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.

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.

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.

Research progress of artesunate in diabetes and its complications

Diabetes is a metabolic disease characterized by abnormally elevated blood glucose levels.Persistent hyperglycemia leads to diabetic nephropathy,diabetic retinopathy,diabetes with periodontal disease and other diabetic complications.These diseases have become the main causes of disability and death in diabetic patients.Artesunate is well known as an antimalarial drug for controlling malaria symptoms.Current studies have shown that artesunate improves diabetes and its complications by protecting islet cells,improving glucose and lipid metabolism,anti-inflammatory and immune regulation.Based on the research status in recent years,this paper focuses on the mechanism of artesunate in diabetes and its complications,to provide a theoretical basis for future diabetes research.

Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

Evaluation of the Effectiveness of Community Pharmacy Services on Rational Medication Use in Elderly Patients with Hypertension and Diabetes

Objective:To explore the effect of community pharmacy services on rational medication use in elderly patients with hypertension and diabetes.Methods:Between November 2022 and December 2023,80 elderly patients with hypertension and diabetes were selected and randomly divided into a control group(routine medication guidance)and an observation group(community pharmacy services),with 40 subjects each.The medication effect scores,blood pressure,blood sugar levels,and quality of life scores before and after intervention were compared between the two groups.Results:Comparison of pharmaceutical knowledge,medication compliance,and safe medication behavior scores showed that the observation group had higher scores as compared to the control group(P<0.05);blood pressure(systolic blood pressure,diastolic blood pressure,heart rate)and blood sugar(fasting blood glucose,2 h postprandial blood glucose,glycated hemoglobin)index levels were compared,and the observation group’s index levels were lower than those of the control group(P<0.05);the scores of physical health,mental health,social relationships,and environment in the observation group were higher than those in the control group(P<0.05).Conclusion:Community pharmacy services improved the rational medication effect of elderly patients with hypertension and diabetes,and improved their blood pressure,blood sugar control levels,and quality of life.

Licorice and its main components on the treatment of diabetes and its complications:A review of in vivo and in vitro studies

Licorice is one of the oldest herbal medicines for its various ethno pharmacological uses.In both Asian and European countries,it has been recorded for treatment of inflammatory diseases.A large number of ingredients have been isolated from licorice,including triterpene saponins and flavonoids,which are normally being considered to be the main biologically active components.In the last decade,licorice has been proved exert anti-diabetic effect in various in vivo and in vitro models of diabetes mellitus.Furthermore,licorice can also antagonize all sorts of diabetes complications,including diabetic nephropathy,atherosclerosis,diabetic retinopathy and neuropathy.Except anti-inflammation,licorice and its active components show anti-diabetic effects by improving insulin resistance and increasing insulin secretion,regulating lipid metabolism,and anti-oxidation.The useful effects of licorice and its active components are due to regulating different pathways and proteins,including NF-κB,AMPK,insulin signaling pathway,MAPK,etc.In this review,we provide an overview of the beneficial effects and related molecular mechanism of licorice and its effective components on improving diabetes and its complications.

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.

Clinical significance of serum miR-129-5p in patients with diabetes mellitus presenting macrovascular complications

BACKGROUND Diabetic macrovascular complications(DMCs)are the most common complications encountered during the course of diabetes mellitus(DM)with extremely high mortality rates.Therefore,there is an urgent need to identify specific and sensitive biomarkers for the early diagnosis of DMCs.AIM To investigate the expression and significance of serum miR-129-5p in patients with DM and macrovascular complications.METHODS Serum samples were collected from 36 healthy controls,58 patients with DM presenting no macrovascular complications,and 62 patients with DMCs.The expression of miR-129-5p was detected using quantitative real-time polymerase chain reaction.Pearson’s correlation assay was performed to analyze the correlation between serum miR-129-5p levels and clinical indicators.Receiver operator characteristic(ROC)analysis was conducted to analyze the diagnostic value of serum miR-129-5p in patients with DM or DMCs.RESULTS There was a 4.378-fold and 7.369-fold increase in serum miR-129-5p expression in the DM(5.346±0.405)and DMCs(8.998±0.631)groups,respectively(P<0.001),compared with the control group(1.221±0.090).In addition,the expression of serum miR-129-5p in patients with DMCs was higher than that in patients with DM,revealing a 1.683-fold increase(P<0.001).Additionally,serum miR-129-5p expression significantly correlated with smoking history,disease duration,and glycated hemoglobin(HbA1c)in patients with DMCs(P<0.001).The area under the ROC curve(AUC)of miR-129-5p as a serum marker was 0.964(95%confidence interval[CI]:0.930-0.997,P<0.001)in distinguishing between patients with DM and healthy controls,whereas the AUC of miR-129-5p as a serum marker was 0.979(95%CI:0.959-0.999,P<0.001)in distinguishing between patients with DMCs and healthy controls.CONCLUSION Elevated serum miR-129-5p expression levels correlate with the development of DMCs and can be utilized as a novel early diagnostic biomarker for DM combined with macrovascular complications.

Comparing the incidence of major cardiovascular events and severe microvascular complications in patients with type 2 diabetes mellitus:A systematic review and meta-analysis

BACKGROUND Type 2 diabetes mellitus(T2DM)causes both macrovascular and microvascular complications.However,currently,selection of glycemic measures and their thresholds to diagnose T2DM,and efficacy outcomes in evaluation of anti-diabetic drugs is predominantly informed by the relation of T2DM to microvascular complications.We can be severely mistaken on T2DM by neglecting macrovascular complications which are generally more severe,if they also occur more commonly than microvascular complications.AIM To compare the incidence of major cardiovascular events(MACEs)and severe microvascular complications(SMICs)in T2DM patients.METHODS MEDLINE,EMBASE,and Cochrane Central Register of Controlled Trials were searched from inception to September 2017.Cohort studies or trials of T2DM patients aged 18 years or older that reported incidence of both MACEs and SMICs were included.MACEs were defined as nonfatal myocardial infarction and stroke,and cardiovascular death,while SMICs included serious retinopathy,nephropathy and diabetic disorder.The relative risk(RR)was estimated as the incidence of MACEs divided by that of SMICs in same patients and combined with meta-analysis in a random-effect model.RESULTS Twelve studies with a total of 16 cohorts and 387376 patients were included,and the combined RR was 2.02(95%CI:1.46–2.79).The higher incidence of MACEs remained in various subgroup and sensitivity analyses.CONCLUSION Patients with T2DM are much more likely to develop MACEs than SMICs.By taking more serious consequences and relatively higher incidence into consideration,macrovascular complications deserve more emphasis in developing the diagnostic criteria of T2DM and in evaluating the efficacy of antidiabetic drugs.

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.

Interstitial lung disease and diabetes

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence has beensteadily increasing all over the world. DM and its associated micro andmacrovascular complications result in significant morbidity and mortality. Themicrovascular complications are usually manifested as retinopathy, neuropathy,nephropathy and macrovascular complications generally affect the cardiovascularsystem. In addition to these complications, DM also affects the lungs because of itsrich vascularity and abundance in connective tissue (collagen and elastin). DMhas been found to cause microvascular complications and proliferation ofextracellular connective tissue in the lungs, leading to decline in lung function in arestrictive pattern. Interstitial lung disease (ILD) includes a diverse group ofdisease conditions characterized by different degrees of inflammation and fibrosisin the pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of thecommon type of idiopathic interstitial pneumonia with a high mortality rate. IPFis characterized by chronic progressive fibrosis leading to progressive respiratoryfailure. In this review we focus on lung as the target organ in DM and theassociation of DM and ILD with special emphasis on IPF.

Type 2 diabetes and quality of life

It is true that a primary goal of diabetes early diagnosis and treatment is quality of life(QoL). The term QoL is still confusing but it is agreed that it composes of four components:The physical component, mental, cogitative component, psychological and social component. Many articles have been written addressing those four components. During the last five years 15500 articles and reviews have been written addressing diabetes and coronary arterial disease, 16100 addressing diabetes and renal function, 28900 addressing diabetes and retinopathy, 16800 addressing diabetic foot ulcers and other 26300 addressing diabetic neuropathy. Moreover 17200 articles are dealing with diabetic sexual dysfunction, 24500 with the correlation of diabetes and depression 17500 about diabetes and dementia, only 1 about diabetes and family functioning and 1950000 about diabetes and QoL, indicating the worldwide interest. In order to confront this metabolic anomaly and its consequences, researchers developed numerous generic and disease specific psychometric tools. With the aid of those psychometric tools the scientific community has started to realize the gruesome effect of diabetes on patients' lives. Diabetic's QoL becomes worse when complications start to develop or comorbidities coexist. Dominant amongst complications, in health-related quality of life(HRQoL) lowering, but not related to risk factors(genetic, the weight of birth, or others) is coronary arterial disease followed by renal failure, blindness, and the combination of micro-and macrovascular complications and in some studies by sexual dysfunction. Moreover many are the comorbidities which deteriorate further the effect of diabetes in a patient life. Among them obesity, hypertension, dyslipidemia, depression, arthritis are the most common. Most intriguing field for research is the interaction of diabetes and depression and in some cases the progression to dementia. Many aspects and combinations of actions are under researchers' microscope regarding the improvement of HRQoL scores. Until now, the studies performed, have demonstrated little to moderate benefit. More of them are needed to draw safe conclusions on the topic of the best combination of actions to optimize the HRQoL scores.

Glucose intolerance and diabetes mellitus in ulcerative colitis: Pathogenetic and therapeutic implications

Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients.The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification.Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications,with potential clinical impact on the follow up and outcome of patients.These diseases share specific complications,such as neuropathy,hepatic steatosis,osteoporosis and venous thrombosis.It is still unknown whether the coexistence of these diseases may increase their occurrence.Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis.Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging.Corticosteroids are the treatment of choice of active ulcerative colitis.Their use may be associated with the onset of glucose intolerance and diabetes,with difficult control of glucose levels andwith complications in diabetic patients.Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review.

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.

Antiglycating effects of citrus flavonoids and associated mechanisms

Glycation of proteins and DNA forms advanced glycation end products(AGEs)causing cell and tissue dysfunction and subsequent various chronic diseases,in particular,metabolic and age-related diseases.Targeted AGE inhibition includes scavengers of reactive carbonyl species(RCS)such as methylglyoxal(MG),glyoxalase-1 enhancers,Nrf2/ARE pathway activators,AGE/RAGE formation inhibitors and other antiglycatng agents.Citrus flavonoids have demonstrated antioxidant and anti-inflammatory effects and are also found to be effective antiglycating agents.Herein,we reviewed the up to date progress of the antiglycation effects of citrus flavonoids and associated mechanisms.Major citrus flavonoids,hesperedin and its aglycone,hesperetin,inhibited glycation by scavenging MG forming mono-or di-flavonoid adducts with MG,enhanced the activity of glyoxase-1,activated Akt/Nrf2 signal pathway while inhibiting AGE/RAGE/NF-κB pathway,reduced the formation of Nε-(carboxylmethyl)lysine(CML)and pentosidine,inhibited aldol reductase activity and decreased the levels of fructosamine.The antiglycating activity and mechanisms of other flavonoids was also summarized in this review.In conclusion,citrus flavonoids possess effective antiglycating activity via different mechanisms,yet there are many challenging questions remaining to be studied in the near future such as in vivo testing and human study of citrus flavonoids for efficacy,effectiveness and adverse effects of citrus flavonoids as a functional food in managing high levels of AGEs and controlling AGE-induced chronic diseases,diabetic complications in particular.

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.

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.

Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors

AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases.METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated.RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P &#x0003c; 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P &#x0003c; 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c &#x02265; 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) &#x0003c; 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI &#x0003c; 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI &#x0003c; 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38).CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms.