Differences in glucose homeostasis and islet injury among diverse mice strains post acute pancreatitis.

Diverse animal models have been used to study postpancreatitis diabetes mellitus (PPDM) development; however, no study has yet conducted a comparative analysis of the specific differences in glucose homeostasis and islet injury between these models. Therefore, we investigated the differences in pancreatic islet injury and glucose homeostasis among diverse strains in a cerulein-induced acute pancreatitis (AP) model to determine the appropriate animal model for PPDM. BALB/cJ, C57BL/6J, C57BL/6 N, and FVB/NJ mice were administered cerulein to induce AP. Serum amylase levels, pancreatic acinar injury, blood glucose homeostasis, islet function, and islet injury were measured and analyzed. All strains exhibited elevated amylase secretion post pancreatitis, and BALB/cJ, C57BL/6J, and C57BL/6 N mice exhibited sex-related differences. All strains exhibited pancreatic acinar injury post pancreatitis but mostly recovered within 15 days. Overall, glucose homeostasis remained balanced post pancreatitis in all strains compared to that in the control groups, except in FVB/NJ male and female mice, which exhibited an imbalance in glucose homeostasis on day 7 post pancreatitis. All the strains, except BALB/cJ mice, exhibited a decline in Homeostasis model assessment-ß(HOMA-ß) values post pancreatitis, with significant decrease in C57BL/6J females and FVB/NJ males. Islet size decreased post pancreatitis in all strains, except BALB/cJ mice. Pancreatic islet insulin secretion levels significantly decreased in male FVB/NJ mice post pancreatitis onset and did not recover within 15 days. Therefore, FVB/NJ male mice are a useful model for studying PPDM.

Deciphering feedback regulation of prostaglandin F2α in blood stasis syndrome using nitrogen-doped porous transition metal carbides.

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.

Ghrelin regulates the proliferation and apoptosis of high glucose-induced islet cells through the PI3K-Akt signaling pathway.

Ghrelin may have therapeutic value in mitigating insulin resistance and type 2 diabetes, based on which we further explore the action mechanism of ghrelin on islet cells in this research. In the course of experiments, MIN6 cells were induced by glucose and then treated with acylated or unacylated ghrelin. The effects of ghrelin on the viability, proliferation, apoptosis, and insulin release of high glucose-induced islet cells were detected by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and enzyme-linked immunosorbent assays, respectively. Meanwhile, cells were treated with LY294002 to explore whether and how the inhibited phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway participated in the internal mechanism of ghrelin-regulating islet cells. Western blotting was performed to quantify the expression levels of Bcl-2, Bax, Cleaved caspase-3, PI3K, and AKT. As a result, ghrelin alleviated high glucose-induced suppression of viability and proliferation and promotion on apoptosis of MIN6 cells. Ghrelin also attenuated the inhibitory effects of high glucose on expression levels of PI3K-Akt signaling axis-related proteins and insulin release in MIN6 cells. Besides, ghrelin weakened the impacts of high glucose on boosting MIN6 cell apoptosis and hindering proliferation through the PI3K-Akt signaling axis. Collectively, ghrelin regulates the proliferation and apoptosis of high glucose-induced islet cells through the PI3K-Akt signaling pathway.

The association between time in the glucose target range and abnormal ankle-brachial index: a cross-sectional analysis.

BACKGROUND: Time in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes. METHODS: We retrospectively collected patients' information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and < 1.3, ≥ 1.3 ABI values. All patients underwent continuous glucose monitoring(CGM), and TIR was defined as the percentage of time in which glucose was in the range of 3.9-10 mmol/L during a 24-h period. Correlations between TIR and abnormal ABI were analyzed using Spearman analysis. And logistic regression was used to explore whether TIR is an independent risk factor for abnormal ABI. RESULTS: The overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P < 0.05). The logistic regression revealed a significant association between TIR and abnormal ABI, while HbA1C and blood glucose variability measures had no explicit correlation with abnormal ABI. Additionally, there was a significant difference in LDL between the low and high ABI groups (P = 0.009), and in Scr between normal and low groups (P = 0.007). And there were significant differences in TIR (P = 0.003), age (P = 0.023), UREA (P = 0.006), ACR (P = 0.004), TAR (P = 0.015), and MBG (P = 0.014) between normal and high ABI groups, and in diabetes duration between both normal and low (P = 0.023) and normal and high (P = 0.006) groups. CONCLUSIONS: In type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases.

Plasma Diaphanous Related Formin 1 Levels Are Associated with Altered Glucose Metabolism and Insulin Resistance in Patients with Polycystic Ovary Syndrome: A Case Control Study.

BACKGROUND: Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS). METHODS: The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. RESULTS: PCOS patients manifested hyperandrogenism, increased luteinizing hormone/follicle-stimulating hormone (LH/FSH), and accumulated body fat and insulin resistance. Plasma DIAPH1 levels were significantly decreased in women with PCOS compared to control participants, and DIAPH1 levels were distinctly reduced in OW PCOS compared to OW control subjects (P < 0.001). DIAPH1 levels correlated with fasting blood glucose (FBG), total cholesterol (TC), the homeostasis model assessment of ß-cell function (HOMA-ß), and LH/FSH in all participants (FBG: r = 0.351, P < 0.0001; TC: r = 0.178, P = 0.029; HOMA-ß: r = -0.211, P = 0.009; LH/FSH: r = -0.172, P = 0.040). Multivariate logistic regression analysis revealed that plasma DIAPH1 levels were an independent risk factor for PCOS. A model containing DIAPH1, BMI, FBG, and testosterone was constructed to predict the risk of PCOS, with a sensitivity of 92.0% and a specificity of 80.9%. A nomogram was constructed to facilitate clinical diagnosis. CONCLUSIONS: These findings suggest the association of plasma DIAPH1 with glucose metabolism, insulin resistance, and sex hormones and support DIAPH1 as a potential predictive factor for PCOS.

mGPDH Deficiency leads to melanoma metastasis via induced NRF2.

Oxidative stress critically influences carcinogenesis and the progression of melanoma, and aggressive malignant melanoma activity is due to its high metastatic ability. Some findings in several cancer cell lines have indicated that mGPDH, a component of the mitochondrial respiratory chain, also modulates oxidative stress. However, the role of mGPDH in melanoma remains elusive. Here, we report that the mGPDH protein level is decreased in human skin melanoma compared to normal skin and decreased in metastatic melanoma compared to primary melanoma. Our in vivo and in vitro experiments indicated that mGPDH depletion accelerated melanoma migration and invasion without affecting proliferation or apoptosis. Mechanistically, we found elevated NRF2 protein levels in human skin melanoma and mGPDH-knockout (ko) metastatic xenografts in the lungs of nude mice. Moreover, in A375 melanoma cells, the loss of mGPDH-induced NRF2 expression but did not affect NRF2 protein degradation. Additionally, melanoma metastasis induced by the loss of mGPDH was rescued by the further down-regulation of NRF2 in vivo and in vitro. Consistently, mGPDH overexpression (oe) depressed NRF2 expression and attenuated the malignant properties of melanoma cells. In conclusion, our findings suggest that mGPDH suppresses melanoma metastasis by inhibiting NRF2 and downstream oxidative signals, highlighting the therapeutic potential of mGPDH for melanoma treatment.

Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centre, randomized, controlled trial.

AIMS: To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: In this 48-week, multi-centre, open-label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c <7.0%, without hypoglycaemia, defined as blood glucose <3.9 mmol/L and weight gain <3.0% after 48 weeks of treatment. RESULTS: Over 48 weeks, a greater proportion of patients achieved the primary endpoint with saxagliptin compared with glimepiride (43.3% vs 31.3%; odds ratio, 1.38, 95% CI, 1.05-1.82; P = 0.019), especially among patients with baseline HbA1c <8.0%, duration <5 years or baseline BMI ≥25 kg/m2 . Mean reduction in HbA1c was similar in the two treatment groups at Week 48 (-0.94% with saxagliptin vs -0.98% with glimepiride; P = 0.439). Bodyweight decreased with saxagliptin, but increased with glimepiride over the treatment period, and the treatment difference was -1.6 kg (P < 0.001) at Week 48. The proportion of patients experiencing hypoglycaemia was much lower with saxagliptin vs glimepiride (3.1% vs 12.8%; P < 0.001). CONCLUSIONS: This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes.

Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves' orbitopathy.

CONTEXT: Graves' orbitopathy (GO) is a potentially sight-threatening disease for which currently available medical therapy is not reliably successful. Mycophenolate mofetil (MMF) is a selective immunosuppressant used widely in many autoimmune diseases. Preliminary studies have shown that MMF is effective in the treatment of active GO. OBJECTIVE: To evaluate the efficacy and safety of MMF in patients with active moderate-to-severe GO. PATIENTS: One hundred and 74 patients with active moderate-to-severe GO were randomized to receive either MMF or glucocorticoids (GC). MAIN OUTCOME MEASURES: The primary outcome was overall response at the 12th and 24th weeks; the outcome assessments included clinical activity score (CAS), soft tissue involvement, pain, visual acuity, proptosis, diplopia and reduction in eye movements. The secondary outcome was changes in those individual parameters. Adverse effects were recorded at each visit. RESULTS: A greater overall response rate was found in the MMF group compared with the GC group at the 24th week (91·3% vs 67·9%, P = 0·000). MMF therapy showed a better CAS response than GC (92·5% vs 70·5% improved, P < 0·05). Patients treated with MMF showed a significantly improved rate of diplopia and proptosis than patients treated with GC at the 24th week (90·4% and 68·8% improved, respectively). Disease reactivation was not observed in the patients treated with MMF but was observed in five patients after GC therapy. Adverse events occurred in 4 of 80 patients treated with MMF (5%), all of which were mild to moderate. A severe adverse event was only observed in one patient treated with GC but not at all in patients treated with MMF. CONCLUSION: Compared with GC treatment, MMF therapy is more effective and safer for patients with active moderate-to-severe GO.

miR-1470 mediates lapatinib induced p27 upregulation by targeting c-jun.

Our previous study indicated that lapatinib induces p27-dependent G(1) arrest through both transcriptional and post-translational mechanisms. Using miRNA microarray technology and quantitative RT-PCR, we further investigated the potential miRNAs that involved in p27 upregulation and Her-2 signaling pathway alteration with lapatinib treatment. A subset of 7 miRNAs was significantly affected in both 0.5 µM and 2.0 µM and 24 h and 48 h lapatinib treatment. Among them, only miR-1470, miR-126, and miR-1208 were identified in the Her-2 pathway after KEGG pathway analysis. However, luciferase reporter assay confirmed that miR-1470 directly recognized the 3'-untranslated region of c-jun transcripts, which was consistent with TargetScan analysis. miR-1470 significantly decreased c-jun expression, thus miR-1470 may repressc-jun activation of cyclinD1 expression, and consequently promoted the upregulation of p27, a key molecule in the cell cycle arrest. Taken together, the present study provided the first evidences that miR-1470 mediated lapatinib induced p27 upregulation by targeting c-jun.

Xuezhikang attenuated the functional and morphological impairment of pancreatic islets in diabetic mice via the inhibition of oxidative stress.

Xuezhikang, purified from red yeast rice, is a traditional Chinese medicine with pleiotropic effects on the cardiovascular system. Oxidative stress plays a crucial role in the dysfunction of pancreas islet in diabetic condition and represents a promising therapeutical target for diabetes mellitus. Therefore, the purpose of this study was to explore the effects and possible mechanisms of xuezhikang on the microenvironment and insulin secretion by pancreatic islets in db/db diabetic mice. Our results showed that xuezhikang decreased the blood glucose level by improving glucose tolerance and insulin secretion in db/db mice. Xuezhikang protected islets from hyperglycemic injury as illustrated by the conserved ß-cell content and microenvironment. Furthermore, xuezhikang potently inhibited the expression of key factors in oxidative stress. In addition, administration of xuezhikang caused an upregulated expression of glucose-sensing apparatus. These observations provide evidence that the influence of xuezhikang on oxidative stress may at least partly account for its protective effects on the microenvironment and insulin secretion function of pancreatic islets in diabetes.

Correlation between time in range and serum uric acid in Chinese patients with type-2 diabetes: an observational cross-sectional study.

BACKGROUND: At present, the relationship between serum uric acid and blood glucose is controversial, and even opposite conclusions have been reached. We aimed to investigate the relationship between time in range and serum uric acid and estimate the influence of serum uric acid on blood glucose fluctuations in Chinese patients with type-2 diabetes mellitus (T2DM). METHODS: A total of 458 hospitalized patients with T2DM were selected. According to the SUA level, patients were divided into four groups by quartile: Q1 (≤ 254.5 µmol/L), Q2 (254.5-306.0 µmol/L), Q3 (306.0-385.5 µmol/L) and Q4 (> 385.5 µmol/L). The differences in general data, TIR and other clinical indicators between the four groups were assessed. Multifactor regression was used to analyze the relationship between subgroups of SUA and TIR, TBR, TAR, MAGE, SD, ADRR, MODD and M value. Curve fitting was used to analyze the association between TIR and SUA and to identify the inflection point. RESULTS: TIR showed an overall increasing trend with increasing SUA, while HbA1c, TAR, MAGE, SD, ADRR, MODD and M value showed an overall decreasing trend with increasing SUA. Multivariate regression analysis showed that, compared with Q1, there was no correlation between SUA and TIR, TAR, ADRR, SD, or MODD in all models of Q2. In the Q3 and Q4 groups, SUA was correlated with SD, MODD, and MAGE in all models. In the Q4 group, SUA was correlated with TIR, TAR, ADRR, and the M value in all models. When SUA > 306 µmol/L (Q3 and Q4), TIR and SUA have a curve-like relationship, and the inflection point of the fitted curve was SUA = 460 mmol/L. Before the inflection point, ß was 0.1, indicating that when SUA increases by 10 mmol/L, the corresponding TIR increases by 1%. After the inflection point, there was no significant difference in the correlation between TIR and SUA (P > 0.05). CONCLUSIONS: There is a close relationship between TIR and SUA in T2DM patients, it is speculated that SUA in a certain range had a positive protective effect on blood glucose control.

Association between serum ß2-microglobulin and left ventricular hypertrophy in patients with type 2 diabetes mellitus: A cross-sectional study.

BACKGROUND: Beta 2-microglobulin (ß2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of ß2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum ß2-MG and LVH in T2DM patients. METHODS: The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum ß2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum ß2-MG quartile. The relationship of serum ß2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. RESULTS: The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum ß2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering ß2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between ß2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of ß2-MG for LVH in T2DM patients. CONCLUSION: Elevated serum ß2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.

Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial.

PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS. METHODS: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-µg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA. RESULTS: Eighty(80%) patients completed the study. Both interventions improved menstrual cycle, polycystic ovaries, LH(luteinizing hormone) and HbA1c(hemoglobin A1c) levels after the 12-week treatment. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI (Body Mass Index), and waist circumference, FBG(fasting blood glucose), AUCI(area under curve of insulin),TC (Total Cholesterol), IL-6(Interleukin-6) and improving insulin sensitivity, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in improving hyperandrogenemia, including T(total testosterone), LH, LH/FSH(Luteinizing hormone/follicle-stimulating hormone), SHBG(sex hormone-binding globulin) and FAI (free androgen index). By contract, GLP-1RA+Met group only improved LH. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9). CONCLUSIONS: Both CPA/EE+Met and GLP-1RA + Met treatment improved reproductive functions in overweight PCOS women. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI, and waist, and improving metabolism, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in reducing hyperandrogenemia. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment. TRIAL REGISTRATION CLINICALTIALS. GOV TRIAL NO: NCT03151005. Registered 12 May, 2017, https://clinicaltrials.gov/ct2/show/NCT03151005 .

Associations of Oral Contraceptive Use With Cardiovascular Disease and All-Cause Death: Evidence From the UK Biobank Cohort Study.

Background The associations of oral contraceptive (OC) use with cardiovascular disease (CVD) and all-cause death remains unclear. We aimed to determine the associations of OC use with incident CVD and all-cause death. Methods and Results This cohort study included 161 017 women who had no CVD at baseline and reported their OC use. We divided OC use into ever use and never use. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs for cardiovascular outcomes and death. Overall, 131 131 (81.4%) of 161 017 participants reported OC use at baseline. The multivariable-adjusted hazard ratios for OC ever users versus never users were 0.92 (95% CI, 0.86-0.99) for all-cause death, 0.91 (95% CI, 0.87-0.96) for incident CVD events, 0.88 (95% CI, 0.81-0.95) for coronary heart disease, 0.87 (95% CI, 0.76-0.99) for heart failure, and 0.92 (95% CI, 0.84-0.99) for atrial fibrillation. However, no significant associations of OC use with CVD death, myocardial infarction, or stroke were observed. Furthermore, the associations of OC use with CVD events were stronger among participants with longer durations of use (P for trend<0.001). Conclusions OC use was not associated with an increased risk of CVD events and all-cause death in women and may even produce an apparent net benefit. In addition, the beneficial effects appeared to be more apparent in participants with longer durations of use.

Compromised browning in white adipose tissue of ageing people.

BACKGROUND: Adipose tissue plays a pivotal role in the pathology of metabolic disorders. In the past decade, brown and brown-like adipose tissues were detected in adult humans and show therapeutic potential in ageing-related metabolic diseases. OBJECTIVE: This study investigated expressions of major brown adipose markers in white adipose tissue (WAT) of different ages. Their associations with metabolic parameters and key adipokines were interrogated. DESIGN: Cross-sectional study, 2019-2021. METHODS: We recruited 21 young, 67 middle-aged, and 34 older patients. Omental adipose tissues were collected, and expressions of key brown markers and adipokines and the adipocyte size were evaluated. The fat depot distribution was evaluated by computed tomography. RESULTS: UCP1 and PRDM16 mRNA expressions declined with ageing in WAT and were more associated with age, than with the body mass index (BMI). The increased visceral adipose tissue (VAT) amount, as well as the VAT to subcutaneous adipose tissue (SAT) ratio, was decreased in the highest tertile of UCP1 expression, while individuals in different PRDM16 mRNA tertiles exhibited similar fat distribution. UCP1 mRNA was positively correlated with ADIPOQ and the strength of the correlation declined with ageing. In contrast, the association between UCP1 and LEP was insignificant in young and middle-aged groups but became significantly correlated in the older-people group. We also found a positive correlation between UCP1 and PRDM16. CONCLUSIONS: PRDM16 and UCP1, despite their key functions in adipose browning, exhibit differential clinical correlations with metabolic features in human WAT in an age-dependent manner. These two genes may participate in the pathogenesis of ageing-related metabolic diseases, but with distinct mechanisms.

Differential correlation between time in range and eGFR or albuminuria in type 2 diabetes.

INTRODUCTION: As a CGM-derived indicator, 'time in range' (TIR) is emerging as a key indicator for accurate assessment of glycaemic control. However, there is few report focusing on the correlation of TIR with albumuria and renal fuction. The aim of this work was to investigate whether TIR, as well as nocturnal TIR and hypoglycaemic events is related to the presence and severity of albuminuria and decrease of eGFR in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 823 patients were enrolled in this study. All patients received continuous glucose monitoring, TIR indicating the percentage of time that blood glucose was in the range of 3.9-10.0 mmol/L. The Spearman analysis was applied to analyze the relationship between TIR (or nocturnal TIR) and ACR. Logistic regression was used to explore whether TIR (or nocturnal TIR) is an independent risk factor for albuminuria. RESULTS: The prevalence of albuminuria decreased with increasing TIR quartiles. Binary logistic regression revealed that TIR as well as nocturnal TIR was obviously related to the presence of albuminuria. Multiple regression analysis found that only nocturnal TIR was obviously related to the severity of albuminuria. In our study, eGFR was significantly associated with the number of hypoglycemic events. CONCLUSIONS: In T2DM patients, TIR and nocturnal TIR is associated with the presence of albuminuria independent of HbA1c and GV metrics. Nocturnal TIR shows better correlation than TIR. The role of TIR especially nocturnal TIR in the evaluation of diabetes kidney disease should be emphasized.

Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus.

Islet ß-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet ß-cell function is beneficial to better management of T2DM. Protecting islet ß-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet ß-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus." This consensus suggests that ß-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet ß-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet ß-cell function, independent of glycemic control.

Glucose metabolism in outpatients with new-onset hypertension in Chinese Han population.

The aim of this study was to assess the prevalence of glucose abnormalities in a Chinese Han population with untreated new-onset hypertension. Four hundred and ninety-nine new-onset hypertensive patients without diabetes were enrolled in this study. An abnormal glucose metabolism was diagnosed in 57.1% of the new-onset hypertensive patients without previously diagnosed diabetes. Stratified by age, the prevalence of diabetes and prediabetes were increased with aging. Male sex, advanced age, higher serum triglycerides, and homeostasis model assessment of insulin resistance levels were all significantly associated with the increased risks of pre-diabetes or diabetes in new-onset hypertensive patients when analyzed by the logistic regression analysis.

Association between osteocalcin, a pivotal marker of bone metabolism, and secretory function of islet beta cells and alpha cells in Chinese patients with type 2 diabetes mellitus: an observational study.

BACKGROUND: Several recent studies have found that Osteocalcin (OCN), a multifunctional protein secreted exclusively by osteoblasts, is beneficial to glucose metabolism and type 2 diabetes mellitus (T2DM). However, the effects of OCN on islets function especially islet ɑ cells function in patients with type 2 diabetes mellitus characterized by a bi-hormonal disease are still unclear. The purpose of this cross-sectional study was to investigate the relationship between serum OCN and the secretion of islet ß cells and ɑ cells in Chinese patients with type 2 diabetes mellitus. METHODS: 204 patients with T2DM were enrolled. Blood glucose (FBG, PBG0.5h, PBG1h, PBG2h, PBG3h), insulin (FINS, INS0.5h, INS1h, INS2h, INS3h), C-peptide (FCP, CP0.5h, CP1h, CP2h, CP3h), and glucagon (GLA0, GLA0.5 h, GLA1h, GLA2h, GLA3h) levels were measured on 0 h, 0.5 h, 1 h, 2 h, and 3 h after a 100 g standard bread meal load. Early postprandial secretion function of islet ß cells was calculated as Δcp0.5h = CP0.5-FCP. The patients were divided into low, medium and high groups (T1, T2 and T3) according to tertiles of OCN. Comparison of parameters among three groups was studied. Correlation analysis confirmed the relationship between OCN and pancreatic secretion. Multiple regression analysis showed independent contributors to pancreatic secretion. MAIN RESULTS: FBG, and PBG2h were the lowest while Δcp0.5h was the highest in the highest tertile group (respectively, p < 0.05). INS3h, area under the curve of insulin (AUCins3h) in T3 Group were significantly lower than T1 Group (respectively, p < 0.05). GLA1h in T3 group was lower than T1 group (p < 0.05), and GLA0.5 h in T3 group was lower than T2 and T1 groups (p < 0.05). Correlation analysis showed OCN was inversely correlated with Homeostatic model of insulin resistance (HOMA-IR), INS3h, AUCins3h (p < 0.05), and was still inversely correlated with FCP, GLA0.5 h, GLA1h, area under the curve of glucagon (AUCgla3h) (respectively, p < 0.05) after adjustment for body mass index (BMI) and alanine aminotransferase (ALT). The multiple regression analysis showed that OCN was independent contributor to Δcp0.5h, GLA0.5h and GLA1h (respectively, p < 0.05). CONCLUSIONS: Higher serum OCN level is closely related to better blood glucose control, higher insulin sensitivity, increased early-phase insulin secretion of islet ß cells and appropriate inhibition of postprandial glucagon secretion of islet ɑ cells in adult patients with type 2 diabetes mellitus.

Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis.

BACKGROUND: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. METHODS: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). RESULTS: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. CONCLUSION: These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.