Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.

Tiliroside protects against diabetic nephropathy in streptozotocininduced diabetes rats by attenuating oxidative stress and inflammation

BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria.AIM To investigate Tiliroside's(Til)protective effect against diabetic nephropathy(DN)in rats under diabetic conditions.METHODS Five groups of six rats each were included in this study:Rats treated with DMSO by intraperitoneal injection as controls,those treated with STZ by intraperitoneal injection,those treated with STZ+Til(25 mg/kg body weight[bwt])or Til(50 mg/kg bwt),and those treated with anti-diabetic medication glibenclamide(600μg/kg bwt).Biochemical markers,fasting blood glucose,food intake,kidney weight,antioxidant enzymes,inflammatory and fibrotic markers,and renal injury were monitored in different groups.Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers.RESULTS Til significantly reduced biochemical markers,fasting blood glucose,food intake,and kidney weight and elevated antioxidant enzymes in diabetic rats.It also mitigated inflammatory and fibrotic markers,lessened renal injury,and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis.CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment,highlighting its promise for future drug development.

Alleviating effects and mechanisms of action of large-leaf yellow tea drinking on diabetes and diabetic nephropathy in mice

Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.

Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats

Diabetic nephropathy is a major cause of end-stage renal disease （ESRD） in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin （90 mg/kg） in neonatal rats and then these rats were treated with rosiglitazone （1.0 mg/kg） in combination with glimepiride （0.5 mg/kg） or with pioglitazone （2.5 mg/kg） in combination with glimepiride （0.5 mg/kg）. Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.

Association of XbaI GLUT1 Polymorphism with Susceptibility to Type 2 Diabetes Mellitus and Diabetic Nephropathy

Objectives: Diabetic nephropathy (DN) is one of the chronic microangiopathic complications of type 2 diabetes (T2DM) and has become the most frequent cause of end-stage renal disease. The XbaI polymorphism in the glucose transporter (GLUT1) has been suggested in the development of DN. We examined the association between XbaI polymorphism of GLUT1 and susceptibility to T2DM and development of DN. Methods: The study included 227 T2DM patients divided into 107 without DN (DM ? DN) and 120 with DN (DM + DN), in addition to 100 apparently healthy controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The GLUT1 XbaI T allele was associated with increased susceptibility to T2DM, when comparing the healthy controls to the whole diabetic group, odds ratio (OR) = 1.899, 95% confidence interval (CI) (1.149 - 3.136), p = 0.011. This association was also significant between healthy controls and DM ? DN OR = 1.997 (1.079 - 3.699), p = 0.026 as well as between healthy controls and DM + DN OR = 1.818 (1.016 - 3.253), p = 0.042. However there was no significant association of XbaI polymorphism with DN when comparing DM ? DN to DM + DN OR = 0.910 (0.474 - 1.747), p = 0.777. Conclusion: XbaI T allele is associated with increased susceptibility to T2DM, but not to development of DN. Further studies are needed to replicate such findings.

RELATION OF HYPERTENSION TO DIABETIC NEPHROPATHY IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS—A PAIR-MATCHED CASE-CONTROL STUDY

To assess the role of hypertension and family history of hypertensio n in the development of nephropathy in patients with non insulin dependent dia betes mellitus (NIDDM).Methods. A retrospective analysis was done on 2 groups of NIDDM patients, one g roup without proteinuria (urine protein< 300mg/24h, n=106) and the other group w ith proteinuria (urine protein≥500mg/24h, n=106). The 2 groups were matched by age(≤±3yrs), sex, ethnic and resident place. Some information of these subject s including demographic; history of disease, family history of diseases, lifesty le and behavior style variables was obtained by questionnaire; some variables w ere measured, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), quantity of protein in 24h urine. Then condi tional logistic regression analysis was performed.Results. Some factors, including history of hypertension, longer duration of hy pertension, higher levels of the past highest SBP and DBP, were independently as sociated with the occurrence risk of diabetic nephropathy (DN). Their correspond ing odd ratios (OR) with 95% confidence intervals (CI) were 2.00(1.17～3.43), 1 .25(1.08～1.46), 1.38(1.15～1.66), and 1.33(1.09～1.62) respectively, but family history of hypertension was not significantly associated with the development o f DN. When the above mentioned relations were respectively adjusted by some pos sible confounding factors, they still existed.Conclusions. History of hypertension, longer duration of hypertension, higher l evels of the past highest SBP and DBP are independent risk factors for DN in Chi nese NIDDM patients.

Relationship Between Postprandial Blood Glucose,Fasting Insulin,and Glycated Hemoglobin Levels and Early Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects.The patients were divided into two groups according to the urinary albumin excretion rate(UAER),with 53 cases in the type 2 diabetes group(UAER<30μg/min)and 43 cases in the early diabetic nephropathy group(30μg/min≤UAER<300μg/min).PBG,FINS,and HbA1c levels were detected in 87 healthy patients.Results:The levels of PBG,FINS,and HbA1c in the early diabetic nephropathy group were higher than those in the control group(P<0.01)and the type 2 diabetes group(P<0.01).Conclusion:PBG,FINS,and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes;thus,controlling the levels of PBG,FINS,and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.

Association of Interleukin-6-174G/C Polymorphism with the Risk of Diabetic Nephropathy in Type 2 Diabetes:A Meta-analysis

Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.

Review on correlation between MiRNA-192 and the pathogenesis of diabetes and treatment progress of diabetic nephropathy

Diabetic nephropathy is a major microvascular complication of diabetes,and it is one of the most common causes of the development of end-stage renal disease in patients with diabetes.MicroRNA is a kind of non-coding single-stranded small molecule RNA,and miRNA-192 is highly expressed in the kidney and plays an important role in the development of diabetic nephropathy.This article reviews the pathogenesis of diabetic nephropathy,the mechanism of action of miRNA-192,and the treatment progress of diabetic nephropathy in order to provide new clues for the diagnosis and treatment of diabetic nephropathy.

Correlation between plasma endostatin and risk of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus and its predictive value

Objective:To explore the plasma endothelium inhibition and type 2 diabetes mellitus patients with Diabetic Nephropathy the correlation between risk and its predictive value.Methods:From January 2015 to January 2017, 202 cases of type 2 diabetes mellitus patients diagnosed and treated in our hospital were selected and divided into observation group and control group according to DN occurrence during follow-up, general data and blood biochemical indexes before treatment were compared between the two groups, Logistic regression was used to analyze independent risk factors of DN, and ROC curve was used to evaluate the predictive effectiveness of different indicators on DN occurrence.Results: A total of 35 developed DN In this study. The mean arterial pressure, HbA1c, UACR and endostatin in observation group were significantly higher than control group, GFR in observation group was significantly lower than control group, multivariate Logistic regression showed that GFR was an independent protective factor for DN, and HbA1c, UACR and endostatin were independent risk factors for DN, The best cut-off point for endostatin prediction of DN occurrence was 43.29 ng/mL, and the AUC was 0.890, significantly better than GFR, HbA1c and UACR, the sensitivity was 85.71%, significantly better than other indicators.Conclusions: Endostatin was significantly associated with DN risk in patients with type 2 diabetes mellitus and had good predictive efficacy.

Inhibition of renin activity by aliskiren ameliorates diabetic nephropathy in type 1 diabetes mouse model

Renin is the rate-limiting enzyme of the reninangiotensin system (RAS). In addition to its enzymatic activity to generate angiotensin I, renin also signals through the (pro)renin receptor to exert angiotensin II-independent effects. In this study we examined the effect of renin inhibition on the development of diabetic nephropathy. Male DBA/2J mice were induced to diabetes with streptozotocin, and the diabetic mice were treated for 16 weeks with saline or aliskiren, a renin enzymatic inhibitor. Aliskiren treatment had little effects on blood glucose and blood pressure in diabetic mice. Saline-treated mice developed progressive albuminuria and glome-rulosclerosis, and aliskiren treatment effectively alleviated albumiuria and glomerulosclerosis. Morphologically aliskiren treatment prevented the thickening of the glomerular basement membrane and reduced podocyte loss. At the molecular levels, aliskiren prevented the decline of slit diaphragm proteins and blocked the synthesis of extracellular matrix and pro-fibrotic factors in the diabetic kidney. Aliskiren treatment results in compensatory renin increase in the glomeruli due to blockade of the negative feedback loop, and also partially suppressed the intracellular signaling mediated by the (pro)renin receptor activated in hyperglycemia. These observations suggest that the therapeutic activity of aliskiren to prevent diabetic renal injury is contributed by inhibition of both the angiotensin II-dependent and -independent pathways. Taken together, it is concluded that inhibition of renin enzymatic activity ameliorates diabetic renal injury in type 1 diabetes, and support the use of aliskiren in diabetes kidney disease.

New perspectives in the management of diabetic nephropathy

Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.

Unleashing the pathological role of epithelial-to-mesenchymal transition in diabetic nephropathy: The intricate connection with multifaceted mechanism

Renal epithelial-to-mesenchymal transition(EMT)is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells,resulting in renal abnormalities,including fibrosis.EMT can cause diabetic neph-ropathy through triggering kidney fibrosis,inflammation,and functional impair-ment.The diverse molecular pathways that drive EMT-mediated renal fibrosis are not utterly known.Targeting key signaling pathways involved in EMT may help ameliorate diabetic nephropathy and improve renal function.In such settings,un-derstanding precisely the complicated signaling networks is critical for develo-ping customized therapies to intervene in EMT-mediated diabetic nephropathy.

Efficacy of a Diabetes Specific Nutritional Supplement (DSNS) on Glycemic Response in Prediabetic Adults: A Two-Armed, Open-Labelled Randomized Controlled Study

It is well known that Diabetes Specific Nutritional Supplements (DSNSs) are linked to improved glycemic control in individuals with diabetes. However, data on efficacy of DSNSs in prediabetics is limited. This was a two-armed, open-labelled, randomized controlled six-week study on 199 prediabetics [30 - 65 years;Glycosylated Hemoglobin (HbA1c) 5.7% - 6.4% and/or Fasting Blood Glucose (FBG) 100-125 mg/dl]. Two parallel phases were conducted: Acute Blood Glucose Response (ABGR) and Intervention phase. Prediabetic participants were randomized into test (n = 100) and control (n = 99). The primary objective was to assess the ABGR of DSNS versus an isocaloric snack, measured by incremental Area under the Curve (iAUC). Test and control received 60 g of DSNS and 56 g of isocaloric snack (cornflakes) respectively, both in 250 ml double-toned milk on visit days 1, 15, 29 and 43. Postprandial Blood Glucose (PPG) was estimated at 30, 60, 90, 120, 150 and 180 minutes. During the 4 weeks intervention phase, the test group received DSNS with lifestyle counselling (DSNS + LC) and was compared with the control receiving lifestyle counselling alone (LC alone). Impact was studied on FBG, HbA1C, anthropometry, body composition, blood pressure, nutrient intake, and physical activity. The impact of DSNS was also studied using CGM between two 14-day phases: CGM1 baseline (days 1 - 14) and CGM2 endline (days 28 - 42). DSNS showed significantly lower PPG versus isocaloric snack at 30 (p 12, and chromium were reported by DSNS + LC versus LC alone. No other significant changes were reported between groups. It may be concluded that DSNS may be considered as a snack for prediabetic or hyperglycemic individuals requiring nutritional support for improved glycemic control.

Establishment of a metabolite diagnostic model for the risk of diabetic nephropathy in type 2 diabetic population:Based on a cross-sectional study in China

Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional investigation was conducted in a hospital setting.Based on medical data,a total of 743 patients from a tertiary hospital were selected and categorized into two groups:the diabetic nephropathy group(DN group)and the non-diabetic nephropathy group(non-DN group).Plasma levels of metabolites,including amino acids and acylcarnitines,were determined using a laser counter measurement system(LC-MS).Subsequently,partial least-squares regression was used to assess the significance of these metabolites.Receiver operating characteristic(ROC)curves were generated for factors that ranked highest in terms of relevance.Model performance was assessed using the curve(AUC).Results:Of the 743 patients with T2DM admitted to the hospital,145 had DN.Compared with the non-DN group,the DN group exhibited elevated systolic blood pressure(P=0.001),high-density lipoprotein cholesterol(P=0.01),and low-density lipoprotein cholesterol(P=0.042).Additionally,the DN group had a higher prevalence of stroke patients(P<0.001)and diabetic retinopathy patients(P<0.001).Finally,a risk model that included citrulline,leucine,tyrosine,valine,propionylcarnitine(C3),and palmitoylcarnitine(C16)was developed.This model achieved an AUC of 0.709,with a 95%confidence interval(CI)ranging from 0.626 to 0.793.Conclusions:A diagnostic model consisting of six plasma metabolites to assess the risk of DN in Chinese patients with T2DM may provide clues for future research.

Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer

BACKGROUND Type II diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with metastases.The effects of T2DM on postoperative chemoresistance rate(CRR)and long-term disease-free survival(DFS)and overall survival(OS)in patients with stage III CC who receive curative resection remain controversial.AIM To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III CC.METHODS This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage III CC from 2018 to 2021.Based on preoperative T2DM history,the patients were categorized into non-DM(n=160)and DM groups(n=118).The latter was further divided into well-controlled(n=73)and poorly controlled(n=45)groups depending on the status of glycemic control.DFS,OS,and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.RESULTS Patients in the DM and non-DM groups demonstrated similar DFS,OS,and CRR(DFS:72.03%vs 78.75%,P=0.178;OS:81.36%vs 83.12%,P=0.638;CRR:14.41%vs 7.5%,P=0.063).Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM(DFS:62.22%vs 78.07%,P=0.021;OS:71.11%vs 87.67%,P=0.011;CRR:24.40%vs 8.22%,P=0.015).High preoperative fasting plasma glucose[DFS:Hazard ratio(HR)=2.684,P<0.001;OS:HR=2.105,P=0.019;CRR:HR=2.214,P=0.005]and glycosylated hemoglobin levels(DFS:HR=2.344,P=0.006;OS:HR=2.119,P=0.021;CRR:HR=2.449,P=0.009)indicated significantly poor prognosis and high CRR,while T2DM history did not(DFS:HR=1.178,P=0.327;OS:HR=0.933,P=0.739;CRR:HR=0.997,P=0.581).CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels,but not T2DM history,were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage III CC.

Association of the glycemic background patterns and the diabetes management efficacy in poorly controlled type 2 diabetes

BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin(HbA1c)≥10%and varying backgrounds of glycemic control.METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months.Participants were categorized into four groups based on prior glycemic history:Newly diagnosed,previously well controlled with recent worsening,previously off-target but now worsening,and HbA1c consistently above 10%.HbA1c levels were monitored quarterly,and patients received medical,educational,and dietary support as needed.The analysis focused on the success rates of good glycemic control and the associated factors within each group.RESULTS The study showed significant improvements in HbA1c levels in all participants.The most significant improvement was observed in individuals newly diagnosed with diabetes:65%achieved an HbA1c target of≤7%.The results varied between participants with different glycemic control histories,followed by decreasing success rates:39%in participants with previously good glycemic control,21%in participants whose glycemic control had deteriorated compared to before,and only 10%in participants with persistently poor control,with mean HbA1c levels of 6.3%,7.7%,8.2%,and 9.7%,respectively.After one year,65.2%of the“newly diagnosed patients”,39.3%in the“previously controlled group”,21.9%in the“previously off-target but now worsened'”group and 10%in the“poorly controlled from the start”group had achieved HbA1c levels of 7 and below.CONCLUSION In poorly controlled diabetes,the rate at which treatment goals are achieved is associated with the glycemic background characteristics,emphasizing the need for tailored strategies.Therefore,different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.

Importance of etiologies of secondary diabetes:How often do we think off in clinical practice?

The article"Secondary diabetes due to different etiologies:Four case reports"by Song et al,published in the World Journal of Clinical Cases,delves into the identi-fication of rare causes of secondary diabetes and emphasizes the necessity for healthcare professionals to recognize these conditions.Failure to do so can result in treatment delays and compromised patient outcomes.The article discusses spe-cific types of diabetes,including maturity onset of diabetes in young,pancreas-related diseases,endocrinopathies,drug-induced diabetes,infections,and con-genital genetic syndromes associated with diabetes mellitus.Case summaries highlight how patients with secondary diabetes,stemming from conditions such as Williams-Beuren syndrome and pituitary adenoma,often exhibit distinct characteristics overlooked in clinical practice.The authors stress the importance of a holistic diagnostic approach and advocate for proactive management through early intervention,including genetic tests and antibody detection.Increased awa-reness and education are crucial for timely identification and proper management,ultimately improving patient well-being.These findings prompt a call to action for healthcare professionals to consider rare causes of secondary diabetes,facili-tating better glycemic control and overall patient care.

Gestational diabetes from A to Z

Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2 DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent welldesigned clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.

The role of innate immunity in diabetic nephropathy and their therapeutic consequences

Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.