The clinical and genetic characteristics of maternally inherited diabetes and deafness (MIDD) with mitochondrial m.3243A > G mutation: A 10-year follow-up observation study and literature review.

Maternally inherited diabetes and deafness (MIDD) is often caused by the m.3243A > G mutation in mitochondrial DNA. Unfortunately, the characteristics of MIDD, especially long-term outcomes and heteroplasmic changes, have not been well described previously. The purpose of this study was to describe the clinical and genetic features of a family with MIDD after 10 years of follow-up.A 33-year-old male patient with typical characteristics of MIDD, including early-onset diabetes, deafness, and low body mass index, was admitted to our department. Further investigation revealed that the vast majority of his maternal relatives suffered from diabetes with or without deafness. A detailed family history was then requested from the patient and a pedigree was constructed. The patient suspected of MIDD was screened for mutations using whole mitochondrial DNA sequencing. Candidate pathogenic variants were then validated in other family members through Sanger sequencing. The patient was diagnosed with MIDD, with inherited m.3243A > G mutation in the mitochondrially encoded tRNA leucine 1 (MT-TL1) gene, after 10 years of symptom onset. The patient was then treated with insulin and coenzyme Q10 to improve mitochondrial function. During the follow-up period, his fasting blood glucose and HbA1c levels were improved and the incidence of diabetic ketoacidosis was significantly reduced. Our findings indicate that whole mitochondrial DNA sequencing should be considered for patients suspected of MIDD to improve the efficiency of diagnosis and prognosis.

Myeloid-derived growth factor and its effects on cardiovascular and metabolic diseases.

Myeloid-derived growth factor (MYDGF) is a paracrine protein produced by bone marrow-derived monocytes and macrophages. Current research shows that it has protective effects on the cardiovascular system, such as repairing heart tissue after myocardial infarction, enhancing cardiomyocyte proliferation, improving cardiac regeneration after myocardial injury, regulating proliferation and survival of endothelial cells, reducing endothelial cell damage, resisting pressure overload-induced heart failure, as well as protecting against atherosclerosis. Furthermore, regarding the metabolic diseases, MYDGF has effects of improving type 2 diabetes mellitus, relieving non-alcoholic fatty liver disease, alleviating glomerular diseases, and resisting osteoporosis. Herein, we will discuss the biology of MYDGF and its effects on cardiovascular and metabolic diseases.

Association between a high triglyceride-glucose index and chronic kidney disease in adult patients with latent autoimmune diabetes.

BACKGROUND: Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride-glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA). METHODS: This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed. RESULTS: A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all P < 0.05). The positive relationship between the TyG index and the urinary albumin/creatinine ratio was significant (r = 0.249, P = 0.010). There was also a significant correlation between the TyG index and the eGFR (r = - 0.211, P = 0.034) after adjusting for confounding factors. The area-under-the-curve value of the TyG index was 0.708 (95% confidence interval: 0.61-0.81, P < 0.001). CONCLUSIONS: The TyG index is significantly associated with the severity of CKD in patients with LADA. This conclusion supports the clinical application of the TyG index for the assessment of kidney disease in patients with LADA.

Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/ß-catenin/NeuroD1 pathway.

BACKGROUND: Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. METHODS: The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)-induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/ß-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. RESULTS: Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-ß signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/ß-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. CONCLUSIONS: Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/ß-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.

The relationship between red blood cell distribution width and islet ß-cell function indexes in patients with latent autoimmune diabetes in adults.

AIMS: The objective of this study is to explore the relationship between red blood cell distribution and islet ß-cell function indexes in patients with Latent Autoimmune Diabetes in Adults. METHODS: A total of 487 LADA patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and laboratory measurements of age, height, weight, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and blood lipids were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCP). Correlations and multiple linear regressions were implemented to determine the association of RDW and islet function indexes. RESULTS: As the increase of serum RDW level, the presence of ß-cell secretion increased(P < 0.05). Correlation analysis indicated that there were significant correlations between RDW and male sex, age, duration, TG, Cr, FCP, and HOMA-ß in all subjects. Multiple linear regressions indicated that RDW was significantly correlated with HOMA-ß in the total population in both unadjusted and adjusted analysis. This finding could be reproduced in the subgroup of low GAD titers for HOMA-ß. RDW were significantly associated with HbA1c in LADA patients with high GAD titers, but the correlation was not found in subgroup with low GAD titers in either unadjusted analyses or adjusted analysis. CONCLUSIONS: RDW is associated with ß-cell function assessed by HOMA-ß after adjusting for covariates in LADA patients with low GAD titers.

Diagnostic Value of the Combined Measurement of Serum HCY and NRG4 in Type 2 Diabetes Mellitus with Early Complicating Diabetic Nephropathy.

PURPOSE: This study aimed to investigate the value of combined detection of HCY and NRG4 in the diagnosis of early diabetic kidney disease (DKD) and to explore the association between the ratio of HCY/NRG4 and DKD. METHODS: A total of 140 diabetic patients and 43 healthy people were prospectively enrolled. The plasma HCY level, NRG4 level and HCY/NRG4 of them were measured to compare their differences and analyze the correlation with DKD. The independent influencing factors of patients with DKD were screened, and the nomograph of DKD occurrence was constructed. RESULTS: The levels of HCY and HCY/NRG4 in diabetic patients were significantly increased, while the level of NRG4 was significantly decreased (p < 0.01). The AUCs of HCY/NRG4 predicted for DKD were 0.961. HCY/NRG4 and the course of DM were independent risk factors for DKD. A predictive nomograph of DKD was constructed, and decision curve analysis (DCA) showed good clinical application value. HCY/NRG4 was positively correlated with Scr, UACR, TG, UA, BUN, TCHOL and LDL and negatively correlated with eGFR and HDL (p < 0.05). CONCLUSIONS: The level of HCY and NRG4 is closely related to the severity of DM, and combined detection of HCY/NRG4 can identify patients with DKD at an early stage.

A region-specific modulation of sleep slow waves on interictal epilepsy markers in focal epilepsy.

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.

Research Progress on Relationship Between Iron Overload and Lower Limb Arterial Disease in Type 2 Diabetes Mellitus.

Iron is one of the most important trace elements in life activities. It participates in a variety of important physiological processes in the body through oxidation-reduction reaction. A large number of studies show that iron overload (IO) is closely related to the progression of diabetes and its various chronic complications. However, the mechanism of iron overload in the pathogenesis of diabetes and the mechanism of iron overload in atherosclerosis (AS) are still controversial, and the relationship between iron overload and diabetic lower extremity arterial disease (LEAD) remains still unclear. Some recent reviews and original research articles suggest further studies to explain the complex relationship between iron metabolism and atherosclerosis. This article reviews the relationship between iron overload and diabetes and its relationship with LEAD, and discusses its mechanisms from various aspects, such as lipid peroxidation induced by iron overload, so as to provide clinical diagnosis and treatment ideas for diabetic lower extremity arterial disease. It is hoped that early evaluation, diagnosis and treatment of LEAD will be inspired.

Improving the clinical ability and quality of endocrinology department with diagnosis-related groups tool.

Background: To evaluate the use of the diagnosis-related groups (DRGs) tool to promote the diagnosis/treatment ability and quality of the endocrinology department under the new policy of grouping payment-related to disease diagnosis. Methods: We compared the income structure of the endocrinology department in a 3a general hospital between the first half of 2019 and the same period in 2021. We also observed the changes in cost efficiency indexes (CEIs), time efficiency indexes (TEIs), case-mix index (CMI), number of DRGs, risk weight (RW) proportion, and surgery number in the inpatient department. Furthermore, the distribution of inpatients with diabetes of the whole hospital and the improvement of treatment efficiency indexes of the sub-specialty department were analyzed. Results: In the first half of 2021, compared with the same period of 2019, the total revenue of the endocrinology department decreased by 20.05%, the average hospitalization cost decreased by 11.72%, the CEI decreased from 1.31 to 1.06, and the TEI decreased from 0.74 to 0.64. Additionally, the number of DRGs increased from 162 to 176, the average CMI value increased from 0.80 to 0.84, and the proportion of RW 1-5 cases increased. Moreover, the number of surgical cases increased by 60.50%, minimally invasive surgery increased by 53.54%, grade 4 surgery increased by 66.67%, and the proportion of entering the clinical pathway increased from 77.76% to 86.64%. From May to August, 2021, the admission rate of endocrinology sub-specialty increased significantly, the number of DRGs showed an increasing trend, and the CEI and TEI decreased significantly. In the first half of 2021, inpatients with diabetes in the departments of rehabilitation, neurology, nephropathy, ophthalmology, and general administration accounted for 21.99-38.54%. Conclusions: The DRGs tool can be used to improve the clinical diagnosis and treatment ability of the endocrinology department, as well as optimize the CEI, TEI, CMI, and RW values. It is an effective way to promote the development of the endocrinology department under the new DRGs payment policy, carry out blood glucose management in the hospital, build endocrinology sub-specialties, and improve surgical and operation capacity.

China's Stem Cell Research and Knowledge Levels of Medical Practitioners and Students.

Over the last few decades, China has greatly expanded its scope of stem cell research, generating various scientific advances and medical applications. However, knowledge of the extent and characteristics of domestic stem cell development, particularly medical workers' opinions, is lacking. This study's purposes were to analyze the growth trends of China's stem cell community and identify the knowledge and attitudes held by Chinese medical workers regarding stem cell research. We found that there are currently 13 high-quality stem cell research centers with more than 400 PhD-level researchers across Mainland China. These centers feature many high-caliber scientists from the stem cell research community. From 1997 through 2019, the National Natural Science Foundation of China allocated roughly $576 million to 8,050 stem cell programs at Chinese universities and research institutions. China's annual publications on stem cells increased from less than 0.6% of the world's total stem cell publications in 1999 to more than 14.1% in 2014. Our survey also revealed that most participants held positive attitudes toward stem cell research, supported further funding, and had high general awareness about stem cells.

Correlation between the platelet-to-lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the correlation between the platelet-to-lymphocyte ratio (PLR) and diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2DM). METHOD: From January 2018 to August 2019, 206 patients with T2DM admitted to the Central Hospital of Wuhan, China, were enrolled in this study, including 104 patients with DFU (DFU group) and 102 patients without DFU (T2DM group). During the same period, 90 healthy subjects were randomly screened as normal controls (NC group). The correlation between PLR and DFU in patients with T2DM was explored by comparing the PLR of the subjects in the three groups. RESULTS: The PLRs of the DFU and T2DM groups were higher than that of the NC group, whereas the PLR of the DFU group was higher than that of the T2DM group (p < 0.05). PLR was positively correlated with the Wagner DFU grade (p < 0.001). Based on logistic regression analysis, PLR was found to be an independent risk factor for DFU (OR =1.029, 95% CI: 1.019 ~ 1.039, p < 0.001). The receiver operating characteristic curve analysis of the PLR showed that the area under the curve of the PLR for predicting diabetic foot ulcer was 0.776 (p < 0.001), and the analysis determined that the optimal critical value of the PLR for predicting DFU was 147.6. CONCLUSION: The PLR is significantly elevated in patients with DFU and positively correlated with the Wagner DFU grade, which might be a valuable marker for early diagnosis and assessment of severity of DFU.

Quantifying the impacts of anthropogenic activity on chemical weathering based on source identification of hydrochemistry: the Liuxi river basin, southern China.

The impact of anthropogenic activity on chemical weathering is still an open and significant topic that requires clarification to improve the understanding of watershed evolution. We analyzed river water and rainwater samples to characterize the variation in hydrochemical characteristics and influencing factors. Samples were taken from the Liuxi River Basin (LRB), the only local drinking water supply for Guangzhou, and we studied geochemical parameters, major ions, and Si concentrations. Moreover, elemental ratios of end-members were determined and a modified-forward model was constructed to identify ion sources and estimate the chemical weathering rate (CWR) and anthropogenic input rate (AIR). Finally, we quantified the impacts of anthropogenic activity on the chemical weathering process. The results showed that the dominant hydrochemical type of river water was identified as HCO3-Ca, and rock weathering was the main contributor to river Na+, Mg2+, Ca2+ and HCO3-, whereas anthropogenic activity contributed the most to K+, Cl-, SO42-, and NO3-. The relatively high silicate weathering rate (SWR) (17.8-18.4 t per km2 per year) and AIR (37.8-60.3 t per km2 per year) were mainly attributed to erosion by nitric and sulfuric acid. The contribution rate of these acids to CWR could be regarded as a proxy quantifying the impact of anthropogenic activity on the chemical weathering process. This accounted for approximately 30% of the total SWR in the LRB. Our results demonstrate the effectiveness of hydrochemical source identification for quantifying the impacts of anthropogenic activity on chemical weathering.

Autologous Bone Marrow Mononuclear Cell Transplantation Therapy Improved Symptoms in Patients with Refractory Diabetic Sensorimotor Polyneuropathy via the Mechanisms of Paracrine and Immunomodulation: A Controlled Study.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-12002570.URL: http://www.chictr.org.cn/showproj.aspx?proj=6981.

The impact of type 2 diabetes and its management on the prognosis of patients with severe COVID-19.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) patients with coronavirus disease 2019 (COVID-19) develop a more severe condition compared to those without diabetes, the mechanisms for this are unknown. Moreover, the impact of treatment with antihyperglycemic drugs and glucocorticoids is unclear. METHODS: From 1584 COVID-19 patients, 364 severe/critical COVID-19 patients with clinical outcome were enrolled for the final analysis, and patients without preexisting T2DM but elevated glucose levels were excluded. Epidemiological data were obtained and clinical status evaluation carried out to assess the impact of T2DM and its management on clinical outcomes. RESULTS: Of 364 enrolled severe COVID-19 inpatients, 114 (31.3%) had a history of T2DM. Twenty-seven (23.7%) T2DM patients died, who had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury compared with non-DM patients. In severe COVID-19 patients with T2DM, we demonstrated a higher risk of all-cause fatality with glucocorticoid treatment (adjusted hazard ratio [HR], 3.61; 95% CI, 1.14-11.46; P = .029) and severe hyperglycemia (fasting plasma glucose ≥11.1 mmol/L; adjusted HR, 11.86; 95% CI, 1.21-116.44; P = .034). CONCLUSIONS: T2DM status aggravated the clinical condition of COVID-19 patients and increased their critical illness risk. Poor fasting blood glucose (≥ 11.1 mmol/L) and glucocorticoid treatment are associated with poor prognosis for T2DM patients with severe COVID-19.

Estimation of chlorophyll-a Concentration of lakes based on SVM algorithm and Landsat 8 OLI images.

Chlorophyll-a (Chl-a) is the main component of phytoplankton and an important index of water quality. Pearson correlation analysis is conducted on measured Chl-a concentration and band reflectance to determine the sensitive bands or multiband combinations of the Chl-a to input to a support vector machine (SVM) model. An indicator ß is defined to evaluate the model performance of fitting and prediction. The model performs well with the lowest ß (decision coefficient, (R2) = 0.774; root mean square error (RMSE) = 22.636 µg/L) of the validation set. The model test results prove that the model performs well. We analyze the impact factors of the model. The seasonal factor affects the model performance significantly; thus, samples from different seasons should be combined to train the model and inverse the water quality. Noise points reduce the model accuracy significantly; therefore, obvious outliers must be excluded at first. Additionally, the sampling method affects model accuracy, and systematic sampling in the descending order of Chl-a concentration is recommended. The combination of SVM algorithm and remote sensing technology provides a convenient, scientific, and real-time method to monitor and control water quality.

ENA-78 Is a Novel Predictor of Wound Healing in Patients with Diabetic Foot Ulcers.

OBJECTIVES: Chronic foot ulceration is a severe complication of diabetes, driving morbidity and mortality. The aim of our study was to identify novel biomarkers of impaired wound healing in diabetic foot ulcers. METHODS: 109 patients with neuropathic diabetic foot ulcers and 30 burn victims otherwise healthy participated. Antibody-coated glass slide arrays were used to determine the levels of 80 human cytokines in pooled plasma or pooled wound exudate of diabetic foot ulcers with rapidly healing (RH, n = 12) and matched nonhealing (NH, n = 12) patients. Potential biomarkers were confirmed in an independent cohort by enzyme-linked immunosorbent assay (ELISA). RESULTS: Protein array profiling identified 27 proteins or 15 proteins significantly altered in protein profiling of pooled plasma or pooled wound exudate of 12 RH patients compared with 12 matched NH patients, respectively. In an independent cohort, quantitative ELISA validation confirmed a decrease in MCP-2 and ENA-78 levels in NH patients versus RH patients or burn victims. After adjusting for the traditional risk factors (sex, age, body mass index, fasting plasma glucose, ulcer area, HbA1C, diabetes duration, hyperlipidemia, and antibiotic therapy), only wound exudate level of ENA-78 remained having a significant association with an increased odds ratio (OR) for wound healing by binary logistic regression analysis (P < 0.05). CONCLUSION: Decreased wound exudate ENA-78 was independently associated with wound healing of patients with diabetic foot. Exudate ENA-78 level is implicated as a novel predictor of wound healing in patients with diabetic foot ulcers.

Wound exudate CXCL6: a potential biomarker for wound healing of diabetic foot ulcers.

AIM: The aim of this study was to investigate the relationship between CXCL-6 levels in wound exudates and healing of diabetic foot ulcers (DFU). MATERIALS & METHODS: One hundred patients with neuropathic DFU were recruited. Wound exudate CXCL-6 levels were measured by enzyme-linked immunosorbent assay. Patients were followed for 24 weeks and divided into rapidly healing and nonhealing groups. RESULTS: Compared with the NH group, the mean CXCL-6 levels in the wound exudates of the rapidly healing group were significantly higher. After adjusting for traditional risk factors, wound exudate CXCL-6 levels were still significantly associated with wound healing. CONCLUSION: CXCL6 is an independent predictor of wound healing in DFU patients and may be a potentially novel therapeutic target for the treatment of DFU.

Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes.

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease, which is common but rarely diagnosed. Noninvasive biomarkers are urgently required to assist in the diagnosis of CLI. Accumulating evidence indicates that miRNAs play an important role in the development of various diseases. In this study, microarray profiling revealed 11 miRNAs with significantly altered expression in four T2DM patients with CLI compared with that in four sex- and age-matched T2DM patients without CLI. In independent cohorts, qRT-PCR validation confirmed the increased miRNA-4739 level in patients with CLI versus patients without CLI. miRNA-4739 levels increased with FPG and HbA1c (all P < 0.05). After adjusting for the risk factors, miRNA-4739 levels were found to be associated with an increased odds ratio (OR) of T2DM with CLI (OR =12.818, 95% confidence intervals (CI) 1.148 to 143.143, P = 0.038). ROC curve analysis revealed that the area under the curve (AUC) of miR-4739+confounding risk factors was 0.94 (95% CI 0.891 to 0.998, P < 0.001), which was higher than that of confounding risk factors (AUC 0.94 vs. 0.91, 95% CI -0.122 to 0.060, P > 0.05) and of miR-4739 (AUC 0.94 vs. 0.69, 95% CI -0.399 to -0.101, P < 0.001), respectively. We conclude that elevated plasma miRNA-4739 levels are independently associated with CLI in T2DM patients. miRNA-4739 is implicated as a novel diagnostic marker and a potential therapeutic target for CLI in diabetes.

MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients.

Type 2 diabetes mellitus (T2DM) is a major contributor to peripheral artery disease (PAD), especially in cases that advance to critical limb ischemia (CLI). Accumulating evidence indicates that miRNAs play an important role in the development of PAD and T2DM. Due to the limited value of current diagnostic methods for CLI in T2DM patients, we compared the miRNA expression profiles of Chinese T2DM patients with or without CLI to find out whether distinctive miRNAs could serve as potential diagnostic biomarkers. We statistically identified 7 miRNAs (hsa-miR-200b-3p, hsa-miR-2115-3p, hsa-miR-431-5p, hsa-miR-486-5p, hsa-miR-210-3p, hsa-miR-1264, hsa-miR-323b-5p) which were up-regulated in the CLI group, whereas other 4 miRNAs (hsa-miR-5579-3p, hsa-miR-665, hsa-miR-4285, hsa-miR-500a-3p) were down-regulated. Our validation test suggested a relatively high diagnostic accuracy of serum hsa-miR-323b-5p levels for the detection of CLI in T2DM patients, with a sensitivity of 62.67% and a specificity of 80.65%. The area under the curve (AUC) for miR-323b-5p + confounding risk factors was 0.94 (95% CI: 0.884-0.994, P < 0.001), which was higher than that for miR-323b-5p. Taken together, our results indicate that circulating hsa-miR-323b-5p could be a promising serum biomarker for the diagnosis of critical limb ischemia in type 2 diabetic patients.