Association between AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes: a cross-sectional investigation.

Objective: This study aimed to explore the association between the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) and diabetic retinopathy (DR) in patients with type 2 diabetes. Methods: In this cross-sectional study, clinical data from 3002 patients with type 2 diabetes admitted to the Department of Endocrinology of our hospital between January 1, 2021, and December 1, 2022, were retrospectively collected. Measurements of AST and ALT were conducted and diabetes-related complications were screened. The association between AST/ALT ratio and diabetic retinopathy was assessed using multivariate logistic regression, and a generalized additive model (GAM) was used to investigate nonlinear relationships. Subgroup analyses and interaction tests were also conducted. Results: Among the 3002 patients, 1590 (52.96%) were male and 1412 (47.04%) were female. The mean AST/ALT ratio was 0.98 ± 0.32, ranging from 0.37 (Min) to 2.17 (Max). Diabetic retinopathy was present in 40.47% of the patients. After multivariate adjustments, for each 0.1 unit increase in AST/ALT ratio, the risk of DR increased by 4% (OR = 1.04, 95% CI: 1.01-1.07, p=0.0053). Higher AST/ALT ratio quartiles were associated with Higher prevalence of DR (OR vs. Q1: Q4 = 1.34 (CI: 1.03-1.75, p=0.0303).The GAM and smoothed curve fit indicated a linear relationship between AST/ALT ratio and DR risk, with no significant interaction effects across different subgroups. Conclusion: Our study demonstrates a positive correlation between the AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes, suggesting its potential role in assessing DR risk.

Inverse association of serum albumin levels with diabetic retinopathy in type 2 diabetic patients: a cross-sectional study.

This study aimed to explore the association between serum albumin (ALB) levels and diabetic retinopathy in patients with type 2 diabetes. In this cross-sectional study, we retrospectively collected clinical data from patients with type 2 diabetes who were admitted to the Endocrinology Department of the Affiliated Hospital of Qingdao University between January 1, 2021, and December 1, 2022. All included patients underwent measurements of serum albumin levels and screening for diabetes-related complications. The association between serum albumin levels and retinopathy was assessed using logistic regression after adjusting for potential confounders. Further, stratified analyses and curve fitting were conducted to delve deeper into the relationship. After inclusion and exclusion criteria were applied, a total of 1947 patients were analyzed. Among these, 982 were male and 965 were female. The mean serum albumin level was 39.86 ± 3.27 g/L. Diabetic retinopathy was present in 41.24% of the patients. After adjusting for potential confounders, we observed a significant inverse association between serum albumin levels and the incidence of retinopathy. Specifically, for every 10 g/L increase in albumin level, the odds of retinopathy decreased (odds ratio [OR] = 0.67; 95% confidence interval [CI] = 0.48-0.94; P = 0.0209).The curve fitting validated the inverse relationship between serum albumin and retinopathy without evidence of non-linearity or threshold saturation effects. Stratified analyses consistently indicated no interaction effects across subgroups. This cross-sectional study identified a significant inverse relationship between serum albumin levels and diabetic retinopathy in patients with type 2 diabetes. However, due to the cross-sectional nature of this study, further prospective studies are warranted to confirm these findings.

A Low-Carbohydrate Diet Realizes Medication Withdrawal: A Possible Opportunity for Effective Glycemic Control.

Objective: Multiple studies have confirmed that diet restrictions can effectively realize glycemic control and reduce metabolic risks in patients with type 2 diabetes mellitus (T2DM). In 2018, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) stated that individuals can select a low-carbohydrate diet (LCD) according to their needs and preferences. Owing to the influence of Chinese traditional eating habits, only a small portion of patients in China have achieved their blood glucose goals. As a result, the Chinese government will incur huge expenditures. Method: This study recruited 134 T2DM participants and randomly assigned them to the LCD group (n = 67) or the low-fat diet (LFD) group (n = 67). All of the patients had a fixed amount of exercise and were guided by clinicians. After a period of dietary washout, all of the patients received corresponding dietary education according to group. The follow-up time was 6 months. The indicators for anthropometry, glycemic control, and medication application parameters were collected and compared between the two groups. Results: There were 121 participants who finally entered the study. The proportions of calories from three major nutrients the participants consumed met the requirements of LCD and LFD. Compared with baseline, the pre-postdifferences of body weight, BMI, and several other indicators were significant except for dosages of insulin used in the LCD group and MES in the LFD group. After the intervention, body weight, body weight index (BMI), fasting blood glucose (FBG), postprandial 2-h blood glucose (PPG), and glycosylated hemoglobin (HbA1c) levels in the LCD group decreased significantly (p < 0.05) compared with the LFD group. The number of patients using lipid-lowering agents was significant higher in the LCD group and lower in the LFD group. However, there was no significant difference between the two groups for antihypertensive, hormone-replacement, and other agents. Conclusions: The LCD diet can decrease body weight, glycemic levels, MES, and lipid-lowering agents more than the LFD diet, thus decreasing cost burden in Chinese patients with T2DM. Strict diet control and monitoring are the keys to managing diabetes.

Ghrelin Alleviates Endoplasmic Reticulum Stress in MC3T3E1 Cells by Inhibiting AMPK Phosphorylation.

Ghrelin is a gastric endocrine peptide that has been found to be involved in the process of energy homeostasis and bone physiology in recent years. To explore the effects of ghrelin on endoplasmic reticulum stress (ERS) in MC3T3E1 cells and its possible mechanism, an ERS model was induced by tunicamycin (TM) in the osteoblast line MC3T3E1. TM at 1.5 µg/mL was selected as the experimental concentration found by CCK8 assay. Through the determination of apoptosis, reactive oxygen species production, and endoplasmic reticulum stress-related gene expression, we found that ERS induced by TM can be relieved by ghrelin in a concentration-dependent manner (P < 0.001). Compared with the TM group, ghrelin reduced the expression of ERS-related marker genes induced by TM. Compared with the GSK621 + TM group without ghrelin pretreatment, the mRNA expression of genes in the ghrelin pretreatment group decreased significantly (P < 0.001). The results of protein analysis showed that the levels of BIP, p-AMPK, and cleaved-caspase3 in the TM group increased significantly, while the levels decreased after ghrelin pretreatment. In group GSK621 + TM compared with group GSK621 + ghrelin+TM, ghrelin pretreatment significantly reduced the level of p-AMPK, which is consistent with the trend of the ERS-related proteins BIP and cleaved-caspase3. In conclusion, ghrelin alleviates the ERS induced by TM in a concentration-dependent manner and may or at least partly alleviate the apoptosis induced by ERS in MC3T3E1 cells by inhibiting the phosphorylation of AMPK.

Identification of Reactive Hypoglycemia with Different Basic BMI and Its Causes by Prolonged Oral Glucose Tolerance Test.

PURPOSE: To identify the population susceptible to reactive hypoglycemia and explain the possible reasons for their susceptibility. METHODS: Ninety-four patients were divided into normal weight, overweight and obese groups before a 75-gram prolonged oral glucose tolerance test (POGTT). The incidence of reactive hypoglycemia (blood glucose ≤3.1 mmol/L or 55 mg/dL at points of 0-4 hours) was compared among three groups, and blood glucose and insulin levels were monitored simultaneously from 0 - 4 hours to assess the level of insulin resistance and insulin sensitivity. Furthermore, the degree of insulin resistance among three groups and within each subgroup (whether hypoglycemia events occurred) was compared. RESULTS: Among the three groups, the incidence of hypoglycemia was significantly different at 3 (P=0.033) and 4 hours (P=0.020). At 4 hours, the incidence of reactive hypoglycemia in the obese group was approximately 3 times that in the normal weight group. The insulin level in obese group at 4 hours was nearly 4 times higher than that in normal group, and the same result also exists in the same subgroup of different groups. In addition, the hypoglycemia subgroup of obese group had higher insulin level than non-hypoglycemia (P=0.000). The homeostasis model assessment of insulin resistance index increased with increasing BMI among the three groups (P=0.000), while the Matsuda index decreased (P=0.000). The comparison of the homeostasis model assessment of insulin resistance index between subgroups in each group showed that the P values were 0.021, 0.038 and 0.085, successively, and the P values for the Matsuda index were 0.019, 0.013 and 0.119, respectively. CONCLUSION: Obese people has higher rate of reactive hypoglycemia than other groups in POGTT, in which insulin resistance may play an important role. But patients who are evaluated for reactive hypoglycemia need to be observed for at least 3 or 4 hours.

Comparison of the Effectiveness and Safety of Vildagliptin Add-On to Metformin Versus Other Oral Dual Antidiabetes Agents in Patients with Type 2 Diabetes: The China Prospective Diabetes Study.

INTRODUCTION: The efficacy and safety of vildagliptin alone or with metformin is well established by randomized trials, but it is unknown whether it can be extrapolated to the real-world setting in Chinese patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness and safety of vildagliptin add-on to metformin versus dual oral antidiabetes drug (OAD), non-vildagliptin combination therapies in real-world Chinese patients with T2DM. METHODS: The China Prospective Diabetes Study was a post-marketing, prospective, multicenter, observational, real-world study conducted in 52 centers. Patients inadequately controlled with OAD monotherapy and who initiated vildagliptin add-on to metformin (VM cohort) or two OADs other than vildagliptin (comparator cohort) were included for the present analysis. The composite primary endpoint was glycated hemoglobin (HbA1c) < 7% and without tolerability events (hypoglycemia, weight gain ≥ 3%, or discontinuation due to gastrointestinal events) at 12 months. Secondary endpoints included change in HbA1c from baseline, subgroup analysis, and tolerability. Propensity score matching analysis was performed to adjust for baseline covariates imbalance (body mass index (BMI) and HbA1c). RESULTS: A total of 604 patients received VM and 670 received comparator therapy. Patients who received VM were younger, more obese, and had a higher baseline HbA1c and a shorter duration of T2DM. After propensity score matching, there were 530 patients per cohort. After 12-month treatment, the success rates of the composite primary endpoint were 50.9% and 33.0% in the VM and comparator cohorts, respectively (P < 0.001; odds ratio = 2.10, 95% confidence interval (CI) 1.64-2.70). Furthermore, the success rates of the composite endpoint were higher with VM across geographic area, BMI, and baseline HbA1c subgroups. Fewer tolerability events occurred in the VM cohort versus the comparator cohort (8.3% vs. 16.2%, P < 0.001; relative risk = 0.51, 95% CI 0.36-0.72). CONCLUSION: Compared with dual OAD non-vildagliptin combination therapies, vildagliptin add-on to metformin is effective and safe to achieve glycemic control in Chinese patients with T2DM. FUNDING: Novartis.

Fasting blood glucose levels in patients with different types of diseases.

Normal human physiology is dependent on a tight control of the fasting blood glucose (FBG) levels. The islets of pancreas maintains FBG levels within a narrow range of 4-6mmol/L by secreting various hormones, especially insulin and glucagon. However, the hormone secretions by the islets of pancreas are governed by a collective effort among pancreas-islet axis, brain-islet axis, liver-islet axis, gut-islet axis, and adipocyte/myocyte-islet axis. Furthermore, the damage of pancreas, vascular system, brain, liver, intestine, adipose, muscle, and other organs and tissues might affect FBG levels through insulin resistance or impaired insulin signaling, which is the hallmark of type 2 diabetes. In this study, 320,572 clinical lab test results of FBG levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found 57/64 diseases including type 2 diabetes, pancreatitis, diabetic nephropathy, and pancreatic cancer had significantly (p<0.05, -Log10p>1.30) increased whereas 6/64 diseases including preeclampsia, Wilms' tumor, and lupus erythematous had significantly decreased FBG levels compared to that of healthy controls. These data indicated that the increased FBG levels might be a general pathophysiological property of diseased tissues or organs and the increased FBG levels might be a consequence but not the cause for either prediabetes or type 2 diabetes.

Correlations of Serum Hormones and Bone Mineral Density with Fracture and Balance Ability of Postmenopausal Patients and Effects of Calcitriol.

BACKGROUND The aim of this study was to analyze the correlations of serum hormones and bone mineral density (BMD) with fracture and balance ability of postmenopausal patients and effects of calcitriol on them. MATERIAL AND METHODS The clinical data of 164 postmenopausal female patients with osteoporosis (OP) treated in our hospital were retrospectively analyzed. RESULTS The incidence rates of OVCF, balance index score (BIS), front-back ratio (FBR), and right-left ratio (RLR) in the normal BMD group, reduced BMD group, and OP group showed increasing trends, and there were statistically significant differences in comparisons among groups (p<0.05). The levels of serum estradiol (E2) and progesterone (P) in the OVCF group were lower than those in the non-OVCF group, and there were statistically significant differences in comparisons between the 2 groups (p<0.05). However, there was no statistically significant difference in the comparison of serum luteinizing hormone (LH) level between the 2 groups (p>0.05). BIS, FBR, and RLR were negatively correlated with E2 and testosterone (T) (p<0.05). With the prolongation of calcitriol treatment time, BIS, FBR, and RLR gradually decreased, but T value gradually increased. At 6 months and 12 months after intervention, BIS, FBR, and RLR had significant differences compared to those before the experiment (p<0.05). (5) Total hip BMD, height, age, and body mass index (BMI) were the independent factors affecting SDI. CONCLUSIONS Hip BMD, age, height, and BMI are significantly correlated with OVCF. Calcitriol treatment can increase lumbar BMD and improve balance ability, and these effects become more obvious with prolongation of intervention time.

Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry.

Limonin (LIM), a furan-containing limonoid, is one of the most abundant components of Dictamnus dasycarpus Turcz. Recent studies demonstrated that LIM has great potential for inhibiting the activity of drug-metabolizing enzymes. However, the mechanisms of LIM-induced enzyme inactivation processes remain unexplored. The main objective of this study was to identify the reactive metabolites of LIM using liquid chromatography-mass spectrometry. Three nucleophiles, glutathione (GSH), N-acetyl cysteine (NAC), and N-acetyl lysine (NAL), were used to trap the reactive metabolites of LIM in in vitro and in vivo models. Two different types of mass spectrometry, a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometry and a LTQ velos Pro ion trap mass spectrometry, were employed to acquire structural information of nucleophile adducts of LIM. In total, six nucleophile adducts of LIM (M1-M6) with their isomers were identified; among them, M1 was a GSH and NAL conjugate of LIM, M2-M4 were glutathione adducts of LIM, M5 was a NAC and NAL conjugate of LIM, and M6 was a NAC adduct of LIM. Additionally, CYP3A4 was found to be the key enzyme responsible for the bioactivation of limonin. This metabolism study largely facilitates the understanding of mechanisms of limonin-induced enzyme inactivation processes.

In silico analysis of the molecular mechanism of postmenopausal osteoporosis.

Postmenopausal osteoporosis (PO) is a common disease in females >50 years of age worldwide and is becoming an increasing burden to society. The present study aimed to assess the molecular mechanism of PO using bioinformatic methods. The gene expression data from patients with PO and normal controls were downloaded from the ArrayExpress database provided by European Bioinformatics Institute. Following the screening of the differentially expressed genes (DEGs) using the Limma package in R language, Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tools. Sequentially, modulators of the DEGs, including transcription factors (TFs) and microRNAs, were predicted by the ChIP Enrichment Analysis databases and WEB­based GEne SeT AnaLysis Toolkit system, respectively. In addition, the protein­protein interaction network of DEGs was constructed via the search tool for the retrieval of interacting genes and then the functional modules were further analyzed via the clusterMaker package and The Biological Networks Gene Ontology package within the Cytoscape software. A total of 482 DEGs, including 279 upregulated and 203 downregulated DEGs, were screened out. DEGs were predominantly enriched in the pathways of fatty acid metabolism, cardiac muscle contraction and DNA replication. TFs, including SMAD4, in addition to microRNAs, including the microRNA­125 (miR­125) family, miR­331 and miR­24, may be the modulators of the DEGs in PO. In addition, the five largest modules were identified with TTN, L1G1, ACADM, UQCRC2 and TRIM63 as the hub proteins, and they were associated with the biological processes of muscle contraction, DNA replication initiation, lipid modification, generation of precursor metabolites and energy, and regulation of acetyl­CoA biosynthetic process, respectively. SMAD4, CACNG1 and TRIM63 are suggested to be important factors in the molecular mechanisms of PO, and miR­331 may be novel potential biomarker for PO.

Uric acid promotes neuronal differentiation of human placenta-derived mesenchymal stem cells in a time- and concentration-dependent manner.

Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM ß-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM ß-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM ß-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM ß-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time- and concentration-dependent manner.

Dynamic analysis of bone marrow mesenchymal stem cells migrating to pancreatic islets using coculture microfluidic chips: An accelerated migrating rate and better survival of pancreatic islets were revealed.

OBJECTIVES: A coculture microfluidic chip had been fabricated to investigate the dynamic process of bone marrow mesenchymal stem cells migrating to the pancreatic islets in vitro. METHODS: We fabricated a coculture microfluidic chip using standard procedures. On the chip, bone marrow mesenchymal stem cells and pancreatic islets were introduced respectively into two microchambers which could be connected by a traffic tunnel. Migration assay was performed along the tunnel, and the function of pancreatic islets was timely evaluated by analysis of insulin secretion in response to high-glucose-challenge. RESULTS: The results showed that some bioactive factors excreted by freshly isolated pancreatic islets could enhance the migrating rate of BM-MSCs. Besides, pancreatic islets also showed a better survival and function by coculturing with bone marrow mesenchymal stem cells. CONCLUSION: The results demonstrated that bone marrow mesenchymal stem cells had the ability to migrate to pancreatic islets and provide an apparent overall preservation for islet function. This microfluidic device was a potentially useful tool to mimic actual biological processes of bone marrow mesenchymal stem cells migrating to the pancreatic islets in vitro.

Adiponectin reduces glucotoxicity-induced apoptosis of INS-1 rat insulin-secreting cells on a microfluidic chip.

Diabetes mellitus is a metabolic disorder characterized by elevated blood sugar and progressive failure of insulin-producing beta-cells. Persistent hyperglycemia and blood sugar fluctuation are two general phenomena in diabetic patients, and both of them can result in an increased frequency of beta-cell apoptosis. Therefore, rescuing pancreatic beta-cells from glucotoxicity-induced beta-cell apoptosis is increasing viewed as a promising means for curing. The aim of this study was to investigate whether adiponectin, an important cytokine expressed in adipose tissue, has a potential for the application as the antiapoptotic strategy. INS-1 rat insulin-secreting cell line was used in this study as a model of pancreatic beta-cells, because INS-1 cells show the susceptibility to glucotoxicity, as seen in beta-cells. INS-1 cells were cultured on a novel microfluidic chip with persistent perfusion and subsequently exposed to sustained high glucose (SHG) (25 mmol/l) or intermittent high glucose (IHG) (11.1 and 25 mmol/l glucose alternating every 12 h) in the absence or presence of adiponectin for 72 h. Using this device, we showed that IHG induced more serious impairment in INS-1 cells than did SHG, and adiponectin partially rescued INS-1 cells from glucotoxicity-induced apoptosis, dysfunction and reduction of insulin gene expression. Simultaneously, the mRNA expression of AMP-activated protein kinase (AMPK), which is a signaling protein that acts to modulate glucose uptake in skeletal muscle, was restored in the presence of adiponectin. Based on the above evidence, we suggest that adiponectin could reduce glucotoxicity-induced apoptosis of beta-cells, at least in part, by transiently activating AMPK signaling pathway.

Basal or bolus dose, which is the key factor in CSII?

OBJECTIVE: To observe the value of HbA(1)c level evaluating the total daily basal insulin dose by continuous subcutaneous insulin infusion (CSII) in 268 patients with type 2 diabetes mellitus. METHODS: 5-point capillary blood glucose was monitored in pre- and post-CSII and the insulin dose which could stabilize blood glucose was defined as the total daily dose of insulin, including basal and bolus total dose. Correlation between HbA(1)c level and total daily dose of insulin in patients with type 2 diabetes mellitus was analyzed. Correlation between HbA(1)c level and 5-point capillary blood glucose was also analyzed. RESULTS: Obvious correlation was observed between HbA(1)c level and the basal total daily dose of insulin if HbA(1)c was more than 9.3% (r=0.635, P<0.05). The average of 5-point capillary blood glucose was best correlated with HbA(1)c and fasting blood glucose next best. CONCLUSION: HbA(1)c level can forecast basal total daily dose of insulin in CSII.