We sought to investigate the association between biological age (BA) acceleration and mortality among adults with diabetes or prediabetes and to assess whether physical activity mediates this association. We included 7,337 participants with diabetes or prediabetes from the 1999–2018 National Health and Nutrition Examination Survey. BA was estimated using the Klemera–Doubal method (KDM). BA acceleration was defined as the residual difference between the estimated BA and chronological age. Cox proportional hazards models were used to examine the association between KDM-BA acceleration and mortality. The mediating effect of physical activity were evaluated to investigate the potential mechanism of the associations between BA acceleration and mortality. Over a median follow-up period of 94 months, 1,445 deaths occurred. Participants in the high tertile of KDM-BA acceleration had a 35

BACKGROUND:To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar).METHODS:In this 16-week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks.RESULTS:Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high-density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00-0.16), and diminished low-density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05-0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to -1.57 mmol/L [95% CI, -2.60 to -0.54]), this difference was abolished in patients whose fasting C-peptide was ≥0.9 ng/mL.CONCLUSION:Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C-peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C-peptide levels be evaluated when using or switching to the novel glucagon-like peptide-1 receptor agonists beinaglutide.TRIAL REGISTRATION:ClinicalTrials.gov: NCT03829891.

Diabetic peripheral neuropathy(DPN)is one of the common chronic complications of diabetes,which seriously affects the life quality of diabetic patients.Therefore,early clinical diagnosis is very important for the prevention and treatment of DPN.Hyperuricemia is a metabolic disease caused by purine nucleotide metabolism disorder.Although a large number of studies have shown that the hyperuricemia may be an independent risk factor for DPN,its potential effects on DPN and mechanisms of action have not been fully elucidated.This paper summarizes the pathogenesis of DPN,introduces the role of uric acid in the pathogenesis of DPN,and expounds that oxidative stress and inflammation are the roles of hyperuricemia in the pathogenesis of DPN,so as to provide references for finding early clinical warning indicators.

Objective To explore the association between insulin resistance(IR)and diabetic kidney disease(DKD)among adults with type 1 diabetes mellitus(T1DM)and compare multiple surro-gate parameters of IR for their associations with DKD in this population.Methods For this cross-sec-tional study,556 adults with classic T1DM admitted into Xijing Hospital between October 2008 and June 2021 were enrolled.Demographic,anthropometric and laboratory data were collected.IR-related parame-ters of estimated glucose disposal rate(eGDR),metabolic score for insulin resistance(METS-IR)and triglyceride-glucose index(TyG)were calculated.They were categorized into two groups of DKD and non-DKD.The relationship between IR and DKD was explored by binary Logistic regression and restricted cu-bic spline(RCS)models.Receiver operating characteristic(ROC)curves were plotted for comparing the discriminatory performance of all parameters.Results Median age was 31.0(24.8,44.0)year and medi-an disease duration 6.0(2.0,12.0)year.The prevalence of DKD was 20.14%.Lower eGDR was associat-ed with a high prevalence of DKD.In multivariable analysis,as compared to quartile 1(Q1),odds ratios(OR,95%CI)of DKD for participants in eGDR calculated with body mass index(eGDRBMI)Q2-Q4 were 1.08(0.40-2.92),0.13(0.03-0.45)and 0.26(0.07-0.83),respectively.The corresponding risk in eGDR calculated with waist-to-hip ratio(eGDRWHR)Q2-Q4 was 0.68(0.20-2.23),0.51(0.15-1.66)and 0.16(0.03-0.72),respectively.TyG,eGDR calculated with waist circumference(eGDRWC),METS-IR,body mass index,waist-to-height ratio and waist-to-hip ratio were not significantly associated with the prevalence of DKD.Subgroup analyses indicated that the association between eGDRBMI and DKD was consistent with overall population in six subgroups of females,age 28-＜40 years and≥40 years,disease duration≥5 years,non-smokers and individuals with a family history of diabetes.RCS hinted at a linear and negative correlation between eGDRBMI,eGDRWHR and the prevalence of DKD.ROC analyses indicated that the cut-off values for identifying DKD were 8.23 mg·kg-1·min-1,7.22 mg·kg-1·min-1 and 7.92 mg·kg-1·min-1 for eGDRBMI,eGDRWHR and eGDRWC,respectively.After adding into a basic model,all three eGDRs demon-strated incremental discriminatory performance.Conclusion IR,reflected by a declining eGDR,is as-sociated with the prevalence of DKD among adults with classic T1DM.And eGDR has demonstrated some potential in identifying DKD in adult classic T1DM and its clinical implication should be validated by more studies.

Background: The potential factors beyond HbA1c that increase the risk of cardiovascular disease and age more quickly in people with diabetes are not yet clear. This study sought to determine the prospective associations between discrepancies in observed and predicted HbA1c levels, also known as the hemoglobin glycation index (HGI), and cardiovascular disease risk. Additionally, the interactions of HGI with accelerated aging in relation to cardiovascular disease risk were evaluated. Method: This cross-sectional study included 9167 adults from the National Health and Nutrition Examination Survey 1999-2010. The HGI is used to assess individual blood glucose variability, and phenotypic age acceleration is employed to evaluate accelerated aging. Regression analysis, restricted cubic spline and mediation analysis explore the potential roles of phenotypic age acceleration in the relationship between HGI and CVD mortality. Results: Among the 9167 eligible participants (aged 20 years or older), 4390 (47.9%) were males, and the median (IQR) age was 48.0 (15.0) years; 4403 (48.0%) had prediabetes and diabetes, and 985 (10.7%) had cardiovascular disease. Restricted cubic splines showed that the association between HGI and CVD risk was nonlinear (p < 0.001). The greater the negative value of the HGI was, the greater the risk of CVD, and the association was independent of age, sex and HbA1c. Mediation analyses confirmed that phenotypic age acceleration acted as a mediator in the association between HGI and CVD risk (mediated effect: OR, 68.7%, 95% CI: 36.4%-153%, P=0.002). Conclusion and Relevance: The HGI serves as a robust biomarker for assessing the acceleration of aging, regardless of HbA1c levels, and is associated with increased susceptibility to cardiovascular disease, particularly among individuals characterized by negative HGI. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The analyses utilized existing data from the NHANES study, and we were not involved in participant recruitment. ### Funding Statement National Natural Science Foundation of China (NSFC): 82070839 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Review Board of the National Center for Health Statistics I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data is available on the website of the America Centers for Disease Control and Prevention (CDC)

Objective:To investigate the relationship between carotid atherosclerosis(CAS)and subclinical left ventricular(LV)dysfunction in type 2 diabetes mellitus patients with preserved LV ejection fraction(LVEF).Methods:A total of 120 patients with type 2 diabetes mellitus who had LVEF≥50% were selected in the Department of Endocrinology, the First Affiliated Hospital of Air Force Medical University from June 2021 to October 2021. The global longitudinal strain(GLS)was obtained by two-dimensional speckle tracking echocardiography(STE)to assess subclinical LV systolic function. The mitral ratio of peak early to late diastolic filling velocity(E/A), and mitral velocity to early diastolic velocity of the mitral annulus(E/E′)ratio were obtained by pulsed tissue Doppler echocardiography to assess LV diastolic function. Acrroding to bilateral carotid ultrasound examination, the subjects were divided into normal carotid arteries group( n=46) and CAS group( n=74). Demographics and biochemical parameters were compared between two groups. Binary logistic regression and Pearson correlation analysis were used to evaluate the relationship between CAS and subclinical LV dysfunction. Results:The CAS group had a higher proportion of men, older age, and a longer duration of diabetes than the normal carotid arteries group(all P<0.05). There was no difference in LVEF and GLS between the two groups [normal carotid arteries group vs CAS group, LVEF: (60.72±4.73)% vs(60.07±4.28)%; GLS: (18.24±3.72)% vs(17.81±3.47)%, respectively; both P>0.05]. However, compared with normal carotid arteries group, E/A ratio was decreased and E/E′ ratio was significantly increased in CAS group(both P<0.01). Pearson correlation analysis showed that GLS was not correlated with carotid plaque thickness and carotid intima-media thickness(CIMT; both P>0.05). By contrast, E/E′ ratio was positively correlated with carotid plaque thickness and CIMT(both P<0.05). Binary logistic regression analysis showed that GLS and E/E′ ratio were not associated with CAS( both P>0.05). However, decreased E/A ratio was significantly associated with the existence of CAS( OR=0.09, 95% CI 0.01-0.67, P=0.018). Conclusions:In type 2 diabetes mellitus patients without overt heart failure and with preserved LVEF, the occurrence of CAS is not associated with subclinical LV systolic impairment assessed by GLS, but is significantly associated with LV diastolic dysfunction, and is independent of traditional cardiovascular risk factors.

Stroke is the leading cause of death and disability worldwide. Novel and effective therapies for ischemic stroke are urgently needed. Here, we report that melatonin receptor 1A (MT1) agonist ramelteon is a neuroprotective drug candidate as demonstrated by comprehensive experimental models of ischemic stroke, including a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia in vivo, organotypic hippocampal slice cultures ex vivo, and cultured neurons in vitro; the neuroprotective effects of ramelteon are diminished in MT1-knockout (KO) mice and MT1-KO cultured neurons. For the first time, we report that the MT1 receptor is significantly depleted in the brain of MCAO mice, and ramelteon treatment significantly recovers the brain MT1 losses in MCAO mice, which is further explained by the Connectivity Map L1000 bioinformatic analysis that shows gene-expression signatures of MCAO mice are negatively connected to melatonin receptor agonist like Ramelteon. We demonstrate that ramelteon improves the cerebral blood flow signals in ischemic stroke that is potentially mediated, at least, partly by mechanisms of activating endothelial nitric oxide synthase. Our results also show that the neuroprotection of ramelteon counteracts reactive oxygen species-induced oxidative stress and activates the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Ramelteon inhibits the mitochondrial and autophagic death pathways in MCAO mice and cultured neurons, consistent with gene set enrichment analysis from a bioinformatics perspective angle. Our data suggest that Ramelteon is a potential neuroprotective drug candidate, and MT1 is the neuroprotective target for ischemic stroke, which provides new insights into stroke therapy. MT1-KO mice and cultured neurons may provide animal and cellular models of accelerated ischemic damage and neuronal cell death.

Objective:The aim of study was to evaluate the effect and safety of pioglitazone-metformin combined treatment in the newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease.Methods:A total of 120 newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease from 8 centers were randomly divided into the control group (metformin hydrochloride) and the test group (pioglitazone hydrochloride and metformin hydrochloride).Results:Compared to the control group, after treatment, the proportion of people with mild and moderate fatty liver increased, and the proportion of people with severe fatty liver decreased, and this change was more obvious in the population with moderate and severe fatty liver. The level of γ-GT decreased in both groups before and after treatment, which was statistically significant, and there was also a statistically significant difference in the level of γ-GT between the two groups after 24 weeks. There were no significant statistically differences in blood lipid, body weight, and waist circumference between the test group and the control group. Logistic regression analysis found that BMI is one of the risk factors for fatty liver. There was also no significant difference in the incidence of serious adverse events between the two groups (control group: 10.00% and test group: 6.67%, P = 0.74).Conclusion:Combined treatment with pioglitazone-metformin can effectively reduce liver fat content and gamma-GT level in newly diagnosed diabetic patients with nonalcoholic fatty liver disease, and adverse events do not increase compared with the control group, showing good safety and tolerance. This trial is registered with ClinicalTrials.gov NCT03796975.

Background. The purpose of this research was to assess the relationship between the severity of diabetic retinopathy (DR) and indexes of left ventricle (LV) structure and function in type 2 diabetes mellitus (T2DM). Methods. Retrospective analysis of 790 patients with T2DM and preserved LV ejection fraction. Retinopathy stages were classified as no DR, early nonproliferative DR, moderate to severe nonproliferative DR, or proliferative DR. The electrocardiogram was used to assess myocardial conduction function. Echocardiography was used to evaluate myocardial structure and function. Results. Patients were divided into three groups based on the DR status: no DR group (NDR, n = 475 ), nonproliferative DR group (NPDR, n = 247 ), and proliferative DR group (PDR, n = 68 ). LV interventricular septal thickness (IVST) increased significantly with more severe retinopathy (NDR: 10.00 ± 1.09 ; NPDR: 10.42 ± 1.21 ; and PDR: 10.66 ± 1.58 ; P < 0.001). Multivariate logistic regression analysis showed that the significant correlation of IVST persisted between subjects with no retinopathy and proliferative DR (odds ratio = 1.35 , P = 0.026 ). Indices of myocardial conduction function were assessed by electrocardiogram differences among groups of retinopathy (all P < 0.001 ). In multiple-adjusted linear regression analyses, the increasing degree of retinopathy was closely correlated with heart rate ( β = 1.593 , P = 0.027 ), PR interval ( β = 4.666 , P = 0.001 ), and QTc interval ( β = 8.807 , P = 0.005 ). Conclusion. The proliferative DR was independently associated with worse cardiac structure and function by echocardiography. Furthermore, the severity of retinopathy significantly correlated with abnormalities of the electrocardiogram in patients with T2DM.

Objectives: The impacts of diabetic peripheral neuropathy (DPN) on clinical manifestations of left ventricular (LV) function in patients suffering from type 2 diabetes mellitus (T2DM) and the preserved LV ejection fraction (LVEF) lack a full evaluation. This study was carried out to investigate the correlation of peripheral neuropathy with subclinical LV systolic dysfunction, accompanied by the exploration of the relevant clinical features of peripheral neuropathy in these patients. Methods: A retrospective analysis was conducted depending on the data of 101 consecutive inpatients with T2DM and preserved LVEF (all ??? 50 %), without coronary artery disease and other histories of heart disease. All subjects received both a nerve conduction assessment and a speckle-tracking echocardiography examination. Global longitudinal strain (GLS) was conducted to assess the subclinical LV systolic function. Results: Forty-six (46 %) patients were diagnosed as DPN according to electrophysiological examination and clinical assessment. A significant difference was revealed in GLS between patients with and without DPN (16.5 ?? 2.8 vs. 19.3 ?? 3.4, p < 0.001). Multiple logistic regression analysis indicated GLS as one of the independent determinative factors for DPN (odds ratio, 0.68; P < 0.001). In addition, motor-sensory nerve conduction exhibited a significant positive correlation with GLS, which may not be revealed between the types of peripheral nerve damage. Conclusions: Despite the preserved LVEF, the subclinical LV myocardial dysfunction may have occurred in T2DM patients with DPN. Peripheral nerve conduction was significantly correlated with GLS. An early assessment of nerve conduction may exert a dual warning significance for the progression of subclinical LV dysfunction in asymptomatic patients with T2DM.

BackgroundWe aimed to examine the association between glycated hemoglobin (HbA1c), microvascular complications, and subclinical left ventricular (LV) systolic dysfunction, and to determine the strength of the correlation in asymptomatic patients with type 2 diabetes mellitus (T2DM). MethodsGlobal longitudinal strain (GLS) was employed to assess the subclinical LV function of 152 enrolled T2DM patients with preserved LV ejection fraction, with the cutoff for subclinical LV systolic dysfunction predefined as GLS < 18%. ResultsAccording to univariate analysis, the reduced GLS exhibited association with the clinical features including HbA1c, triglyceride, systolic blood pressure, fasting glucose, heart rate, diabetic retinopathy, and urinary albumin creatinine ratio (UACR) (all p < .05). After the factors of gender, age, and related clinical covariables adjusted, multiple logistic regression analysis revealed the HbA1c (odds ratio [OR] 1.66; 95% confidence interval [CI] 1.30-2.13; p < .001), UACR (OR 2.48; 95% CI 1.12-5.47; p = .025) and triglyceride (OR 1.84; 95% CI 1.12-3.03; p = .017) as the independent risk factors for the reduced GLS. Receiver operating characteristic curve showed a predictive value of the HbA1c for the subclinical LV systolic dysfunction (area under curve: 0.74; p < .001). ConclusionsIn asymptomatic T2DM patients, subclinical LV systolic dysfunction was associated with HbA1c, diabetic complications, and triglyceride. More prominently, HbA1c may exert a prognostic significance for the progression of myocardial damage.

Abstract Background We aimed to examine the association between glycated hemoglobin (HbA1c), microvascular complications, and subclinical left ventricular (LV) systolic dysfunction, and to determine the strength of the correlation in asymptomatic patients with type 2 diabetes mellitus (T2DM). Methods Global longitudinal strain (GLS) was employed to assess the subclinical LV function of 152 enrolled T2DM patients with preserved LV ejection fraction, with the cutoff for subclinical LV systolic dysfunction predefined as GLS < 18%. Results According to univariate analysis, the reduced GLS exhibited association with the clinical features including HbA1c, triglyceride, systolic blood pressure, fasting glucose, heart rate, diabetic retinopathy, and urinary albumin creatinine ratio (UACR) (all p < .05). After the factors of gender, age, and related clinical covariables adjusted, multiple logistic regression analysis revealed the HbA1c (odds ratio [OR] 1.66; 95% confidence interval [CI] 1.30–2.13; p < .001), UACR (OR 2.48; 95% CI 1.12–5.47; p = .025) and triglyceride (OR 1.84; 95% CI 1.12–3.03; p = .017) as the independent risk factors for the reduced GLS. Receiver operating characteristic curve showed a predictive value of the HbA1c for the subclinical LV systolic dysfunction (area under curve: 0.74; p < .001). Conclusions In asymptomatic T2DM patients, subclinical LV systolic dysfunction was associated with HbA1c, diabetic complications, and triglyceride. More prominently, HbA1c may exert a prognostic significance for the progression of myocardial damage.

Objective:To investigate the correlation between different obesity indices and the incidence of hyperuricemia (HUA) and hypertension in patients with type 2 diabetes mellitus (T2DM) older than 50 years old.Methods:As a cross-sectional study, the subjects were chosen from a prospective study on the epidemiology of lower extremity arterial disease in Chinese patients with T2DM from June 2016 to January 2017. The height, weight, waist circumference (WC) (traditional obesity index), hip circumference, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) of the subjects were collected. Three traditional obesity indices [body mass index (BMI), waist hip ratio (WHR), and waist height ratio (WHtR)], as well as five new obesity indices [visceral fat index (VAI), body roundness index (BRI), a body shape index (ABSI), lipid accumulation index (LAP), and relative fat mass (RFM)], were calculated. Logistic regression analysis was used to analyze the correlation between different obesity indices and the occurrence of HUA and hypertension. The area under the receiver operating characteristic curve (AUC) was used to compare the value of different obesity indices in predicting HUA and hypertension.Results:A total of 6 646 patients with T2DM were finally included in the study. There were 964 cases in HUA group and 5 682 cases in non-HUA group. There were 4 388 cases in the hypertension group and 2 258 cases in the non-hypertension group. Multivariate logistic regression results showed that after adjusting for confounding factors, except for the new obesity index ABSI, other obesity indices [four traditional obesity indices (WC, BMI, WHR, WHtR) and four new obesity indices (VAI, BRI, LAP, RFM)] were positively correlated with the occurrence of HUA ( P<0.05). The AUC of male VAI and LAP for predicting HUA were 0.654 and 0.651, respectively, while the AUC of female VAI and LAP for predicting HUA were both 0.671, which were higher than the traditional indices. In men, the nine obesity indices were all positively associated with the occurrence of hypertension ( P<0.05), and the AUC (0.643) of ABSI was the highest. In women, except for VAI and ABSI, the seven obesity indices were positively correlated with hypertension ( P<0.05), and the AUC (0.620) of BMI was the highest. Conclusions:In T2DM patients over the age of 50, BMI, WC, WHR, WHtR, VAI, BRI, LAP, RFM were all positively correlated with the occurrence of HUA. The new obesity indices VAI and LAP had certain advantages over traditional indices in HUA risk screening and population health intervention. In men, nine obesity indices were positively correlated with the occurrence of hypertension. Compared with traditional indices, ABSI had certain advantages in the monitoring and intervention of hypertension in this population. In women, except VAI and ABSI, 7 obesity indices were positively correlated with hypertension.

Background The triglyceride glucose (TyG) index has been considered a new biomarker for the diagnosis of angiocardiopathy and insulin resistance. However, the association of the TyG index with subclinical left ventricular (LV) systolic dysfunction still lacks comprehensive exploration. This study was carried out to examine this relationship in patients with type 2 diabetes mellitus (T2DM). Methods A total of 150 T2DM patients with preserved LV ejection fraction (LVEF ≥ 50%) from June 2021 to December 2021 were included in this study. The subclinical LV function was evaluated through global longitudinal strain (GLS), with the predefined GLS < 18% as the cutoff for subclinical LV systolic dysfunction. The TyG index calculation was obtained according to ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2), which was then stratified into quartiles (TyG index—Q). Results Analyses of clinical characteristics in the four TyG indexes-Q (Q1 (TyG index ≤ 8.89) n = 38, Q2 (8.89 < TyG index ≤ 9.44) n = 37, Q3 (9.44 < TyG index ≤ 9.83) n = 38, and Q4 (TyG index > 9.83) n = 37) were conducted. A negative correlation of the TyG index with GLS ( r = -0.307, P < 0.001) was revealed according to correlation analysis. After gender and age were adjusted in multimodel logistic regression analysis, the higher TyG index (OR 6.86; 95% CI 2.44 to 19.30; P < 0.001, Q4 vs Q1) showed a significant association with GLS < 18%, which was still maintained after further adjustment for related clinical confounding factors (OR 5.23, 95% CI 1.12 to 24.51, p = 0.036, Q4 vs Q1). Receiver operator characteristic analysis indicated a diagnostic capacity of the TyG index for GLS < 18% (area under curve: 0.678; P < 0.001). Conclusions A higher TyG index had a significant association with subclinical LV systolic dysfunction in T2DM patients with preserved ejection fraction, and the TyG index may have the potential to exert predictive value for myocardial damage.

BACKGROUND:Diabetic encephalopathy(DE) is a neurological complication of diabetes, and its pathogenesis is unclear. Current studies indicate that insulin receptors and downstream signaling pathways play a key role in the occurrence and development of DE. Additionally, CLC-3, a member of the CLC family of anion channels and transporters, is closely related to the secretion and processing of insulin. Here, we investigated the changes and putative roles of CLC-3 in diabetic encephalopathy. RESULTS:To this aim, we combined lentivirus and adeno-associated virus gene transfer to change the expression level of CLC-3 in the HT-22 hippocampal cell line and hippocampal CA1. We studied the role of CLC-3 in DE through the Morris water maze test.CLC-3 expression increased significantly in HT-22 cells cultured with high glucose and STZ-induced DE model hippocampus. Moreover, Insulin receptor(IR) and downstream PI3K/AKT/GSK3β signaling pathways were also dysfunctional. After knocking down CLC-3, impaired cell proliferation, apoptosis, IR and the downstream PI3K/AKT/GSK3β signaling pathways were significantly improved. However, when CLC-3 was overexpressed, the neurotoxicity induced by high glucose was further aggravated. Rescue experiments found that through the use of inhibitors such as GSK3β, the PI3K/AKT/GSK3β signaling pathways pathway changes with the use of inhibition, and the expression of related downstream signaling molecules such as Tau and p-Tau also changes accordingly. Using adeno-associated virus gene transfer to knock down CLC-3 in the hippocampal CA1 of the DE model, the IR caused by DE and the dysfunction of the downstream PI3K/AKT/GSK3β signaling pathway were significantly improved. In addition, the impaired spatial recognition of DE was partially restored. CONCLUSION:Our study proposes that CLC-3, as a key molecule, may regulate insulin receptor signaling and downstream PI3K/AKT/GSK3β signaling pathways and affect the pathogenesis of diabetic encephalopathy.

Objective The purpose of this study is to describe the current clinical situation of patients with painful diabetic peripheral neuropathy (DPN) and related anxiety, depression, and the quality of life of patients in mainland China, and to report the current status of the use of analgesics. Methods Between June 15, 2021, and October 15, 2021, a total of 401 participants participated in the study. Recruitment was carried out using a multi-level sampling method. Participants’ demographics, medical history, analgesic use, Michigan Symptom Score (MNSI), Numerical Rating Scale (NRS) pain score, Patient Health Questionnaire 9 (PHQ-9) score, Generalized Anxiety Disorder 7 (GAD) -7) Score, quality of life score (SF-12) and diabetes treatment status were collected. Results Among the participants, there were 236 male patients and female patients. Participants were 322 patients over 40 years old. Regarding the use of analgesics: 132 patients reported using analgesics, 221 patients reported not using analgesics, and 48 patients reported having used analgesics. The results of the scale showed that the scores of NRS, GAD-7, PHQ-9 and SF-12 were 5.12 ± 2.15, 6.33 ± 3.67, 8.46 ± 4.07 and 47.84 ± 19.92 for patients who used analgesics, Compared with patients who did not use analgesics (NRS: 1.99 ± 1.7, GAD-7: 1.81 ± 2.81, PHQ-9: 3.13 ± 4.10, SF-12: 78.34 ± 21.66) there are significant differences (p< 0.001). In addition, patients’ NRS scores are also closely related to GAD-7, PHQ-9 and SF-12 scores. Conclusion The severity of symptoms, mental status and quality of life of patients who used analgesics were more severe than those of patients who did not use analgesics. Pregabalin is still the preferred analgesic for patients with painful DPN, and the use of opioids in my country is extremely low, which is consistent with current international guidelines. Age, diabetic duration, DPN duration, PHQ-9 score, GAD-7 score and SF-12 scores are closely related to NRS pain scores. In addition, there are still a considerable number of patients who have not used analgesics due to financial burdens and other reasons, suggesting that China still has insufficient pain management in DPN patients.

目的:探究人SST抗独特型卵黄抗体对大鼠胰腺SST受体定位、荧光共定位及对胰腺内分泌功能的调节作用,探讨其能否用于糖尿病治疗.方法:DAB染色观察大鼠胰腺SST受体分布.免疫荧光共定位观察大鼠胰岛SST受体与内分泌激素共定位.大鼠腹腔注射SST抗独特型卵黄抗体,ELISA检测不同时间点大鼠血浆胰高血糖素、胰岛素和血糖水平.建立糖尿病大鼠模型,腹腔注射人SST抗独特型卵黄抗体,血糖仪检测治疗前后血糖水平.糖耐量实验检测糖尿病大鼠糖耐量水平.结果:DAB染色显示,SST受体免疫反应阳性物质除分布于胰岛细胞外,还分布于胰岛毛细血管内皮细胞和淋巴细胞.免疫荧光共定位显示,SST受体与生长抑素共定位于D细胞,与胰高血糖素共定位于A细胞,与胰岛素共定位于B细胞.ELISA显示注射SST抗独特型卵黄抗体后不同时间点,大鼠胰高血糖素水平逐渐下降(P<0.01).胰岛素水平明显降低,30 min时差异有统计学意义(P<0.01).不同时间点大鼠血糖水平逐渐降低(P<0.05).糖尿病大鼠腹腔注射SST抗独特型卵黄抗体后,大鼠血糖水平逐渐降低,治疗后第5～10天差异有统计学意义(P<0.05).糖耐量实验同样显示治疗组相比于不治疗组糖耐量明显改善(P<0.01).结论:人SST抗独特型卵黄抗体可与SST受体不同亚型结合,并能模拟SST功能调节胰岛内分泌激素及血糖水平,对糖尿病大鼠有明显降血糖作用,提示其对糖尿病可能有治疗效果.

[This corrects the article DOI: 10.3389/fendo.2021.615409.].

Objective:To investigate the association between glycated hemoglobin A 1c (HbA 1c) and subclinical left ventricular (LV) systolic function in patients with type 2 diabetes mellitus (T2DM). Methods:T2DM patients who consecutively admitted to the Department of Endocrinology, First Affiliated Hospital of Air Force Medical University, Shaanxi Province from June to December 2021 were selected. The age, heart rate, systolic blood pressure, fasting plasma glucose (FPG), HbA 1c, triglyceride (TG) and urinary albumin to creatinine ratio (UACR), LV global longitudinal strain (GLS) were collected. According to the GLS results, patients were divided into three groups: T1 (GLS≤16.6%), T2 (16.6%19.4%). One-way analysis of variance, Fisher exact test or chi-square test, and Kruskal-Wallis H test were used to compare the differences in clinical characteristics and metabolic indexes among groups. Pearson correlation analysis was used to evaluate the correlation between HbA 1c and GLS, and multiple linear regression analysis was used to analyze the influencing factors of LV subclinical myocardial systolic dysfunction in patients with T2DM. Results:A total of 152 patients were included. There were 51 cases in T1 group, 51 cases in T2 group, and 50 cases in T3 group. HbA 1c level decreased with increasing GLS group [(10.01±2.39)% vs. (8.69±1.77)% vs. (7.78±1.38)%, P<0.001]. Pearson correlation analysis showed that HbA 1c was negatively correlated with GLS ( r=-0.48, P<0.001). The results of univariate linear regression analysis showed that HbA 1c, age, heart rate, systolic blood pressure, FPG, TG and UACR were significantly correlated with GLS (all P<0.05). Multivariate analysis showed that HbA 1c was independently associated with GLS ( β=-0.613, P<0.001). In addition, the results showed that logUACR was an independent and major risk factor for reduced GLS ( β=-1.010, P=0.024). Conclusions:HbA 1c was negatively associated with the progression of LV subclinical systolic function in patients with T2DM. High UACR level was the main influencing factor of LV longitudinal dysfunction.