Correlation between glycated hemoglobin A1c,urinary microalbumin,urinary creatinine,β2 microglobulin,retinol binding protein and diabetic retinopathy

BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopathy(DR)can be hidden,with few symptoms.Therefore,the preliminary screening of diabetic patients should identify DR as soon as possible,delay disease progression,and play a vital role in its diagnosis and treatment.AIM To investigate the correlation between glycated hemoglobin A1c(HbA1c),urinary microalbumin(U-mALB),urinary creatinine(U-CR),mALB/U-CR ratio,β2 microglobulin(β2MG),retinol binding protein(RBP)and DR.METHODS A total of 180 patients with type 2 diabetes mellitus attending the Second People’s Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists.Based on whether they had combined retinopathy and its degree,68 patients with diabetes mellitus without retinopathy(NDR)were assigned to the NDR group,54 patients with non-proliferative DR(NPDR)to the NPDR group,and 58 patients with proliferative DR to the PDR group.General data,and HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR results were collected from the patients and compared among the groups.Pearson's correlation method was used to analyze the correlation between HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR indices,and multiple linear regression was applied to identify the risk factors for DR.Receiver operator characteristic(ROC)curves were also drawn.RESULTS The differences in age,gender,systolic and diastolic blood pressure between the groups were not statistically significantly(P>0.05),but the difference in disease duration was statistically significant(P<0.05).The differences in fasting blood glucose,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,total cholesterol,and triglyceride between the groups were not statistically significant(P>0.05).HbA1c in the PDR group was higher than that in the NPDR and NDR groups(P<0.05).The levels of mALB,β2MG,RBP,mALB/U-CR and UCR in the PDR group were higher than those in the NPDR and NDR groups(P<0.05).Multiple linear regression analysis showed that disease duration,HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR were risk factors for the development of DR.The ROC curve showed that the area under the curve(AUC)for the combination of indices(HbA1c+mALB+mALB/U-CR+U-CR+β2MG+RBP)was 0.958,with a sensitivity of 94.83%and specificity of 96.72%,which was higher than the AUC for single index prediction(P<0.05).CONCLUSION HbA1c,mALB,mALB/U-CR,U-CR,β2MG and RBP can reflect the development of DR and are risk factors affecting PDR,and the combination of these six indices has predictive value for PDR.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.

Association of NFkB1 Gene Polymorphism with Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with or without Renal Involvement in Eastern India

Aims: To evaluate the association of Nuclear factor kappa B1(NFkB1) gene polymorphism with inflammatory markers Urinary Monocyte Chemoattractant Protein 1 (UMCP1) and Tumor Necrosis Factor alfa (TNF alfa) in Patients of diabetes mellitus with or without renal involvement in Eastern India. Material and Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in between September 2018 to September 2019 were recruited in this study. Patients were subjected to blood and urine investigations. DNA extraction and Restriction fragment Length Polymorphism (RFLP) was done in Department of Biochemistry. Controls were unrelated healthy attendants with no history of Diabetes Mellitus, HTN, Chronic Kidney Disease (CKD). Results: Mean Systolic BP, Fasting Blood Glucose, Post Prandial Blood Glucose, HBA1c, Total Cholesterol were significantly higher in diabetes mellitus and diabetic nephropathy groups than control group. Estimated Glomerular Filtration Rate was significantly lower in diabetic nephropathy (p value < 0.001). UMCP1, Urinary Albumin Creatinine Ratio, TNF alfa were higher in diabetes mellitus and nephropathy with p value (<0.001, 0.006 < 0.001) respectively. In between DM and Diabetic Nephropathy groups nfkb1 gene expression, umcp1 and tnf alfa levels were significantly increased in Diabetic nephropathy with p value 0.019, <0.01, 0.001 respectively. Insertion/insertion NFkB1 gene polymorphisms were more in diabetic nephropathy group and were positively correlated with inflammatory markers UMCP1 (r = 0.517, p < 0.01) and TNF alfa (r = 0.172, p = 0.19). Conclusion: insertion/insertion NFkB1 gene polymorphism increases the risk of nephropathy by 2.52 times (OR = 2.52, 95% CI: 0.04 - 0.63, p value = 0.019) in diabetes patients in eastern India.

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus:a cross-sectional cohort study

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM)and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease(DKD).A total of 390 patients with T2DM were divided into three groups:normal albuminuria(UACR<30 mg/g,n=136,NA),microalbuminuria(UACR at 30-300 mg/g,n=132,MA),and clinical albuminuria(UACR>300 mg/g,n=122,CA).Circulating miR-154-5p,inflammatory(C-reactive protein(CRP);erythrocyte sedimentation rate(ESR);and tumor necrosis factor-a(TNF-α)and fibrotic markers(vascular endothelial growth factor(VEGF);transforming growth factor-β1(TGF-β1);and fibronectin(FN),and other biochemical indicators were assessed via real-time PCR,enzyme-linked immunosorbent assay,and chemiluminescence assay in patients with T2DM and 138 control subjects(NC).UACR,miR-154-5p,glycated hemoglobin(HbA1c),serum creatinine(sCr),blood urea nitrogen(BUN),ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were significantly higher and the estimated glomerular filtration rate(eGFR)was significantly lower in NA,MA,and CA groups than in NC subjects(P<0.05).Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c,sCr,BUN,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN and negatively correlated with eGFR(P<0.05).miR-154-5p,HbA1c,sCr,BUN,eGFR,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were important factors affecting UACR.These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.