Unveiling the hidden impact: Subclinical hypercortisolism and its subtle influence on bone health.

In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward-looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.

TG: A Mediator of the Relationship of Serum Uric Acid to Creatinine Ratio and Nonalcoholic Fatty Liver Disease in Non-Obese Patients with Type 2 Diabetes.

Background: The study estimated the association between NAFLD and SUA/Cr in Chinese non-obese patients with type 2 diabetes mellitus (T2DM) and also investigated mediating effect of TG. Methods: All patients were divided into NAFLD group (n = 420) and non-NAFLD group (n = 347). The differences of biochemical indicators between the two groups were compared. The link between SUA/Cr and other parameters was checked through Spearman correlation analysis. Differences in the incidence rate of NAFLD between SUA/Cr and TG 3 tertile subgroups were tested by chi-squared. To explore the independent influence of SUA/Cr and TG on NAFLD, logistic regression was performed. The predictive value of SUA/Cr and SUA/Cr combined with BMI for NAFLD was analyzed using ROC curves. In addition, to confirm whether TG has a mediating effect on the link of SUA/Cr and NAFLD, we conducted a mediating analysis. Results: NAFLD group had higher SUA/Cr values than individuals without NAFLD (P < 0.01). SUA/Cr was linked with TC and TG (r = 0.081, 0.215 respectively). NAFLD prevalence increased progressively from quartile 1 to quartile 3 of SUA/Cr (44% vs 57% vs 62%). Prevalence of NAFLD increased from quartile 1 to quartile 3 of TG (35.8% vs 58.7% vs 69.9%). Analysis of the logistic regression revealed that SUA/Cr and TG were statistically linked with NAFLD. The ROC curve pointed out that the area under the curve (AUC), sensitivity and specificity of SUA/Cr were 0.59, 0.629 and 0.522, respectively. The AUC, sensitivity and specificity for SUA/Cr combined with BMI were 0.719, 0.644 and 0.677, separately. The mediation analysis showed a statistically direct effect of SUA/Cr on NAFLD (ß=0.148, 95% CI: 0.0393, 0.2585). The function of SUA/Cr on NAFLD partially mediated by TG (ß=0.1571, 95% CI: 0.0704, 0.2869). Conclusion: SUA/Cr was significantly associated with NAFLD in non-obese T2DM patients, and TG partially mediated this association. SUA/Cr can be applied to predict for NAFLD.

Geriatric nutritional risk index is correlated with islet function but not insulin resistance in elderly patients with type 2 diabetes: A retrospective study.

The geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that can predict poor prognosis in elderly subjects. The aim of this study was to evaluate the association between GNRI and both islet function and insulin sensitivity in patients with type 2 diabetes mellitus. This research carries significant implications for the integrated treatment and nutritional management of this patient population. A total of 173 patients with type 2 diabetes mellitus, aged 60 years or older, who were hospitalized in the Endocrinology Department at Hebei General Hospital from February 2018 to June 2021, were selected as the research subjects. These subjects were divided into 4 groups according to the quartile of their GNRI values: T1 (GNRI < 99.4, n = 43), T2 (99.4 ≤ GNRI < 103, n = 43), T3 (103 ≤ GNRI < 106.3, n = 43), and T4 (GNRI ≥ 106.3, n = 44). Glucose, insulin, and C-peptide concentrations were tested at 0, 30, 60, 120, and 180 minutes during a 75 g oral glucose tolerance test. The homeostasis model assessment for insulin resistance and the homeostasis model assessment for ß cell function index were calculated. As the GNRI value increased, the levels of total protein, albumin, hemoglobin, alanine transaminase, aspartate aminotransferase, and 25-hydroxyvitamin D increased significantly. The area under the curve for blood glucose decreased significantly across the 4 groups, while the AUCs for insulin and C-peptide showed an overall increasing trend. ß Cell function index increased significantly with the increase of GNRI; meanwhile, both the early-phase insulin secretion index and the late-phase insulin secretion index increased significantly. Although there was an increasing trend, homeostasis model assessment for insulin resistance did not change significantly among the 4 groups. This study indicates that elderly type 2 diabetes patients with higher nutritional risk have worse islet function, while insulin sensitivity is not associated with nutritional risk.

Red blood cell membrane-coated functionalized Cu-doped metal organic framework nanoformulations as a biomimetic platform for improved chemo-/chemodynamic/photothermal synergistic therapy.

Nanoformulations for combining chemotherapy, chemodynamic therapy, and photothermal therapy have enormous potential in tumor treatment. Coating nanoformulations with cell membranes endows them with homologous cellular mimicry, enabling nanoformulations to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused multifunctional biomimetic nanoformulations based on Cu-doped zeolitic imidazolate framework-8 (ZIF-8). Hydroxycamptothecin (HCPT), a clinical anti-tumor drug, was encapsulated into ZIF-8, which was subsequently coated with polydopamine (PDA) and red blood cell membrane. The as-fabricated biomimetic nanoformulations showed an enhanced cell uptake in vitro and the potential to prolong blood circulation in vivo, producing effective synergistic chemotherapy, chemodynamic therapy, and photothermal therapy under the 808 nm laser irradiation. Together, the biomimetic nanoformulations showed a prolonged blood circulation and evasion of immune recognition in vivo to provide a bio-inspired strategy which may have the potential for the multi-synergistic therapy of breast cancer.

Red Blood Cell Membrane-Camouflaged Polydopamine and Bioactive Glass Composite Nanoformulation for Combined Chemo/Chemodynamic/Photothermal Therapy.

Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an "all-in-one" nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.

Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study.

Objective: Previous studies have shown that oxymatrine (OMT) can improve high-fat-high-fructose-diet-induced non-alcoholic fatty liver disease (NAFLD), and our study aimed to explore its possible metabolic potential mechanisms. Methods: Wistar rats were fed a high-fat-high-fructose diet for 8 weeks and treated with oxymatrine by gavage for the last 4 weeks. We measured biochemical indicators and pathological changes in each group and used liquid chromatography-mass spectrometry (LC-MS) to analyze changes in metabolites in the serum and liver of the rats. Results: The results showed that OMT can alleviate the high-fat-high-fructose-induced weight gain and hepatic lipid deposition in rats. Metabolomic analysis showed that the level of eicosapentaenoic acid (EPA) was downregulated and levels of desmosterol and d-galactose were upregulated in livers fed with HFDHFr. The levels of L-isoleucine, L-valine, arachidonic acid (AA), taurocholic acid (TCA), chenodeoxycholyltaurine (TDCA), isocitrate, and glutathione (GSH) were downregulated in the liver, whereas those of linoleic acid (LA), phosphocholine (PC), glycerophosphocholine (GPC), and oxidized glutathione (GSSG) were upregulated in the serum treated with OMT. Conclusion: In summary, OMT can improve HFDHFr-induced NAFLD, and metabolomic analysis can provide an early warning for the development of NAFLD as well as provide a rationale for therapeutic targets.

Correlation Between the Levels of ANGPTL3, ANGPTL4, ANGPTL8 and Postprandial Triglyceride-Rich Lipoprotein (TRL).

Purpose: To investigate the effects of different angiopoietin-like proteins (ANGPTLs) on postprandial hypertriglyceridemia (PPT) by analyzing changes in serum lipid, ANGPTL3, ANGPTL4, and ANGPTL8 levels before and after a high-fat diet in individuals with normal fasting lipid and oral glucose tolerance test results. Patients and Methods: Exactly 103 volunteers were recruited for an oral fat tolerance test (OFTT). Blood samples were obtained at 0, 2, and 4 h after eating to detect relevant indicators. PPT was defined as triglyceride (TG) levels ≥ 2.5 mmol/L. According to the test results, the participants were divided into two groups: postprandial normal triglycerides (PNT) and PPT. The levels of blood lipids and ANGPTL3, ANGPTL4, and ANGPTL8 were compared between the two groups. Results: There were differences in the body mass index (BMI), waist circumference (WC), fasting total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), triglyceride-rich lipoprotein cholesterol (TRL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), ApoA1/ApoB, fasting blood glucose (FBG), fasting insulin (FINS), ANGPTL4, and ANGPTL8 between the two groups. In the PNT group, the TG level increased from baseline at 2 and 4 h, TRL-C increased from baseline at 4 h, and ANGPTL8 decreased from baseline at 2 and 4 h. After OFTT, the levels of TG, TRL-C, ANGPTL3, and ANGPTL4 in the PPT group gradually increased; ANGPTL8 gradually decreased. Fasting ANGPTL3 was positively associated with age, TC, HDL-C, TRL-C, and ApoA1, and negatively associated with systolic blood pressure. Fasting ANGPTL4 was positively correlated with weight, WC, BMI, TC, TG, LDL-C, TRL-C, non-HDL-C, ApoB, FBG, and FINS, and negatively correlated with ApoA1/ApoB and fasting ANGPTL8. Binary logistic regression analysis indicated that ANGPTL4 and ANGPTL8 were significant predictors of PPT. Conclusion: PPT occurrence is closely associated with changes in ANGPTL4 and ANGPTL8 levels.

High Atherogenic Risk in Ketosis-Prone Type 2 Diabetic Individuals with Ketosis Episodes: A Cross-Sectional Study.

Purpose: Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS. Patients and Methods: A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters. Results: The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (ß = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (ß = -0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients. Conclusion: Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.

Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer.

Introduction: Emerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed. Methods: The high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored. Results: We identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2. Discussion: Together, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers.

Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis.

Objective: In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Method: We used Stata 17.0 for the NMA. Eligible Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and Embase databases until December 2022. Two researchers independently screened the available studies. The Cochrane Risk of Bias tool was used to assess the risk of bias in the included studies. We used GRADEprofiler (version3.6) to analyze the evidence certainty. Primary outcomes such as liver fat content (LFC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, as well as secondary outcomes such as γ-glutamyltransferase (γGGT) and body weight, were evaluated. Then, each intervention was ranked by the surface under the cumulative ranking curve (SUCRA). As a supplement, we drew forest plots of subgroup using RevMan (version 5.4). Results: Fourteen RCTs involving 1666 participants were included in the present study. The NMA results showed that exenatide (bid) was the best treatment for improving LFC compared with other agents, liraglutide, dulaglutide, semaglutide (qw) and placebo), and the SUCRA values were 66.8%. Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%). The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02]. As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4]. The quality of evidence was assessed as moderate or low. Conclusion: The daily GLP-1RAs may be more effective in primary outcomes. And the daily semaglutide may be the most effective treatment for NAFLD and T2DM among the six interventions.

Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study.

Purpose: The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications. Methods: A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were sub-classified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and ß-crosslaps (ß-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications. Results: After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [O, p < 0.001] and increased serum P1NP levels , p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, ß-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and ß-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD. Conclusion: Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.

Serum 25-Hydroxyvitamin D Levels in Type 2 Diabetes Patients in North China: Seasonality and the Association between Vitamin D Status and Glycosylated Hemoglobin Levels.

Background and Aims: Previous studies have reported a correlation between vitamin D levels and seasonality in healthy populations. However, there are few studies on the seasonal variation in vitamin D levels and its relationship with glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to investigate seasonal changes in serum 25-hydroxyvitamin D [25(OH)D] levels and the associations between these vitamin D concentrations and HbA1c levels in T2DM patients in Hebei, China. Methods: A cross-sectional study of 1,074 individuals with T2DM was conducted from May 2018 to September 2021. Levels of 25(OH)D in these patients were assessed based on both sex and season, and relevant clinical or laboratory variables that could impact vitamin D status were also considered. Results: In the T2DM patient cohort, the mean blood 25(OH)D levels were 17.05 ng/mL. A total of 698 patients (65.0%) had insufficient serum 25(OH)D levels. The vitamin D deficiency rates were significantly higher in the winter and spring compared to the autumn (P < 0.05), indicating that seasonal fluctuations can have a significant impact on 25(OH)D levels. The levels of vitamin D inadequacy were highest in the winter (74%), and females were more likely than males to be deficient (73.4% vs. 59.5%, P < 0.001). In comparison to the winter and spring, both males and females showed higher 25(OH)D levels in the summer (P < 0.001). HbA1c levels were 8.9% higher in those with vitamin D deficiencies than in nondeficient patients (P < 0.001). HbA1c and vitamin D levels were negatively correlated (r = -0.119, P < 0.001). Conclusion: Vitamin D deficiencies are particularly prevalent among T2DM patients in Hebei, China, with exceptionally high rates in the winter and spring. Female T2DM patients were at an elevated risk of vitamin D deficiency, and vitamin D levels were negatively correlated with HbA1c.

Anticentromere antibody positive patients with primary Sjögren's syndrome have distinctive clinical and immunological characteristics.

OBJECTIVES: To investigate the clinical manifestations, immunological characteristics, circulating lymphocyte subsets and risk factors of anticentromere antibody (ACA) positive patients with primary Sjögren's syndrome (pSS). METHODS: Data of 333 patients with newly diagnosed pSS were collected and analysed retrospectively. The demographic features, glandular dysfunction, extraglandular manifestations, laboratory data, peripheral blood lymphocyte profiles and serum cytokines were compared between ACA-positive and ACA-negative pSS patients. Logistic regression analysis was used to evaluate the association between ACA and pSS characteristics. RESULTS: The prevalence of ACA among pSS patients was 13.5%. ACA-positive pSS patients were older at diagnosis and had longer disease duration. Xerostomia, xerophthalmia, parotid enlargement, Raynaud's phenomenon (RP), lung and digestive system involvement were more common in ACA-positive group, whereas haematological involvement such as leukopenia was more common in the ACA-negative group. Less frequency of rheumatoid factor, hypergammaglobulinaemia, anti-SSA and anti-SSB positivity, as well as higher positivity rate of ANA were observed in ACA-positive pSS patients, who exhibited a lower ESSDAI. In addition, decreased B cells and elevated NK cells were found in ACA-positive patients. Multivariate analysis identified that disease duration longer than 5 years, parotid enlargement, normal immunoglobulin and the absence of anti-SSA antibody were risk factors of ACA-positive pSS. CONCLUSIONS: ACA positive pSS patients have distinctive clinical manifestations and less severe immunological features, present a lower disease activity and lower activation of the humoral immune system. Physicians should pay attention to RP, lung and liver involvement in this subset of pSS.

Serum Cortistatin Level in Type 2 Diabetes Mellitus and Its Relationship with Nonalcoholic Fatty Liver Disease.

Purpose: To evaluate serum cortistatin (CST) levels in type 2 diabetes mellitus (T2DM) patients with or without non-alcoholic fatty liver disease (NAFLD) and to examine the relationship between CST and NAFLD. Methods: A total of 90 T2DM patients, which included 56 NAFLD patients (referred to as DM+NAFLD group) and 34 patients without NAFLD (DM-only group), and 83 non-diabetes individuals that included 39 NAFLD patients (NAFLD-only group) and 44 without NAFLD that acted as the normal-control group (NC group). The differences in the serum CST levels between the groups were compared, and the correlations between CST and other variables were calculated by applying both correlational analysis and multiple linear regression analysis. Results: The mean serum CST levels were significantly lower in the DM+NAFLD and DM groups than in the NC group (P < 0.05). In addition, the CST levels were lower in the DM group relative to that in the NAFLD group (P < 0.05). However, no statistical difference was noted in the serum CST between diabetic patients with and without NAFLD (P > 0.05). Similarly, in the non-diabetic group, the serum CST level was not significantly different between individuals with and without NAFLD (P > 0.05). Furthermore, the serum CST levels were negatively associated with the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), and insulin cell function index (HOMA-ß). Conversely, the serum CST levels were positively associated with high-density lipoprotein cholesterol (HDL-C). The data obtained through multiple linear regression implied that LDL-C and HOMA-ß, but not HOMA-IR, were closely related to serum CST levels. Conclusion: T2DM was related to decreased serum CST. However, serum CST was correlated with HOMA-ß in T2DM patients, while HOMA-IR was not. There was no correlation between CST and NAFLD.

Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

Purpose: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are frequently co-occurring diseases. Liver fibrosis (LF), with increasing incidence, has a prognostic value for NAFLD mortality. Our study aimed to investigate the relevant factors for FL in T2DM individuals with NAFLD. Patients and Methods: A total of 565 T2DM patients with NAFLD from Hebei General Hospital participated in the study. Patients underwent an abdominal ultrasound, a questionnaire and laboratory tests. The fibrosis-4 index (FIB-4) was used to evaluate LF, with FIB ≥1.3 indicating LF and FIB ≥2.67 indicating F3-4 fibrosis. Results: Compared with NLF group, LF group had higher levels of systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT). The glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL), glycated hemoglobin (HbA1c), and platelets (PLT) in LF patients were lower than those without LF. Patients with LF were older than those without LF. ALT, AST, and GGT in patients with severe LF were higher than those with mild LF, while platelet was lower. Age, SBP, duration of diabetes, ALT, AST, and GGT were positively correlated with FIB-4, while eGFR, TC, LDL, and HbA1c were negatively correlated with FIB-4. Logistic regression showed that age, SBP, ALT, GGT, LDL, and PLT were independently associated with LF. Conclusion: For T2DM patients combined with NAFLD, older age, higher SBP, higher ALT, higher GGT, lower LDL, and lower PLT were relevant factors for LF.

Association Between Serum Vitamin D Levels and Ketosis Episodes in Hospitalized Patients with Newly Diagnosed Ketosis-Prone Type 2 Diabetes.

Purpose: This study aimed to investigate the relationship between 25-hydroxyvitamin D (25OHD) and the onset of ketosis in newly diagnosed patients with ketosis-prone type 2 diabetes (KPT2D). Patients and Methods: A total of 162 patients with non-autoimmune newly diagnosed diabetes mellitus were included in this cross-sectional study. Patients were classified into KPT2D (n = 71) or non-ketotic type 2 diabetes (NKT2D, n = 91). Anthropometric parameters, islet functions, biochemical parameters, and body composition were determined in both KPT2D and NKT2D groups. Correlation analysis was performed to determine the associations between 25OHD and plasma ketones. The risk factors associated with ketosis episodes in patients with new-onset KPT2D were evaluated using binary logistic regression analysis. Results: Vitamin D deficiency was observed in both patients with KPT2D and NKT2D. Compared with the NKT2D group, serum 25OHD values were lower in the participants of the KPT2D group [14.20 (10.68, 19.52) vs 16.98 (13.54,2.96) ng/mL, P = 0.011]. Serum 25OHD was associated with plasma ketones (R = -0.387). Serum 25OHD is an independent protective factor for ketosis or ketoacidosis episodes in patients with new onset of KPT2D (P = 0.037, OR = 0.921). Conclusion: Vitamin D levels are associated with ketosis episodes in patients with KPT2D. Serum 25OHD is an independent protective factor for ketosis episodes in patients with KPT2D.

Circulating Bone Morphogenetic Protein-9 is Decreased in Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease.

Objective: We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD. Methods: One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed. Results: Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P<0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P<0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor. Conclusion: Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.

Association Between Triglyceride-Glucose Index and Serum Uric Acid Levels: A Biochemical Study on Anthropometry in Non-Obese Type 2 Diabetes Mellitus Patients.

Purpose: The triglyceride-glucose index (TyG) is positively correlated with serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). However, whether this relationship exists in non-obese T2DM patients remains unknown. The study investigated the relationship between TyG and SUA in Chinese non-obese T2DM patients and examined the prognostic value of TyG in hyperuricemia (HUA). Patients and Methods: In total, 719 T2DM patients who were not obese were enrolled from among those who visited the Hebei General Hospital. The patients were categorized into groups according to their SUA levels. The relationship between TyG and clinical parameters was examined through correlation analysis. To consider covariates and examine the independent impact of TyG on HUA, logistic regression was performed. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of TyG and homeostasis model assessment of insulin resistance (HOMA-IR) for HUA. Results: The HUA prevalence was 12.10%. TyG was statistically different among the four SUA groups, with lower TyG levels in the Q1, Q2, and Q3 groups than that in the Q4 group. TyG was positively correlated with SUA (r = 0.176, P < 0.001). Logistic regression exhibited that TyG and SUA were independently correlated (OR = 2.427, 95% CI = 1.134-5.195, P = 0.022) even after adjustment for confounding factors. The ROC curve showed that the predictive value of TyG for HUA was higher than that of HOMA-IR (AUROC = 0.613, P = 0.001). Conclusion: TyG was positively correlated with SUA in non-obese T2DM patients. TyG may better predict HUA in non-obese T2DM patients than HOMA-IR.

Oral fat tolerance testing identifies abnormal pancreatic ß-cell function and insulin resistance in individuals with normal glucose tolerance.

AIMS/INTRODUCTION: Insulin sensitivity and ß-cell function are affected by lipid metabolism disorders, even before the onset of type 2 diabetes. People are in the postprandial state most of the time. Therefore, identifying postprandial hyperlipemia is important. This study aimed to assess patients with abnormalities in lipid metabolism, but with normal glucose tolerance, using oral fat tolerance testing (OFTT) to identify defects in insulin sensitivity and ß-cell function. MATERIALS AND METHODS: We included 248 volunteers with normal glucose tolerance who underwent OFTT. They were divided into three groups in accordance with their fasting and 4-h postprandial triglyceride (TG) concentrations. Their lipid concentrations during OFTT were compared. The disposition index (DI) was applied to estimate ß-cell function, and the Matsuda insulin sensitivity index (ISIM ) was used to assess insulin sensitivity. We used multiple linear regression analysis to estimate the relationships of fasting and postprandial TG concentrations with ß-cell function and insulin sensitivity . RESULTS: The changes in TG concentrations during OFTT were more marked than those in low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol or total cholesterol concentrations. As lipid metabolism deteriorated, the ISIM and the DI gradually decreased. Multiple linear regression analysis showed that fasting and 4-h postprandial TG concentrations affected LnISIM and LnDI. CONCLUSIONS: In individuals with normal glucose tolerance, ß-cell function and insulin sensitivity gradually decrease with a deterioration in the lipid profile. Not only fasting TG, but also postprandial TG concentrations are independent risk factors for impaired ß-cell function and insulin resistance.

Quantitative proteomics analysis based on tandem mass tag labeling coupled with labeling coupled with liquid chromatography-tandem mass spectrometry discovers the effect of silibinin on non-alcoholic fatty liver disease in mice.

In recent years, the beneficial effects of silibinin (SIL) on nonalcoholic fatty liver disease (NAFLD) have attracted widespread attention. We tried to study the intervention effect of SIL on NAFLD, and explore the potential mechanisms and targets of SIL on NAFLD improvement. Thirty-three male C57BL6/J mice were divided into three groups, and, respectively, fed a normal diet (ND), a high-fat diet (HFD) or a HFD given SIL treatment (HFD+SIL). Biochemical indexes and histopathological changes of mice in each group were detected. In addition, quantitative proteomics analysis based on tandem mass tag (TMT) labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis was performed on protein changes in the livers. SIL could reduce the weight of mice, reduce liver lipid deposition, and improve glucose metabolism. Through comparison among the three experimental groups, a total of 30 overlapping proteins were found. These identified proteins were closely linked to liver lipid metabolism and energy homeostasis. Moreover, some drug targets were found, namely perilipin-2, phosphatidate phosphatase LPIN1, farnesyl pyrophosphate synthase, and glutathione S-transferase A1. In conclusions, high-fat diet increases the expressions of proteins implicated in lipid synthesis and transport in the liver, which can result in disorders of liver lipid metabolism. SIL can decrease liver lipid deposition and increase insulin sensitivity by regulating the expressions of these proteins. It not only improves the disorder of lipid metabolism in vivo, but also improves the disorder of glucose metabolism.