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.

Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines

BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.

Sitagliptin in treatment of diabetes complicated by chronic hepatitis C

To the Editor: A high prevalence of glucose intolerance in patients with chronic hepatitis C has been reported, [1] and there is a significant association of chronic hepatitis C with diabetes mellitus (DM). [2] But DM has been suggested to be associated with the onset of hepatocellular carcinoma

COMMENTS ON THE STUDY OF ACUPOINT COMBINATION AND REMEDIES FOR TREATMENT OF DIABETES MELLITUS WITH ACUPUNCTURE AND MOXIBUSTION

In the present paper, the author reviews the progresses in the study on acumoxi (acupuncture-moxi-bustion) treatment of diabetes mellitus (DM) from Chinese ancient classical works, Chinese and foreign journals. The therapeutic results reveal that acupuncture treatment of DM is effective in improving DM patients' symptoms via vagal-nerve reflex, regulation of neuroendocrine and immune functions. The author holds that ① correct selection of acupoints in accordance with syndrome differentiation and the related meridians and combined application of acupuncture and Chinese herbal medicines (for oral administration) are the key points for raising the therapeutic effect; and ② acupoint combination and curative methods need to be researched further.

Gestational diabetes mellitus and COVID-19:The epidemic during the pandemic

During the global coronavirus disease 2019(COVID-19)pandemic,people worldwide have experienced an unprecedented rise in psychological distress and anxiety.In addition to this challenging situation,the prevalence of diabetes mellitus(DM),a hidden epidemic,has been steadily increasing in recent years.Lower-middle-income countries have faced significant barriers in providing accessible prenatal care and promoting a healthy diet for pregnant women,and the pandemic has made these challenges even more difficult to overcome.Pregnant women are at a higher risk of developing complications such as hypertension,preeclampsia,and gestational diabetes,all of which can have adverse implications for both maternal and fetal health.The occurrence of gestational diabetes has been on the rise,and it is possible that the pandemic has worsened its prevalence.Although data is limited,studies conducted in Italy and Canada suggest that the pandemic has had an impact on gestational diabetes rates,especially among women in their first trimester of pregnancy.The significant disruptions to daily routines caused by the pandemic,such as limited exercise options,indicate a possible link between COVID-19 and an increased likelihood of experiencing higher levels of weight gain during pregnancy.Notably,individuals in the United States with singleton pregnancies are at a significantly higher risk of excessive gestational weight gain,making this association particularly important to consider.Although comprehensive data is currently lacking,it is important for clinical researchers to explore the possibility of establishing correlations between the stress experienced during the pandemic,its consequences such as gestational gain weight,and the increasing incidence of gestational DM.This knowledge would contribute to better preventive measures and support for pregnant individuals during challenging times.

Can the management of depression in type 2 diabetes be democratized?

Both type 2 diabetes and depression are common and are projected to increase.There is increasing evidence for a bidirectional relationship between the two.Diabetes is a risk factor for depression;contrariwise,individuals with depression are at greater risk of developing diabetes.They are a burden for both the individual and the society.Co-existent depression worsens diabetic control because of obesity,insulin resistance and the adverse metabolic effects of anti-diabetes medicines.In addition,compliance to lifestyle measures required for diabetes is also compromised such as following a specific diet,taking proper medications on time,getting metabolic parameters assessed and maintaining a sleep cycle.Depression occurs in many grades;mild depression is more common in diabetes than frank or full-blown depression leading to suicide.Unfortunately,there are not enough trained and accessible mental health professionals such as psychologists or psychiatrists to deal with the increasing burden of depression in diabetes.Therefore,alternate models for management of mild to moderate depression are required.There is evidence that a team-approach by employing health care assistants can lower the risk of cardiac risk factors.INtegrating DEPrEssioN and Diabetes treatmENT study was carried out to determine whether the team-approach using non-health care professionals could be effective in managing mild to moderate depression and to study its effects on metabolic parameters among subjects with type 2 diabetes mellitus.The international study,carried out in four independent centers in India assessed the impact of a trained but not qualified non-psychiatrist in coordinating and forming a fulcrum between the patient,the family and the consultant endocrinologist/diabetologist.The interventions were fine-tuned to be culturally appropriate by qualitative interviews before they began.It was shown that the outcomes of both depression and diabetes could be improved by the employment of a clinical care coordinator.It is possible to scale up the studies to wider geographical areas and health-care organizations.

Comparison of Snellen and Early Treatment Diabetic Retinopathy Study charts using a computer simulation

AIM：To compare accuracy,reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study（ETDRS）charts,two main tools used to measure visual acuity（VA）.·M ETHODS：A computer simulation was programmed to run multiple virtual patients,each with a unique set of assigned parameters,including VA,false-positive and false-negative error values.For each virtual patient,assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 log MAR units（equivalent to 20/200 to 20/20）.Each of 30 000virtual patients were run ten times on each of the two VA charts.·RESULTS：Average test duration（expressed as the total number of characters presented during the test±SD）was12.6±11.1 and 31.2±14.7 characters,for the Snellen and ETDRS,respectively.Accuracy,defined as the absolute difference（±SD）between the assigned VA and the measured VA,expressed in log MAR units,was superior in the ETDRS charts：0.12±0.14 and 0.08±0.08,for the Snellen and ETDRS charts,respectively.Reproducibility,expressed as test-retest variability,was superior in the ETDRS charts：0.23±0.17 and 0.11±0.09 log MAR units,for the Snellen and ETDRS charts,respectively.·CONCLUSION：A comparison of true（assigned）VA to measured VA,demonstrated,on average,better accuracy and reproducibility of the ETDRS chart,but at the penalty of significantly longer test duration.These differences were most pronounced in the low VA range.The reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.

TCM Stage Differentiation Treatment of Diabetic Gangrene——An Observation on Microcirculatory Changes

Microcirculatory changes and therapeutic effects in 39 non-insulin dependent diabetes mellitus (NIDDM) cases were evaluated. Under the same basic treatment in both groups, the treatment group (21 cases) was treated with TCM drugs according to its stages and compared with the control group (18 cases, treated with 654-2). The results showed that the microcirculatory cumulative scores were significantly decreased in both groups (P<0.05), but the decrease in the treatment group was more marked (P<0.05). In the treatment group, 15 cases were cured, 3 markedly effective, 2 effective and 1 ineffective; while in the control group, 13 cases were cured, 1 markedly effective and 4 ineffective. Statistically, there is no significant difference between the 2 groups (P>0.05) in therapeutic effects.

Treatment of Painful Diabetic Neuropathy With Catgut-Embedding in Acupoints

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THERAPEUTIC EFFECT OF NON-SURGICAL TREATMENT OF CHRONIC PERIODONTITIS IN DIABETIC CHINESE

Objective To observe the therapeutic effect of non-surgical treatment on diabetic Chinese withchronic periodontitis. Methods Moderate to advanced chronic periodontitis ( CP) was studied in 36 diabetes mellitus (DM) patients classified as 20 with high and fluctuating blood glucose level (DM-H) and 16 with relatively low and stable blood glucose level (DM-L). 28 non-DM CP patients acted as controls (Non-DM). Plaque index (PlI) , gingival index (GI) , bleeding on probing (BOP) , probing depth (PD) and clinical attachment loss (AL) of all patients were recorded at 6 sites on each tooth at the baseline and 1, 3 and 6 months after oral hygiene instruction (OHI), scaling and root planing. Results It was found that the short-term effect of non-surgical periodon-tal procedure had resulted in significant resolution of gingival inflammation and pronounced reduction in pocket depth and gain of attachment loss in both DM and Non-DM CP patients. Conclusion The pilot study suggested that non-surgical periodontal treatment allowed for favorable treatment responses in a group of Chinese diabetic subjects with chronic periodontitis and that their various profiles of blood glucose did not influence the short-term healing response to OHI, scaling and root planning.

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)production and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1a(HIF-1a),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H_(2)O_(2) signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1a,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

Design and analysis of high-risk medical device clinical trials for diabetes monitoring and treatment: a review

Class III medical devices are those devices that support or sustain human life or prevent impairment of human health but,when used,pose high risks to the patients.There were 15 class III medical devices that were approved by the US Food and Drug Administration from September 1,2005 to December 31,2018 for glucose monitoring and diabetes treatment.In this article,we reviewed the study design and statistical analysis in clinical trials that were conducted to provide evidences for safety and effectiveness of these medical devices.Two exemplars of clinical trials for"Eversense continuous glucose monitoring system"and"t:slim X2 Insulin Pump with Basal-IQ Technology"are discussed in details.

Efficacy and safety of puerarin injection in treatment of diabetic peripheral neuropathy: a systematic review and Meta-analysis of randomized controlled trials

OBJECTIVE: To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of diabeticperi pheral neuropathy(DPN).METHODS: Randomized controlled trials investigating the efficacy of puerarin injection on DPN were searched for in China National Knowledge Infrastructure Database, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from establishment to April 30.Two reviewers independently retrieved and extracted the information.The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.2 software.RESULTS: Twenty-two studies involving 1664 participants were included. The quality of the studies was found to be relatively low. Meta-analysis showed that puerarin injection combined with western medication was more effective than conventional therapy for rate, nerve conduction velocity(NCV), and hemorheology index. Six adverse drug reactions(ADRs) from puerarin injection were reported in two studies. Reactions included facial flushing, palpitations, and pain at infusion locations. However,noserious ADRs were reported.CONCLUSION: Puerarin injection was effective for the treatment of DPN. Puerarin can improve the total effective rate, correct NCV that was decreased by diabetes, and improve the hemorheology index.Puerarin was also relatively safe clinically. However,since the articles included in the study were not high-quality, more studies should be conducted to strengthen their findings.

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes:a pilot study

Mesenchymal stem cells(MSC)have been used in clinical trials for severe diabetes,a chronic disease with high morbidity and mortality.Bone marrow is the traditional source of human MSC,but human term placenta appears to be an alternative and more readily available source.Here,the therapeutic effect of human placenta-derived MSC(PD-MSC)was studied in type 2 diabetes patients with longer duration,islet cell dysfunction,high insulin doses as well as poor glycemic control in order to evaluate the safety,efficacy and feasibility of PD-MSC treatment in type 2 diabetes(T2D).Ten patients with T2D received three intravenous infusions of PDSC,with one month interval of infusion.The total number of PDSC for each patient was(1.22–1.51)×10^(6)/kg,with an average of 1.35×10^(6)/kg.All of the patients were followed up after therapy for at least 3 months.A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU(P<0.01),and the C-peptide level was increased from 4.1±3.7 ng/mL to 5.6±3.8 ng/mL(P<0.05)respectively after therapy.In 4 of 10 responders their insulin doses reduced more than 50%after infusion.The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment(P<0.05).No fever,chills,liver damage and other side effects were reported.The renal function and cardiac function were improved after infusion.The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple,safe and effective therapeutic approach for T2D patients with islet cell dysfunction.Further large-scale,randomized and well-controlled clinical studies will be required to substantiate these observations.

Strategies and Methods for the Treatment of Diabetic Neuropathy Using Integrative Chinese and Western Medicine

Diabetic neuropathy （DN） is the most common metabolic neuropathy in clinics, not only in diabetes patients （〉60%）, but also in pre-diabetic （8%） and normal persons （5%）^（1）. Its pathogenesis has not been fully understood up to now. It is generally believed that it is related to the increase in glycation endoproducts （AGEs） caused by hyperglycemia,

Nerve Regeneration Should Be Highly Valued in the Treatment of Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy （DPN） is the most common chronic complication of the long-term complications of diabetes, affecting up to 90% of patients during the progress of the disease. Many parts of the nerve system, including the sensory nerves, motor nerves and autonomic nerves, can be affected, leading to various clinical features.

α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo

Peptides are increasingly important resources for biological and therapeutic development,however,their intrinsic susceptibility to proteolytic degradation represents a big hurdle.As a natural agonist for GLP-1R,glucagon-like peptide 1(GLP-1)is of significant clinical interest for the treatment of type-2 diabetes mellitus,but its in vivo instability and short half-life have largely prevented its therapeutic application.Here,we describe the rational design of a series of a/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists.Certain GLP-1 hybrid analogues exhibited enhanced stability(t_(1/2)>14 days)compared to t_(1/2)(<1 day)of GLP-1 in the blood plasma and in vivo.These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment.Additionally,our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.