Combined detection of urinary biomarkers noninvasively predicts extent of renal injury in patients with early diabetic kidney disease with kidney qi deficiency syndrome: A retrospective investigation.

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-ß-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.

One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study.

BACKGROUND: The preservation or restoration of ß cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. METHODS: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. RESULTS: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. CONCLUSION: One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet ß cell preservation during the first year after diagnosis compared to standard treatment alone. TRIAL REGISTRATION: ChiCTR2100045434 . Registered on April 15, 2021-retrospectively registered, http://www.chictr.org.cn/.

Association analysis between the tag single nucleotide polymorphisms of DENND1A and the risk of polycystic ovary syndrome in Chinese Han women.

BACKGROUND: The DENND1A gene is one of the most important sites associated with polycystic ovary syndrome (PCOS). We attempted to analyze the correlation between five single nucleotide polymorphisms (SNPs) in the DENND1A gene and the development of PCOS. METHODS: A total of 346 PCOS patients and 225 normal ovulatory women were involved in the case-control study. Clinical variables and hormones were recorded. According to the Hap Map database, five tagging SNPs (rs2479106, rs2768819, rs2670139, rs2536951 and rs2479102) in the DENND1A gene were identified. The TaqMan probe and the PCR-RFLP (restriction fragment length polymorphism) methods were used for revealing these genotypes. TaqMan Genotype Software was used to analyze the alleles of the five SNPs. RESULTS: Linkage disequilibrium and the gene frequency analysis demonstrated that the CCGGG haplotype might increase the risk of PCOS (P = 0.038, OR = 1.89, 95% CI = 1.027-3.481). Significant differences were found in genotypic and allelic distributions at the rs2536951 and rs2479102 loci between PCOS women and controls (P <  0.001). The LH levels and LH/FSH ratios were higher in PCOS patients than in the control group. A detailed analysis revealed that for the rs2479106 locus, these two values were significantly different in the control subjects who had AA, AG and GG genotypes (P = 0.013 and P = 0.007, respectively), and for the rs2468819 locus, these two values were significantly different among the PCOS patients with AA, AG and GG genotypes (P = 0.013 and 0.002, respectively). CONCLUSIONS: The tagging SNPs rs2479106 and rs2468819 in the DENND1A gene are associated with PCOS in the Chinese population, whereas rs2670139, rs2536951 and rs2479102 are not correlated with PCOS in the same population.

Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial.

AIMS/INTRODUCTION: To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. MATERIALS AND METHODS: A total of 85 patients were randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using dual-energy X-ray absorptiometry. RESULTS: Liraglutide and metformin reduced total, trunk, limb, android and gynoid fat mass; this also led to weight reduction. However, gliclazide treatment produced no significant changes in weight or fat mass, likely because reductions in fat mass were concomitant with increases in lean tissue mass. Blood glucose concentrations and glycated hemoglobin levels improved in all treatment arms; levels of the latter were lower in patients treated with liraglutide and metformin. Serum alanine aminotransferase concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase concentrations were reduced only by liraglutide and metformin. In all patients, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with decreases in serum alanine aminotransferase and aspartate aminotransferase levels, whereas reductions in waist circumference were positively correlated with lower serum alanine aminotransferase levels. CONCLUSIONS: Compared with gliclazide, liraglutide and metformin monotherapies result in greater weight loss, reductions in body fat mass, and better blood glucose control among type 2 diabetes mellitus patients with non-alcoholic fatty liver disease. Reductions in weight, fat mass and waist circumference favorably affect hepatic function.

Effects of exenatide versus insulin glargine on body composition in overweight and obese T2DM patients: a randomized controlled trial.

BACKGROUND: Weight loss, especially fat mass reduction, helps to improve blood glucose control, insulin sensitivity, and ß-cell function. This study aimed to compare the effect of exenatide and glargine on body composition in overweight and obese patients with type 2 diabetes (T2DM) who do not achieve adequate glycemic control with metformin. METHODS: We performed a prospective, randomized study of 37 overweight or obese patients with T2DM who had inadequate glycemic control with metformin. The patients were treated with either exenatide or glargine for 16 weeks. Dual-energy X-ray absorptiometry was used to assess body composition. RESULTS: Post-intervention weight, body mass index (BMI), waist circumference, body mass, and fat mass were lower in patients treated with exenatide, while weight and BMI significantly increased with glargine. Reductions in weight, BMI, body fat mass, and percent fat mass (except for gynoid) were greater with exenatide than with glargine, and percent lean tissue (other than the limbs) increased with exenatide. In all body regions except for the limbs, fat mass decreased with exenatide to a greater extent than lean tissue. Glucose control, insulin resistance, and ß-cell function were not different between the treatment groups. CONCLUSIONS: For overweight and obese patients whose T2DM was inadequately controlled with metformin, exenatide and glargine achieved similar improvements in glycemic control, insulin sensitivity, and ß-cell function.However, exenatide produced better weight and fat mass reduction, which were beneficial for blood glucose control. Our findings may guide the selection of appropriate drugs for glycemic and weight control. TRIAL REGISTRATION: NCT02325960, registered 25 December 2014.

Comparison of Glycemic Variability in Chinese T2DM Patients Treated with Exenatide or Insulin Glargine: A Randomized Controlled Trial.

INTRODUCTION: Increasing the frequency of blood glucose monitoring aids the evaluation of glycemic variability and blood glucose control by antidiabetic drugs. It remains unclear, however, whether GLP-1 receptor agonists or basal insulin has a better effect on glycemic variability in type 2 diabetes mellitus (T2DM) patients who are inadequately controlled by metformin. We used a continuous glucose monitoring system (CGMS) to compare patients on a GLP-1 receptor agonist with patients on basal insulin in terms of glycemic variability. METHODS: This prospective randomized study assigned T2DM patients treated with metformin (N = 39) to either exenatide treatment or insulin glargine treatment for 16 weeks. Glycemic variability was assessed using a CGMS; hemoglobin A1c (HbA1c), ß-cell function, weight, body mass index (BMI), and waist circumference were also evaluated. RESULTS: Mean blood glucose level, continuous overlapping net glycemic action, mean amplitude of glycemic excursions, percentage of the time that the blood glucose value was > 10.0 mmol/L, and highest blood glucose level (P  < 0.01-0.05) significantly decreased in both groups. Standard deviation of the mean glucose value, largest amplitude of glycemic excursions, and waist circumference significantly decreased for those treated with exenatide (P  < 0.05), while no changes were observed with insulin glargine treatment. Percentage of the time that the blood glucose value was > 7.8 mmol/L decreased after insulin glargine use (P  < 0.05) but not with the exenatide intervention. Similar decreases in fasting blood glucose and HbA1c and increases in the 1/homeostasis model assessment of insulin resistance, disposition index 30, and disposition index 120 were observed in both groups (P  < 0.01-0.05). Reductions in weight and BMI were greater with exenatide than with insulin glargine treatment (P  < 0.05). CONCLUSIONS: In overweight and obese patients with T2DM inadequately controlled by metformin, exenatide and insulin glargine have similar efficacies in terms of glycemic variability, HbA1c alleviation, and ß-cell function, but exenatide has a greater effect on body weight and BMI.

Multi-glycoside of Tripterygium wilfordii Hook. f. attenuates glomerulosclerosis in a rat model of diabetic nephropathy by exerting anti-microinflammatory effects without affecting hyperglycemia.

Multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) has been proven to be clinically effective in relieving microinflammation in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain unclear. In the process of early DN, microinflammation and activation of p38 mitogen­activated protein kinase (MAPK) and canonical nuclear factor (NF)-κB signaling pathways are the important mechanisms by which hyperglycemia contributes to glomerulosclerosis (GS). Therefore, this study aimed to examine the ameliorative effects of GTW on GS, and then to clarify its anti­microinflammatory mechanisms by inhibiting p38 MAPK and NF-κB signaling activities in the kidney. All rats were divided into 4 groups: the sham group, the sham + GTW group, the vehicle group and the GTW group. The suitable dose of GTW and vehicle were daily administered for 8 weeks after the induction of DN by unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The general status of the rats, biochemical parameters, renal histological changes and macrophages in glomeruli, as well as expression of the key proteins in the p38 MAPK and canonical NF-κB signaling pathways and inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and transforming growth factor (TGF)-ß1 in the kidney were examined, respectively. The results revealed that, GTW improved the general cond-ition and biochemical parameters of the rats, but did not lower blood glucose; GTW attenuated GS and suppressed glomerular microinflammation including the infiltration of ED1+ cells in glomeruli and the protein overexpression of TNF-α, IL-1ß and TGF-ß1 in the kidney; GTW inhibited the protein overexpression of key signaling molecules of p38 MAPK and canonical NF-κB pathways in the kidney including phosphorylated p38 MAPK, phosphorylated inhibitor protein IκB and NF-κB (p65). On the whole, we expounded that GTW, as a natural regulator in vivo, alleviates GS without affecting hyperglycemia, by exerting anti-microinflammatory effects, including reducing macrophage infiltration in glomeruli, suppressing TNF-α, IL-1ß and TGF-ß1 overexpression in the kidney and inhibiting p38 MAPK and NF-κB signaling activities.

Expression and Histopathological Significance of Disabled-2 in Aldosterone-Producing Adenoma.

The current pathological diagnosis of aldosterone-producing adenoma (APA) is challenging because no histological markers of aldosterone production are available in routine practice. A previous study demonstrated that Disabled-2 (DAB2) is a specific marker of the zona glomerulosa (ZG) in rodents. The aim of the present study was to investigate the significance of immunohistochemical staining to detect DAB2 in the adrenal tissue of patients with APA. We investigated the expression of DAB2 in 36 adrenal glands with APA, 23 adrenal glands with cortisol-producing adenoma (CPA), and 33 adrenal glands with non-functioning adenoma (NFA). Immunohistochemical staining was performed using anti-DAB2 antibodies on paraffin-embedded sections. We analysed the expression of DAB2 semi-quantitatively by scoring staining intensity, and assessed the correlation of this information with the clinical findings. DAB2 mRNA expression in adenoma tissues was evaluated by RT-PCR. DAB2 was highly expressed in the ZG in normal human adrenal glands. DAB2 expression was heterogeneous in APA, with spotted, strong staining noted in most samples (25 of 36 APA). CPA and NFA also exhibited extensive low or moderate DAB2 expression. DAB2 mRNA was significantly increased and positively correlated with CYP11B2 in APA (p<0.05). In APA, the DAB2 score adjusted for tumour volume was positively correlated with plasma aldosterone (p<0.05). Patients with low or moderate DAB2 staining more frequently exhibited high blood pressure and were diagnosed at a younger age compared with patients with high DAB2 staining. The present study clearly demonstrates that DAB2 is a specific marker of the ZG in normal human adrenal glands but that DAB2 immunostaining is not sufficiently powerful for histopathological diagnosis of APA. DAB2 might be involved in excessive aldosterone biosynthesis and correlate with specific clinical characteristics of APA patients.

[Pathomechanisms of podocyte injury in diabetic nephropathy and interventional effects of Chinese herbal medicine].

Podocyte injury is closely related to proteinuria in the progress of diabetic nephropathy(DN). The pathological characters of podocyte injury mainly refer to the change of podocyte form and function, including foot process effacement, reduction of podocyte number and density, podocyte apoptosis, podocyte epithelial-mesenchymal transdifferentiation(EMT)and podocyte hypertrophy. These pathological damages are controlled by multiple signaling pathways in the kidney, such as mammalian target of rapamycin(mTOR)/autophagy pathway, transforming growth factor(TGF)-ß1 pathway and Notch pathway. For podocyte injuries induced by high glucose or in murine models of DN, some Chinese herbal medicine(CHM)extracts, such as multiglycoside of Tripterygium wilfordii(GTW), triptolide(TP), astragaloside IV(AS-IV), astragalus polysaccharide(APS)and Panax notoginseng saponins(PNS), have the protective effects in vivo or in vitro. The preliminary studies in China showed that GTW improves podocyte injury in the DN model rats probably through regulating the activity of mTORC1 signaling pathway in the kidney. Therefore, it is the developmental direction for the further study to clarify the interventional effects of CHM based on podocyte injury-related signaling pathway in DN.

Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases. Recently, Huangkui capsule (HKC), a Chinese patent medicine extracted from AM, has been widely applied to the clinical therapy of renal fibrosis in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain ambiguous. The goal of this study is to expound the mechanism in vivo of HKC in order to deepen the understanding of its clinical effects, by using the approaches of contrasting the dose-effects of HKC on oxidative stress (OS) in the kidney compared to α-lipoic acid (LA), and then demonstrating whether and how anti-oxidative properties of HKC or LA might be beneficial for the treatment of renal fibrosis in vivo. MATERIALS AND METHODS: Thirty-three rats were divided into 5 groups, a Sham group, a Vehicle group, a L-HKC group, a H-HKC group and a LA group. The different doses of HKC, LA and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with streptozotocin (STZ) intraperitoneal injections. Rat's general status, biochemical parameters, renal histological changes and OS indicators, as well as the key protein expressions in p38 mitogen-activated protein kinase (p38MAPK)/serine-threonine kinase (Akt) signaling pathways and downstream cytokines including transforming growth factor (TGF)-ß1 and tumor necrosis factor (TNF)-α were examined, respectively. RESULTS: HKC and LA ameliorated body weight, kidney weight, urinary albumin and renal function including blood urea nitrogen and serum uric acid, attenuated renal fibrosis including the cell numbers and extracellular matrix rate in glomerulus, and controlled OS indicators including malondialdehyde, total superoxide dismutase, 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase 4, but did not lower blood glucose in DN model rats. Among them, the anti-renal fibrosis effect of H-HKC was better than that of LA. In addition, HKC simultaneously down-regulated the protein expressions of phosphorylated p38MAPK, phosphorylated Akt (p-Akt), TGF-ß1 and TNF-α in the kidney of DN model rats, unlike HKC, LA only down-regulated p-Akt and TNF-α protein expressions. CONCLUSION: We have demonstrated that HKC, similar to LA, is renoprotective via attenuating OS and renal fibrosis in the DN rat model. The potential mechanisms by which HKC and LA exert their therapeutic effects in vivo are respectively through down-regulating the activation of p38MAPK and/or Akt pathways as well as the expressions of TGF-ß1 and/or TNF-α in the kidney. Our findings thus provide the useful information about a clinical combination of HKC and LA in early DN patients.

[Regulative mechanisms of mammalian target of rapamycin signaling pathway in glomerular hypertrophy in diabetic nephropathy and interventional effects of Chinese herbal medicine].

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.

[Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine].

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.

Haplotype analysis of single nucleotide polymorphisms in anti-Müllerian hormone gene in Chinese PCOS women.

PURPOSE: Anti-Müllerian hormone (AMH) inhibits FSH-stimulated follicle growth and aromatase activity. The three fold higher serum AMH in PCOS patients may account for the increased number of small follicles and androgen level. We attempted to determine whether polymorphisms in AMH gene were associated with PCOS in Chinese han population. METHODS: A case-control study involving 475 PCOS patients and 512 normoovulatory women was conducted. Rs10407022 and rs8112524 were two tagging SNPs selected according to the HapMap database. Taqman assay was used for rs8112524 genotyping, and PCR-RFLP method for rs10407022. RESULTS: No significant difference was found in genotypic or allelic distributions of both of the two SNPs, rs10407022 and rs8112524, between PCOS women and controls. LH level and progesterone level were significantly higher in rs8112524 AA genotype in PCOS group (P = 0.012, 0.014 respectively). TA haplotype might enhance susceptibility to PCOS (P = 0.013, OR = 4.996, 95 % CI = 2.001-5.251), and GA haplotype might be protective (P = 0.000, OR = 0.117, 95 % CI = 0.049-0.417). CONCLUSIONS: Although individual TagSNPs in AMH gene do not affect susceptibility to PCOS, haplotypes of the two SNPs were associated with PCOS risk, as TA haplotype might enhance susceptibility to PCOS and GA inversely.

[Characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy and its regression analysis with traditional Chinese medicine symptom].

To analyze the characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy (DN) and its compliance with traditional Chinese medicine (TCM)symptom, for the sake of providing a basis for clarifying the rules of TCM syndrome differentiation in DN. Adopting the traditional epidemiological retrospective method, thirty-eight TCM syndromes and urinary protein with medium or low molecular weight, as well as urinary enzyme, including 24 h urinary protein (Upro), urinary albumin( UAlb), urinary retinal binding protein( URBP), urinary cystatin C (UCysC), urinary N-acetyl-beta-D-glucosaminidase (UNAG), were collected from 108 patients with stage III DN, and a multiple factor regression analysis between them was conducted. As the results, the levels of Upro, UAlb, URBP, UCysC, and UNAG were increased in 108 patients with stage III DN. Qi-Yin deficiency type was the major type. The level of UAlb in patients with Qi-Yin deficiency type was significantly higher than those without Qi-Yin deficiency type (P < 0.05). The elevation of Upro with the factors as swift digestion with rapid hungering, lassitude and lack of strength, weakness of waist and knees was complied, the elevation of UA1b with the factors as dry mouth with desire to drink, the elevation of URBP with the factors as numbness of extremities, shortness of breath, the elevation of UCysC with the factors as clear urine in large amounts, and the elevation of UNAG with the factors as frequent micturition, were complied respectively. In conclusion, for 108 stage III DN patients. The increase in urinary protein spectrum including UAlb, URBP, UCysC, and UNAG is the major characteristic. Shen and Pi are the major organs related to the appearance of urinary protein; Pi-Shen deficiency is the basic pathogenesis. The level of UAlb is taken as one of the objective syndrome factors for Qi-Yin deficiency type. The levels of UNAG and UCysC are possibly the objective syndrome factors for Shen-Qi deficiency type.