Risk factors for developing osteoporosis in diabetic kidney disease and its correlation with calcium-phosphorus metabolism,FGF23,and Klotho

BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Estrogen restores disordered lipid metabolism in visceral fat of prediabetic mice

BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully elucidated.AIM To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.METHODS Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body composition.The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software.Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,respectively.RESULTS Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous E2.Conversely,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 treatment.Notably,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 adminis-tration.This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.CONCLUSION In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes

BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes,the report is as follows.AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus(T2DM).METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis.Metabolic indicators were collected preoperatively,as well as at 3 and 6 months postoperative.The metabolic indicators analyzed included body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),2-hour blood glucose(PBG),glycated hemoglobin(HbA1c),fasting C-peptide,2-hour C-peptide(PCP),fasting insulin(Fins),2-hour insulin(Pins),insulin resistance index(HOMA-IR),βCellular function index(HOMA-β),alanine aminotransferase,aspartate aminotransferase,serum total cholesterol(TC),low-density lipoprotein cholesterol(L DL-C),triglycerides(TG),high-density lipoprotein,and uric acid(UA)levels.RESULTS SBP,DBP,PBG,HbA1c,LDL-C,and TG were all significantly lower 3 months postoperative vs preoperative values;body weight,BMI,SBP,DBP,FBG,PBG,HbA1c,TC,TG,UA,and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months;and PCP,Fins,Pins,and HOMA-βwere all significantly higher 6 months postoperative vs at 3 months(all P<0.05).CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

Epidemiological and Hemato-Biochemical Profiles of Diabetic Patients at the Diabetology, Endocrinology, and Metabolic Diseases Department of the Alpha Oumar Diallo Regional Hospital, Kindia (Republic of Guinea)

This study aims to enhance the healthcare services for diabetic patients in the administrative region of Kindia by suggesting dietary interventions to assist diabetics in better managing their condition. Conducted over a period of six months, from February 18 to July 18, 2021, this prospective and descriptive cross-sectional study involved 220 diabetic patients. Among these, 48 patients (22%) maintained balanced glucose levels (2 g/l). Positive glycosuria was observed in 54% of the patients, whereas 46% demonstrated normal glycosuria. An analysis of urinary parameters revealed that 15% of the patients had abnormal Ketone Bodies. Normal HbA1c levels (9%) HbA1c levels. Hematological assessments indicated significant variation: 56% of the patients had low hemoglobin levels, 4% suffered from hyper-eosinophilia, and 1% each from hyper-basophilia and hyper-hemoglobinemia. The anemic profile was characterized as mild anemia in 75%, moderate anemia in 20%, and severe anemia in 5%. Furthermore, 25% of patients were affected by Microcytic anemia and 75% by Normocytic anemia. Demographically, women constituted 65% of the study group compared to 35% of men. The most represented age bracket was 41 to 60 years, accounting for 52% of the patients, while those between 61 and 80 years comprised 36%. Every district in Kindia was impacted by diabetes.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

The research progress of epigenetics and metabolic memory in diabetic kidney disease

Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with genetics,advanced glycosylation end-product deposition,polyol pathway and protein C activation,lipid metabolism abnormalities,microcirculatory dysfunction,oxidative stress,inflammatory factors,and the kallikrein-kinin system.Epigenetics is the science studying gene expression regulation without changes in the DNA sequence.In recent years,increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD.For instance,epigenetic modifications such as DNA methylation,histone modifications,and non-coding RNAs can influence the expression of DKD-related genes,thereby regulating the development and progression of DKD.On the other hand,metabolic memory is an important concept in DKD research.Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors.This state can influence cell function and fate.In DKD,metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells,affecting their function and fate,ultimately leading to the development and progression of DKD.Therefore,to further explore the pathogenesis of DKD,research on epigenetics should be strengthened,aiming to provide new ideas and methods for the prevention and treatment of DKD.

Establishment of a metabolite diagnostic model for the risk of diabetic nephropathy in type 2 diabetic population:Based on a cross-sectional study in China

Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional investigation was conducted in a hospital setting.Based on medical data,a total of 743 patients from a tertiary hospital were selected and categorized into two groups:the diabetic nephropathy group(DN group)and the non-diabetic nephropathy group(non-DN group).Plasma levels of metabolites,including amino acids and acylcarnitines,were determined using a laser counter measurement system(LC-MS).Subsequently,partial least-squares regression was used to assess the significance of these metabolites.Receiver operating characteristic(ROC)curves were generated for factors that ranked highest in terms of relevance.Model performance was assessed using the curve(AUC).Results:Of the 743 patients with T2DM admitted to the hospital,145 had DN.Compared with the non-DN group,the DN group exhibited elevated systolic blood pressure(P=0.001),high-density lipoprotein cholesterol(P=0.01),and low-density lipoprotein cholesterol(P=0.042).Additionally,the DN group had a higher prevalence of stroke patients(P<0.001)and diabetic retinopathy patients(P<0.001).Finally,a risk model that included citrulline,leucine,tyrosine,valine,propionylcarnitine(C3),and palmitoylcarnitine(C16)was developed.This model achieved an AUC of 0.709,with a 95%confidence interval(CI)ranging from 0.626 to 0.793.Conclusions:A diagnostic model consisting of six plasma metabolites to assess the risk of DN in Chinese patients with T2DM may provide clues for future research.

Effects of sleeve gastrectomy with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats

AIM To explore the effect of sleeve gastrectomy(SG) with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats.METHODS Diabetic rats, which were induced by high-fat diet(HFD), nicotinamide and low-dose streptozotocin, underwent sham operations, SG, SG with jejuno-ileal loop(SG-JI) and SG with jejuno-jejunal loop(SG-JJ) followed by postoperative HFD. Then, at the time points of baseline and 2, 12 and 24 wk postoperatively, we determined and compared several variables, including the area under the curve for the results of oral glucose tolerance test(AUCOGTT), serum levels of triglyceride, cholesterol and ghrelin in fasting state, homeostasis model assessment of insulin resistance(HOMA-IR), body weight, calorie intake, glucagon-like peptide(GLP)-1 and insulin secretions after glucose gavage at dose of 1 g/kg.RESULTS At 2 wk postoperatively, rats that underwent SG, SGJJ and SG-JI, compared with sham-operated(SHAM)rats, demonstrated lower body weight, calorie intake and ghrelin(P < 0.05 vs SHAM), enhanced secretion of insulin and GLP-1 after glucose gavage(P < 0.05 vs SHAM), improved AUCOGTT, HOMA-IR, fasting serum triglyceride and cholesterol(AUCOGTT: 1616.9 ± 83.2, 837.4 ± 83.7, 874.9 ± 97.2 and 812.6 ± 81.9, P < 0.05 vs SHAM; HOMA-IR: 4.31 ± 0.54, 2.94 ± 0.22, 3.17 ± 0.37 and 3.41 ± 0.22, P < 0.05 vs SHAM; Triglyceride: 2.35 ± 0.17, 1.87 ± 0.23, 1.98 ± 0.30 and 2.04 ± 0.21 mmol/L, P < 0.05 vs SHAM; Cholesterol: 1.84 ± 0.21, 1.53 ± 0.20, 1.52 ± 0.20 and 1.46 ± 0.23 mmol/L). At 12 wk postoperatively, rats receiving SG-JJ and SG-JI had lower body weight, reduced levels of triglyceride and cholesterol and elevated level of GLP-1 compared to those receiving SG(P < 0.05 vs SG). At 24 wk after surgery, compared with SG, the advantage of SG-JJ and SG-JI for glucolipid metabolism was still evident(P < 0.05 vs SG). SG-JI had a better performance in lipid metabolism and GLP-1 secretion of rats than did SG-JJ.CONCLUSION SG combined with intestinal loop induces better glycolipid metabolism than simple SG, with the lipid metabolism being more improved with SG-JI compared to SG-JJ.

Linking uric acid metabolism to diabetic complications

Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.

Hepcidin and Iron Metabolism in Non-diabetic Obese and Type 2 Diabetic Rats

Summary： The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups： control group, non-diabetic obese group and type 2 dia- betic group （n=20 each）. The rats were evaluated physiologically and biochemically. The hepatic histo- pathological changes were observed using haematoxylin and eosin （HE） staining. The mRNA expres- sion patterns of hepcidin, interleukin-6 （IL-6）, hypoxia-inducible factor （HIF） and ferroportin （Fpn） in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further ana- lyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly （P〈0.001）. However, there was no significant difference in soluble transferring receptor （sTfR）：ferritin ratio among the three groups （P〉0.05）. The real-time RT-PCR, immunohistochemistry and Western blotting results all re- vealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group （P〈0.001）. The expression levels of hep- cidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant differ- ence （P〉0.05）. However, the protein expression levels of hepcidin in type 2 diabetic group were sig- nificantly higher than those in non-diabetic obese group （P〈0.05）. Compared to control group, the ex- pression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels ofFpn mRNA decreased （P〈0.05）. However, the expression lev- els ofHIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal ex- pression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron re- lease from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.

Influence ofα-Lipoic acid adjuvant therapy on sugar metabolism,peripheral nerve conduction velocity and oxidative stress in patients with diabetic peripheral neuropathy

Objective: To explore the influence of α-Lipoic acid adjuvant therapy on glucose metabolism, peripheral nerve conduction velocity and oxidative stress in patients with diabetic peripheral neuropathy. Methods: A total of 92 cases of patients with diabetic peripheral neuropathy were divided into observation group and control group according to the odd and even admission number, 46 cases in each group. All patients were given the conventional treatment, on this basis, patients in control group were given orally Pancreatic Kinionoge, patients in observation group were given α-Lipoic acid intravenous injection. They were treated for 14 d. The following indicators were observed in two groups before and after treatment: glucose metabolic index: fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG) and glycosylated hemoglobin (HbA1c);peripheral nerve conduction velocity, median nerve, sensory nerve conduction velocity of nervus peroneus communis (MCV) and motor nerve conduction velocity (SCV), ankle arm index (ABI) and inner diameter of lower limb artery (femoral artery, dorsalis pedis artery, popliteal artery), oxidative stress indicators: superoxide dismutase (SOD) and malondialdehyde (MDA). Results: Compared with before treatment, the FBG, 2hPBG, HbA1c level in two groups after treatment were significantly reduced, but the difference of intergroup after treatment was no statistical significance;MCV and SCV of median nerve and nervus peroneus communis was increased significantly than control group after treatment, moreover MCV and SCV of median nerve and nervus peroneus communis in observation group were higher than control group after treatment, the difference was significant. After treatment, ABI and femoral artery, dorsalis pedis arteries, popliteal artery inner diameter in two groups were increased significantly, moreover after treatment the above level in observation group was obviously higher than control group, there was significant difference. After treatment, the MDA in observation group were reduced significantly and SOD level increased significantly, difference was statistically significant compared with before treatment and control group after the treatment;The difference in control group compared between before treatment and after treatment had no statistical significance. Conclusion: Diabetic peripheral neuropathy treated adjuvantly by α-Lipoic acid can significantly improve lower limb blood supply, improve the peripheral nerve conduction velocity, reduce level of oxidative stress, the effect on glucose metabolism still need long course of observation.

Non-Diabetic Nephropathies among Diabetic Patients of the Nephrology Department of Dakar

Introduction: Diabetic nephropathy is the most common cause of kidney disease in diabetics. However, in some cases the clinical symptoms is not typical and nephropathy may be different from diabetic and require the use of renal biopsy (RB) which is not usually indicated unless non-diabetic nephropathy (NND) is suspected. The objective of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) among the diabetic patients and to analyse the different predictive factors of its occurrence. Patients and methods: It was a retrospective, descriptive and analytical study which is carried out at the nephrology department of Aristide Le DANTEC hospital of Dakar over a period of 60 months. Diabetics with suspected NDN diagnosis based on renal anomalie that is associated with a recent diabetes, Acute renal failure with rapid progress, Diabetic retinopathy’s absence, and Extrarenal signs (cutaneous, digestive and articular) associated with an acute renal failure. Microscopic haematuria was included. The epidemiological, clinical, biological and histological parameters were collected and analysed using the SPSS, 3.5 version software. Results: Out of 34 biopsied diabetic patients, 12 had NDN that is a prevalence of 35, 3%. The average age was 49.88 ± 4.15 years, 0.78 for the sex-ratio and the mean duration of diabetes is 12.53 ± 4.7 years. Glomerular syndrome was found in 30 patients (88.23%), vascular nephropathy syndrome in 3 patients (8.82%) and tubule-interstitial nephropathy syndrome in only one patient (2.94%). Diabetic retinopathy (DR) and microscopic haematuria (HU) respectively existed in 10 patients (34%) and 15 patients (44. 12%). The Kidney biopsy (KB) indications were renal abnormalities associated with recent diabetes, acute renal failure with rapid progress, absence of DR, extrarenal signs associated with acute renal failure and microscopic haematuria. Twenty-two patients (64.7%) had diabetic nephropathy (DN) and 12 patients (38.2%) presented a NDN. Predictive factors of NDN diagnosis were a shorter diabetes duration (P = 0.0008), high blood pressure (P = 0.0015) and absence of DR (P = 0.005). Conclusion: Our data show that kidney injury in a diabetic is not always diabetic nephropathy. The Kidney biopsy (KB) is often needed in order to adopt an effective management.

Study on the protective mechanism of Yizhiren regulating lipid metabolism in mice with diabetic nephropathy

Objective:To study the protective mechanism of Yizhiren on the diabetic nephropathy(DN)mouse model based on network pharmacology and metabolomics.Methods:Urea nitrogen,urinary creatinine,urinary albumin were detected in each group of mice,and pathological sections of mice kidney were observed.TCMSP database was used to search for the components and targets of Yizhiren,GeneCards database was used to search for DN-related genes,and drug-component-target-disease network and KEGG signaling pathway were constructed.The fecal samples of mice in the Yizhiren group and the Saline group were collected,metabolomics techniques were used to screen different metabolites,and potential metabolic pathways were analyzed using KEGG database.Results:Compared with the model group,Yizhiren significantly reduced the levels of urea nitrogen,urinary creatinine and urinary albumin in DN mice(P<0.05 or P<0.01),and improved the renal pathology of mice.It was predicted that Yizhiren had 4 effective components and 28 potential targets for treating DN.The KEGG enriched 43 signal pathways,and the main metabolic pathway was lipid metabolism.A total of 584 different metabolites were screened from feces of the two groups(P<0.05).The main metabolic pathways were lipid metabolism,namely sphingolipid metabolism and glycerol phospholipid metabolism,among which the metabolites contained mainly sphingolipin,phosphatidylcholine,lysophosphatidylcholine and phosphatidylethanolamine.Compared with the normal saline group,these four metabolites in Yizhiren decreased significantly(P<0.01 or P<0.001).Conclusion:The protective mechanism of Yizhiren in DN mice may be related to the regulation of sphingolipid metabolism,glycerol phospholipid metabolism and the disorder of its metabolites.

Effects of paricalcitol combined with hemodiafiltration on bonemetabolism-related indexes in patients with diabetic nephropathy and chronic renal failure

BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficacy prediction model.AIM To determine the effects of paricalcitol combined with hemodiafiltration on bonemetabolism-related indexes in patients with DN and chronic renal failure(CRF),and to construct an efficacy prediction model.METHODS We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022.We selected 94 patients who met the inclusion and exclusion criteria.Patients were assigned to a dialysis group(n=45)and a joint group(n=49)in relation to therapeutic regimen.The clinical efficacy of the two groups was compared after treatment.The changes in laboratory indexes after treatment were evaluated,and the two groups were compared for the incidence of adverse reactions.The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed.RESULTS The dialysis group showed a notably worse improvement in clinical efficacy than the joint group(P=0.017).After treatment,the joint group showed notably lower serum levels of serum creatinine,uric acid(UA)and blood urea nitrogen(BUN)than the dialysis group(P<0.05).After treatment,the joint group had lower serum levels of phosphorus,procollagen type I amino-terminal propeptide(PINP)and intact parathyroid hormone than the dialysis group,but a higher calcium level(P<0.001).Both groups had a similar incidence of adverse reactions(P>0.05).According to least absolute shrinkage and selection operator regression analysis,UA,BUN,phosphorus and PINP were related to treatment efficacy.According to further comparison,the non-improvement group had higher risk scores than the improvement group(P<0.0001),and the area under the curve of the risk score in efficacy prediction was 0.945.CONCLUSION For treatment of CRF and DN,combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients,with good safety.

Yiqi Yangyin and Huatan Quyu granule can improve skeletal muscle energy metabolism in a type 2 diabetic rat model by promoting the AMPK/SIRT/PGC-1α signalling pathway

Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.

Effect of resistance + aerobic exercise on insulin resistance, plaque properties and lipid metabolism in patients with diabetic macroangiopathy

Objective: To study the effect of resistance + aerobic exercise on insulin resistance, plaque properties and lipid metabolism in patients with diabetic macroangiopathy. Methods:Patients with type 2 diabetes mellitus complicated by macroangiopathy who were treated in Zigong Third People's Hospital between February 2015 and April 2016 were selected as the research subjects and randomly divided into exercise group and the control group who received resistance + aerobic exercise combined with hypoglycemic therapy and routine hypoglycemic therapy respectively. The insulin resistance indexes, plaque property indexes and lipid metabolism indexes were detected before intervention and 16 weeks after intervention. Results: 16 weeks after inclusion, serum F-Ins, MCP-1, YKL-40, MMP9, CatK, Caspase-3, TG, LDL, Resistin, Leptin and Visfatin contents of both groups of patients were significantly lower than those before inclusion, and serum F-Ins, MCP-1, YKL-40, MMP9, CatK, Caspase-3, TG, LDL, Resistin, Leptin and Visfatin contents of exercise group were significantly lower than those of control group. Conclusion: Resistance + aerobic exercise can improve the insulin resistance and lipid metabolism and stabilize the plaque properties in patients with diabetic macroangiopathy.