Background Experiencing a hyperglycaemic crisis is associated with a short- and long-term increased risk of mortality. We aimed to develop an explainable machine learning model for predicting 3-year mortality and providing individualized risk factor assessment of patients with hyperglycaemic crisis after admission. Methods Based on five representative machine learning algorithms, we trained prediction models on data from patients with hyperglycaemic crisis admitted to two tertiary hospitals between 2016 and 2020. The models were internally validated by tenfold cross-validation and externally validated using previously unseen data from two other tertiary hospitals. A SHapley Additive exPlanations algorithm was used to interpret the predictions of the best performing model, and the relative importance of the features in the model was compared with the traditional statistical test results. Results A total of 337 patients with hyperglycaemic crisis were enrolled in the study, 3-year mortality was 13.6% (46 patients). 257 patients were used to train the models, and 80 patients were used for model validation. The Light Gradient Boosting Machine model performed best across testing cohorts (area under the ROC curve 0.89 [95% CI 0.77–0.97]). Advanced age, higher blood glucose and blood urea nitrogen were the three most important predictors for increased mortality. Conclusion The developed explainable model can provide estimates of the mortality and visual contribution of the features to the prediction for an individual patient with hyperglycaemic crisis. Advanced age, metabolic disorders, and impaired renal and cardiac function were important factors that predicted non-survival. Trial Registration Number: ChiCTR1800015981, 2018/05/04.

Background The long-term clinical outcome of poor prognosis in patients with diabetic hyperglycaemic crisis episodes (HCE) remains unknown, which may be related to acute organ injury (AOI) and its continuous damage after hospital discharge. This study aimed to observe the clinical differences and relevant risk factors in HCE with or without AOI. Methods A total of 339 inpatients were divided into an AOI group (n=69) and a non-AOI group (n=270), and their differences and risk factors were explored. The differences in clinical outcomes and prediction models for evaluating the long-term adverse events after hospital discharge were established. Results The mortality among cases complicated by AOI was significantly higher than that among patients without AOI [8 (11.59%) vs. 11 (4.07%), Q = 0.034] during hospitalization. After a 2-year follow-up, the mortality was also significantly higher in patients with concomitant AOI than in patients without AOI after hospital discharge during follow-up [13 (21.31%) vs. 15 (5.8%), Q < 0.001]. The long-term adverse events in patients with concomitant AOI were significantly higher than those in patients without AOI during follow-up [15 (24.59%) vs. 31 (11.97%), Q = 0.015]. Furthermore, Blood β-hydroxybutyric acid (P = 0.003), Cystatin C (P <0.001), serum potassium levels (P = 0.001) were significantly associated with long-term adverse events after hospital discharge. Conclusions The long-term prognosis of HCE patients complicated with AOI was significantly worse than that of HCE patients without AOI. The laboratory indicators were closely correlated with AOI, and future studies should explore the improvement of clinical outcome in response to timely interventions.

ObjectiveTo investigate the prevalence and risk factors of diabetic kidney disease (DKD) among the patients with type 2 diabetes mellitus (T2DM) in rural and urban communities in the Chongqing Main City. MethodsA total of 735 T2DM patients from rural and urban communities in the Chongqing Main City were selected by stratified cluster random sampling. They were compared in terms of demographic characteristics, physical test results, metabolic indicators, compliance rate of diabetes comprehensive control and DKD prevalence. Multivariate logistic regression model was used to analyze the risk factors of DKD. Results①The prevalence of DKD was 31.3% in the T2DM patients, and was higher in the rural communities than that in the urban communities (35.9% vs 28.1%, P<0.01). ② There were statistical differences in the demographic characteristics, physical test results, metabolic indicators, and compliance rates between the patients from the urban and rural communities (P<0.05). ③ Systolic blood pressure (SBP, OR=2.393), course of diabetes (OR=2.471) and level of triglyceride (TG, OR=1.988) were independent risk factors, while taking ACEI (angiotensin converting enzyme inhibitors) or ARBs (angiotensin-receptor blockers, OR=0.163) were protective factors for DKD in the patients of rural communities. And, age (OR=1.682), SBP (OR=2.201), course of diabetes (OR=1.644), HbA1c (OR=2.844), uric acid (OR=2.182) were independent risk factors for those in the urban communities. ConclusionThe prevalence of DKD is higher in the rural communities than that in the urban communities. Attention should be paid to hyperlipidemia in rural communities. Blood glucose control should be strengthened in urban communities, and physicians should correct hyperuricemia and pay attention to the DKD screening in elderly population.

Inflammation and oxidative stress are key steps in the progression of non-alcoholic steatohepatitis (NASH). Intervention in these two processes will therefore benefit NASH treatment. Peroxisome proliferator-activated receptor gamma (PPAR gamma), as a multiple functional transcription factor, has been reported to be involved in the prevention of NASH progression. However, the mechanism by which PPAR gamma prevents NASH remains to be elucidated. The present study demonstrated that the level of PPAR gamma was inversely correlated with that of microRNA (miRNA/miRs)-21-5p in both mice and humans with NASH. Activation of PPAR gamma inhibited lipid droplet accumulation, hepatic inflammation and oxidative stress by downregulating miR-21-5p in an in vitro model. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that PPAR gamma suppressed transcriptional activity of miR-21-5p and bound to miR-21-5p promoter region. Furthermore, PPAR gamma downregulated miR-21-5p while miR-21-5p upregulated secreted frizzled-related protein 5 (SFRP5) by targeting the 3 '-UTR of its mRNA. In vivo experiments revealed that PPAR gamma repressed inflammation and oxidative stress and miR-21-5p expression while increased SFRP5 level in a NASH mouse model. In summary, PPAR gamma attenuates inflammation and oxidative stress in NASH by modulating the miR-21-5p/SFRP5 pathway, thus holding promise of a new target for NASH treatment.

Inwardly rectifying potassium (Kir) channels make it easier for K+ to enter into a cell and subsequently regulate cellular biological functions. Kir5.1 (encoded by KCNJ16) alone can form a homotetramer and can form heterotetramers with Kir4.1 (encoded by KCNJ10) or Kir4.2 (encoded by KCNJ15). In most cases, homomeric Kir5.1 is non-functional, while heteromeric Kir5.1 on the cell membrane contributes to the inward flow of K+ ions, which can be regulated by intracellular pH and a variety of signaling mechanisms. In the form of a heterotetramer, Kir5.1 regulates Kir4.1/4.2 activity and is involved in the maintenance of nephron function. Actually, homomeric Kir5.1 may also play a very important role in diseases, including in the ventilatory response to hypoxia and hypercapnia, hearing impairment, cardiovascular disease and cancer. With an increase in the number of studies into the roles of Kir channels, researchers are paying more attention to the pathophysiological functions of Kir5.1. This minireview provides an overview regarding these Kir5.1 roles.

We first compared long-term clinical outcomes in treating critical limb ischemia (CLI) and foot ulcer in patients with diabetes between autologous bone marrow mesenchymal stem cell (BMMSC) and bone-marrow-derived mononuclear cell (BMMNC) transplants. Forty-one patients were enrolled and followed up for 3 years. They received an 18-day standard treatment before stem cell transplantation. Patients with bilateral CLI and foot ulcer were injected intramuscularly or basally with BMMSC, BMMNC, or normal saline (NS). Cox model analysis showed significant differences in the hazard ratio (HR) for amputation with treatment by BMMSC (HR 0.21 [95% CI (0.05, 0.95)], P = 0.043), infection of foot (HR 5.30 [95% CI (1.89, 14.92)], P = 0.002), and age ≥64 (HR 3.01 [95% CI (1.11, 8.15)], P = 0.030), but no significant differences by BMMNC at 9 months after transplantation. Regarding ulcer healing and recurrence rate, the BMMSC group demonstrated a significant difference from the NS group during the 3–6 months after transplantation or healing, but the BMMNC group did not. This trial suggests that, compared with BMMNC treatment, BMMSC treatment leads to a longer time of limb salvage and blood flow improvement, and, when compared with conventional therapy, it can promote limb blood flow and ulcerative healing, and reduce ulcer recurrence and amputation within 9 months.

PURPOSE:To assess the role of serum pigment epithelium-derived factor (PEDF) in the occurrence and development of proteinuria and renal dysfunction and determine its relevant signaling pathway.METHODS:We analyzed serum PEDF, creatinine, the urinary albumin-to-creatinine ratio, and renal morphology of normal or streptozotocin (STZ)-induced diabetic mice, before and after treatment with PEDF. In vitro, podocytes were stimulated with PEDF under normal or high-glucose conditions; permeability was measured by the transwell assay with fluorescein isothiocyanate (FITC)-dextran; and F-actin cytoskeleton was analyzed by phalloidin staining. Apoptosis was assessed by flow cytometry. RhoA activity and ROCK1, ZO-1, nephrin, and podocin levels were detected by Western blotting.RESULTS:Diabetic mice exhibited a high serum PEDF level. In vivo, elevated serum PEDF led to proteinuria, increased serum creatinine, and podocyte foot process fusion in normal or diabetic mice. In vitro, both high-glucose and PEDF stimulation activated the RhoA/ROCK1 pathway in podocytes and promoted cell permeability, F-actin rearrangement, and apoptosis. Inhibition of RhoA/ROCK1 alleviated the damage from these effects.CONCLUSIONS:Elevated serum PEDF aggravates the development of proteinuria and renal dysfunction by inducing F-actin arrangement, foot process fusion, and apoptosis of podocytes in both normal and diabetic mice, and this effect may be mediated by activation of the RhoA/ROCK1 pathway.

目的 探讨镍纹样蛋白(meteorin-like protein,Metrnl)与非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的相关性,并分析NAFLD的影响因素.方法 选取2017-2018年我科门诊及住院NAFLD患者183例,其中男性115例,女性68例.同期体检的健康者210例为对照组,其中男性88例,女性122例.收集两组受试者的一般临床资料,进行相关实验室生化检查及血清Metrnl水平测定,比较两组间的差异.Spearman相关分析探讨血清Metrnl与NAFLD及各代谢指标的相关性,通过Logistic回归分析探讨NAFLD发病的影响因素.结果 NAFLD组血清Metrnl水平低于对照组(P＜0.05).血清Metrnl与年龄、谷氨酰转肽酶(GGT)、谷丙转氨酶(ALT)、尿酸、血糖、胰岛素抵抗指数(HOMA-IR)、低密度脂蛋白(LDL-C)、甘油三酯(TG)、体质量、体质量指数(BMI)、收缩压、舒张压呈负相关,与谷草转氨酶(AST)、高密度脂蛋白(HDL-C)呈正相关.多因素Logistic回归分析发现尿酸、血糖、HDL-C、BMI、舒张压和血清Metrnl为NAFLD的独立影响因素.结论 血清Metrnl降低是NAFLD发生的独立危险因素,Metrnl与NAFLD及代谢性疾病相关指标密切相关.

Objective To investigate the relationship between blood pH,blood glucose,myocardial enzymes and amylase in patients with diabetic ketoacidosis,and to provide a reference for the clinical diagnosis and treatment of diabetic ketoacidosis patients.Methods The clinical data of 135 diabetic patients with diabetic ketoacidosis admitted from February 2016 to September 2017 in our hospital were retrospectively analyzed.According to their severity,the patients were divided into mild,moderate and severe groups with 45 cases in each group.The changes of blood pH and blood glucose level were observed in three groups of patients.The changes of blood amylase,lipids and myocardial enzymes were compared among the three groups.Spearman correlation analysis was used to analyze the correlation between blood pH,blood glucose,myocardial enzymes and amylase.Results With diabetic ketoacidosis patients' condition aggravate,their blood pH value gradually decreased,blood glucose levels gradually increased;The levels of TG,serum amylase,CPK and AST in severe group and moderate group were significantly higher than those in mild group (severe group:t =5.419,P ＜ 0.01,t =4.089,P ＜ 0.01,t =11.285,P＜0.01,t=3.181,P＜0.001;moderate group:t =2.441,P ＜0.008,t =2.273,P＜0.013,t=7.644,P＜0.01,t =2.325,P ＜ 0.011),TC levels were significantly lower than those in the mild group (severe group:t =3.635,P ＜0.000;moderate group:t =1.758,P ＜ 0.041);serum TG,CPK,CPK-MB,LDH,AST and serum amylase gradually increased high,TC level gradually decreased.There was a positive correlation between blood pH and TC,AST and LDH (r =0.418,P=0.018;r=0.432,P=0.012;r=0.454,P=0.002,r=-0.425,P=0.013).There was a negative correlation between blood glucose and TC,AST and LDH (r =-0.405,P =0.028;r =0.418,P =0.010).There was a positive correlation with TG level (r =0.436,P =0.012).There was no correlation between pH value and blood glucose level with CPK-MB and CPK.The blood pH value of patients with diabetic ketoacidosis is negatively correlated with the level of serum amylase,LDH and AST,and there is a positive correlation between the blood glucose level and the level of serum amylase,LDH and AST in patients with diabetic ketoacidosis.

Objective: To analyze the relationship of Adaptor protein containing PH domain, PTB domain and leucine zipper motif1 (APPL1), adipocyte fatty acid binding protein (AFABP) and homeostasis model assessment-Insulin resistance (HOMA-IR) in type 2 diabetes mellitus (T2 DM) patients. Methods: A total of 100 patients with T2 DM, who were treated in Chongqing Southwest Hospital from June 2015 to May 2016, were chosen as patients group, and another 100 healthy people, who underwent physical examination in this hospital during the same period, were chosen as healthy group. Fasting blood glucose (FPG), fasting serum insulin (FINS), hemoglobin A1 c (Hb A1 c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), APPL1, AFABP of the subjects were detected. HOMA-IR and body mass index (BMI) were calculated according to the formula. The correlation between APPL1, AFABP and the other indexes were analyzed. Results: There was no significant difference in the levels of TC, HDL and LDL between patients groups and healthy group (P＞0.05). BMI, FPG, FINS, Hb A1 c, TG, HOMA-IR, APPL1, AFABP of the patients group were significantly higher than those of the healthy group (P＜0.05). APPL1 was negatively associated with BMI, FINS, Hb A1 c and HOMA-IR (P＜0.05), while positively associated with FPG (P＜0.05). AFABP was positively associated with BMI, FPG, FINS, Hb A1 c and HOMA-IR (P＜0.05). Conclusion: APPL1 and AFABP are higher in the patients with T2 DM, and they are linearly related with HOMA-IR, which suggests that APPLl and AFABP may correlate with insulin resistance. The study provides a theoretical basis for APPL1 and AFABP used as a new target in the treatment of T2 DM.

Abnormal lipid metabolism, renal lipid accumulation and lipotoxicity are associated with the pathological features of glomerulopathy. However, the mechanisms by which lipid accumulation leads to the development or progression of this disease have not been fully elucidated. In this work, we have identified a role for the rate-limiting enzyme in lipolysis, adipose triglyceride lipase (ATGL; also called patatin-like phospholipase domain-containing protein 2), in renal lipid metabolism and kidney disease. ATGL-deficient (Atgl(-/-)) mice displayed albuminuria, accompanied by ectopic deposition of fat in the kidney. Magnetic resonance imaging demonstrated that the contrast agent gadopentetic acid was retained in kidney tissue, suggesting defects in the glomerular filtration barrier. Furthermore, transmission electron microscopy revealed lipid deposits in the podocyte, along with foot process fusion and morphological changes suggestive of apoptosis. Indeed, shRNA-mediated depletion of ATGL promoted podocyte apoptosis, accompanied by increased levels of intracellular reactive oxygen species (ROS) and F-actin fibre redistribution. These effects could be partially reversed by treatment with the antioxidant Nacetylcysteine. These data suggest that ATGL deficiency induces renal lipid accumulation, proteinuria and glomerular filtration barrier dysfunction and implicate increased intracellular ROS levels in inducing podocyte F-actin rearrangement, foot process fusion and apoptosis that underlie these pathological features.

Secreted frizzled-related protein 5 (SFRP5) is a newly identified adipokine. SFRP5 expression increases during the differentiation and maturation of adipocytes, but the factors regulating SFRP5 expression during this process remain unclear. This study showed that peroxisome proliferator-activated receptor γ (PPARγ) adenovirus transfection could enhance the SFRP5 expression of 3T3-L1 adipocytes. Three potential binding sites of PPARγ in the SFRP5 promoter domain were found by bioinformatics analysis. Luciferase reporter gene assay demonstrated that PPARγ regulated the activity of the SFRP5 promoter through cis-acting elements at − 2,284–−1,500 bp. Further experiments verified that PPARγ could specifically bind to the SFRP5 promoter at − 2,284–−2,263 bp using chromatin immunoprecipitation and electrophoretic mobility shift assay. These results suggest that SFRP5 be a target gene of PPARγ, and its expression may be under the transcriptional regulation of PPARγ.

Decreased phosphorylation in the insulin signalling pathway is a hallmark of insulin resistance. The causes of this phenomenon are complicated and multifactorial. Recently, genomic analyses have identified ARL15 as a new candidate gene related to diabetes. However, the ARL15 protein function remains unclear. Here, we show that ARL15 is upregulated by insulin stimulation. This effect was impaired in insulin-resistant pathophysiology in TNF-α-treated C2C12 myotubes and in the skeletal muscles of leptin knockout mice. In addition, ARL15 localized to the cytoplasm in the resting state and accumulated in the Golgi apparatus around the nucleus upon insulin stimulation. ARL15 overexpression can enhance the phosphorylation of the key insulin signalling pathway molecules IR, IRS1 and AKT in C2C12 myotubes. Moreover, ARL15 knockdown can also specifically inhibit the phosphorylation of PDPK1 Ser241, thereby reducing PDPK1 activity and its downstream phosphorylation of AKT Thr308. Co-immunoprecipitation assays identified ASAP2 as an ARL15-interacting protein. In conclusion, we have identified that ARL15 acts as an insulin-sensitizing effector molecule to upregulate the phosphorylation of members of the canonical IR/IRS1/PDPK1/AKT insulin pathway by interacting with its GAP ASAP2 and activating PDPK1. This research may provide new insights into GTPase-mediated insulin signalling regulation and facilitate the development of new pharmacotherapeutic targets for insulin sensitization.

目的 探索骨形态发生蛋白7(bone morphogenetic protein 7,BMP7)对2型糖尿病小鼠糖代谢的影响及其机制.方法 将8周龄雄性C57BL/6小鼠,采用小剂量链脲佐菌素注射联合高脂喂养建立2型糖尿病小鼠模型.将建模成功的小鼠分为4组(n=20)∶2型糖尿病模型组,PBS对照组(PBS腹腔注射),BMP7低剂量组(BMP7,100 μg/kg,隔日腹腔注射),BMP7高剂量组(BMP7,200 μg/kg,隔日腹腔注射).4周后,分别检测血糖、血总胆固醇、甘油三酯、血清胰岛素水平、体质量的变化,并计算胰岛素分泌指数HOMA-β和胰岛素抵抗指数HOMA-IR.取小鼠胰腺,Western blot检测蛋白激酶D1(protein kinase D1,PKD1)及磷酸化PKD1的表达变化.结果 与2型糖尿病模型组和PBS对照组相比,BMP7高剂量组和低剂量组的血糖、甘油三酯均明显降低(P＜0.05),而血清胰岛素水平、HOMA-β均显著升高(P＜0.05).BMP7低剂量组和BMP7高剂量组的体质量均低于对照组(P＜0.05),BMP7高剂量组的HOMA-IR低于对照组(P＜0.05).Western blot检测发现BMP7处理组的PKD1蛋白表达量与对照组相比差异均无统计学意义(P＞0.05),但磷酸化PKD1水平均明显升高(P＜0.05).结论 BMP7可以促进2型糖尿病小鼠的胰岛素分泌和改善其胰岛素敏感性,从而降低血糖,其改善胰岛素分泌作用可能与增加PKD1磷酸化有关.

目的:构建人锌转运体8(Zinctransporter 8,ZnT-8)羧基端原核表达载体,表达和纯化人ZnT-8羧基端(ZnT-8-COOH)重组蛋白,为寻找1型糖尿病新型免疫调节剂创造条件.方法:人ZnT-8-COOH cDNA克隆入pET-32a载体,在大肠杆菌BL21中利用异丙基-硫代-β-D-半乳糖苷(isopropyl-thio-β-D-galactoside,IPTG)诱导表达,经十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和Western blot鉴定表达产物,镍离子亲和层析纯化重组蛋白.40只4周龄的雌性非肥胖型糖尿病(non obese diabetic,NOD)小鼠随机分为ZnT-8重组蛋白预处理组及生理盐水对照组,分别腹腔注射ZnT-8重组蛋白和生理盐水,每周测量各组NOD小鼠体质量,检测血糖、血清C肽水平.结果:经PCR扩增后得到306 bp的DNA片段,成功构建到pET-32a表达载体上,经测序分析序列正确;ZnT-8重组蛋白在大肠杆BL21中获得成功表达,并得以有效纯化.ZnT-8重组蛋白预处理组NOD小鼠与生理盐水对照组相比,28周龄时ZnT-8重组蛋白预处理组的体质量高于生理盐水对照组(P＜0.05).28周龄时ZnT-8重组蛋白预处理组的血糖低于生理盐水对照组(P＜0.05);28周龄时ZnT-8重组蛋白预处理组的血清C肽水平高于生理盐水对照组(P＜0.05).结论:成功制备人ZnT-8-COOH重组蛋白,并初步证实了其对1型糖尿病的免疫调节作用.

Objective To evaluate the treatment effect of negative pressure wound therapy ( NPWT) followed by ultrasonic debridement surgical system ( UDSS) in patients with diabetic foot. Methods Forty-seven diabetic foot ulcer patients( WagnerⅡ~Ⅲ) were divided into two groups,of which 26 patients treated with UDSS combined NPWT,and 21 patients treated with traditional surgical debridement combined NPWT were control group. Cure rate, markedly effective rate and adverse reaction and complication were compared between two groups. Results Compared with control group,the experiment group had higher markedly effective rate in the first week(P<0. 05),and healing rates were higher in the 2th,4th,6th,12th weeks (P<0. 05). There were no differences in the adverse reactions and complications between the two groups. Conclusion UDSS combined with NPWT can accelerate wound cure,may play an important role for the treatment of diabetic foot ulcer.

Ethnopharmacological relevance: Mongolian medicine is an important constituent of traditional Chinese medicine. Its representative prescription, Li-Gan-Shi-Liu-Ba-Wei-San (LGSLBWS), is widely used for long-term treatment of chronic liver disease and nonalcoholic fatty liver disease (NAFLD).Aim of the study: This study explored the effects and mechanism of LGSLBWS on NAFLD.Materials and methods: NAFLD rat model was established with high-fat diet. The effects of LGSLBWS on lipid metabolism, liver function, and hepatic morphology were observed in NAFLD rats. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver, as well as the expression levels of peroxisome proliferator-activated receptor (PPAR)alpha, PPAR beta, inhibitor of nuclear factor kappa B alpha(I kappa B alpha), and inducible nitric oxide synthase (iNOS) were all detected. Finally, the effects of LGSLBWS on fatty acid oxidation, PPAR alpha, PPAR beta, I kappa B alpha, and iNOS were determined in HepG2 cells.Results: LGSLBWS significantly reduced the fat deposition in the liver and the serum aspartate aminotransferase levels in NAFLD rats. Serum triglyceride and free fatty acid levels were reduced by LGSLBWS. Total cholesterol and triglyceride contents in the liver were also downregulated. SOD and MDA levels were increased and decreased by LGSLBWS, respectively. LGSLBWS can significantly promote fatty acid oxidation of HepG2 cells. Upregulation of PPAR alpha, PPAR beta, and I kappa B alpha and downregulation of iNOS by LGSLBWS were both observed in the NAFLD model and HepG2 cells.Conclusions: LGSLBWS can significantly improve NAFLD by enhancing fatty acid oxidation and alleviating oxidative stress. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

AIMS:The assessment of transcutaneous oxygen pressure (TcPO2) may serve as a non-invasive and lower-cost alternative to nerve conduction studies (NCSs) for the diagnosis of diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether the measurement of TcPO2 is useful for evaluating DPN.METHODS:We performed a cross-sectional study of 381 consecutive hospitalized diabetic patients classified by clinical examination and NCS as having DPN. Anthropometric and metabolic parameters were assessed. The TcPO2 examination was performed in both supine and sitting positions.RESULTS:Three hundred and one patients had DPN. The TcPO2 in both the supine and sitting positions was highest in the Non-DPN group and lower in the confirmed DPN group than the other three groups (p<0.001). The Non-DPN group had the lowest sitting-supine position difference in TcPO2 among the groups (p<0.001). The risk factors strongly associated with DPN included sitting-supine position difference in TcPO2 (OR=4.971, p<0.001), diabetic retinopathy (DR) (odds ratio [OR]=3.794, p=0.002), and HbA1c (OR=1.534, p=0.033). The area under the curve (AUC) of the sitting-supine position difference in TcPO2 was 0.722 and revealed an optimal cut-off point for the identification of DPN (19.5 mmHg) that had a sensitivity of 0.611 and a specificity of 0.738 based on AUC analysis.CONCLUSIONS:This large study of diabetic patients confirms that the sitting-supine position difference in TcPO2 is higher in DPN patients than control subjects, indicating that TcPO2 examination is a promising valuable diagnostic tool for DPN.

Aims A20 is a negative regulator of nuclear factor kappa B activation and the central gatekeeper in inflammation and immunity. While its role in type 1 diabetes has been widely studied, its expression level in immune cells from type 2 diabetes (T2D) and latent autoimmune diabetes in adult (LADA) patients remains unclear. This study aimed to clarify whether the expression of A20 is altered in patients with T2D or LADA. Methods Quantitative real-time polymerase chain reaction and western blotting were utilized to determine the expression of A20 mRNA and protein respectively in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n = 36) or LADA (n = 17) and sex- and age-matched healthy controls (n = 34). Results The mRNA and protein expression of A20 in PBMCs from T2D and LADA patients was significantly decreased compared with healthy controls (P < 0.05). Furthermore, A20 mRNA and protein expression was significantly lower in newly diagnosed T2D patients (≤1 year since diagnosis) than in patients with a long T2D duration (>1 year since diagnosis) (P < 0.05). Conclusions Our results suggest that decreased expression of A20 in PBMCs may be involved in the pathogenesis of diabetes, and targeting A20 may offer a potential therapeutic tool in the treatment of diabetes.