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 intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes mellitus

AIM: To evaluate the effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes by comparing the therapeutic effects of intensive and standard treatment in patients with type Ⅱ diabetes. METHODS: A total of 107 patients with type Ⅱ diabetes were randomly assigned into intensive and standard treatment groups. Patients in the intensive treatment group received preterax (perindopril/ indapamide) to control blood pressure, and gliclazide (diamicron) MR to control blood glucose. Patients in the standard treatment group received routine medications or placebo. Urinary microalbumin (UMA), urinary creatinine (UCR), the UMA/ UCR ratio, and visual acuity were monitored according to the study design of the ADVANCE trial. Direct ophthalmoscopy and seven-field stereoscopic retinal photography were used to examine the fundi at baseline,and repeated after 5 years of treatment. RESULTS: The characteristics of patients in both groups were well balanced at baseline. After 5 years of treatment, visual acuity was found to be decreased in the standard group (P=0.04), but remained stable in the intensive group. The severity of diabetic retinopathy had not progressed in patients in the intensive group, but had deteriorated in the standard group (P=0.0006). The UMA/UCR ratio was not obviously changed in patients in the intensive group, whereas it was significantly increased in the standard group (P=0.00). CONCLUSION: Intensive control of blood glucose and blood pressure can decrease the incidence or slow the progression of microvascular complications in patients with type Ⅱ diabetes, and maintain stable vision.

Stationary Treatment Compared with Individualized Chinese Medicine for Type 2 Diabetes Patients with Microvascular Complications:Study Protocol for a Randomized Controlled Trial

Background： Microvascular complications in type 2 diabetes （T2DM）, including diabatic retinopathy （DR）, diabetic kidney disease （DKD）, diabetic peripheral neuropathy （DPN） are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. Chinese medicine （CM） has been widely used for treating diabetic mettitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. Objective： To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. Methods： This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups： DR study group （32 cases） and a corresponding control group （32 cases）, DR＋DKD study group （64 cases） and a corresponding control group （64 cases）, DR＋DPN study group （64 cases） and a corresponding control group （64 cases）, DR＋DKD＋DPN study group （56 cases） and a corresponding control group （56 cases）. The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. Conclusion： This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. （Registration No. ChiCTR-IPR-15007072）

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.

Semaglutide-eye-catching results

Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and,more recently,at higher doses,for the treatment of obesity.Both diseases are reaching epidemic proportions and often coexist,posing patients with a high risk for cardiovascular disease and death.Therefore,an agent such as semaglutide,which offers clinically significant weight loss and cardiovascular benefits,is essential and will be increasingly used in high-risk patients.However,during the SUSTAIN clinical trial program(Semaglutide Unabated Sustainability in treatment of type 2 diabetes),a safety issue concerning the progression and worsening of diabetic retinopathy emerged.The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction,a phenomenon also associated with insulin treatment and bariatric surgery.Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes.In this minireview,we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.

Rapid correction of hyperglycemia:A necessity but at what price?A brief report of a patient living with type 1 diabetes

BACKGROUND The correction and control of chronic hyperglycemia are the management goals of patients living with diabetes.Chronic hyperglycemia is the main factor inducing diabetes-related complications.However,in certain situations,the rapid and intense correction of chronic hyperglycemia can paradoxically favor the onset of microvascular complications.CASE SUMMARY In this case report,we describe the case of a 25-year-old woman living with type 1 diabetes since the age of 9 years.Her diabetes was chronic and unstable but without complications.During an unplanned pregnancy,her diabetes was intensely managed with the rapid correction of her hyperglycemia.However,over the following 2 years,she developed numerous degenerative microvascular complications:Charcot neuroarthropathy with multiple joint involvement,severe proliferative diabetic retinopathy,gastroparesis,bladder voiding disorders,and end-stage renal failure requiring hemodialysis.CONCLUSION In the literature to date,the occurrence of multiple microvascular complications following the rapid correction of chronic hyperglycemia has been rarely described in the same individual.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

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

Angiogenin gene polymorphism A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population?

Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se- quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus （129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa- tients） and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

Effectiveness of quality of care for patients with type 2 diabetes in China:findings from the Shanghai Integration Model(SIM)

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and intermediate outcomes were determined.The patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)years.The percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 years.Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive medication.In conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target level.The percentage of patients who achieved all three target levels needs significant improvement.