Sodium-glucose Cotransporter-2 Inhibitors induced euglycemic diabetic ketoacidosis:A meta summary of case reports

BACKGROUND Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are commonly prescribed to manage patients with diabetes mellitus.These agents may rarely lead to the development of euglycemic diabetic ketoacidosis(EDKA),which may complicate the disease course of these patients.AIM To analyze the demographic profile,predisposing factors,symptomology,clinical interventions and outcomes of patients presenting with EDKA secondary to SGLT2i use by reviewing the published case reports and series.METHODS We performed a systematic search of PubMed,Science Direct,Google Scholar and Reference Citation Analysis databases using the terms“canagliflozin”OR“empagliflozin”OR“dapagliflozin”OR“SGLT2 inhibitors”OR“Sodium-glucose cotransporter-2”AND“euglycemia”OR“euglycemic diabetic ketoacidosis”OR“metabolic acidosis”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported EDKA secondary to SGLT2i.Furthermore,the data were filtered from the literature published in the English language and on adults(>18 years).We excluded:(1)Conference abstracts;and(2)Case reports or series which did not have individual biochemical data.All the case reports and case series were evaluated.The data extracted included patient demographics,clinical symptomatology,clinical interventions,intensive care unit course,need for organ support and outcomes.RESULTS Overall,108 case reports and 17 cases series with 169 unique patients that met all the inclusion criteria were included.The majority of patients were females(54.4%,n=92),and the commonly reported symptoms were gastrointestinal(nausea/vomiting 65.1%,abdominal pain 37.3%)and respiratory(breathlessness 30.8%).One hundred and forty-nine(88.2%)patients had underlying type II diabetes,and the most commonly involved SGLT-2 inhibitor reported was empagliflozin(46.8%).A triggering factor was reported in most patients(78.7%),the commonest being acute severe infection(37.9%),which included patients with sepsis,coronavirus disease 2019,other viral illnesses,and acute pancreatitis.61.5%were reported to require intensive unit care,but only a minority of patients required organ support in the form of invasive mechanical ventilation(13%),vasopressors(6.5%)or renal replacement therapy(5.9%).The overall mortality rate was only 2.4%.CONCLUSION Patients on SGLT2i may rarely develop EDKA,especially in the presence of certain predisposing factors,including severe acute infections and following major surgery.The signs and symptoms of EDKA may be similar to that of DKA but with normal blood sugar levels,which may make the diagnosis challenging.Outcomes of EDKA are good if recognized early and corrective actions are taken.Hence,physicians managing such patients must be aware of this potential complication and must educate their patients accordingly to ensure early diagnosis and management.

Clinical and biochemical predictors of intensive care unit admission among patients with diabetic ketoacidosis

BACKGROUND Diabetic ketoacidosis(DKA)contributes to 94%of diabetes-related hospital admissions,and its incidence is rising.Due to the complexity of its management and the need for rigorous monitoring,many DKA patients are managed in the intensive care unit(ICU).However,studies comparing DKA patients managed in ICU to non-ICU settings show an increase in healthcare costs without significantly affecting patient outcomes.It is,therefore,essential to identify suitable candidates for ICU care in DKA patients.AIM To evaluate factors that predict the requirement for ICU care in DKA patients.METHODS This retrospective study included consecutive patients with index DKA episodes who presented to the emergency department of four general hospitals of Hamad Medical Corporation,Doha,Qatar,between January 2015 and March 2021.All adult patients(>14 years)fulfilling the American Diabetes Association criteria for DKA diagnosis were included.RESULTS We included 922 patients with DKA in the final analysis,of which 229(25%)were managed in the ICU.Compared to non-ICU patients,patients admitted to ICU were older[mean(SD)age of 40.4±13.7 years vs 34.5±14.6 years;P<0.001],had a higher body mass index[median(IQR)of 24.6(21.5-28.4)kg/m2 vs 23.7(20.3-27.9)kg/m2;P<0.030],had T2DM(61.6%)and were predominantly males(69%vs 31%;P<0.020).ICU patients had a higher white blood cell count[median(IQR)of 15.1(10.2-21.2)×103/uL vs 11.2(7.9-15.7)×103/uL,P<0.001],urea[median(IQR)of 6.5(4.6-10.3)mmol/L vs 5.6(4.0-8.0)mmol/L;P<0.001],creatinine[median(IQR)of 99(75-144)mmol/L vs 82(63-144)mmol/L;P<0.001],C-reactive protein[median(IQR)of 27(9-83)mg/L vs 14(5-33)mg/L;P<0.001]and anion gap[median(IQR)of 24.0(19.2-29.0)mEq/L vs 22(17-27)mEq/L;P<0.001];while a lower venous pH[mean(SD)of 7.10±0.15 vs 7.20±0.13;P<0.001]and bicarbonate level[mean(SD)of 9.2±4.1 mmol/L vs 11.6±4.3 mmol/L;P<0.001]at admission than those not requiring ICU management of DKA(P<0.001).Patients in the ICU group had a longer LOS[median(IQR)of 4.2(2.7-7.1)d vs 2.0(1.0-3.9)d;P<0.001]and DKA duration[median(IQR)of 24(13-37)h vs 15(19-24)h,P<0.001]than those not requiring ICU admission.In the multivariate logistic regression analysis model,age,Asian ethnicity,concurrent coronavirus disease 2019(COVID-19)infection,DKA severity,DKA trigger,and NSTEMI were the main predicting factors for ICU admission.CONCLUSION In the largest tertiary center in Qatar,25%of all DKA patients required ICU admission.Older age,T2DM,newly onset DM,an infectious trigger of DKA,moderate-severe DKA,concurrent NSTEMI,and COVID-19 infection are some factors that predict ICU requirement in a DKA patient.

Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports

BACKGROUND Diabetic ketoacidosis(DKA)manifests as hyperglycemia,metabolic acidosis,and ketosis.However,euglycemic DKA(eu-DKA)conceals severe DKA with glucose levels below 200 mg/dL.Sodium-glucose cotransporter-2(SGLT2)inhibitors can induce eu-DKA in diabetic patients.Notably,coronavirus disease 2019(COVID-19)-infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets.This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis.Additionally,we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors,providing indispensable insights for healthcare professionals managing this specific patient population.AIM To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.METHODS We conducted an exhaustive search across prominent electronic databases,including PubMed,SCOPUS,Web of Science,and Google Scholar.This search encompassed the period from December 2019 to May 2022,incorporating published studies and pre-prints.The search terms employed encompassed“SGLT2 inhibitors”,“euglycemic DKA”,“COVID-19”,and related variations.By incorporating these diverse sources,our objective was to ensure a thorough exploration of the existing literature on this subject,thereby augmenting the validity and robustness of our findings.RESULTS Our search yielded a total of seven case reports and one case series,collectively comprising a cohort of twelve patients.These reports detailed instances of eu-DKA in individuals with COVID-19.Crucially,all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication.Upon admission,all oral medications were promptly discontinued,and the patients were initiated on intravenous insulin therapy to effectively manage the DKA.Encouragingly,eleven patients demonstrated a favorable outcome,while regrettably,one patient succumbed to the condition.Subsequently,SGLT2 were discontinued for all patients upon their discharge from the hospital.These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2,underscoring the critical importance of prompt intervention and vigilant medication adjustments.CONCLUSION Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA,as well as encountering adverse outcomes in the context of COVID-19,despite maintaining satisfactory glycemic control.The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous.Consequently,this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.

Adult Patient with Diabetic Ketoacidosis and Rhabdomyolysis

Rhabdomyolysis, acute kidney injury and diabetic ketoacidosis all are life-threatening conditions. Coincidence of them can be missed because the patient is usually asymptomatic or has mild symptoms related to rhabdomyolysis. The development of rhabdomyolysis as a complication of diabetic ketoacidosis is not well understood and only a few clinical studies address the phenomenon. We are reporting, along with a literature review, a 39-year-old male, who presented with diabetic ketoacidosis complicated with rhabdomyolysis and acute kidney injury. To the best of our knowledge, this is the first case reported in the United Arab Emirates. We highlight the syndrome because it is curable with early detection and proper treatment.

Diagnosis and Treatment of Diabetic Ketoacidosis Mellitus with Guillain-Barré Syndrome: A Case Report

This article reports the diagnosis and treatment of a case of Diabetic ketoacidosis with Guillain-Barré syndrome. Diabetic ketoacidosis (DKA) is the most common acute diabetes mellitus, often diabetes and infection, insulin withdrawal or interruption of the history of triggers, with hyperglycemia, ketoacidosis, and acid poisoning as the main symptoms, rapid onset of ill-ness, and serious illness. Guillain-Barré syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with frequent respiratory or gastrointestinal tract infections and low clinical incidence before 1 - 3 weeks. This case was characterized by a headache with vomiting acute onset, a relatively clear diagnosis of diabetic ketoacidosis, a symmetrical decrease in muscle strength in the extremities, and recovery of consciousness after aggressive correction of environmental disturbance in electrolytes, but very poor muscle strength in the extremities, protein-cell segregation in cerebrospinal fluid (CSF). Considering Guillain-Barré syndrome, the patient’s muscle strength gradually recovered after treatment with proglobulin shock. At present, the pathogenesis of the two is not clear, but because of its rapid progress, clinicians should raise awareness of diabetic ketoacidosis combined with Guillain-Barré syndrome, early diagnosis, and active treatment. Inform consent has been obtained from the patient for this report.

COVID-19 vaccination and diabetic ketoacidosis

An efficient coronavirus disease 2019(COVID-19)vaccine is urgently required to fight the pandemic due to its high transmission rate and quick dissemination.There have been numerous reports on the side effects of the COVID-19 immunization,with a focus on its negative effects.Clinical endocrinology is extremely interested in the endocrine issue that arises after receiving the COVID-19 vaccine.As was already mentioned,after receiving the COVID-19 vaccine,many clinical problems could occur.Additionally,there are some compelling reports on diabetes.After receiving the COVID-19 vaccine,a patient experienced hyperosmolar hyperglycemia state,a case of newly-onset type 2 diabetes.There has also been information on a potential connection between the COVID-19 vaccine and diabetic ketoacidosis.Common symptoms include thirst,polydipsia,polyuria,palpitations,a lack of appetite,and weariness.In extremely rare clinical circumstances,a COVID-19 vaccine recipient may develop diabetes complications such as hyperglycemia and ketoacidosis.In these circumstances,routine clinical care has a successful track record.It is advised to give vaccine recipients who are vulnerable to problems,such as those with type 1 diabetes as an underlying illness,extra attention.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.

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

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

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathwaye

Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.

Global trends in diabetic eye disease research from 2012 to 2021

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

Prognostic Factors for Diabetic Foot at CNHU-HKM

Introduction: Predictions on the prevalence of diabetes mellitus, according to the International Diabetes Federation, indicated 9.3% in 2019 and nearly 10.9% of the general population in 2045. In Benin, the increase in this prevalence, according to the World Health Organization (WHO), is constantly increasing. Diabetic foot is one of its most common complications. The aim of this work was to study the prognostic factors of diabetic foot in the Department of Endocrinology, Metabolism and Nutrition of the CNHU-HKM of Cotonou. Patients and method: This is a descriptive and analytical retrospective study of the prognostic factors of diabetic foot over a period of 3 years from January 2019 to December 2021 in patients who have been hospitalized or followed on an outpatient basis for diabetic foot in the Endocrinology, Metabolism and Nutrition Department of the CNHU-HKM of Cotonou. Results: A total of 112 patients were included in this study. The average age of the patients was 59.70 ± 2.10 years. A male predominance was noted with a sex ratio (M/F) of 1.7. Mixed gangrene and phlegmons were the most common lesions. According to the classification of diabetic feet according to the University of Texas, 59.1% of patients had a 100% risk of amputation. Ten patients died from sepsis (8.9%). The average blood glucose on admission was 2.74 ± 0.23 g/l, reflecting the glycemic imbalance in these patients. There is a statistically significant association between the duration of progression of diabetes, the type of lesion and amputation. Patients whose diabetes has lasted more than 30 years and patients who are not monitored have a greater risk of death. Conclusion: Diabetic patients most often consulted at a late stage, compromising conservative treatment. The duration of diabetes and the type of lesion on admission were the main factors leading to amputation, thus compromising the functional prognosis. As for death, it was mainly linked to irregular monitoring of diabetes and the duration of diabetes. Effective prevention and management of diabetic feet requires patient education about the diabetic foot and systematic screening of at-risk feet in consultation.

Intraocular lens selection in diabetic patients:How to increase the odds for success

The incidence of cataracts is significantly higher in diabetic individuals,particularly in younger age groups,with rates quadrupled in those under 65 and doubled in those over 65 compared to non-diabetics.Cataract surgery in diabetic patients poses many challenges:Poor epithelial healing,decreased corneal sensitivity,increased central corneal thickness,decreased endothelial cell count,variable topography,poor pupillary dilatation,anterior capsular phimosis,posterior capsular opacification(PCO),chances of progression of diabetic retinopathy(DR),zonular weakness,and vitreous prolapse and diabetic macular edema.Selection of an appropriate intraocular lens(IOL)is crucial for visual rehabilitation and monitoring DR.The choice of IOL in diabetic cataract patients is a challenging scenario.Square-edge IOLs are favored for their capacity to mitigate PCO,whereas hydrophilic counterparts may incur calcification in the setting of proliferative DR.The advisability of premium IOLs for achieving spectacle independence warrants judicious evaluation,particularly in the presence of advanced retinopathy.Optimal IOL placement within the capsular bag is advocated to minimize postoperative complications.Rigorous preoperative assessment and informed patient counseling regarding IOL options are indispensable for optimizing surgical outcomes.This review article covers various aspects regarding the choice of IOLs in different case scenarios and complications in the diabetic population.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Impact of COVID-19-related lifestyle changes on diabetic macular edema

AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office visits.METHODS:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021.Period 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was March 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).Main outcome measures included visual acuity,body mass index(BMI),blood pressure(BP),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DME treatment(s)received at each visit.To facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT imaging.RESULTS:There was no change of BMI,systolic BP,and diastolic BP between any of the time periods.HbA1c showed a very small increase from period 1(7.6%)to period 2(7.8%,P=0.015)and decreased back to 7.6%at period 3(P=0.12).Macular thickness decreased for 100%of macular regions.The central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(P=0.0045).After analysis of multiple variables including HbA1c,BMI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in DME.CONCLUSION:DME doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant improvement.While identifying a mechanism behind our findings is beyond the scope of this study,potential explanations may include a delay in retinal changes beyond our study period,an unexpected increase in treatment frequency despite pandemic restrictions,and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.

Surgical management of the diabetic foot:The current evidence

The prevalence of diabetes mellitus and its associated complications,particularly diabetic foot pathologies,poses significant healthcare challenges and economic burdens globally.This review synthesises current evidence on the surgical management of the diabetic foot,focusing on the interplay between neuropathy,ischemia,and infection that commonly culminates in ulcers,infections,and,in severe cases,amputations.The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies,as diabetic foot complications are a leading cause of hospital admissions among diabetic patients,significantly impacting morbidity and mortality rates.This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers,infections,and skeletal pathologies such as Charcot arthropathy,emphasising the critical role of early diagnosis,comprehensive management strategies,and interdisciplinary care in mitigating adverse outcomes.In addressing surgical interventions,this review evaluates conservative surgeries,amputations,and reconstructive procedures,highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies.The integration of advanced diagnostic tools,novel surgical techniques,and postoperative care,including offloading and infection control,are discussed in the context of optimising healing and preserving limb function.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Diabetic Macroangioapathy at the Internal Medicine Department of the Abass Ndao Hospital Center (About 359 Cases)

Introduction: Macroangiopathy plays an important role, with a high prevalence of morbidity and mortality in diabetic patients. The aim was to study the epidemiological, clinical, paraclinical, therapeutic and evolutionary profile of macroangiopathy in diabetic patients in the internal medicine department of the Abass Ndao hospital. Patients and methods: This was a descriptive and analytical cross-sectional study. Our investigations were recruited over a 7-year period (January 1, 2016 to December 31, 2022). Results: Three hundred and fifty-nine (359) patients (10.22%) were enrolled. The mean age was 62.83 years, with extremes ranging from 17 to 98 years. The [60 - 69] age group was more representative (37.32%). Women accounted for 180 cases (50.1%), with a sex ratio (m/f) of 0.99. The average duration of diabetes was 11.86 years. Average consultation time was 38.07 days, with extremes ranging from 1 to 368 days. Average hospital stay was 7.65 days. Inaugural diabetes was noted in 12 cases (3.34%). Type 2 diabetes accounted for 95.82% (n = 344) of patients. Hypertension was present in 150 patients (41.8%). Patients with 2 risk factors accounted for 173 cases (48.18%). Nineteen patients had already had a stroke (5.29% of cases). Fourteen (14) patients (4.2%) were amputees. Obliterative arteriopathy of the lower limbs (AOMI) was noted in 193 patients (54%). Stroke was noted in 101 patients (28%). Ischemic heart disease (IHD) was noted in 38 patients (11%). AOMI was more common in males (110 patients, 57%) than in females (43%). Seventy-three (73) patients (20.3%) died. Predictors of death were age over 60 and the existence of more than two cardiovascular risk factors. Conclusion: Diabetic macroangiopathy is a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.

Retinal vascular morphological characteristics in diabetic retinopathy: an artificial intelligence study using a transfer learning system to analyze ultra-wide field images

AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.

Magnesium promotes vascularization and osseointegration in diabetic states

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.