 0.001 for trend). Conclusions GA/HbA1C ratio is closely and negatively associated with MAFLD in T2DM subjects, which may attribute to that GA/HbA1C ratio reflects the degree of insulin resistance. GA/HbA1C ratio may act as a simple and practical indicator to evaluate the risk of MAFLD in T2DM.

Recent studies suggest that histone modification is one of the mechanisms regulating inflammatory cytokine gene expression in hyperglycemic conditions. However, it remains unknown how histone methylation is initiated and involved in changes of inflammatory cytokine gene expression under high glucose (HG) conditions. Our aim was to investigate whether H3K9 methylation was involved in HG-induced expression of inflammatory cytokines in macrophages. Expression profile of cytokine genes under hyperglycemia in THP-1-derived macrophages was determined by human cytokine antibody array. Based on the results from the human cytokine antibody array analyses, the H3K9me3 levels of 4 inflammatory cytokine genes, including interleukin-6 (IL-6), IL-12p40, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β under HG were determined by ChIP assays. Furthermore, the expression of these 4 inflammatory cytokine genes under either HG or chaetocin (an inhibitor of SUV39H1 methyltransferase) exposure or overexpression of SUV39H1 (a H3K9me3-specific methyltransferase) was analyzed by quantitative polymerase chain reaction. Macrophages cultured in HG conditions showed increased gene expression and decreased H3K9me3 levels of inflammatory cytokine genes compared with macrophages incubated in normal glucose (NG) culture. Inhibition of SUV39H1 with chaetocin in NG-treated macrophages also increased the expression of IL-6, IL-12p40, MIP-1α, and MIP-1β. Furthermore, inhibition of SUV39H1 with chaetocin in HG-treated macrophages further increased the expression of these inflammatory cytokines. Contrarily, NG-treated macrophages transfected with SUV39H1 plasmids show decreased expression of inflammatory cytokines. Furthermore, overexpression of SUV39H1 in HG-treated macrophages alleviated the expression of inflammatory cytokines under HG conditions. Finally, HG also increases the expression of inflammation cytokines in mouse bone marrow-derived macrophages. Our data demonstrated that HG increases the expression of inflammatory cytokines in macrophages through decreased H3K9me3 levels, which was partly mediated by SUV39H1. Dysregulation of epigenetic histone modification may be one of the underlying mechanisms for HG-induced inflammatory cytokine expression in macrophages.

We previously reported on the comparison of proteomic data between seven tissue types of a novel “iron prawn” species. However, no transcripts or metabolic information are available for this species. We therefore performed shotgun LC–MS/MS metabonomic and RNA-seq analyses of the total protein from “iron prawns”. KEGG analysis revealed that the largest group consisted of a total of 114 KEGG pathway proteins, comparing the “iron prawns” with the normal prawns. A total of 423 peptides, corresponding to metabolic pathways, ABC transporters, starch and sucrose metabolism, insulin resistance/secretion, fatty digestion and absorption, and lipid metabolism, were identified. The pathways of carbohydrate and amino acid metabolism decreased in female iron prawns, while organic acid and its derivatives increased. However, the pathway of organic acid and its derivatives decreased and lipid metabolism increased in the male iron prawns. The pathways of choline metabolism in cancer and glycerophospholipid/histidine/propanoate metabolism have been significantly affected in iron prawns. Our work provides insight into the understanding of the formation mechanism of the “iron prawn”.