Mitigating diabetes-related complications:Empowering metformin with cholecalciferol and taurine supplementation in type 2 diabetic rats

BACKGROUND Type 2 diabetes is one of the most prevalent chronic diseases worldwide,significantly impacting patients'quality of life.Current treatment options like metformin(MET)effectively counteract hyperglycemia but fail to alleviate diabetes-associated complications such as retinopathy,neuropathy,nephropathy,hepatopathy,and cardiovascular diseases.AIM To propose the supplementation of cholecalciferol(CHO)and taurine(TAU)to enhance MET efficacy in controlling diabetes while minimizing the risk of associated complications.METHODS The study involved sixty rats,including ten non-diabetic control rats and fifty experimental rats with type 2 diabetes induced by streptozotocin.The experimental rats were further subdivided into positive control and treatment subgroups.The four treatment groups were randomly allocated to a single MET treatment or MET combined with supplements either CHO,TAU,or both.RESULTS Diabetic rats exhibited elevated levels of glucose,insulin,Homeostasis Model Assessment of Insulin Resistance(HOMA-IR),glycated hemoglobin percentage,lipid markers,aspartate aminotransferase,and malondialdehyde,along with reduced levels of antioxidant enzymes(catalase and superoxide dismutase).The administration of CHO and TAU supplements alongside MET in diabetic rats led to a noticeable recovery of islet mass.The antioxidative,anti-inflammatory,and anti-apoptotic properties of the proposed combination therapy significantly ameliorated the aforementioned abnormalities.CONCLUSION The supplementation of CHO and TAU with MET showed the potential to significantly improve metabolic parameters and protect against diabetic complications through its antioxidative,anti-inflammatory,and antiapoptotic effects.

Development of diabetic complications and influencing factors among 32653 type 2 diabetes patients:retrospective cohort study using a multi-state Markov

Background:Patients with type 2 diabetes are at high risk for developing multiple chronic complications.However,there is a lack of studies of the cumulative number of diabetic complications in China.Methods:A retrospective cohort study was performed from 2009 to 2021.Type 2 diabetes patients who were first diagnosed after the age of 35 years between January 1,2009,and December 31,2017,were included.Five states were defined according to the number of chronic complications:no(S0),one(S1),two(S2),three(S3),and four or more complications(S4).A multi-state Markov model was constructed to estimate transition probability,transition intensity,mean sojourn time,and the possible factors for each state.Results:The study included 32653 type 2 diabetes patients(mean age,59.59 years;15929(48.8%)male),and mean follow-up time of 7.75 years.In all,4375 transitions were observed.The 12-year transition probability of from state S0 to S1 was the lowest at 16.4%,while that from S2 to S3 was the highest,at 45.6%.Higher fasting blood glucose,lower high-density lipoprotein cholesterol,higher total cholesterol,and an unhealthy diet were associated with higher risk of progression from S0 to S1.Being female,less than 60 years old,weekly physical activity,and vegetarian diet decreased this risk.Being female and less than 60 years old reduced the likelihood of transition from S1 to S2,whereas lower high-density lipoprotein cholesterol increased this likelihood.Conclusions:Following the occurrence of two complications in type 2 diabetes patients,the risk for accumulating a third complication within a short time is significantly increased.It is important to take advantage of the stable window period when patients have fewer than two complications,strengthen the monitoring of blood glucose and blood lipids,and encourage patients to maintain good living habits to prevent further deterioration.

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.

From Diabetes to Diabetic Complications:Role of Autophagy

Diabetes and its complications reduce quality of life and are life-limiting.At present,diabetes treatment consists of hypoglycemic agents to control blood glucose and the use of insulin-sensitizing drugs to overcome insulin resistance.In diabetes,autophagy is impaired and thus there is poor intracellular environment homeostasis.Pancreaticβ-cells and insulin target tissues are protected by enhancing autophagy.Autophagy decreasesβ-cell apoptosis,promotesβ-cell proliferation,and alleviates insulin resistance.Autophagy in diabetes is regulated by the mammalian target of rapamycin(mTOR)/adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)pathway and others.Autophagy enhancers can likely be used as a treatment for diabetes and its complications.This review examines the evidence linking autophagy to diabetes.

Recent therapeutic targets for the prevention and management of diabetic complications

Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing world.Currently used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often underestimated.Although a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical implementation.This editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area.

Virtual screening of flavonoids from Jatropha gossypiifolia L.as potential drugs for diabetic complications

Background:Diabetes mellitus is a chronic metabolic disease that is a risk factor for epidemic pathologies.Under hyperglycemic conditions,the enzyme aldose reductase catalyzes the formation of sorbitol in the metabolism of glucose via polyols,leading to the development of diabetic complications.Therefore,inhibitors of this enzyme are therapeutic targets for the prophylaxis and treatment of these conditions.Methods:In this study,a generalized linear regression model was developed to analyze flavonoids-obtained from a database-that have been tested as inhibitors of aldose reductase.In this sense,the molecular descriptors implemented in DRAGON and MATLAB software were used to determine the correlation between the chemical structure of the inhibitors and their pharmacological activity.The model was validated according to the Organisation for Economic Co-operation and Development Standards and subsequently used for the virtual screening of the flavonoids identified in Jatropha gossypiifolia L.Results:The proposed model showed a good fit for its statistical parameters(R2=0.95).In addition,it showed good predictive power(R2 ext=0.94)and robustness(Q2 LOO=0.92).The experimental chemical space wherein the predictions were reliable(domain of application)was also defined.Finally,the model was used to identify 10 flavonoids from Jatropha gossypiifolia L.as candidates for natural drugs.Compounds with a low probability of oral absorption were identified,among which the elagic acid biflavonoid showed the greatest promise(pIC50 predicted=9.75).Conclusion:The Jatropha gossypiifolia L.species harbors flavonoids with high potential as inhibitors of the aldose reductase enzyme,in which the biflavonoid ellagic acid was shown to be the most promising inhibitor of the aldose reductase enzyme,suggesting its possible use in the treatment of the late complications of diabetes mellitus.

Knowledge, Attitude and Practice on Common Diabetic Patients among Diabetic Complications at Egyptian Hospital in Mogadishu, Somalia

Diabetes is a chronic illness that occurs when the pancreas stops producing insulin or when the body cannot use the produced insulin. Insulin is a hormone produced by the pancreas that helps glucose from meals enters the body’s cells for energy. The overall goal is to assess diabetes patients’ knowledge, attitudes, and behaviors about prevalent diabetic complications. This research used a descriptive qualitative methodology to assess diabetes complication knowledge, attitude, and practice. Ninety-eight diabetic patients were visiting the Egyptian Hospital in Mogadishu for four weeks. The data was collected using questionnaires. Finally, SPSS 20 was utilized for analysis. The research was performed from May to July 2020 with a non-probability sample size of 98 diabetics. The bulk of responders were aged 40 - 60 (36.7%). Type 2 was the most common (47.96%). 44.9% of respondents had diabetes for more than ten years. 60.2% had regular checkups, and 54.1 percent had therapy. 52% of participants were on a diet. 63.3% of respondents do not exercise often. However, most responders know the common issues (75%). Less than half of those polled had problems (41.8%). 22% incidence of Diabetic ketoacidosis. 78.6% of respondents know variables that decrease diabetes complications, whereas 22.4% do not. 37.8% of respondents saw a doctor for diabetes problems, whereas 62.2% did not. Diabetic patients’ knowledge, attitude, and practice were satisfactory for fundamental illness entanglements and self-testing. These findings may also be due to patient notification and, therefore, long-term illness that leads them to get acquainted with things alone. However, the tendency for regular exercise was low, which may produce more specific consequences of illness. Conclusion: We find that DM patients’ KAP was adequate in terms of knowledge of diabetic complications. These results may explain the patients’ long-standing illness, which forces them to discover things independently. At the same time, just a handful of them were familiar with vasculopathy and cardiovascular disorders. However, the researchers discovered low level of attitudes and practice toward regular exercise and insufficient levels of attitudes and practice toward diet management and treatment adherence. In general, this degree of KAP is suboptimal and requires further assessment of KAP obstacles in Somalia.

Potential mechanism of teneligliptin in the treatment of diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM),a complication of diabetes,poses a significant threat to public health,both its diagnosis and treatment presents challenges.Teneligliptin has promising applications and research implications in the treat-ment of diabetes mellitus.Zhang et al observed the therapeutic effect of tenelig-liptin on cardiac function in mice with DCM.They validated that teneligliptin’s mechanism of action in treating DCM involves cardiomyocyte protection and inhibition of NLRP3 inflammasome activity.Given that the NLRP3 inflammasome plays a crucial role in the onset and progression of DCM,it presents a promising therapeutic target.Nevertheless,further clinical validation is required to ascertain the preventive and therapeutic efficacy of teneligliptin in DCM.

Effects of vitamin family members on insulin resistance and diabetes complications

The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Application value of high-pressure-resistant peripherally inserted central catheters in enhanced computer tomography of diabetic patients with malignant tumors

BACKGROUND Individuals with diabetes mellitus have a higher risk of developing malignant tumors,and diagnosing these tumors can be challenging.AIM To confirm the benefits of using peripherally inserted central catheters(PICCs)in contrast-enhanced computerized tomography(CECT)for diagnostic imaging in diabetic patients with malignant tumors and to provide a research basis for follow-up research.METHODS This retrospective study analyzed 204 diabetic patients with malignancies treated at The Second Affiliated Hospital,Jiangxi Medical College,Nanchang University,from January 2024 to June 2024.The patients were divided into two groups:A control group(n=102)with indwelling peripheral intravenous catheters and a research group(n=102)with high-pressure-resistant PICC.The study compared baseline data,the incidence of iodine contrast extravasation during CECT,the incidence of adverse events(discomfort,redness and swelling at the puncture site,and blood oozing),imaging quality,nursing time,intubation success rate,number of venipuncture attempts,and catheter maintenance cost.RESULTS Male patients accounted for 51.96%in the control group and 55.88%in the research group;the average age was(59.68±11.82)years in the control group and(61.41±12.92)years in the research group;the proportions of lung cancer,colorectal cancer,and gastric cancer patients in the control group were 42.16%,38.24%,and 19.61%,respectively,while those in the research group were 34.31%,37.25%,and 28.43%,respectively.Except for the gender distribution,age,and cancer type mentioned above,other general information such as underlying diseases,puncture location,and long-term chemotherapy shows no significant differences as tested(P>0.05).The results showed that the research group had significantly reduced incidence of iodine contrast extravasation(7 vs 1,P=0.031),similar incidence of adverse events(11 vs 7,P=0.324),reduced nursing time[(18.50±2.68)minutes vs(13.26±3.00)minutes,P=0.000],fewer venipuncture attempts[(2.21±0.78)times vs(1.49±0.58)times,P=0.000],lower catheter maintenance cost[(1251.79±205.47)China yuan(CNY)vs(1019.25±117.28)CNY,P=0.000],increased intubation success rate(16.67%vs 58.82%,P=0.000),and better imaging quality(85.29%vs 94.12%,P=0.038).CONCLUSION High-pressure-resistant PICCs can lessen the physical burden of diabetic patients during nursing,reduce treatment costs,and improve the efficiency and quality of imaging for diagnosis malignant tumors.

Therapeutic Effect of Intragastric Administration of Jiangtang Shuxin Recipe Suspension on Diabetic Heart Failure in Rats and Its Mechanism

[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided into five groups,with 10 rats in each group.DHF models were prepared in the low-dose group,high-dose group,Western medicine group,and model group except the control group.Rats in the low-dose and high-dose groups were given 1.0 and 1.5 g/(kg·d)Jiangtang Shuxin recipe suspension by gavage,respectively.Rats in the Western medicine group were given gliquidone and benazepril by gavage for 2 months,and were fed with high-fat diet.Rats in the control group were fed with ordinary diet.Fasting blood glucose(FBG),serum triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),pathological morphology of myocardial tissue,NF-κB p65 protein and IκBαprotein were compared among groups.[Results]Compared with the control group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH increased,while the level of serum HDL-C decreased.The myocardial tissue was seriously damaged,and the expression of NF-κB p65 protein increased,while the expression of IκBαprotein decreased in the other four gruops(all P<0.05).Compared with the model group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,while the serum HDL-C level increased.The myocardial tissue damage was alleviated,and the expression of NF-κB p65 protein decreased,while the expression of IκBαprotein increased in the low-dose group,high-dose group and Western medicine group(all P<0.05).Compared with the Western medicine group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,and the level of serum HDL-C increased in the high-dose group(all P<0.05).[Conclusions]Jiangtang Shuxin recipe has a therapeutic effect on DHF in rats,with the best effect in the high-dose group.It can not only alleviate high glucose and high fat state,but also reduce myocardial injury and inflammation,and improve the pathological morphology of myocardial cells.The mechanism may be related to its inhibition of NF-кB signaling pathway.

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials

OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were（diabetic peripheral neuropathy or diabetic neuropathy or DPN） AND（α-lipoic acid or lipoic acid or thioctic acid） AND epalrestat. DATA SELECTION： All of the eligible studies met the following inclusion criteria：（1） Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.（2） The minimum duration of treatment was 2 weeks.（3） The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.（4） Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES： The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity（MNCV）, median sensory nerve conduction velocity（SNCV）, peroneal MNCV and peroneal SNCV.RESULTS： Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies（RR = 1.29, 95% CI： 1.21–1.38; RR = 1.43, 95% CI： 1.34–1.54, respectively）. ALA plus epalrestat combination therapy also significantly improved median MNCV（WMD = 5.41, 95% CI： 2.07–8.75）, median SNCV（WMD = 5.87, 95% CI： 1.52–10.22）, peroneal MNCV（WMD = 5.59, 95% CI： 2.70–8.47） and peroneal SNCV（WMD = 4.57, 95% CI： 2.46–6.68）.CONCLUSION： ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.

Diabetic foot ulcers:Classification,risk factors and management

Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection,amputation,and death,and is affecting increasing numbers of patients with diabetes mellitus.The pathogenesis of foot ulcers is complex,and different factors play major roles in different stages.The refractory nature of foot ulcer is reflected in that even after healing there is still a high recurrence rate and amputation rate,which means that management and nursing plans need to be considered carefully.The importance of establishment of measures for prevention and management of DFU has been emphasized.Therefore,a validated and appropriate DFU classification matching the progression is necessary for clinical diagnosis and management.In the first part of this review,we list several commonly used classification systems and describe their application conditions,scope,strengths,and limitations;in the second part,we briefly introduce the common risk factors for DFU,such as neuropathy,peripheral artery disease,foot deformities,diabetes complications,and obesity.Focusing on the relationship between the risk factors and DFU progression may facilitate prevention and timely management;in the last part,we emphasize the importance of preventive education,characterize several of the most frequently used management approaches,including glycemic control,exercise,offloading,and infection control,and call for taking into account and weighing the quality of life during the formulation of treatment plans.Multidisciplinary intervention and management of diabetic foot ulcers(DFUs)based on the effective and systematic combination of these three components will contribute to the prevention and treatment of DFUs,and improve their prognosis.

Euglycemic diabetic ketoacidosis:A missed diagnosis

Euglycemic diabetic ketoacidosis(DKA)is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose(less than 11 mmol/L).The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units;it may delay diagnosis and treatment causing worse outcomes.Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus.With the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management,euglycemic DKA incidence has increased.The other causes of euglycemic DKA include pregnancy,fasting,bariatric surgery,gastroparesis,insulin pump failure,cocaine intoxication,chronic liver disease and glycogen storage disease.The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit,milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio.Euglycemic DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine ketones.The diagnostic workup includes arterial blood gas for metabolic acidosis,serum ketones and exclusion of other causes of high anion gap metabolic acidosis.Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration,electrolytes deficit and insulin replacement.The dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis,ketonemia and to avoid hypoglycemia.

Fuzzy expert system for diagnosing diabetic neuropathy

AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists' perspectives(n= 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system.RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease,(the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net(Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity(true positive rate)(89%), specificity(true negative rate)(98%), and accuracy(a proportion of true results, both positive and negative)(93%).CONCLUSION The system designed in this study can help specialistsand general practitioners to diagnose the disease more quickly to improve the quality of care for patients.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats

Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.

Macular integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema

AIM： To respectively evaluate macular morphological features and functional parameters by using spectraldomain optical coherence tomography（SD-OCT） and macular integrity assessment（MAIA） in patients with diabetic macular edema（DME）. METHODS： This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity（BCVA） measurement, MAIA microperimetry, and SDOCT. DME morphology, including central retinal thickness（CRT） and central retinal volume（CRV）; integrity of the external limiting membrane（ELM） and photoreceptor inner segment/outer segment（IS/OS） junction; and the deposition of hard macular exudates were assessed within a 1000-μm central subfield area. MAIA microperimetry parameters evaluated were average threshold（AT）-retinal sensitivity, macular integrity index（MI）, fixation points within a circle of radius 1°（P1） and 2°（P2）, and bivariate contour ellipse area considering 63% and 95% of the fixation points（A63 and A95, respectively）. RESULTS： MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA（log MAR）, total AT, AT within 1000-μm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA（log MAR）, AT within 1000-μm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION： Functional（BCVA and visual field） and morphological parameters（retinal thickness） were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.

Keeping an eye on the diabetic foot: The connection between diabetic eye disease and wound healing in the lower extremity

Diabetic eye disease is strongly associated with the development of diabetic foot ulcers(DFUs).DFUs are a common and significant complication of diabetes mellitus(DM)that arise from a combination of micro-and macrovascular compromise.Hyperglycemia and associated metabolic dysfunction in DM lead to impaired wound healing,immune dysregulation,peripheral vascular disease,and diabetic neuropathy that predisposes the lower extremities to repetitive injury and progressive tissue damage that may ultimately necessitate amputation.Diabetic retinopathy(DR)is caused by cumulative damage to the retinal microvasculature from hyperglycemia and other diabetes-associated factors.The severity of DR is closely associated with the development of DFUs and the need for lower extremity revascularization procedures and/or amputation.Like the lower extremity,the eye may also suffer end-organ damage from macrovascular compromise in the form of cranial neuropathies that impair its motility,cause optic neuropathy,or result in partial or complete blindness.Additionally,poor perfusion of the eye can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy or neovascular glaucoma,both serious,visionthreatening conditions.Finally,diabetic corneal ulcers and DFUs share many aspects of impaired wound healing resulting from neurovascular,sensory,and immunologic compromise.Notably,alterations in serum biomarkers,such as hemoglobin A1c,ceruloplasmin,creatinine,low-density lipoprotein,and highdensity lipoprotein,are associated with both DR and DFUs.Monitoring these parameters can aid in prognosticating long-term outcomes and shed light on shared pathogenic mechanisms that lead to end-organ damage.The frequent cooccurrence of diabetic eye and foot problems mandate that patients affected by either condition undergo reciprocal comprehensive eye and foot evaluations in addition to optimizing diabetes management.

Psychometric Properties of the Swedish Version of the Fear of Complications Questionnaire

Objectives: To translate and evaluate the psychometric properties of the Swedish version of the Fear of Complications Questionnaire. Design: Cross-sectional study design and scale development. Settings: Totally, 469 adults (response rate 63.5%) with Type 1 diabetes completed the questionnaires. Participants were recruited from two university hospitals in Sweden. Participants: Eligible patients were those who met the following inclusion criteria: diagnosed with Type 1 diabetes, diabetes duration of at least 1 year and aged at least 18 years. Methods: The Fear of Complications Questionnaire was translated using the forward-backward translation method. Factor analyses of the questionnaire were performed in two steps using both exploratory and confirmatory factor analysis. Convergent validity was examined using the Hospital Anxiety and Depression Scale and the Fear of Hypoglycaemia Fear Survey. Internal consistency was estimated using Cronbach’s alpha. Results: Exploratory factor analysis supported a two-factor solution. One factor contained three items having to do with fear of kidney-related complications and one factor included the rest of items concerning fear of other diabetes-related complications, as well as fear of complications in general. Internal consistency was high Cronbach’s alpha 0.96. The findings also gave support for convergent validity, with significant positive correlations between measures (r = 0.51 to 0.54). Conclusion: The clinical relevance of the identified two-factor model with a structure of one dominant subdomain may be considered. We suggest, however a one-factor model covering all the items as a relevant basis to assess fear of complications among people with Type 1 diabetes.