Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

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.

Acute Metabolic Complications of Diabetes in the Oueme-Plateau Provincial Teaching Hospital: Epidemiological, Clinical, Paraclinical and Evolutionary Aspects

Introduction: Diabetes mellitus, a metabolic disease, is now an important public health problem across the world. Our aim was to study the epidemiological, clinical, paraclinical, and evolutionary aspects of acute metabolic complications (AMC) of diabetes in the endocrinology department of the Oueme-Plateau Provincial Teaching Hospital. Methods: This was a descriptive cross-sectional study with data collection based on the medical records of patients presenting with acute metabolic complications of diabetes in the endocrinology department of the Oueme-Plateau Provincial Teaching Hospital during the 3 years study period (from January 2020 to December 2022). Results: Over 788 patients hospitalized during the study period, 157 had an acute metabolic complication of diabetes, which is a hospital prevalence of 19.9%. Among these 157 cases, 140 were suitable for analysis and therefore constituted our study sample. The mean age of the patients was 49.9 ± 14.7 years, with 19 as minimum and 90 years as maximum. Most of them were women (52.4%). Hypertensive diabetics accounted for 54.9% of cases. Ketoacidosis was the most common complication (62.1%), followed by hyperosmolar hyperglycemic syndrome (23.6%) and hypoglycemia (14.3%). Infection (69.3%) and therapeutic noncompliance (22.9%) were the most common triggers. The average length period of their hospital stay was 7.1 ± 5.1 days, and the outcome was satisfactory in 87.9% of the cases. Unfortunately, there were 3.6% deaths during hospitalization. Conclusion: Acute metabolic complications of diabetes were dominated by ketoacidosis. Infection was the dominant factor in decompensation. Therapeutic education of diabetic patients as well as clinical and biological monitoring must be more stringent and rigorous.

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.

Prevalence and risk factors of wound complications after transtibial amputation in patients with diabetic foot

BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

Diabetes mellitus is a prevalent disorder with multi-system manifestations,causing a significant burden in terms of disability and deaths globally.Angio-tensin receptor-neprilysin inhibitor(ARNI)belongs to a class of medications for treating heart failure,with the benefits of reducing hospitalization rates and mortality.This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications,discussing possible physiological and molecular mechanisms,with insights for future applications.

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Ocular Complications in Diabetic Patients: Prevalence, Impact on Quality of Life, and Implications for Healthcare

Introduction: Diabetes, a chronic disease characterized by persistent hyperglycemia, poses a major global health challenge. In Gabon, 10% of the population is affected by this condition, highlighting the need to actively understand and manage it. Ocular complications of diabetes, including diabetic retinopathy, glaucoma, and cataracts, have a devastating impact on patients quality of life and represent a crucial issue for healthcare systems. Methodology: This study conducted in Libreville from February 9, 2022, to April 15, 2022, was cross-sectional, longitudinal, and descriptive, with prospective data collection. Participants were diabetic patients regularly followed in the endocrinology department of CHUL, who were referred for a comprehensive ophthalmological examination at CHUO. Sampling was exhaustive, with strict inclusion criteria aimed at ensuring the representativeness of the study population. Results: The mean age of participants was 57.5 ± 13.2 years with a male-to-female ratio of 0.8. Personal histories were dominated by hypertension, while family histories were dominated by diabetes. Ocular complications of diabetes included refractive disorders (78.9%), cataracts (31.7%), glaucoma (78.9%), and diabetic retinopathy (13.7%). These ocular complications had a significant impact on participants’ quality of life, leading to impaired vision (78.9%), difficulties in carrying out daily activities (62.2%), the need for caregiver assistance (50.3%), high levels of stress and anxiety (68.9%), regular medication intake (71.4%), adherence to a specific diet (55.9%), and frequent blood glucose monitoring (74.5%). Conclusion: This study highlights the major impact of diabetic ocular complications on patients’ quality of life.

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.

Advanced glycation end products:Key mediator and therapeutic target of cardiovascular complications in diabetes

The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in 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.

Effect of resveratrol in gestational diabetes mellitus and its complications

The incidence rate of diabetes in pregnancy is about 20%,and diabetes in pregnancy will have a long-term impact on the metabolic health of mothers and their offspring.Mothers may have elevated blood glucose,which may lead to blood pressure disease,kidney disease,decreased resistance and secondary infection during pregnancy.The offspring may suffer from abnormal embryonic development,intrauterine growth restriction,obesity,autism,and other adverse consequences.Resveratrol(RSV)is a natural polyphenol compound,which is found in more than 70 plant species and their products,such as Polygonum cuspidatum,seeds of grapes,peanuts,blueberries,bilberries,and cranberries.Previous studies have shown that RSV has a potential beneficial effect on complex pregnancy,including improving the indicators of diabetes and pregnancy diabetes syndrome.This article has reviewed the molecular targets and signaling pathways of RSV,including AMP-activated protein kinase,mitogen-activated protein kinases,silent information regulator sirtuin 1,miR-23a-3p,reactive oxygen species,potassium channels and CX3C chemokine ligand 1,and the effect of RSV on gestational diabetes mellitus(GDM)and its complications.RSV improves the indicators of GDM by improving glucose metabolism and insulin tolerance,regulating blood lipids and plasma adipokines,and modulating embryonic oxidative stress and apoptosis.Furthermore,RSV can ameliorate the GDM complications by reducing oxidative stress,reducing the effects on placentation,reducing the adverse effects on embryonic development,reducing offspring's healthy risk,and so on.Thus,this review is of great significance for providing more options and possibilities for further research on medication of gestational diabetes.

Early neonatal complications in pregnant women with gestational diabetes mellitus and the effects of glycemic control on neonatal infection

BACKGROUND Gestational diabetes mellitus(GDM)has become increasingly prevalent globally.Glycemic control in pregnant women with GDM has a critical role in neonatal complications.AIM To analyze the early neonatal complications in GDM,and examine the effect of blood glucose control level on neonatal infection.METHODS The clinical data of 236 pregnant women with GDM and 240 healthy pregnant women and newborns during from March 2020 to December 2021 the same period were retrospectively analyzed,and the early complications in newborns in the two groups were compared.The patients were divided into the conforming glycemic control group(CGC group)and the non-conforming glycemic control group(NCGC group)based on whether glycemic control in the pregnant women with GDM conformed to standards.Baseline data,immune function,infectionrelated markers,and infection rates in neonates were compared between the two groups.RESULTS The incidence of neonatal complications in the 236 neonates in the GDM group was significantly higher than that in the control group(P<0.05).Pregnant women with GDM in the NCGC group(n=178)had significantly higher fasting plasma glucose,2 h postprandial blood glucose and glycated hemoglobin A1C levels than those in the CGC group(n=58)(P<0.05).There were no differences in baseline data between the two groups(P>0.05).Additionally,the NCGC group had significantly decreased peripheral blood CD3^(+),CD4^(+),CD8^(+)T cell ratios,CD4/CD8 ratios and immunoglobulin G in neonates compared with the CGC group(P<0.05),while white blood cells,serum procalcitonin and C-reactive protein levels increased significantly.The neonatal infection rate was also significantly increased in the NCGC group(P<0.05).CONCLUSION The risk of neonatal complications increased in pregnant women with GDM.Poor glycemic control decreased neonatal immune function,and increased the incidence of neonatal infections.

Prevalence and Correlates of Macrovascular Complications at Type 2 Diabetes Diagnosis in a Tertiary Hospital in Yaoundé, Cameroon

Introduction: The presence of vascular complications at type 2 diabetes (T2D) diagnosis is a heavy burden for developing countries. We aimed to determine the prevalence and correlates of macrovascular complications at T2D diagnosis in Yaoundé, Cameroon. Materials and Methods: We conducted a cross-sectional study at the Essos Hospital Center in Yaoundé from January 2017 to June 2021. We recruited patients newly diagnosed with T2D who, simultaneously, with assessed macrovascular complications including stroke, myocardial infarction (MI) and arterial foot ulcer (AFU). Correlates were investigated using Chi square test and logistic regressions. The significance level was set at 5%. Results: In all, 286 newly diagnosed diabetic patients (51.7% being men) were included. The mean age was 52.6 ± 12.3 years. Prevalent cardiovascular risk factors at diabetes diagnosis were a dyslipidemia (63.6%), sedentary lifestyle (57.7%) and family history of type 2 diabetes (51.6%). The prevalence of macrovascular complications was 17.5% with 8.4% stroke, 5.6% myocardial infarction and 3.4% arterial foot ulcer. Hypertension was associated with all macrovascular complications (p Conclusion: Macrovascular complications are frequent at type 2 diabetes diagnosis and are represented by stroke and myocardial infarction in our study, highlighting the importance of cardiovascular risk evaluation and reduction in people with diabetes right from diagnosis.

Balancing act:The dilemma of rapid hyperglycemia correction in diabetes management

The global diabetes surge poses a critical public health challenge,emphasizing the need for effective glycemic control.However,rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications,necessitating a reevaluation of the speed and intensity of glycemic correction.Theories suggest swift blood sugar reductions may cause inflammation,oxidative stress,and neurovascular changes,resulting in complications.Healthcare providers should cautiously approach aggressive glycemic control,especially in long-standing,poorly controlled diabetes.Preventing and managing these complications requires a personalized,comprehensive approach with education,monitoring,and interdisciplinary care.Diabetes management must balance short and longterm goals,prioritizing overall well-being.This editorial underscores the need for a personalized,nuanced approach,focusing on equilibrium between glycemic control and avoiding overcorrection.

Are treatment options used for adult-onset type 2 diabetes mellitus(equally)available and effective for children and adolescents?

Youth-onset type 2 diabetes mellitus(T2DM),influenced by an increase in obesity,is a rising problem worldwide.Pathophysiological mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance,along with increa-sed hepatic fasting glucose production accompanied by inadequate first and second-phase insulin secretion.Moreover,the incretin effect is reduced.The initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes mellitus.Therefore,immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type,while further therapy adjustments are prone to patients’pheno-type.New agents with proven glycemic and beyond glycemia benefits,such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors,used in the adult population of T2DM patients,might become increasingly important in the treatment armamentarium.Moreover,metabolic surgery is an option for markedly obese(body mass index>35 kg/m^(2))children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions fail.In this mini-review,we will discuss the potential of treatment options considering new data available from randomized control trials,including individuals with adult-onset type diabetes mellitus.

Challenges and pitfalls of youth-onset type 2 diabetes

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Metabolic complications of psychotropic medications in psychiatric disorders:Emerging role of de novo lipogenesis and therapeutic consideration

Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical symptoms in patients with PDs,their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes,obesity and non-alcoholic fatty liver disease(NAFLD).The mechanism(s)underlying these metabolic abnormalities is not clear;however,lipid/fatty acid accumulation due to enhanced de novo lipogenesis(DNL)has been shown to reduce membrane fluidity,increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities.Intriguingly,emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity,diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs.In support of this,several adjunctive drugs comprising of anti-oxidants and antiinflammatory agents,that are used in treating PDs in combination with psychotropic medications,have been shown to reduce insulin resistance and development of NAFLD.In conclusion,the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities,and a new avenue for translational research and therapeutic drug designing in PDs.

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.

Type 2 diabetes in children and adolescents:Exploring the disease heterogeneity and research gaps to optimum management

Over the past 20 years,the incidence and prevalence of type 2 diabetes mellitus(T2DM)in children and adolescents have increased,particularly in racial and ethnic minorities.Despite the rise in T2DM in children and adolescents,the pathophysiology and progression of disease in this population are not clearly understood.Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM.Furthermore,the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients,mostly due to the challenges of implementing clinical trials.A better understanding of the mechanisms underlying the development and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies.This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.