Complications In Diabetic Patients Research Articles

Identification of key genes and mechanisms of epicardial adipose tissue in patients with diabetes through bioinformatic analysis.

BackgroundIn recent years, peri-organ fat has emerged as a diagnostic and therapeutic target in metabolic diseases, including diabetes mellitus. Here, we performed a comprehensive analysis of epicardial adipose tissue (EAT) transcriptome expression differences between diabetic and non-diabetic participants and explored the possible mechanisms using various bioinformatic tools.MethodsRNA-seq datasets GSE108971 and GSE179455 for EAT between diabetic and non-diabetic patients were obtained from the public functional genomics database Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using the R package DESeq2, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Next, a PPI (protein–protein interaction) network was constructed, and hub genes were mined using STRING and Cytoscape. Additionally, CIBERSORT was used to analyze the immune cell infiltration, and key transcription factors were predicted based on ChEA3.ResultsBy comparing EAT samples between diabetic and non-diabetic patients, a total of 238 DEGs were identified, including 161 upregulated genes and 77 downregulated genes. A total of 10 genes (IL-1β, CD274, PDCD1, ITGAX, PRDM1, LAG3, TNFRSF18, CCL20, IL1RN, and SPP1) were selected as hub genes. GO and KEGG analysis showed that DEGs were mainly enriched in the inflammatory response and cytokine activity. Immune cell infiltration analysis indicated that macrophage M2 and T cells CD4 memory resting accounted for the largest proportion of these immune cells. CSRNP1, RELB, NFKB2, SNAI1, and FOSB were detected as potential transcription factors.ConclusionComprehensive bioinformatic analysis was used to compare the difference in EAT between diabetic and non-diabetic patients. Several hub genes, transcription factors, and immune cell infiltration were identified. Diabetic EAT is significantly different in the inflammatory response and cytokine activity. These findings may provide new targets for the diagnosis and treatment of diabetes, as well as reduce potential cardiovascular complications in diabetic patients through EAT modification.

Gastrointestinal and Liver Complications in Patients with Diabetes Mellitus-A Review of the Literature.

The number of diabetes mellitus patients has increased over the last few years in developing countries, along with obesity and sedentary lifestyle. Besides macroangiopathy and microangiopathy, damage to the nerve fibers of the peripheral nervous system is the most common chronic complication of diabetes. Digestive complications in diabetic patients represent a consequence of diabetic autonomic neuropathy involving the gastrointestinal tract, but unfortunately not always evaluated by diabetologists. Aside from the complications encountered in the digestive tract, patients with diabetes mellitus are prone to developing liver diseases. This review will describe the prevalence of these complications, the modality of diagnosis, and therapeutical solutions in order to reduce the risk of progression of these complications in diabetic subjects.

P37. Postoperative hematocrit predicts postoperative complications in diabetic patients undergoing spinal deformity surgery

P37. Postoperative hematocrit predicts postoperative complications in diabetic patients undergoing spinal deformity surgery

S-144 lack of association between glycated hemoglobin and adverse outcomes in diabetic patients undergoing ventral hernia repair: an ACHQC study.

Elevated preoperative glycated hemoglobin (HbA1c) is believed to predict complications in diabetic patients undergoing ventral hernia repair (VHR). Our objective was to assess the association between HbA1c and outcomes of VHR in diabetic patients. We conducted a retrospective cohort study using the Abdominal Core Health Quality Collaborative (ACHQC) database. We included adult diabetic patients who underwent elective VHR with an available HbA1c result. The patients were divided into two groups (HbA1c < 8% and HbA1c ≥ 8%). Patient demographics, comorbidities, hernia characteristics, operative details, and surgical outcomes were compared. Multivariable logistic regression analysis of complications was performed. Cox proportional hazard regression was used to assess probability of composite recurrence at different HbA1c levels. 2167 patients met the inclusion criteria (HbA1c < 8% = 1,776 and HbA1c ≥ 8% = 391). Median age was 61years and median body mass index was 34kg/m2. 75% had an American Society of Anesthesiology class of 3. The median HbA1c was 6.5% in the HbA1c < 8% group versus 8.7% in the HbA1c ≥ 8% group. 73% were incisional hernias, 34% were recurrent, and median hernia width was 6cm. Open approach was used in 63% and myofascial release was performed in 46%. Median follow-up was 27days. There were no clinically significant differences in the rates of overall 30-day complications, wound complications, reoperation, readmission, mortality, length of stay and quality of life and pain scores between the two groups. Regression analyses did not identify an association between HbA1c and the rates of complications, surgical site infection or composite recurrence across the spectrum of HbA1c values. Our study finds no evidence of an association between HbA1c and operative outcomes in diabetic patients undergoing elective VHR.

Antiglycation, antioxidant and cytotoxicity activities of crude extract of Turnera ulmifolia L. before and after microencapsulation process

Turnera ulmifolia L. is used in folk medicine and it is known to have anti-hyperglycemic effect on the organism in order to reduce complications in diabetic patients. Glycation process is directly related to oxidative stress, acting as an important endogenous source, inducing the production of free radicals, and thus increasing the production of reactive oxygen species. The encapsulation technology on natural compounds can minimize and even mitigate the risk of loss of biological activity in order to maintain their activities against oxidative stress and glycation. The present study aimed to evaluate the antiglycation and antioxidant activities of T. ulmifolia extract before and after encapsulation and cytotoxicity of the crude extract. This study presents important information about the biological activities, highlighting antioxidant and antiglycation potential and no cytotoxicity of Turnera ulmifolia crude extract, a species of genus Turnera that has been poorly studied. T. ulmifolia crude extract presented flavonoids as main active compounds. The results showed a promising activity in scavenging free and peroxyl radicals, chelating iron ions and inhibiting BSA glycation. In addition, this study showed the possible encapsulation of bioactive compounds using maltodextrin as wall material.

Increased postoperative glycemic variability is associated with increased mortality in diabetic patients undergoing hip arthroplasty for hip fracture.

Increased glycemic variability (GV) during hospitalization has been associated with increased rates of surgical site and periprosthetic joint infections (PJI) following elective total joint arthroplasty. Uncertainty exists surrounding GV as a predictor for complications in urgent arthroplasty cases following hip fractures. In this study, we evaluated the association between GV and postoperative complications in diabetic patients undergoing total hip arthroplasty (THA) and hemiarthroplasty (HA) for hip fractures. We analyzed data on 2421 consecutive patients who underwent THA or HA at our institution from 2011 to 2020. Patients with a known diagnosis of diabetes mellitus who had a minimum of three postoperative glucose values taken within the first week after surgery were included. GV was assessed using a coefficient of variation. Outcomes included short- and long-term mortality, reoperations, prosthetic joint infection (PJI) requiring revision and readmissions for any cause. The final cohort consisted of 482 patients (294 females, 188 males). Higher GV was associated with an increased 90-day mortality (p = 0.017). GV was not associated with 30-day mortality (p = 0.45), readmissions of any cause at 30 or 90days (p = 0.99, p = 0.91, respectively), reoperation of any cause (p = 0.91) or PJI requiring revision surgery (p = 0.42). Higher GV in the postoperative period is associated with increased rates of mortality in diabetic patients following THA and HA for hip fractures. Efforts should be made to monitor and control glucose variability in the postoperative period.

Predicting diabetic nephropathy in type 2 diabetic patients using machine learning algorithms.

Global healthcare centers today are challenged by the dramatic increase in the prevalence of diabetes. Also, complications from diabetes are a major cause of deaths worldwide. One of the most frequent microvascular complications in diabetic patients is diabetic nephropathy (DN) which is the leading cause of death and end-stage renal disease (ESRD). Despite the different risk factors for DN identified in previous research, machine learning (ML) methods can help determine the importance of the predictors and prioritize them. The main focus of this investigation is on predicting the incidence of DN in type 2 diabetic mellitus (T2DM) patients using ML algorithms. Demographic information, laboratory results, and examinations on 6235 patients with T2DM covering a period of 10years (2011-2020) were extracted from the electronic database of the Diabetes Clinic of the Imam Khomeini Hospital Complex (IKHC) in Iran. Recursive feature elimination using the cross-validation (RFECV) technique was then used with the three classification algorithms to select the important risk factors. Next, five ML algorithms were used to construct a predictive model for DN in T2DM patients. Finally, the results of the algorithms were evaluated according to the AUC criteria and the one with the best performance in terms of prediction and classification was selected. The 18 DN risk factors selected by RFECV were age, diabetes duration, BMI, SBP, hypertension, retinopathy, ALT, CVD, 2HPP, uric acid, HbA1c, waist-to-hip ratio, cholesterol, LDL, HDL, FBS, triglyceride, and serum insulin. Based on a 10-fold cross-validation, the best performance among the five classification algorithms was that of the random forest with 85% AUC. This investigation validates the known risk factors for DN and emphasizes the importance of controlling the blood pressure, weight, cholesterol, and blood sugar of T2DM patients. In addition, as an example of the application of ML approaches in medical predictions, the findings of this study demonstrate the advantages of using these techniques.

Hypoglycemic unawareness: challenges, triggers, and recommendations in patients with hypoglycemic unawareness: a case report

BackgroundHypoglycemia is a fairly common complication in diabetic patients, particularly in those on insulin therapy. Hypoglycemia symptoms are classified into two types: autonomic and neuroglycopenic symptoms. If a person develops neuroglycopenic symptoms before the appearance of autonomic symptoms or is asymptomatic until blood sugar levels are very low, the patient will develop hypoglycemic unawareness (HU).Case presentationA 25-year-old Iranian woman with HU presented with a severe hypoglycemic episode. This episode was characterized by loss of consciousness and focal neural deficits, which were unusual symptoms in the patient, who was a medical intern with type 1 diabetes and currently being treated with regular and NPH insulin.ConclusionsHypoglycemia is a common complication in diabetic patients receiving oral or insulin therapy. A patient who is unaware of their condition may experience severe and potentially fatal episodes. These incidents can negatively affect their daily lives as well as their careers and jobs. Hypoglycemia-associated autonomic failure is a possible cause for patients with multiple episodes of severe hypoglycemia. IThe use of a continuous glucose monitoring device with an alarm, if available, can be an excellent option for these patients.

Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.

The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

Multi-Model Domain Adaptation for Diabetic Retinopathy Classification.

Diabetic retinopathy (DR) is one of the most threatening complications in diabetic patients, leading to permanent blindness without timely treatment. However, DR screening is not only a time-consuming task that requires experienced ophthalmologists but also easy to produce misdiagnosis. In recent years, deep learning techniques based on convolutional neural networks have attracted increasing research attention in medical image analysis, especially for DR diagnosis. However, dataset labeling is expensive work and it is necessary for existing deep-learning-based DR detection models. For this study, a novel domain adaptation method (multi-model domain adaptation) is developed for unsupervised DR classification in unlabeled retinal images. At the same time, it only exploits discriminative information from multiple source models without access to any data. In detail, we integrate a weight mechanism into the multi-model-based domain adaptation by measuring the importance of each source domain in a novel way, and a weighted pseudo-labeling strategy is attached to the source feature extractors for training the target DR classification model. Extensive experiments are performed on four source datasets (DDR, IDRiD, Messidor, and Messidor-2) to a target domain APTOS 2019, showing that MMDA produces competitive performance for present state-of-the-art methods for DR classification. As a novel DR detection approach, this article presents a new domain adaptation solution for medical image analysis when the source data is unavailable.

Development and internal validation of a model to predict type 2 diabetic complications after gestational diabetes

Gestational diabetes mellitus (GDM) increases the risk of early-onset type 2 diabetes, which further exacerbates the risk of developing diabetic complications such as kidney, circulatory, and neurological complications. Yet, existing models have solely focused on the prediction of type 2 diabetes, and not of its complications, which are arguably the most clinically relevant outcomes. Our aim was to develop a prediction model for type 2 diabetic complications in patients with GDM. Using provincial administrative data from Quebec, Canada, we developed a model to predict type 2 diabetic complications within 10 years among 90,143 women with GDM. The model was internally validated and assessed for discrimination, calibration, and risk stratification accuracy. The incidence of diabetic complications was 3.8 (95% confidence interval (CI) 3.4–4.3) per 10,000 person-years. The final prediction model included maternal age, socioeconomic deprivation, substance use disorder, gestational age at delivery, severe maternal morbidity, previous pregnancy complications, and hypertensive disorders of pregnancy. The model had good discrimination [area under the curve (AUROC) 0.72 (95% CI 0.69–0.74)] and calibration (slope ≥ 0.9) to predict diabetic complications. In the highest category of the risk stratification table, the positive likelihood ratio was 8.68 (95% CI 4.14–18.23), thereby showing a moderate ability to identify women at highest risk of developing type 2 diabetic complications. Our model predicts the risk of type 2 diabetic complications with moderate accuracy and, once externally validated, may prove to be a useful tool in the management of women after GDM.

A Prospective Cohort Study on Diabetic Foot Infections with Emphasis on Identifiable Risk Factors in Patients Attending Tertiary Care Centre

Background: Foot infections are one of the most commonly observed complications in diabetic patients and are associated with high morbidity and risk of lower extremity amputation. Foot infections account for about 20% of all hospitalizations in people with diabetes and at least 50% of all non-traumatic lower-limb amputations performed annually.&#x0D; Objective: To identify the risk factors in patients with diabetic foot infections attending tertiary care centre.&#x0D; Method: It is a longitudinal prospective study in which patients attending the tertiary care centre with diabetic foot infections meeting the inclusion criteria were enrolled after obtaining the informed consent form.&#x0D; Results and discussion: The results of this study revealed that the overall prevalence of DFI was seen more in males (61.42%) when compared to females (38.57%). The results also showed that the risk of DFI was more with trauma(44.28%) followed by the long duration of DM (28.57%) &gt; wound (15.71%) &gt; uncontrolled DM &amp; prior foot ulcer (5.7%) which indicates a lack of awareness, longer duration of DM, poor glycemic control were the main risk factors causing diabetic foot problems. Conclusion: The results suggest that lack of awareness, poor glycemic control, and long duration of diabetes were the main risk factors causing DFI. Therefore, efforts to prevent infections should be targeted at people with traumatic foot wounds especially those that are chronic and recurrent. Foot care education would be the foremost important way of dealing with this serious problem.&#x0D; Keywords: Morbidity, lower-extremity amputation, trauma, glycemic control.

Noncoding RNAs in diabetic nephropathy

Abstract Diabetic nephropathy (DN) is a major microvascular complication in diabetic patients. It has become the leading cause of end-stage renal disease (ESRD) in individuals living in urban areas undergoing dialysis. DN diagnosis primarily depends on the course of diabetes and the detection of albuminuria. However, the onset of DN is obscure, and many patients have already developed ESRD when they are diagnosed with DN. Hence, early diagnosis of DN progression and early interventional strategies are essential. Noncoding RNAs (ncRNAs) are a class of RNA transcripts that are transcribed from DNA but are not translated into proteins. They play an important role in regulating gene expression and protein synthesis. Several studies have demonstrated that ncRNAs are abundantly present in the blood, urine, and tissues and have the potential to aid in the diagnosis and treatment of DN. This review focuses on the role of microRNAs, long ncRNAs, and circular RNAs in DN and their potential value as biomarkers and therapeutic targets.

Polyherbal formulation exerts wound healing, anti-inflammatory, angiogenic and antimicrobial properties: Potential role in the treatment of diabetic foot ulcers

Diabetic foot ulcer (DFU) is a common and devastating complication in diabetic patients and is associated with an elevated risk of amputation and mortality. DFU remains a major therapeutic challenge due to poor understanding of its underlying pathogenesis. This complication is characterized by impaired wound healing; however, mechanisms causing this impairment are complicated and involve interactions between many different cell types and infections. In addition to other conventional DFU treatments, herbal foot baths are also common, although little is known about their mechanisms of action, and they contain a wide variety of herbal ingredients. In this study, we aimed to examine the effects of three polyherbal formulations consisting of medicinal plants used in traditional Thai herbal foot baths on wound healing, anti-inflammation, angiogenesis, and extracellular matrix modulation using high-concentration glucose-treated human keratinocytes, in addition to antibacterial evaluation. Our results showed that formulation 3 (F3) possessed the greatest potential to restore the impairment of keratinocytes caused by high glucose concentrations. We found that F3 could inhibit the growth of Staphylococcus aureus, accelerate wound healing, and upregulate the expression of TIMP-1, VEGF, and TGF-β, and downregulate the expression of TNF-α, IL-6, and MMP-9. Collectively, these data support the potential of F3 for therapeutic development in the treatment of DFU.

Eating disorders and carbohydrate metabolism interrelations

Abstract Introduction: Eating disorders are characterised by persistent disturbances in eating behavior, resulting in severe carbohydrate homeostasis changes. The aim of the study is to review mutual correlations between eating disorders, with emphasis on anorexia nervosa, and carbohydrate metabolism, including glycemia and the levels of relevant hormones. Material and methods: A priori general inclusion criteria were established and included patients with eating disorders or with glucose metabolism disorders. A MEDLINE database review was carried out. Relevant articles have been extracted and approved by supervisor. Results: 40 studies got included in the review. Patients with active anorexia nervosa display low levels of fasting and postprandial glucose, decreased lipid metabolism, and decreased pancreatic endocrine activity. Insulin levels remain changed even after patient’s re-nourishment – insulin response tends to be delayed and decreased compared to patients without anorexia history. Eating disorders are associated with poorer glycemic control and a higher percentage of diabetic complications in patients with pre-existing diabetes – mostly type I. There are also reports of higher carbohydrate metabolism disturbances among patients with eating disorders. Conclusions: Carbohydrate metabolism disorders and eating disorders are clearly interrelated, although data on the nature of these relationships are still lacking. Treatment of eating disorders is not possible without normalizing eating patterns, thus also carbohydrate metabolism. However, it is not usual to monitor the mental state in terms of eating disorders potential development in patients during the treatment of carbohydrate disorders. According to existing data, this approach should be changed due to the risk of anorexia nervosa and other eating disorders in this group.

Dynamics of FABP4 and CTRP3 biomarkers in patients with acute myocardial infarction and type 2 diabetes mellitus

The aim of the work was to study the characteristics of adipokine metabolism based on the analysis of fatty acid binding protein 4 (FABP4) and C1q/tumour necrosis factor-related protein-3 (CTRP3) levels and their dynamics in non-diabetic and diabetic patients with cardiovascular (CV) complications of acute myocardial infarction (AMI).&#x0D; Materials and methods. The study was carried out between 2018 and 2020 and involved 134 AMI patients with or without type 2 diabetes mellitus (DM) aged 59.00 [52.75; 66.00] years. The control group consisted of 20 healthy individuals with the mean age of 56.50 [48.50; 61.75] years. The serum levels of FABP4 and CTRP3 were measured by enzyme-linked immunosorbent assay on days 1 and 10 of hospital stay.&#x0D; Results. The mean levels of FABP4 were elevated on day 1 in AMI patients with type 2 DM (group II) compared to those in AMI patients (group I) and the control individuals (p&lt;0.05). The FABP4 concentrations on day 10 were 7.68 [6.42; 8.42] ng/ml and 8.31 [6.92; 9.63] ng/ml (p&lt;0.05) in groups I and II, respectively. The CTRP3 levels were lower in group II on day 1 as compared to those in group I and the control group patients (p&lt;0.001). After 10 days, the levels of CTRP3 were 287.56 [271.48; 300.58] ng/ml and 262.01 [225.32; 288.84] ng/ml) (p&lt;0.001) in groups I and II, respectively. In the presence of early AMI complications in diabetic patients, the levels of FABP4 remained elevated on day 10, and the levels of CTRP3 were low compared to those in diabetic patients without AMI complications (p&lt;0.05).&#x0D; Conclusions. The characteristics of adipokine metabolism in AMI patients have been revealed: the worsened imbalance in adipokine metabolism in type 2 DM due to the difference in FABP4 and CTRP3 levels. Special mention should be made of severely deteriorated adipokine metabolism in diabetic patients with CV complications

High Inflammatory Factor Levels Increase Cardiovascular Complications in Diabetic Patients Undergoing Coronary Artery Bypass Grafting.

Objective To investigate the association between inflammation and clinical outcomes of coronary artery bypass grafting (CABG) in diabetic patients. Methods A total of 300 diabetic patients with coronary heart disease who underwent CABG were selected. Patients were divided into a group with cardiovascular events (32 in the MACCE group) and a group without cardiovascular events (268 in the non-MACCE group) according to whether cardiovascular events occurred within 30 days. The differences in clinical parameters; serum levels of TNF-α, IL-6, IL-18, IL-1β, and CRP; factors associated with the occurrence of MACCE; and risk factors affecting the midterm all-cause mortality of patients were compared between the two groups. Results The serum levels of TNF-α, IL-6, IL-18, and CRP in the MACCE group were significantly higher than those in the non-MACCE group (p < 0.05). Gender, smoking, hyperlipidemia, duration of diabetes, and levels of TNF-α, IL-6, IL-18, and CRP were closely related to the occurrence of MACCE. The Kaplan-Meier survival analysis evaluation results showed that the levels of IL-6 and CRP significantly affected the midterm all-cause mortality rate (p < 0.05). Multivariate Cox regression analysis showed that the advanced age, hypertension, hyperlipidemia, long duration of diabetes, elevated serum IL-6, and CRP levels could be used as risk factors for midterm all-cause mortality. Conclusions Inflammation levels in diabetic patients are associated with complications and midterm all-cause mortality in patients undergoing coronary artery bypass grafting.

Astragalus Polysaccharides/PVA Nanofiber Membranes Containing Astragaloside IV-Loaded Liposomes and Their Potential Use for Wound Healing.

Delayed wound healing is a common and serious complication in diabetic patients, especially the slow healing of foot ulcers, which seriously affects the quality of life of patients and is also the most important risk factor for lower limb amputation. The multifunctional novel dressing prepared by loading the polymer nanofibers with anti-inflammatory and prohealing plant extracts can promote the wound repair of these ulcers by electrospinning technology. Liposomes are nanoparticles prepared from phospholipids and have been widely used as drug delivery systems. Liposomes can be combined with electrospun nanofibrous webs to facilitate local and sustained delivery of loaded bioactive substances. In this study, liposomes were prepared with astragaloside IV (AS) by employing a modified ethanol injection method and conducting the physical and chemical characterization (e.g., the particle size, polydispersity index, zeta potential, and entrapment efficiency). Astragalus polysaccharides were extracted from Astragalus membranaceus. Subsequently, we prepared the electrospun polyvinyl alcohol (PVA)/astragalus polysaccharide (APS)/astragaloside IV (AS) nanofibers. The morphology of the produced ASL/APS/PVA, APS/PVA, and PVA nanofibers were analyzed by scanning electron microscopy (SEM), and it turns out that the addition of astragalus extract made the fiber diameter smaller and the fibers arranged neatly with no dripping. An induced diabetic rat model was built, and a diabetic ulcer model was built by total cortical resection to assess the prorepair ability of the prepared nanofibers. According to in vivo animal experiments, the nanofibrous membrane loaded with APS and ASL was reported to inhibit the occurrence of wound inflammation, enhance the deposition of collagen fibers (P < 0.05) and the repair of regenerated epithelium (P < 0.05), and effectively strengthen the wound healing of diabetic rats (P < 0.05). In brief, PVA-loaded APS/ASL nanofibrous membranes refer to a prominent wound healing dressing material, which can effectively facilitate the healing of diabetic wounds, and they are demonstrated to be highly promising for application in diabetic wound dressings and tissue engineering.

Metabonomic Characteristics of Myocardial Diastolic Dysfunction in Type 2 Diabetic Cardiomyopathy Patients.

Diabetic cardiomyopathy (DCM) is one of the most essential cardiovascular complications in diabetic patients associated with glucose and lipid metabolism disorder, fibrosis, oxidative stress, and inflammation in cardiomyocytes. Despite increasing research on the molecular pathogenesis of DCM, it is still unclear whether metabolic pathways and alterations are probably involved in the development of DCM. This study aims to characterize the metabolites of DCM and to identify the relationship between metabolites and their biological processes or biological states through untargeted metabolic profiling. UPLC-MS/MS was applied to profile plasma metabolites from 78 patients with diabetes (39 diabetes with DCM and 39 diabetes without DCM as controls). A total of 2,806 biochemical were detected. Compared to those of DM patients, 78 differential metabolites in the positive-ion mode were identified in DCM patients, including 33 up-regulated and 45 down-regulated metabolites; however, there were only six differential metabolites identified in the negative mode including four up-regulated and two down-regulated metabolites. Alterations of several serum metabolites, including lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the development of DCM. KEGG enrichment analysis showed that there were three signaling pathways (metabolic pathways, porphyrin, chlorophyll metabolism, and lysine degradation) that were changed in both negative- and positive-ion modes. Our results demonstrated that differential metabolites and lipids have specific effects on DCM. These results expanded our understanding of the metabolic characteristics of DCM and may provide a clue in the future investigation of reducing the incidence of DCM. Furthermore, the metabolites identified here may provide clues for clinical management and the development of effective drugs.

MO624: The Relationship Between Renal Tubular Epithelial Cell Necroptosis and The Severity of Diabetic Nephropathy

Abstract BACKGROUND AND AIMS Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target. METHOD A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions. RESULTS Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049). CONCLUSION The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.