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.

Agmatine ameliorates diabetes type 2-induced nephropathy in rats

Objective:To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy.Methods:A single dose of streptozotocin(40 mg/kg)coupled with a fructose diet induced diabetes in Wistar rats.Agmatine(40 and 80 mg/kg)was administered to rats for 12 weeks.The body weight and fasting blood glucose were measured weekly.Insulin level,urine output,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C were also determined at the end of the experiment.Furthermore,superoxide dismutase,glutathione,interleukin-1β,interleukin-6,and tumor necrosis factor-alpha were evaluated in kidney tissue.Histopathological study was also performed using hematoxylin and eosin staining.Results:Agmatine at both doses significantly increased final body weight,and lowered fasting blood glucose,urine output,insulin,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C levels compared with the diabetic group(P<0.05).Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats.Moreover,the histopathological changes in renal structure were ameliorated by agmatine treatment.Conclusions:Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress.The molecular mechanisms of its nephroprotective actions need to be investigated in future study.

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.

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Mizagliflozin ameliorates diabetes induced kidney injury by inhibitor inhibit inflammation and oxidative stress

BACKGROUND Mizagliflozin(MIZ)is a specific inhibitor of sodium-glucose cotransport protein 1(SGLT1)originally developed as a medication for diabetes.AIM To explore the impact of MIZ on diabetic nephropathy(DN).METHODS Diabetic mice were created using db/db mice.They were administered either a low dose(0.5 mg/kg)or a high dose(1.0 mg/kg)of the SGLT1 inhibitor MIZ via stomach gavage for 8 weeks.Subsequently,mesangial cells(MCs)were isolated and subjected to high glucose conditions in culture to assess the effects of MIZ on DN.RESULTS The results showed that low doses of MIZ significantly reduced albuminuria to a level comparable to that achieved with high doses in db/db mice.High doses of MIZ led to a substantial increase in body weight in mice,along with decreased blood glucose levels and food intake.Moreover,the intervention with high-dose MIZ notably decreased the expression of extracellular matrix genes,such as collagen type 1 alpha 1 mRNA levels.While the expression of SGLT1 increased after exposure to high glucose,it decreased following treatment with MIZ.Furthermore,MIZ intervention was more effective in improving lactate dehydrogenase levels in MCs induced by high glucose compared to canagliflozin.MIZ also significantly elevated levels of antioxidant enzymes superoxide dismutase,catalase,and glutathione,while reducing malondialdehyde levels.CONCLUSION These findings indicate that MIZ can ameliorate DN by inhibiting SGLT1,inflammation,and oxidative stress.

Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.

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.

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.

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.

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.

Study of Lipid Abnormalities in Type 2 Diabetes Mellitus Patients with Nephropathy in Eastern India

Background: Diabetic nephropathy is one of the major complications of diabetes. Nephropathy patients must be evaluated for dyslipidemia as it is an established risk factor for cardiovascular events. We compared the degree of dyslipidemia among type 2 diabetes mellitus (T2DM) subjects with or without nephropathy and analyzed the factors associated with nephropathy among them. Methods: In this retrospective study, T2DM patients with overt nephropathy were enrolled in the study group (n = 50);without nephropathy were enrolled in the control group (n = 50). Both groups were matched for age duration of diabetes. After taking informed consent anthropometrical clinical examinations were done. Biochemical investigations (Total cholesterol, TG, HDL, LDL, VLDL, sdLDL-C, S. urea, S. creatinine were done in SCB MCH, Biochemistry department. Urine microalbumin per gm of creatinine was done. TG/HDL-C ratio, a surrogate marker for small, dense, LDL particles (sdLDL), and estimated glomerular filtration rate (eGFR) were calculated using equations. Results were analyzed statistically using SPSS version 20. Results: Mean Total cholesterol, TG, LDL, sdLDL are significantly high in nephropathy patients with p values 0.026, 0.012, 0.014, 0.04 respectively. Estimated GFR has a significant positive correlation with TCHOL (r = &minus;0.850, p = 0.01), TG (r = &minus;0.14, p = 0.008), LDL (r = &minus;0.62 p = 0.037). Estimated GFR has a significant negative correlation with S. urea (r = &minus;0.587, p ≤ 0.01), S. creatinine (r = &minus;0.59, p ≤ 0.01), UACR (r = &minus;0.47, p ≤ 0.01). Dyslipidema sdLDL is significantly more in nephropathy group in comparison to diabetic group with p values 0.033, 0.045 respectively. Conclusion: Our study shows that dyslipidemia was highly prevalent among subjects with nephropathy. So cardiovascular risks can be averted by regular screening for dyslipidemia in diabetic nephropathy patients.

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.

益肾健脾通络方调节Th17/Treg失衡改善DKD小鼠肾损伤的作用机制研究

目的:探讨益肾健脾通络方对糖尿病肾脏病(DKD)小鼠辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡及Notch信号通路的影响。方法:SPF级雄性C57BL/6N小鼠60只,随机选取10只为正常对照组,剩余50只小鼠腹腔注射链脲佐菌素构建DKD小鼠模型。将造模成功的小鼠随机分为5组,分别为模型组、厄贝沙坦(25 mg/kg)组及益肾健脾通络方高(生药5.2 g/kg)、中(生药2.6 g/kg)、低(生药1.3 g/kg)剂量组。各组小鼠均每天固定时间灌胃给药,连续12 w,正常对照组和模型组灌胃相应体积生理盐水。生化分析仪检测各组小鼠FBG、HbA1c、TC、LDL、Scr、BUN及尿液中mALB、UTP水平;通过HE、Masson、PAS染色观察小鼠肾组织病理学变化;ELISA检测血清NGAL、Lp-PLA2水平;流式细胞术检测外周血单个核细胞中Th17、Treg细胞的比例;Western Blot检测肾组织中Notch信号通路的Notch1、Jagged1蛋白表达。结果:给药12 w后,与正常对照组比较,模型组小鼠肾组织系膜细胞空泡化,大量肾小管管腔肿胀破裂,基底膜增厚;FBG、HbAIc、TC、LDL、Scr、BUN、NGAL、Lp-PLA2和尿液中mALB、UTP水平及肾组织中Notch1、Jagged1蛋白表达显著升高,Treg比例显著降低,Th17比例显著升高(P<0.05)。与模型组比较,厄贝沙坦组和益肾健脾通络方高剂量组肾组织病理损伤明显改善;FBG、HbAIc、TC、LDL、Scr、BUN、NGAL、Lp-PLA2和尿液中mALB、UTP水平及肾组织中Notch1、Jagged1蛋白表达显著降低,Treg比例显著升高,Th17比例显著降低(P<0.05)。高剂量益肾健脾通络方的作用与厄贝沙坦相当。结论:益肾健脾通络方可能通过抑制Notch信号通路调节Th17/Treg失衡,减轻DKD小鼠肾损伤。

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.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Diversity of Intestinal Flora in Elderly Patients with Type 2 Diabetes Mellitus with Early Nephropathy

Objective:To investigate the intestinal flora in elderly patients with type 2 diabetes mellitus with early nephropathy.Methods:43 elderly patients with type 2 diabetes mellitus with early nephropathy(diabetic nephropathy group)and 51 elderly patients with type 2 diabetes mellitus(type 2 diabetes mellitus group)admitted to our hospital from January 2021 to October 2022 were retrospectively analyzed,with 39 healthy people who underwent a physical examination in our hospital during the same period as the control group.The fecal specimens of the three groups were collected,and the 16S rDNAs of bacteria in the fecal samples were extracted,amplified,and sequenced for intestinal flora operational taxonomic unit(OTU)classification and Alpha diversity analysis.Results:(1)Intestinal flora OTUs:there were 545 intestinal flora OTUs unique to the control group,424 intestinal flora OTUs unique to diabetic nephropathy,and 321 intestinal flora OTUs unique to the type 2 diabetes group.There were 403 intestinal flora OTUs common to the control group and diabetic nephropathy group,256 intestinal flora OTUs common to the control group and type 2 diabetes group,and 298 intestinal flora OTUs common to the type 2 diabetes group and diabetic nephropathy group.235 intestinal flora OTUs were common to all 3 groups of subjects.(2)Alpha diversity:The statistical analysis indicated that there was a statistically significant difference(P<0.05)in the Alpha diversity of intestinal flora,as assessed by the Ace index and Simpson’s index,among the three subject groups.However,no statistical significance(P>0.05)was observed when comparing the Chao 1 index and Shannon index.Further observation of the Ace index and Simpson index in the three groups revealed that both the diabetic nephropathy group and the type 2 diabetes mellitus group had lower values than the control group.Conclusion:The diversity of intestinal flora decreases in elderly patients with type 2 diabetes mellitus with early nephropathy.

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.

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.

Antidiabetic effects of Tetracarpidium conophorum seed on biomarkers of diabetes-induced nephropathy in rats

Objective:To investigate antidiabetic effects of Tetracarpidium conophorum seed(TECOSE)against biomarkers of diabetes-induced nephropathy in rats.Methods:Powdered seed(500 g)of TECOSE was extracted with 5 L of 100%methanol for 72 h followed by concentration of filtrate.Diabetes was induced in rats with 75 mg/kg body weight intraperitoneal streptozotocin.The rats were randomly divided into five groups(n=5 in each group)namely group A-normal control,group B-diabetic control,groups C,D and E were diabetic rats treated with 500 mg/kg body weight TECOSE orally,7 mg/kg body weight metformin orally and subcutaneous 0.3 IU/kg body weight Humulin^R,respectively.All rats were treated once daily for 2 weeks.Blood samples and urine were collected for biochemical estimations.Kidney was harvested for histomorphological studies.Results:TECOSE(500 mg/kg body weight)significantly(P<0.05)reduced blood sugar levels as effective as metformin and insulin.The plant extract also significantly(P<0.05)reduced levels of serum urea,creatinine and uric acid,proteinuria,ketonuria,hematuria and glycosuria while it significantly(P<0.05)increased glomerular filtration rate.Histomorphological study of the kidney of untreated diabetic rats showed features suggestive of glomerulosclerosis and tubular necrosis while that of treatments with TECOSE extract,metformin and insulin showed near normal histoarchitectures.Conclusions:Streptozotocin at 75 mg/kg body weight induces diabetic nephropathy in rats and TECOSE possesses potentials to prevent diabetic renal damage.

Evaluation of Type of Nephropathy in Patients of Type-2 Diabetes Mellitus

Background of the Study, Aims and Objectives: There are very few studies on histological patterns of diabetic nephropathy in our part of country. The aim of this study was to evaluate the renal involvement in patients with Type-2 diabetes mellitus (T2DM), assess the histopathological changes and establish a clinico-pathological correlation. Subjects, Method and Materials: Thirty two Type 2 DM patients with nephropathy, after screening consecutive hundred(100) Type 2 Diabetics admitted to the Medicine Department were evaluated for renal involvement by kidney biopsy and histopathological study. Statistical analysis was done by student’s t-test, chi-square and linear regression analysis. Results: Thirty two patients (32) with diabetic nephropathy (20 males and 12 females) formed the study group out of hundred (100) consecutive Type-2 diabetes mellitus patients (58 males and 42 females) admitted to Medicine Department of SCB Medical College Hospital, Cuttack. The frequency of occurrence of clinical diabetic nephropathy was 32%. Most of the patients were having duration of DM of 6-10 years (87.5%). Pedal edema was found in 96.87%, hypertension in 87.5% patients respectively. Regression analysis showed that durations of DM and HbA1c were the two significant risk factors (P Histopathologically, diffuse glomerulosclerosis was the most common form of renal abnormality found in 93.75% followed by nodular glomerulosclerosis in 62.50% with overlap in many patients, membranous nephropathy in 12.5% and focal necrotising glomerulonephritis in 6.25% respectively. There was no statistically significant clinicopathological correlation observed between clinical and biochemical parameters in patients harbouring the two predominant histological types of nephropathy i.e. diffuse and nodular glomerulosclerosis with respect to age, sex, duration of diabetes, body mass index, systolic blood pressure, HbA1c, 24 hour urinary protein, creatinine clearance, serum urea, serum creatinine or lipid profile. Conclusion: Durations of diabetes and HbA1c were found to be strongly associated with development of diabetic nephropathy. Diffuse glomerulosclerosis was the most common form of renal abnormality found in 93.75% followed by nodular glomerulosclerosis in 62.50% of patients.