Effect of exogenous free N^(ε)-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction:neuroinflammation,and metabolic disorders

Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.

NLRP3 Inflammasome in Relation to Glucose and Lipid Metabolism, and Insulin Resistance in Diabetes and Pre-Diabetes

Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA1C, TG, LDL-C, FINs, and HOMA-IR were higher (P β were lower (P P β were seen (P P β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.

Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease

BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

Serum tumor markers:Can they clinically implicate in type 2 diabetes mellitus?

“Serum tumor markers expression(CA19-9,CA242,and CEA)and its clinical implications in type 2 diabetes mellitus”authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus(T2DM).The study explores the diagnostic accuracy of tumor markers,particularly cancer antigen 19-9(CA19-9),CA242,and carcinoembryonic antigen,in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%,employing receiver operating characteristic curve analysis.Though study offers valuable insights into the potential utility of tumor markers in clinical practice,caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost.Additionally,the study overlooks potential confounding factors like smoking and alcohol consumption.Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases,warranting further investigation into their diagnostic and prognostic implications.While Meng and Shi represent a significant contribution to the field,more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

Relationship Between Serum microRNA-372-3p and Glucose Transporter 4 Levels and Insulin Resistance in Gestational Diabetes Mellitus

Objective:To observe the changes in insulin resistance in patients with gestational diabetes mellitus(GDM)based on the detection of serum microRNA-372-3p and glucose transporter protein 4(GLUT4)levels.Methods:We conducted a retrospective cohort study of 42 patients who were diagnosed with GDM and hospitalized in our hospital during the period from January 2017 to December 2021 and another 42 patients who had normal pregnancy during the same period by collecting their clinical data.We analyzed their serum microRNA expression profiles and miR-372-3p levels to study the relationship between GDM and insulin resistance.Results:The relative expression of miR-372-3p in the serum of patients in the GDM group was significantly higher than that of patients in the control group,but the GLUT 4 level of the GDM group was significantly lower than that of the control group(P<0.05).Compared with the control group,the GDM group had significantly higher levels of fasting blood glucose(FBG),fasting insulin(FINS),2-hour postprandial blood glucose(2h-BG),total cholesterol(TC),triglyceride(TG),and homeostatic model assessment for insulin resistance(HOMA-IR)index but significantly lower homeostasis model assessment ofβ-cell function(HOMA-β)index(P<0.05).The relative expression of miR-372-3p in serum was independently and positively correlated with HOMA-IR,while the level of GLUT4 was independently and negatively correlated with HOMA-IR(P<0.05).Conclusion:Glycosylated hemoglobin test in the early stages of pregnancy(12–13 weeks of gestation)is important to ensure the health of pregnant women and fetuses.The screening and intervention for elevated glucose in pregnant women act as a guideline for the treatment of GDM.Patients with insulin resistance and related complications such as hyperinsulinemia and hypoglycemia should be given priority.

Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.

Glycated Haemoglobin in Diagnosis of Diabetes Mellitus and Pre-diabetes among Middle-aged and Elderly Population:Shanghai Changfeng Study

Objective To investigate the optimal glycated haemoglobin （HbAlc） cut off points and evaluate the impact of HbAlc on diabetes and pre-diabetes in middle-aged and elderly population. Methods Subjects were recruited from Shanghai Changfeng Study. A total of 1 973 community-based participants （age_〉45） without known diabetes underwent oral glucose tolerance test （OG3-r） by using a 75-g oral glucose load and HbAlc was measured by using high performance liquid chromatography （HPLC）. Subjects were classified as normal glucose tolerance （NGT）, pre-diabetes（impaired glucose regulation, IGR） and new diagnosed diabetes （NDD） per 1999 WHO criteria. Two tests are compared with receiver operating characteristic curve （ROC）. Results Among 1973 subjects, 271 （13.7%） were diagnosed as NDD and 474 （24.0%） as IGR by using OGTT. HbAlc was 5.7%_＋0.7% in this population. Use of 6.5% as the HbAIC cutoff point has sensitivity of 38.7% and specificity of 98.5%. We recommend 6.0% as a better cutoff value for diagnosis of diabetes in this population （AUC 0.829, 95% CI 0.798-0.860, P〈0.001） with its sensitivity and specificity as 66.1% and 86.8%. For IGR, the results showed low sensitivity （44.9%） and specificity （66.7%） with an AUC of 0.571 for HbAlc when 5.8% was used as the cutoff point. Participants detected with HbAlc_〉6.0% were associated with nearly the same metabolic characteristics, including body mass index （BMI）, blood pressure, lipid profile and urine albumin-creatinine ratio （uACR） compared with diabetic subjects detected by OGTT. Conclusion The optimum HbAlc cutoff point for diabetes in our study population was lower than ADA criteria, and HbAlc may not be used to identify IGR.

Increased Arterial Stiffness in Subjects with Pre-diabetes among Middle Aged Population in Beijing,China

Objective To investigate the relationship between arterial stiffness and pre-diabetes when assessed by the new glycosylated hemoglobin Ale （HbAlc） 5.7%-6.4% criterion or by impaired fasting glucose in middle aged Chinese. Methods 1122 adults aged 55 years or younger in the health examination centers for physical check-ups were enrolled in the two large-sized Tertiary Comprehensive Hospitals in Beijing from June 2011 to June 2012 after excluding those who previously had been diagnosed or treated as diabetes or cardiovascular disease. Subjects with a diagnosis of pre-diabetes according to impaired fasting glucose （IFG） （fasting plasma glucose （FPG） levels at 5.6-6.9 mmol/L）, HbA^c levels at 5.7%-6.4%, or both, were classified into four groups for observation： （1） Normoglycaemia （HbA^c〈5.7% and FPG 〈5.6 mmol/L）; （2） IFG alone （FPG levels at 5.6-6.9 mmol/L and HbA1c〈5.7% ）; （3） HbAI~ 5.7%-6.4% alone （HbA^c levels at 5.7%-6.4% and FPG 〈5.6 mmol/L）; and （4） both HbA1c 5.7%-6.4% and IFG （l-lbA1~ levels at 5.7%-6.4% and FPG levels at 5.6-6.9 mmol/L）. All subjects were measured for weight, height, waist circumference, blood pressure, fasting plasma glucose, HbA1c, lipid profile and brachial-ankle pulse wave velocity （baPWV）. Results The mean values of baPWV were 1282±8, 1311±10, 1398±30, and 1418_±27 cm/s （Mean_±SE） in Normoglycaemia, HbA~ 5.7%-6.4% alone, IFG alone and the both HbAlc 5.7%-6.4% and IFG groups, respectively. After adjusting for age, gender, blood pressure, BMI and triglyceride, baPWV was significantly higher in subjects with both HbAlc5.7%-6.4% and iFG compared among the subjects with Normoglycaemia （1350±14 vs. 1301±6 cm/s, P=0.002） and HbA1c 5.7%-6.4% alone （1350±14 vs. 1309±8 cm/s, P=0.013）.Conclusion Subjects with pre-diabetes exhibited a greater arterial stiffness.

Update on pre-diabetes: Focus on diagnostic criteria and cardiovascular risk

Pre-diabetes, which is typically defined as blood glucose concentrations higher than normal but lower than thediabetes threshold, is a high-risk state for diabetes and cardiovascular disease development. As such, it represents three groups of individuals: Those with impaired fasting glucose(IFG), those with impaired glucose tolerance(IGT) and those with a glycated haemoglobin(HbA1c) between 39-46 mmol/mol. Several clinical trials have shown the important role of IFG, IGT and HbA1c -pre-diabetes as predictive tools for the risk of developing type 2 diabetes. Moreover, with regard to cardiovascular disease, pre-diabetes is associated with more advanced vascular damage compared with normoglycaemia, independently of confounding factors. In view of these observations, diagnosis of pre-diabetes is mandatory to prevent or delay the development of the disease and its complications; however, a number of previous studies reported that the concordance between pre-diabetes diagnoses made by IFG, IGT or HbA1c is scarce and there are conflicting data as to which of these methods best predicts cardiovascular disease. This review highlights recent studies and cur-rent controversies in the field. In consideration of the expected increased use of HbA1c as a screening tool to identify individuals with alteration of glycaemic homeo-stasis, we focused on the evidence regarding the ability of HbA1c as a diagnostic tool for pre-diabetes and as a useful marker in identifying patients who have an increased risk for cardiovascular disease. Finally, we reviewed the current evidence regarding non-traditional glycaemic biomarkers and their use as alternatives to or additions to traditional ones.

Correlation of Liver Enzymes with Diabetes and Pre-diabetes in Middle-aged Rural Population in China

The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus（T2DM） and pre-diabetes（pre-DM） in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test（OGTT） was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases（ALT and GGT）, Hb A1 C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose（IFG）, impaired glucose tolerance（IGT）, impaired fasting glucose combined with impaired glucose tolerance（IFG＋IGT） and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio（WHR）, blood pressure, fasting blood glucose（FBG）, high density lipoprotein-cholesterol（HDL-C）, and liver enzymes（ALT and GGT）. Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance（IR） in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.

Prevalence rates and cardiometabolic determinants of diabetes mellitus and pre-diabetes with projected coronary heart disease at bank site of Brazzaville

Background: Aim: Congolese Bank employees are often inactive without valid information on the burden of dysglycemia and cardiometabolic risk. This study aims to assess the prevalence rates of diabetes mellitus (DM) and pre-diabetes and to identify the environmental, genetic and cardiometabolic risk factors associated with Type 2 diabetes mellitus (T2DM) and pre-diabetes among Congolese bank employees. Methods: In representative 126 bank employees from Brazzaville, Congo, Central Africa, Abdominal obesity, dyslipidemia and metabolic syndrome (MetS) were defined by IDF for Europe, NCEP-ATPIII and IDF criteria modified for Central Africa. Projected high 10-year total risk of coronary heart disease (CHD) ≥20% was calculated using Framingham scores. Results: Out of the employees, 16% and 21.4% had DM and pre-diabetes, respectively. The rate of T2DM among diabetics was estimated 90%. Aging, high total cholesterol, high LDL-cholesterol, high conicity index and longer urban residence after migration were significantly associated with pre-diabetes. Physical inactivity, smoking, excessive alcohol intake, abdominal obesity, female gender, low HDL-C, hypertension, CHD, projected high 10-year total CHD risk, age ≥ 55 years, urban residence, Southern area residence, high socioeconomic status, non married status, MetS/NCEP, MetS/IDF for Europe and MetS/IDF for Africa were significantly associated with T2DM.MetS/IDF for Africa was the only independent determinant of T2DM. Conclusion: Urgent prevention and intervention programme are needed to curb the alarming increase in DM, T2DM, pre-diabetes.

Prevalence and Correlates of Prediabetes and Diabetes Results-I: A Screening Plan in a Selected Military Community in Central Saudi Arabia

Background: Diabetes is a chronic disease of a genetic and environmental background. If it is not diagnosed and controlled early, it can have devastating complications. Aim: Measure and analyze the prevalence and risks of prediabetes and diabetes among recruits enlisted in the Wadi Al-Dawasir (WD) military zone, central Saudi Arabia. The influence of some demographic criteria, weight, and blood pressure upon blood glucose level would be evaluated. Methods: A cross sectional design was utilized, whereas predesigned questionnaire and clinical interview were used to screen the study population. Results: The participants’ median age was 33.7 (IQR 11.9), mean body mass index (BMI) was 27.6 ± 5.4 kg/m2. Out of 531 recruits screened, almost two-thirds were either overweight (34.7%) or obese (29.9%). The mean waist circumference (WC) was 94.7 ± 13.3 cm;and 27.9% had central obesity (WC ≥102 cm). Random plasma glucose (RPG) median accounted 106 mg/dl (IQR 21). The participants’ RPG levels significantly increased by age (U = 19697.0), by BMI [H(df 5) = 59.6], and by WC (U = 25,670.5), (p rho(df 503) = 0.241, p U 3515, p 25 to ≥40 kg/m2) more than normal subjects [46 (87%) vs. 5 (0.9%)], [χ2(df 5) = 18.8, p Conclusions: Prediabetes and uncontrolled diabetes are relatively prevalent among Saudi recruits’ community. An insufficient influence of obesity for developing diabetes symptoms in the study population may well be attributed to time factor separating the two variables. A preventive approach to revert the predisposition of prediabetes in WD recruits population is quite promising.

Changes before and after improvement of subjective sleep state of a man diagnosed with pre-diabetes and sleep disorder

The purpose of this case study was to examine the changes before and after improvements of the subjective sleep status of Mr A, a 40-year-old man diagnosed with pre-diabetes and a sleep disorder. Data were collected using a Holter monitor for 24 hours a day for 3 days to assess autonomic nervous activity by recording bed-time and waking time activity (activity counts: ACs). Mr. A kept a diary of activities and completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The study revealed that subjective sleeping hours correlated almost precisely with those measured by the actigraph and as described in the diary. Both the parasympathetic and sympathetic nervous system activities were imbalanced. However, no correlation was observed between the ACs and autonomic nervous activity. Subjective sleep state according to the PSQI score improved remarkably by dietary and exercise therapy from 13 to 3 points, after six months, with corresponding high level sleep satisfaction level. Significant correlations were observed between ACs and high-frequency spectral power of R-R intervals, and between ACs and the low-frequency/high frequency ratio of spectral power of R-R intervals. Although Mr. A’s sleep satisfaction level has improved, the autonomic nervous system activity remained different from that of healthy people.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

PRE-084通过调节神经元MAM改善1型糖尿病小鼠的学习记忆障碍

目的糖尿病小鼠可表现出学习记忆功能障碍,探究Sigma-1受体激动剂PRE-084对1型糖尿病小鼠海马区神经元及认知损伤的影响。方法将20只8~10周龄链脲佐菌素诱导的1型糖尿病小鼠和20只对照小鼠随机分为4组(CON+Vehicle、CON+PRE-084、T1DM+Vehicle和T1DM+PRE-084组);分别用添加PRE-084及对照溶剂的高糖培养基培养小鼠原代神经元。监测并记录各组小鼠的体质量、饮食饮水量及空腹血糖水平,利用新物体识别实验检测小鼠的学习记忆能力,透射电镜检测小鼠海马CA1区神经元MAM结构的变化,生化试剂盒检测小鼠海马区ATP、活性氧(ROS)的表达水平;利用CCK8和细胞ROS试剂盒检测原代神经元的细胞活力和ROS水平。结果PRE-084可降低糖尿病小鼠体质量、饮食饮水量和血糖。PRE-084明显缓解1型糖尿病小鼠的学习记忆障碍,改善糖尿病小鼠海马CA1区神经元MAM结构的变化,升高糖尿病小鼠海马区ATP的水平,降低糖尿病小鼠海马区及高糖条件下神经元中ROS表达水平。结论Sigma-1受体激动剂PRE-084改善1型糖尿病小鼠学习记忆障碍可能与海马区神经元MAM结构变化、ATP产量增加及ROS生成减少相关。

Type 2 diabetes mellitus and CA 19-9 levels

AIM： To prospectively investigate serum CA 19-9 levels in type 2 diabetic patients in comparison with age and gender-matched control subjects.METHODS： We recorded duration of diabetes and examined fasting glucose levels, HbAlc levels and serum CA 19-9 levels in 76 type 2 diabetic patients and 76 controls. Abdominal CT was performed in order to eliminate abdominal malignancy in the diabetic and control groups.RESULTS： The average CA 19-9 level was 46.0 ± 22.4 U/mL for diabetic patients whereas it was 9.97± 7.1 U/mL for the control group （P 〈 0.001 ）. Regression analysis showed a positive correlation between diabetes and CA 19-9 independent from age, gender, glucose level and HbAlc level （t = 8.8, P 〈 001 ）. Two of the diabetic patients were excluded from the study because of abdominal malignancy shown by CT at the initial evaluation. For all patients, abdominal CT showed no pancreatic abnormalities. CONCLUSION： CA 19-9 is a tumor-associated antigen, which is elevated in pancreatic, upper gastrointestinal tract, ovarian hepatocellular, and colorectal cancers, as well as in inflammatory conditions of the hepatobiliary system, biliary obstruction and in thyroid diseases. Diabetes has been claimed to be a risk factor for pancreatic cancer, which is increasing its incidence and has one of the lowest survival rates of all cancers. CA 19-9 is used in the diagnosis of pancreatic cancer but is also a marker of pancreatic tissue damage that might be caused by diabetes. We propose that a higher cutoff value of CA 19-9 should be used in diabetics to differentiate benign and malignant pancreatic disease, and subtle elevations of CA 19-9 in diabetics should be considered as the indication of exocrine pancreatic dysfunction.

Association of Interleukin-6-174G/C Polymorphism with the Risk of Diabetic Nephropathy in Type 2 Diabetes:A Meta-analysis

Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.

Usefulness of CA 19–9 for pancreatic cancer screening in patients with new-onset diabetes

Background： Generally, carbohydrate antigen 19–9 （CA 19–9） is not useful for screening pancreatic cancerin the asymptomatic general population. This study aimed to evaluate the utility of CA 19–9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes.