Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT). Patients and methods: In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed. Results: Serum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403). Conclusion: Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities: The FOCUS Randomized Clinical Trial.

Importance: Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. Objective: To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Intervention: Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. Main Outcomes and Measures: The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. Results: A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. Conclusions and Relevance: The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Trial Registration: Chinese Clinical Trial Register: ChiCTR1900023241.

Serum Gamma Glutamyltransferase: A Biomarker for Identifying Postprandial Hypertriglyceridemia.

Purpose: Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG. Patients and Methods:  For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed. Results: The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG. Conclusion: Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.

Correlation Between Serum Vitamin E and HOMA-IR in Patients with T2DM.

Background: Peroxidation is one of the important causes of insulin resistance (IR), and vitamin E is a natural antioxidant, and there may be some correlation between serum vitamin E levels and insulin resistance. Purpose: The correlation between serum vitamin E and insulin resistance in type 2 diabetes mellitus (T2DM) population. Methods: Two hundred and forty-two people (119 with T2DM) were included. One hundred and nineteen patients with T2DM were selected as the case group, and 123 people with non-T2DM were selected as the control group. People insulin resistance was detected by the homeostasis model assessment method (HOMA-IR) greater than 2.69 were included in the diabetic insulin resistance group, and those with HOMA-IR less than 2.69 were included in the diabetic non-insulin resistance group. Record the general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Correlation analysis, logistic regression, trend analysis, and restricted cubic spline (RCS) were performed using SPSS 25.0 and R 4.1.1 software. Correlation analysis, logistic regression, trend analysis, restricted cubic spline (RCS) analysis were conducted on general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Results: The logistic regression results showed that after adjusting for confounding factors, vitamin E was an independent influencing factor for insulin resistance in T2DM patients (P < 0.001). The trend analysis results show that with the decrease of serum vitamin E levels, the risk of insulin resistance in T2DM patients gradually increases. The RCS results showed that the risk of insulin resistance was significantly increased when the serum vitamin E level was lower than 10,575.23 ng/mL. Conclusion: Serum vitamin E levels are lower in T2DM patients than in healthy populations; Vitamin E is an independent influencing factor for HOMA-IR in T2DM patients. The risk of insulin resistance gradually increases in T2DM patients as serum vitamin E levels decrease. Vitamin E is a risk factor for insulin resistance at serum vitamin E levels below 10,575.23 ng/mL. At higher serum vitamin E levels than 10,575.23 ng/mL, vitamin E is a protective factor for insulin resistance.

SIRT3 rs11246020 Polymorphism Associated Postprandial Triglyceride Dysmetabolism.

Purpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism. Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism. Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219-0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032). Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.

Resveratrol Delays Diabetic Cardiomyopathy Fibrosis by Regulating Mitochondrial Autophagy.

Objective: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. Methods: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice. Western blot staining was performed on myocardial tissues to assess the protein expression levels of p-AMPK, SIRT1, SIRT3, p22, GP91, p-IRE1α, XBP1s PINK, Parkin, LC3I, and Beclin. Mouse myocardial cells were cultured in vitro and intervened with a high-sugar high-fat diet, resveratrol, and GSK690693 (an AMPK inhibitor) to observe the protein expression levels of p-AMPK, p22, XBP1s, and PINK in mouse myocardial cells in each group. Results: Results from echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy showed that resveratrol administration alleviated cardiac damage, myocardial fibrosis, myocardial cell apoptosis, and mitochondrial autophagy in DCM mice. Resveratrol administration promoted the expression of phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1), and sirtuin 3 (SIRT3) in the myocardial tissue of mice, while lowering the elevated protein expression levels of p22 subunit (p22), guanine nucleotide-binding protein q polypeptide 1 (GP91), phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1α), X-box binding protein 1 spliced form (XBP1s), PTEN-induced putative kinase 1 (PINK), Parkin, microtubule-associated proteins light chain 3 isoform I (LC3I), and Beclin (Bcl-2 interacting protein) caused by DCM. GSK690693 (an AMPK inhibitor) suppressed the expression of p-AMPK, SIRT1, and SIRT3 and enhanced the protein expression of p22, XBP1s, and PINK. Conclusion: Resveratrol postpones dilated cardiomyopathy fibrosis by regulating the mitochondrial autophagy response through the AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1)-mediated inositol-requiring enzyme 1 alpha (IRE1α)/PTEN-induced putative kinase 1 (PINK) signaling pathway.

A novel immune-related gene signature for diagnosis and potential immunotherapy of microsatellite stable endometrial carcinoma.

An immune-related gene signature (IRGS) was established to better understand the molecular and immunologic characteristics of microsatellite instable (MSI) and microsatellite stable (MSS) endometrial carcinoma (EC), and provide potential immunotherapy directions for MSS patients. Top 20 immune-related hub genes were screened by weight gene coexpression network analysis (WGCNA), and an IRGS was further established through Cox regression analysis. The molecular and immune characteristics were clarified in IRGS high and low risk groups. Expression and MS status validation of the IRGS were conducted through quantitative real-time Polymerase Chain Reaction (rt-qPCR) and immunohistochemistry (IHC) analysis. The IRGS includes 2 oncogenes (AGTR1 and HTR3C) and 2 tumor suppressor genes (CD3E and SERPIND1). Patients in IRGS high-risk group were more with MSS status, higher tumor grade, later FIGO stage, serous histology and elder ages compared with IRGS low-risk group (P < 0.05). Besides, patients in MSS group were more FIGO stages II-IV (42.7% vs. 26%), serous histology (35.7% vs. 5.3%) and with higher IRGS risk score (1.51 ± 3.11 vs. 1.02 ± 0.67) (P < 0.05) than patients in MSI group. Furthermore, patients in IRGS high-risk group had higher tumor purity, more Macrophages M1 and Macrophages M2 infiltrating, higher proportion of Macrophages M2 and Dendritic cells activated, lower proportion of T cells regulatory (Tregs), lower tumor mutation burden (TMB). Correspondingly, subjects in IRGS low-risk group had higher immunphenoscores than IRGS high-risk group. The relative mRNA level of AGTR1 and HTR3C were gradually increase, while CD3E and SERPIND1 were reversed in rt-qPCR. Through IHC experiments, AGTR1(69.2% vs 30%, P = 0.074) and HTR3C (76.9% vs 30%, P = 0.024) had higher positive staining rates in ECs than non-ECs. While SERPIND1 (84.6% vs 20%, P = 0.003) and CD3E (61.5% vs 40%, P = 0.000) had higher positive staining rates in non-ECs. IRGS is a potential diagnostic and prognostic biomarker for EC. IRGS low risk group might benefit from immune checkpoint inhibitors, while IRGS high risk group deserve other potential immunotherapy.

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.

Inverse association between adult height and diabetes risk in a cohort study of Chinese population.

Recent studies linking adult height to diabetes risk remain controversial and few were from Asia. This study, therefore, aimed to explore the association of adult height with diabetes risk in a Chinese population. This retrospective cohort study was a secondary analysis of data from the DATADRYAD website, involving 211,172 non-diabetic individuals aged ≥ 20 years from the health screening program in China. Cox regression models were employed to evaluate hazard ratios (HRs) with 95% confidence interval (CI) of diabetes related to height. During an average 3.12-year follow-up, 4156 (1.97%) subjects reported developing diabetes. After adjusting for potential confounding factors, an inverse association of height with diabetes risk was observed among men and women [HR per 10 cm (95% CI), 0.78 (0.73-0.83) and 0.76 (0.68-0.86), respectively]. Moreover, subgroup analyses indicated the inverse association was only detected in individuals with aged < 70 years, fasting plasma glucose (FPG) < 6.1 mmol/L, and men with body mass index (BMI) < 28 kg/m2. In brief, height is inversely associated with diabetes risk in Chinese adults. Specifically, this association appears to be more pronounced in individuals with aged < 70 years, FPG < 6.1 mmol/L, and men with BMI < 28 kg/m2.

Resveratrol improves palmitic acid­induced insulin resistance via the DDIT4/mTOR pathway in C2C12 cells.

The present study aimed to establish a model of palmitic acid (PA)­induced insulin resistance (IR) in C2C12 cells and to determine the mechanism underlying how resveratrol (RSV) improves IR. C2C12 cells were divided into the control (CON), PA, PA + RSV, PA + RSV + DNA damage­inducible transcript 4 (DDIT4)­small interfering (si)RNA and PA + RSV + MHY1485 (mTOR agonist) groups. Glucose contents in culture medium and triglyceride contents in cells were determined. Oil red O staining was performed to observe the pathological changes in the cells. Reverse transcription­quantitative PCR and western blotting were conducted to evaluate the mRNA and protein expression levels, respectively, of DDIT4, mTOR, p70 ribosomal protein S6 kinase (p70S6K), insulin receptor substrate (IRS)­1, PI3K, AKT and glucose transporter 4 (GLUT4). Compared with in the CON group, glucose uptake was decreased, cellular lipid deposition was increased, phosphorylated (p)­IRS­1, p­mTOR and p­p70S6K protein expression levels were increased, and p­PI3K, p­AKT, GLUT4 and DDIT4 protein expression levels were decreased in the PA group. By contrast, compared with in the PA group, culture medium glucose content and cellular lipid deposition were decreased, p­PI3K, p­AKT, GLUT4 and DDIT4 protein expression levels were increased, p­IRS­1 protein expression levels were decreased, and mTOR and p70S6K mRNA and protein expression levels were decreased in the PA + RSV group. Compared with in the PA + RSV group, DDIT4 protein and mRNA expression levels were reduced in the PA + RSV + DDIT4­siRNA group, but showed no change in the PA + RSV + MHY1485 group. Following transfection with DDIT4­siRNA or treatment with MHY1485, the effects of RSV on improving IR and lipid metabolism were weakened, mTOR and p70S6K protein expression levels were upregulated, p­PI3K, p­AKT and GLUT4 protein expression levels were down­regulated, p­IRS­1 protein expression levels were upregulated, and culture medium glucose content and cellular lipid deposition were increased. In conclusion, RSV may improve PA­induced IR in C2C12 cells through the DDIT4/mTOR/IRS­1/PI3K/AKT/GLUT4 signaling pathway, as well as via improvements in glucose and lipid metabolism.

Serum Fibroblast Growth Factor 21 Level After an Oral Fat Tolerance Test is Related to Postprandial Free Fatty Acid Level.

Purpose: The relationship between blood lipids and fibroblast growth factor (FGF) 21 in the postprandial period remains unclear. To investigate this, we observed the changes in blood lipid levels after an oral fat tolerance test (OFTT) and examined the short-term effects on FGF21. Patients and Methods: A total of 158 non-diabetic adult volunteers who underwent OFTT were randomly recruited from the Hebei General Hospital. Participants were stratified into three groups according to fasting and 4-h postprandial triglyceride levels: normal fat tolerance (NFT), impaired fat tolerance (IFT), and hypertriglyceridemia (HTG). Blood samples were collected at 2-h intervals for 6 h. Circulating total cholesterol levels, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, free fatty acids (FFA), and FGF21 were assessed. Results: Fasting FGF21 levels increased progressively in the NFT, IFT, and HTG groups and were strongly correlated with FFA levels (r = 0.531, P < 0.001). During the OFTT, the FFA and FGF21 levels decreased and then increased after reaching a nadir at 2 and 4 h, respectively. After adjusting for potential risk factors, the FFA incremental area under the curve (iAUC) was an independent influencing factor of FGF21 iAUC (P = 0.005). Conclusion: Fasting FGF21 levels showed a strong positive correlation with FFA. During OFTT, changes in FGF21 levels were closely associated with alterations in FFA exogenously changed by OFTT. Moreover, they were linearly related to each other. Therefore, the serum FGF21 level is positively correlated to the FFA level in the postprandial period.

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.

A bibliometric analysis and visualization of literature on non-fasting lipid research from 2012 to 2022.

Background: Non-fasting lipid assessment can help predict cardiovascular disease risks and is linked to multiple diseases, particularly diabetes. The significance of non-fasting lipid levels in routine screening and postprandial lipid tests for potential dyslipidemia has not been conclusively determined. Various new lipid-lowering strategies have been developed to improve non-fasting dyslipidemia. Therefore, analysis of scientific outputs over the past decade is essential to reveal trends, hotspots, and frontier areas for future research in this field. Methods: The Science Citation Index Expanded in the Web of Science Core Collection database was searched for publications related to non-fasting lipid research from 2012 to 2022. The regional distributions, authors, disciplines, journals, references, and keywords of the studies were analyzed using the bibliometric software VOSviewer and CiteSpace. Results: A total of 4160 articles and reviews that met the inclusion criteria were included in this study. The output trend was established to be stable and the number of citation indices has been persistently increasing. A total of 104 countries/regions, 4668 organizations, and 20782 authors were involved in this research area. In terms of country, the United States had the largest number of publications (979). The University of Copenhagen was the most productive institution, publishing 148 papers. Professor Børge G Nordestgaard has made the most significant contribution to this field. Nutrients was the most productive journal while the American Journal of Clinical Nutrition was the highest co-cited journal. Analysis of co-cited references indicated that lipid-lowering strategies, statin therapy, high-fat meals, insulin resistance, physical exercise, and fructose were hotspots. Analysis of co-cited keywords revealed that apolipoprotein B, especially apolipoprotein B48, is becoming a key research focus. The keywords "gut microbiota" and "meal timing" were the most extensively studied. Conclusion: The causal relationship between non-fasting dyslipidemia and diseases is currently being explored and the standards for non-fasting or postprandial lipid assessment are continuously being updated. Among the hotspots, lipid-lowering strategies are a potential research direction. Apolipoprotein B48, gut microbiota, and chrononutrition are the research frontiers. This initial bibliometric analysis of non-fasting lipids will enable researchers to monitor swift transformations and recognize novel concepts for upcoming research.

Associations Between Serum Folate Level and HOMA-IR in Chinese Patients with Type 2 Diabetes Mellitus.

Background: Adequate intake of folic acid (FA) has been proven essential for metabolism, cellular homeostasis, and antioxidant effects in diabetic patients. Our aim was to evaluate the association between serum folate levels and the risk of insulin resistance in patients with type 2 diabetes mellitus (T2DM) and to provide new ideas and approaches for reducing the risk of T2DM. Methods: This was a case-control study involving 412 participants (206 with T2DM). Anthropometric parameters, islet function, biochemical parameters and body composition of T2DM group and control group were determined. Correlation analysis and logistic regression were used to evaluate the risk factors associated with the onset of insulin resistance in T2DM. Results: The folate levels in type 2 diabetic patients with insulin resistance were significantly lower than those in patients without insulin resistance. Logistic regression showed that FA and high-density lipoprotein were independent influencing factors for insulin resistance in diabetic patients (P < 0.05). After adjusting for confounding factors, the degree of insulin resistance in diabetic patients was in a significant inverse relationship with folate levels (P< 0.05). We also found that below the serum FA threshold of 7.09 ng/mL insulin resistance was significantly more elevated. Conclusion: Our findings suggest that the risk of insulin resistance increases with the decrease in serum FA levels in T2DM patients. Monitoring folate levels in these patients and FA supplementation are warranted preventive measures.

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.

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.

Association of serum NOD-like receptor protein 3 levels with impaired fat tolerance and hypertriglyceridemia.

The NOD-like receptor protein 3 (NLRP3) inflammasome plays a key role in lipid metabolism. We used an oral fat tolerance test (OFTT) to detect whether serum NLRP3 levels differed in people with different fat tolerances and evaluate whether NLRP3 was associated with impaired fat tolerance (IFT) and hypertriglyceridemia (HTG). We performed the OFTT using 176 volunteers. The groups were divided according to fasting and postprandial triglyceride (TG) levels: 1) normal fat tolerance (NFT) group (TG at 0 h <1.7 mmol/L and TG at any time point <2.5 mmol/L); 2) IFT group (TG at 0 h <1.7 mmol/L and TG at any time point >2.5 mmol/L); and 3) HTG group (TG at 0 h ≥1.7 mmol/L). With decreased lipid tolerance, the TG and NLRP3 levels increased gradually before a high-fat meal and at any time point after 0 h. NLRP3 levels reached a peak 2 h after meal consumption in all three groups. After adjustment for confounding indicators, logistic regression analysis revealed that fasting serum NLRP3 levels were positively associated with both IFT and HTG (for IFT, odds ratio [OR]: 1.079 [1.037-1.123], p < 0.001; for HTG, OR: 1.085 [1.049-1.123], p < 0.001). According to the receiver operating characteristic curve, fasting serum NLRP3 levels were an effective biomarker for IFT and HTG diagnosis. These results indicate that the fasting serum NLRP3 is an independent risk factor for IFT and HTG, and is a valuable indicator for the early diagnosis of IFT and HTG.

The relationship between NAFLD and retinol-binding protein 4 - an updated systematic review and meta-analysis.

PURPOSE: Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD. METHODS: A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases. RESULTS: In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11-0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10-0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression. CONCLUSION: The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.

Meta-analysis of Serum Vitamin B12 Levels and Diabetic Retinopathy in Type 2 Diabetes.

BACKGROUND: Previous studies have shown an association between low serum vitamin B12 levels and the risk of diabetic retinopathy (DR) in type 2 diabetes, but the conclusions from various studies were inconsistent. Therefore, we collected relevant data from various databases to perform a meta-analysis and address the inconsistencies in these studies. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang and CQVIP for eligible studies published up to April 10, 2022, and performed a meta-analysis using Stata software to assess the association between serum vitamin B12 levels and DR. RESULTS: A total of 15 studies were included in this meta-analysis. Statistical analysis showed that serum vitamin B12 levels were significantly reduced in patients with type 2 diabetic retinopathy ,WMD 95% CI = -68.91 (-76.76, -61.06) (p <0.00001, I2 = 88.30%). In subgroup analyses by ethnicity, an association between low serum vitamin B12 levels and DR risk was found in East Asian, South Asian and mixed populations, but not in Caucasian populations. CONCLUSIONS: This meta-analysis analyzed vitamin B12 in patients with type 2 diabetic retinopathy and emphasized the importance of monitoring serum vitamin B12 levels in patients with type 2 diabetic retinopathy, but this meta-analysis still has deficiencies and limitations, and more clinical studies are needed to confirm this conclusion in the future.

SLC2A9 rs1014290 Polymorphism is Associated with Prediabetes and Type 2 Diabetes.

Purpose: To investigate the association of the A/G rs1014290 polymorphism in SLC2A9 with type 2 diabetes (T2DM) and prediabetes mellitus (pre-DM). Patients and Methods. We enrolled 1058 patients who attended the Hebei General Hospital, Shijiazhuang, Hebei Province, China. The patients underwent general testing and oral glucose tolerance tests and were divided into three groups: 352 patients newly diagnosed with T2DM, 358 patients with pre-DM, and 348 healthy controls. The single nucleotide polymorphism (SNP) was detected by ligase detection reactions. The χ 2 test, one-way ANOVA, and binary logistic regression analysis were used to analyze the results. Results: In the T2DM group, the GG genotype frequency at the rs1014290 locus was significantly lower (14.8%) than it was in the healthy controls. Furthermore, the GG genotype group was associated with a reduced risk of T2DM in unadjusted and confounder-adjusted models compared with the risk in the AA genotype group. The G allele in the SLC2A9 rs1014290 locus decreased susceptibility to T2DM. In the pre-DM group, the GG and AG genotype groups had no significant correlation with the risk of pre-DM in any of the models. In the T2DM group, the uric acid level was significantly lower in the GG genotype group. In the T2DM and pre-DM groups, the HOMA-ß levels were significantly higher in the GA (P < 0.001) and GG (P < 0.001) genotype groups than it was in the AA genotype group, and HOMA-IR was significantly lower in the GA (P < 0.001) and GG (P < 0.001) genotype groups than it was in the AA genotype group. Conclusion: The A/G (rs1014290) SNP in SLC2A9 is closely related to the occurrence and development of diabetes.