OBJECTIVES: The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage. METHODS: A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR. RESULTS: Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage. CONCLUSIONS The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.
Humans ; Diabetes Mellitus, Type 2/complications* ; Creatinine ; Vitamin D-Binding Protein/urine* ; Lipocalin-2/urine* ; Kidney/metabolism* ; Glomerular Filtration Rate ; Biomarkers

To investigate the correlation of serum long noncoding RNA-metastasis associated lung adenocarcinoma transcript 1(LncRNA MALAT1) and serum amyloid A(SAA) with diabetic kidney disease. Retrospective research was used, and 40 patients with type 2 diabetes and 80 patients with type 2 diabetic kidney disease patients who were treated in Tianjin Medical University Chu Hsien-I Memorial Hospital from August 2021 to February 2022 were selected, and 40 healthy subjects were selected during the same period. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect serum LncRNA MALAT1. SAA were detected with enzyme linked immunosorbent assay (ELISA). Automatic biochemistry analyzer was used to detect serum creatinine (CREA) and low-density lipoprotein cholesterol(LDL-C),automatic blood glucose analyzer to detect serum fasting plasma glucose (FPG), automatic glycated hemoglobin analyzer to detect hemoglobin A1C (HbA1c), and automatic immunoassay analyzer to detect urinary albumin to creatinine ratio(UACR). Differences between groups were compared by t test and analysis of variance. Pearson analysis was used to analyze the correlation between MALAT1, SAA and other indicators. Receiver operating characteristic curve(ROC) was used to evaluate the auxiliary diagnostic value of MALAT1 and SAA for diabetic kidney disease. The results showed that MALAT1 and SAA in the diabetic kidney disease with mass albuminuria group were higher than those in the type 2 diabetes mellitus group (q=8.57, P<0.01; q=11.09, P<0.01) and the diabetic kidney disease with microalbuminuria group (q=3.96, P<0.05; q=7.85, P<0.01). MALAT1 had a high correlation with UACR, CREA, SAA, HbA1c and FPG (r value was 0.706, 0.643, 0.578, 0.553, and 0.524, all P<0.01), and SAA had a high correlation with UACR, HbA1c and FPG (r value was 0.664, 0.617, and 0.595, all P<0.01). ROC curve analysis of the diagnostic value of LncRNA MALAT1 and protein SAA for diabetic kidney disease showed that the areas under curve (AUC) were 0.741 and 0.744, respectively. The combined diagnostic value of the two was the greatest (AUC=0.801). In summary, MALAT1 and SAA were elevated in the serum of patients with type 2 diabetes. Their concentrations in the serum of group with diabetic kidney disease were higher than that in the type 2 diabetes group, and the serum concentrations of MALAT1 and SAA in group with mass albuminuria are higher than the group with microalbuminuria. MALAT1 and SAA were both closely related to UACR and HbA1c, and there is a correlation between them. Both of them may have ancillary diagnostic value for diabetic kidney disease.
Humans ; RNA, Long Noncoding/metabolism* ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies/urine* ; Retrospective Studies ; Glycated Hemoglobin ; Serum Amyloid A Protein ; Albuminuria

Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy; however, the underlying mechanism has not been fully elucidated. In this study, we aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules. Methods 8-week-old male db/db mice (n=8), a type 2 diabetic nephropathy model, administered with nuclear factor kappa-B (NF-κB) inhibitor parthenolide (PTN, 1 mg/kg) intraperitoneally every other day for 8 weeks, were as the treatment group. Meanwhile, the age-matched male db/m mice (n=5) and db/db mice (n=8) were treated with saline as the control group and type 2 diabetic nephropathy group. When the mice were sacrificed, blood and urine were collected to examine homeostasis model assessment of insulin resistance (HOMA-IR) and urine albumin creatinine ratio, and kidney samples were used to analyze histopathologic changes with periodic acid-Schiff (PAS) staining, NF-κB p65, phosphorylation of AKT (p-AKT), amnionless and cubilin expressions with immunohistochemistry as well as western blot, and the albumin uptake of renal tubules by using immunofluorescence. In addition, HKC cells were divided into the insulin group treated with insulin alone, the TNF-α group treated with insulin and tumor necrosis factor (TNF-α), and the TNF-α+PTN group exposed to PTN, insulin and TNF-α. The levels of albumin uptake and expression levels of NF-κB p65, p-IRS-1/IRS-1, p-AKT/AKT, amnionless and cubilin in HKC cells were measured. Results Compared with the db/db group, the db/db+PTN group demonstrated decreased levels of HOMA-IR (36.83±14.09 vs. 31.07±28.05) and urine albumin creatinine ratio (190.3±7.3 vs. 143.0±97.6 mg/mmol); however, the differences were not statistically significant (P>0.05). Periodic acid-Schiff staining showed PTN could alleviate the glomerular hypertrophy and reduce the matrix in mesangial areas of db/db mice. The renal expression of NF-κB p65 was increased and p-AKT (s473) decreased in the db/db group compared with the db/m group (P<0.05). PTN significantly reduced the renal expression of NF-κB p65 and ameliorated the decline of p-AKT (s473) compared with the db/db group (P<0.05). Compared with the db/m group, the expression of amnionless and cubilin decreased and albumin uptake in tubules were reduced in the db/db group (P<0.05), and PTN could significantly increase the expression of cubilin (P<0.05), and improve albumin uptake in tubules. Insulin promoted albumin uptake and the expression of amnionless and cubilin in HKC cells (P<0.05). TNF-α stimulated the expression of NF-κB p65, increased p-IRS-1 (s307) and reduced p-AKT (s473) in HKC cells (P<0.05). In the TNF-α+PTN group, the expression of NF-κB p65 declined and p-IRS-1 (s307) and p-AKT (s473) were restored, compared with the TNF-α group (P<0.05). The expression of amnionless and cubilin decreased in the TNF-α group (P<0.05), and PTN could significantly increase the expression of cubilin (P<0.05). Conclusions Inflammation caused damage to insulin signaling, which reduced amnionless-cubilin expression and albumin uptake. PTN could reduce inflammation and remodel the impaired insulin signaling pathway, which promoted the expression of cubilin and albumin uptake. Our study can shed light on the role of inflammation in the reduction of albumin uptake of renal tubules in type 2 diabetic nephropathy.
Albumins/pharmacokinetics* ; Albuminuria/urine* ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Cell Line ; Creatinine/urine* ; Diabetes Mellitus, Type 2/complications* ; Diabetic Nephropathies/metabolism* ; Humans ; Insulin Resistance ; Kidney Tubules, Proximal/metabolism* ; Male ; Mice ; NF-kappa B/metabolism* ; Receptors, Cell Surface/metabolism* ; Sesquiterpenes/pharmacology*

Objective: To explore the relationship between environmental factors as urinary cadmium and type 2 diabetes mellitus (DM) in adults. Methods: Case-control study was adopted, including 166 cases and 427 controls. General characteristics of the subjects were collected by a structured questionnaire. FPG, biochemical indexes and urinary cadmium (UCd) were detected respectively, while UCd was corrected with creatinine. Unconditioned logistic regression model was applied to analyze the relationship between UCd and DM. Results: Levels of UCd appeared higher in cases with the following characteristics as: having primary school education (P=0.016), being female (P=0.013), being non-smokers (P=0.014) or non-alcoholic (P=0.025), and with BMI>25.00 kg/m(2) (P=0.040, P=0.025) than those appeared in the control group. Same results were shown in the 60-69 years (P=0.024) old group. Data from the unconditional logistic regression analysis showed that family history of DM (OR=3.19, 95%CI: 1.45-7.03), education status (OR=1.50,95%CI: 1.08-2.08) and UCd (OR=1.61, 95%CI: 1.08-2.41) were influencing factors on DM. Conclusion: A close association between UCd and DM was noticed. UCd appeared a risk factor on DM that called for setting up related prevention program to reduce the exposure of Cd and to control the risk on DM.
Adult ; Cadmium/urine* ; Case-Control Studies ; China/epidemiology* ; Creatinine ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Humans ; Risk Factors ; Socioeconomic Factors

Biomarkers ; urine ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; pathology ; urine ; Enzyme-Linked Immunosorbent Assay ; Hepatitis A Virus Cellular Receptor 1 ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; urine ; Kidney Diseases ; pathology ; urine ; Lipocalin-2 ; urine ; Membrane Proteins ; urine ; Sialoglycoproteins ; urine ; Tissue Inhibitor of Metalloproteinase-2 ; urine

BACKGROUND: Albuminuria is generally known as a sensitive marker of renal and cardiovascular dysfunction. It can be used to help predict the occurrence of nephropathy and cardiovascular disorders in diabetes. Individuals with prediabetes have a tendency to develop macrovascular and microvascular pathology, resulting in an increased risk of retinopathy, cardiovascular diseases, and chronic renal diseases. We evaluated the clinical value of a strip test for measuring the urinary albumin-to-creatinine ratio (ACR) in prediabetes and diabetes. METHODS: Spot urine samples were obtained from 226 prediabetic and 275 diabetic subjects during regular health checkups. Urinary ACR was measured by using strip and laboratory quantitative tests. RESULTS: The positive rates of albuminuria measured by using the ACR strip test were 15.5% (microalbuminuria, 14.6%; macroalbuminuria, 0.9%) and 30.5% (microalbuminuria, 25.1%; macroalbuminuria, 5.5%) in prediabetes and diabetes, respectively. In the prediabetic population, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ACR strip method were 92.0%, 94.0%, 65.7%, 99.0%, and 93.8%, respectively; the corresponding values in the diabetic population were 80.0%, 91.6%, 81.0%, 91.1%, and 88.0%, respectively. The median [interquartile range] ACR values in the strip tests for measurement ranges of <30, 30-300, and >300 mg/g were 9.4 [6.3-15.4], 46.9 [26.5-87.7], and 368.8 [296.2-575.2] mg/g, respectively, using the laboratory method. CONCLUSIONS: The ACR strip test showed high sensitivity, specificity, and negative predictive value, suggesting that the test can be used to screen for albuminuria in cases of prediabetes and diabetes.
Adult ; Aged ; Aged, 80 and over ; Albumins/*analysis ; Creatinine/*urine ; Diabetes Mellitus, Type 2/pathology/urine ; Female ; Humans ; *Immunoassay ; Male ; Middle Aged ; Prediabetic State/pathology/urine ; Reagent Strips/chemistry

BACKGROUND: With the advent of sodium glucose co-transporter 2 inhibitors to control glucose and treat diabetes, laboratory data aided by either timed or spot glucose levels in the urine could be used as an alternative marker of drug response. The aim of this study was to assess the agreement between overnight urinary glucose excretion (UGE) and morning spot urinary glucose-to-creatinine ratio (UGCR). METHODS: In this prospective cross-sectional study, we enrolled a total of 215 participants with either normal glucose tolerance (NGT), pre-diabetes, or type 2 diabetes mellitus (T2DM). To exclude external factors such as food intake and physical activity, urine samples collected overnight at an 8-hr interval and the first-voided morning spot urine were collected and compared. RESULTS: The median values of overnight 8-hr UGE in participants with NGT (N=14), pre-diabetes (N=41), and T2DM (N=160) were 35.0 mg, 35.6 mg, and 653.4 mg, respectively. In participants with T2DM, the median values of overnight 8-hr UGCR and first-voided morning spot UGCR (M-UGCR) were 1.37 mg/mg and 0.16 mg/mg, respectively. Quantitative analyses using an intraclass correlation coefficient (ICC) demonstrated a good reliability of measurement of the overnight 8-hr UGCR and M-UGCR (ICC=0.943, P<0.001). The M-UGCR was also significantly related to the overnight 8-hr UGE (r=0.828, P<0.001). CONCLUSIONS: M-UGCR and overnight 8-hr UGCR showed good agreement, suggesting that M-UGCR be used as a simple index for estimating overnight amounts of UGE in patients with T2DM.
Adult ; Aged ; Blood Glucose/analysis ; Creatinine/*urine ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/*pathology ; Female ; Glucose/*analysis/metabolism ; Humans ; Linear Models ; Male ; Middle Aged ; Prospective Studies ; Urinalysis

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.
Adult ; Biomarkers/blood ; Body Mass Index ; C-Reactive Protein/analysis ; Chemokines/*blood ; Creatinine/blood/urine ; Diabetes Mellitus, Type 2/*blood/diagnosis ; Female ; Humans ; Insulin/blood ; Intercellular Signaling Peptides and Proteins/*blood ; Intra-Abdominal Fat/*pathology ; Linear Models ; Lipocalins/blood ; Male ; Middle Aged ; Obesity/complications ; Triglycerides/blood

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.
Albuminuria ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Curcumin/*pharmacology ; Diabetes Mellitus, Type 2/*metabolism/urine ; Diabetic Nephropathies/complications/*drug therapy/metabolism/pathology ; Gene Expression/drug effects ; Inflammation ; Kidney/drug effects/metabolism/physiopathology ; Kidney Glomerulus/metabolism/physiopathology ; Lipid Metabolism/*drug effects ; Male ; Malondialdehyde/metabolism/urine ; Oxidative Stress/*drug effects ; Rats ; Rats, Inbred OLETF ; Rats, Long-Evans ; Superoxide Dismutase/metabolism

Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.
Aged ; Albumins/analysis ; Albuminuria/*complications ; Arthritis, Rheumatoid/complications/*diagnosis ; Cardiovascular Diseases/etiology ; Cluster Analysis ; Creatinine/urine ; Diabetes Mellitus, Type 2/complications ; Female ; Humans ; Male ; Middle Aged ; Pulse Wave Analysis ; Risk Factors ; Vascular Stiffness/*physiology