Correlation of ACR and TcPO2 in diabetic kidney disease patients: A pilot study.

OBJECTIVE: Transcutaneous oxygen pressure (TcPO2) is used to assess microcirculation clinically; however, it is not widely available especially in rural hospital. The study was designed to explore potential alternatively biomarkers to assess microcirculation in diabetic kidney disease (DKD). METHODS: A total of 404 patients from Xuzhou first hospital were recruited according to the case records system. Patients were grouped via the ratio of albuminuria and creatinine (ACR; <30 mg/g, 30-300 mg/g, >300 mg/g). Biomarkers in different ACR groups were compared by analysis of variance. Correlation analysis was determined by Pearson or Spearman analysis and binary logistic regression. The receiver operating characteristics (ROC) curve was performed to elucidate the prediction effect of ACR on TcPO2. RESULTS: A total of 404 diabetic patients were recruited with 248 patients diagnosed as DKD and 156 non-DKDs. Age and cystatin C were significantly higher in the ACR3 group compared with those in the ACR1 group, whereas glomerular filtration rate, low-density lipoprotein cholesterol, and TcPO2 were markedly decreased in the ACR3 group (p < .05). Frequency of low TcPO2 (<40 mm Hg) was markedly increased as increment of ACR stages with 30.2% in the ACR3 group (p < .01). There was a negative correlation between TcPO2 and age, ACR, chronic kidney disease (CKD), fast blood glucose, diabetes mellitus (DM) duration, and diabetic neuropathy. Further, binary logistic regression showed ACR was an independent influence factor for low TcPO2. After adjusting for age, gender, hypertension, DM duration, body mass index, glycated hemoglobin, diabetic neuropathy, and CKD, ACR was still an independent influence factor for TcPO2 (odds ratio = 2.464, p < .01). The area under the ROC curve was 0.768 (95% confidence interval: 0.700-0.836, p < .001) for ACR. The analysis of ROC curves revealed a best cutoff for ACR was 75.25 mg/g and yielded a sensitivity of 71.7% and a specificity of 71.7%. CONCLUSIONS: ACR could be used as an alternative biomarker for assessing microcirculation in DKD patients.

Protective effects of nattokinase against microvasculopathy and neuroinflammation in diabetic retinopathy.

AIMS: Diabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost-effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism. METHODS: A mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood-retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment. RESULTS: NK administration significantly improved the blood-retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes-induced gliosis and inflammatory response and protected retinal neurons from diabetes-induced injury. NK also improved high glucose-induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes-induced inflammation partially by modulating HMGB1 signaling in the activated microglia. CONCLUSIONS: This study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin-induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

Computerized nailfold video-capillaroscopy in type 2 diabetes: A cross-sectional study on 102 outpatients.

BACKGROUND: Type 2 diabetes (T2D) is a chronic disease that negatively affects vascular health. A careful assessment of chronic complications, including microcirculation, is mandatory. The computerized nailfold video-capillaroscopy (CNVC) accurately examines the nailfold microvasculature, but its suitability in T2D is currently under investigation. AIMS: To describe nailfold microvasculature in T2D patients regarding the level of glucose control and chronic microvascular and macrovascular complications. METHODS: This is a cross-sectional study on 102 consecutive and unselected outpatients with T2D who had undergone CNVC examination. The examination was carried out by using an electronic video-capillaroscope with 300x magnification. Capillaroscopic appearance and capillary changes were described according to well-established parameters. Capillaroscopic parameters were compared between patients with poor glucose control (HbA1c ≥7%) and those with better glucose control (HbA1c <7%) and between patients with chronic complications and those without. Chronic complications were deduced from the anamnestic, laboratory, and instrumental data and the five-item International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Nailfold capillaries in patients with HbA1c ≥7% were thicker (p = .019) and longer (p = .021) than in those with better glucose control. Ectasias (p = .017) and microaneurysms (p = .045) were more frequently observed in patients with HbA1c ≥7.0% than those with HbA1c <7.0%. Patients with ED, compared to those without, had a lower frequency of bizarre-shaped capillaries (p = .02). Microaneurysms (p = .02) were more frequently described in patients with carotid stenosis (>20%) than those without. CONCLUSION: Relevant nailfold microvascular alterations were observed in T2D, most of which were associated with poor glycemic control, ED, and carotid stenosis. Further investigation is needed to recognize the role of CNVC in predicting the onset and evolution of chronic complications and monitoring the effectiveness of antihyperglycemic treatments on microcirculation.

Glomerular cell cross talk in diabetic kidney diseases.

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes mellitus. It is the leading inducement of end-stage renal disease (ESRD), and its global incidence has been increasing at an alarming rate. The strict control of blood pressure and blood glucose can delay the progression of DKD, but intensive treatment is challenging to maintain. Studies to date have failed to find a complete cure. The glomerulus's alterations and injuries play a pivotal role in the initiation and development of DKD. A wealth of data indicates that the interdependent relationship between resident cells in the glomerulus will provide clues to the mechanism of DKD and new ways for therapeutic intervention. This review summarizes the significant findings of glomerular cell cross talk in DKD, focusing on cellular signaling pathways, regulators, and potential novel avenues for treating progressive DKD.

C3c deposition predicts worse renal outcomes in patients with biopsy-proven diabetic kidney disease in type 2 diabetes mellitus.

BACKGROUND: Although extensive efforts have been paid to identify reliable predictors for renal outcomes of diabetic kidney disease (DKD) patients in type 2 diabetes mellitus (T2DM), there are still only a limited number of predictive factors for DKD progression. Increasing evidence reported the role of the overactivated complement system in the pathogenesis of DKD. Whether renal complement depositions are associated with renal outcomes of DKD in T2DM is of interest. METHODS: A total of 213 biopsy-proven DKD patients with T2DM were retrospectively recruited. Clinical and pathological data of the patients were analyzed. Kaplan-Meier analysis and Cox regression analysis were performed to explore predictors of end-stage renal disease (ESRD). RESULTS: During a median follow-up of 23.0 (12.0, 39.0) months, 100/213 (46.9%) patients progressed to ESRD. C3c and C1q deposition were observed in 133/213 (62.4%) and 45/213 (21.1%) patients, respectively. Kaplan-Meier analysis revealed patients with C3c or C1q deposition had significantly worse renal outcomes compared with those without C3c or C1q deposition (p = .001 and p < .001, respectively). Univariate and multivariate Cox regression analysis demonstrated proteinuria (per 1 g/24 h increase, hazard ratio [HR] 1.134, 95% confidence interval [CI] [1.079, 1.191], p < .001), interstitial fibrosis and tubular atrophy score (score 2 and 3 vs. 0 and 1, HR 3.925, 95% CI [1.855, 8.304], p < .001), and C3c deposition (per 1+ increase, HR 1.299, 95% CI [1.073, 1.573], p = .007) were independent predictors for ESRD in DKD patients with T2DM. CONCLUSIONS: C3c deposition in the kidney was associated with worse renal outcomes and was an independent predictor for ESRD in DKD patients with T2DM.

A study on the status of normoalbuminuric renal insufficiency among type 2 diabetes mellitus patients: A multicenter study based on a Chinese population.

BACKGROUND: Patients with normoalbuminuria and a reduced estimated glomerular filtration rate (eGFR) account for a considerable proportion of type 2 diabetes patients. The aim of this research was to investigate the epidemiological and clinical characteristics of normoalbuminuric kidney disease in a Chinese population. METHODS: We included 8131 diabetic patients from a multicenter prospective study in China. Based on eGFR and urinary albumin-to-creatinine ratio (UACR), participants were stratified into four groups-normal albuminuria, albuminuria, normoalbuminuria with eGFR < 60 mL/min/1.73 m2 , and albuminuria with eGFR < 60 mL/min/1.73 m2 . Clinical parameters and characteristics of patients with normoalbuminuria and eGFR < 60 mL/min/1.73 m2 were retrospectively analyzed. RESULTS: A total of 1060 out of 8131 individuals with diabetes had decreased eGFR (<60 mL/min/1.73 m2 ). Normoalbuminuria accounted for 63.3% of participants with eGFR < 60 mL/min/1.73 m2 , and microalbuminuria and macroalbuminuria accounted for 30.1% and 6.3%, respectively. Patients with normoalbuminuria and reduced eGFR were more frequently male, older, and had higher levels of triglycerides than patients with normal albuminuria and eGFR. We also detected a correlation between lower extremity arterial disease, newly diagnosed diabetes, and normoalbuminuria-reduced eGFR. Compared with participants with both albuminuria and eGFR decline, those with normoalbuminuria had better metabolic indicators, including systolic blood pressure and glycosylated hemoglobin, and shorter diabetes duration. Even in the normal range, UACR has a significant correlation with the risk of eGFR insufficiency. CONCLUSIONS: Normoalbuminuric renal insufficiency, characterized by male sex, older age, a higher level of triglyceride levels, and a higher risk of lower extremity arterial disease, accounted for a dominant proportion of diabetic patients with eGFR decline.

Effects of SGLT2 inhibitors on patients with diabetic kidney disease: A preliminary study on the basis of podocyturia.

BACKGROUND: The aim of this study was to investigate the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the glomerulus through the evaluation of podocyturia in patients with diabetic kidney disease (DKD). METHODS: The study population was composed of 40 male patients with type 2 diabetes mellitus; 22 of them received SGLT2i (SGLT2i group), and the others who did not were the control. The DKD-related parameters of patients were monitored before SGLT2i initiation, and then in the third and sixth month of the follow-up period. Patients' demographic, clinical, laboratory, and follow-up data were obtained from medical charts. Microalbuminuria was measured in 24-h urine. The number of podocytes in the urine was determined by immunocytochemical staining of two different markers, namely podocalyxin (podx) and synaptopodin (synpo). Concentrations of urine stromal cell-derived factor 1a and vascular endothelial growth factor cytokines were quantified with an enzyme-linked immunosorbent assay kit. RESULTS: At the end of the follow-up period, decreases in glycosylated hemoglobin, glucose, systolic and diastolic blood pressure, uric acid level, and microalbuminuria, and improvement in body mass index level and weight loss were significant for the SGLT2i group. On the other hand, there was no significant difference in terms of these parameters in the control group. The excretion of synaptopodin-positive (synpo+ ) and podocalyxin-positive (podx+ ) cells was significantly reduced at the end of the follow-up period for the SGLT2i group, while there was no significant change for the control. CONCLUSIONS: At the end of the follow-up period, male patients receiving SGLT2i had better DKD-related parameters and podocyturia levels compared to baseline and the control group. Our data support the notion that SGLT2i might have structural benefits for glomerular health.

A novel index, Chinese visceral adiposity index is closely associated with urinary albumin-creatinine ratio in Chinese community adults, especially in hypertensive or hyperglycemic population: Results from the REACTION study.

BACKGROUND: The association between the Chinese Visceral Adiposity Index (CVAI) and urinary albumin to creatinine ratio (UACR) has not been illustrated. The current study aimed to investigate the association between CVAI and UACR and to compare the discriminative power of CVAI, triglyceride, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with UACR in the Chinese community population. METHODS: This study included 34 732 participants from the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. Binary logistic regression analyses were performed to detect the association between CVAI, triglyceride, BMI, WC, WHR and UACR. RESULTS: Binary logistic regression analysis showed that, after adjusting for potential confounders, in women, CVAI (odds ratio [OR]:1.16, 95% confidence interval [CI]: 1.01-1.34) and triglyceride (OR: 1.18, 95% CI: 1.04-1.33) were associated with UACR, whereas BMI, WC, and WHR were not associated with UACR; in men, CVAI (OR: 1.24, 95% CI: 1.02-1.50), WC (OR: 1.21, 95% CI 1.00-1.48), and triglycerides (OR: 1.18, 95% CI 0.97-1.44) were associated with UACR, whereas BMI and WHR were not associated with UACR. Stratified analysis showed that the correlation between CVAI and UACR was stronger in the population with 5.6 ≤ fasting blood glucose (FBG) <7.0 or 7.8 ≤ post-load blood glucose (PBG) <11.1 mmol/L, FBG ≥7.0 or PBG ≥11.1, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. CONCLUSIONS: In the Chinese general population, CVAI and UACR were significantly associated in both genders. At higher CVAI levels, the population with prediabetes, diabetes, and hypertension has a more significant association between CVAI and UACR.

Current gaps in management and timely referral of cardiorenal complications among people with type 2 diabetes mellitus in the Middle East and African countries: Expert recommendations.

The upsurge of type 2 diabetes mellitus is a major public health concern in the Middle East and North Africa (MENA) and Africa (AFR) region, with cardiorenal complications (CRCs) being the predominant cause of premature morbidity and mortality. High prevalence of cardiometabolic risk factors, lack of awareness among patients and physicians, deficient infrastructure, and economic constraints lead to a cascade of CRCs at a significantly earlier age in MENA and AFR. In this review, we present consensus recommendations by experts in MENA and AFR, highlighting region-specific challenges and potential solutions for management of CRCs. Health professionals who understand sociocultural barriers can significantly increase patient awareness and encourage health-seeking behavior through simple educational tools. Increasing physician knowledge on early identification of CRCs and personalized treatment based on risk stratification, alongside optimum glycemic control, can mitigate therapeutic inertia. Early diagnosis of high-risk people with regular and systematic monitoring of cardiorenal parameters, development of region-specific care pathways for timely referral to specialists, followed by guideline-recommended care with novel antidiabetics are imperative. Adherence to guideline-recommended care can catalyze utilization of sodium glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists with demonstrated cardiorenal benefits-thus paving the way for overcoming care gaps in a cost-effective manner. Leveraging digital technology like electronic medical records can help generate real-world data and provide insights on voids in adoption of newer antidiabetic medications. A patient-centric approach, collaborative care among physicians from different specialties, alongside involvement of policy makers are key for improving patient outcomes and quality of care in MENA and AFR.

A stratified analysis of a deep learning algorithm in the diagnosis of diabetic retinopathy in a real-world study.

BACKGROUND: The aim of our research was to prospectively explore the clinical value of a deep learning algorithm (DLA) to detect referable diabetic retinopathy (DR) in different subgroups stratified by types of diabetes, blood pressure, sex, BMI, age, glycosylated hemoglobin (HbA1c), diabetes duration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) at a real-world diabetes center in China. METHODS: A total of 1147 diabetic patients from Shanghai General Hospital were recruited from October 2018 to August 2019. Retinal fundus images were graded by the DLA, and the detection of referable DR (moderate nonproliferative DR or worse) was compared with a reference standard generated by one certified retinal specialist with more than 12 years of experience. The performance of DLA across different subgroups stratified by types of diabetes, blood pressure, sex, BMI, age, HbA1c, diabetes duration, UACR, and eGFR was evaluated. RESULTS: For all 1674 gradable images, the area under the receiver operating curve, sensitivity, and specificity of the DLA for referable DR were 0.942 (95% CI, 0.920-0.964), 85.1% (95% CI, 83.4%-86.8%), and 95.6% (95% CI, 94.6%-96.6%), respectively. The DLA showed consistent performance across most subgroups, while it showed superior performance in the subgroups of patients with type 1 diabetes, UACR ≥ 30 mg/g, and eGFR < 90 mL/min/1.73m2 . CONCLUSIONS: This study showed that the DLA was a reliable alternative method for the detection of referable DR and performed superior in patients with type 1 diabetes and diabetic nephropathy who were prone to DR.

Low-dose colchicine in type 2 diabetes with microalbuminuria: A double-blind randomized clinical trial.

BACKGROUND: Neutrophil-related chronic inflammation (NRCI) may contribute to the pathogenesis of diabetic kidney disease (DKD). We evaluated whether blocking NRCI with low-dose colchicine prevents DKD. METHODS: A double-blind, randomized, placebo-controlled study was conducted. A total of 160 patients with type 2 diabetes (T2D) and microalbuminuria (urinary albumin creatinine ratio [UACR] 30 to 300 mg/g Cr) who received angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) for at least 3 months were included. Subjects were 1:1 randomized to a placebo or colchicine group (0.5 mg/day). RESULTS: The primary end point was the incidence of overt nephropathy (UACR > 300 mg/g Cr). During the 36 months, 38 patients (51.4%) in colchicine group and 39 (54.1%) in the control group developed overt nephropathy (hazard ratio, 1.066; 95% confidence interval, 0.679-1.673; P = .78). Compared with placebo, colchicine modestly lowered levels of NRCI parameters (P values <.05 for high-sensitivity C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil-to-lymphocyte ratio), whereas the changes of UACR and estimated glomerular filtration rate (eGFR) were similar between the two groups. There were no significant differences between the two groups in drug-related adverse events, including infection, gastrointestinal symptoms, and limb numbness. CONCLUSIONS: In patients with T2D with microalbuminuria, low-dose colchicine effectively and safely lowered NRCI but did not prevent the incidence of overt nephropathy.

Genetic variants of ABCC8 and phenotypic features in Chinese early onset diabetes.

BACKGROUND: ABCC8 variants cause neonatal diabetes, maturity onset diabetes of the young (MODY), and hyperinsulinemic hypoglycemia because of activating or inactivating variants. In this study we used targeted exon sequencing to investigate genetic variants of ABCC8 and phenotypic features in Chinese patients with early onset diabetes (EOD). METHODS: A cross-sectional study of 543 Chinese patients with EOD was recruited and the exons of them were conducted targeted sequencing. The pathogenicity of ABCC8 variants was defined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline. The phenotypes of patients owing to ABCC8 variants (ABCC8-MODY) were characterized. RESULTS: Among the 543 participants, eight (1.5%) patients with ABCC8-MODY were identified. They harbored eight missense ABCC8 variants (p.R306C, p.E1326K, and p.R1379H, previously reported; p.R298C, p.F1176C, p.R1221W, p.K1358R, and p.I1404V) classified as likely pathogenic. Two family members with ABCC8-MODY were also confirmed. The average diagnosed age of the 10 patients was 26.8 ± 12.9 years. The majority of them had unsatisfactory glucose control, 80% of them had diabetic kidney disease, and neurological features were not observed. CONCLUSION: Using targeted exon sequencing followed by pathogenicity analysis, we could be able to make genetic diagnoses for eight (1.5%) patients with ABCC8-MODY. The phenotype was variable with higher risk of diabetic microvascular complications. Genetic diagnosis is conducive for facilitating the personalized treatment of ABCC8-MODY.

Combining glomerular basement membrane and tubular basement membrane assessment improves the prediction of diabetic end-stage renal disease.

BACKGROUND: To address the prognostic value of combining tubular basement membrane (TBM) and glomerular basement membrane (GBM) thickness in diabetic nephropathy (DN). METHODS: This retrospective study enrolled 110 patients with type 2 diabetes and biopsy-proven DN from 2011 to 2018. The pathological findings were confirmed according to the Renal Pathology Society classifications. GBM and TBM thicknesses were determined using the Haas' direct measurement/arithmetic mean method and orthogonal intercept method, respectively. Cox proportional hazard models were used to investigate the hazard ratios (HRs) for the influence of combined GBM and TBM thickness for predicting end-stage renal disease (ESRD). RESULTS: Patients were assigned to three groups according to the median GBM and TBM thickness: GBMlo TBMlo (GBM < 681 nm and TBM < 1200 nm), GBMhi TBMlo /GBMlo TBMhi (GBM ≥ 681 nm and TBM < 1200 nm, or GBM < 681 nm and TBM ≥ 1200 nm), and GBMhi TBMhi (GBM ≥ 681 nm and TBM ≥ 1200 nm). The GBMhi TBMlo /GBMlo TBMhi and GBMhi TBMhi groups displayed poorer renal function, a more severe glomerular classification and interstitial inflammation, and poorer renal survival rates than the GBMlo TBMlo group The GBMhi TBMlo /GBMlo TBMhi and GBMhi TBMhi groups had adjusted HRs of 1.49 (95% confidence interval [CI], 1.21-9.75) and 3.07 (95% CI, 2.87-12.78), respectively, compared with the GBMlo TBMlo group. CONCLUSIONS: TBM thickness enhanced GBM thickness for renal prognosis in patients with type 2 diabetes.

Variation of IgG N-linked glycosylation profile in diabetic retinopathy.

BACKGROUND: The relationship of immunoglobulin G (IgG) glycosylation with diabetes and diabetic nephropathy has been reported, but its role in diabetic retinopathy (DR) remains unclear. We aimed to investigate and validate the association of IgG glycosylation with DR. METHODS: We analyzed the IgG N-linked glycosylation profile and primarily selected candidate glycans by lasso (least absolute shrinkage and selection operator) regression analysis in the discovery population. The findings were validated in the replication population using a binary logistics model. The association between the significant glycosylation panel and clinical features was illustrated with Spearman's coefficient. The results were confirmed by sensitivity analyses. RESULTS: Among 16 selected glycan candidates using lasso, two IgG glycans (GP15, GP20) and two derived traits (IGP32, IGP54) were identified and validated to be significantly associated with DR (P < .05), and the combined adjusted odds ratios (ORs) were 0.587, 0.613, 1.970, and 0.593, respectively. The glycosylation panel showed a weak correlation with clinical features, except for age. In addition, the results remained consistent when the subjects with prediabetes were excluded from the controls, and the adjusted ORs were 0.677, 0.738, 1.597, and 0.678 in the whole population. Furthermore, in the 1:3 rematched population, a significant association was observed, apart from GP20. CONCLUSIONS: The IgG glycosylation profile, reflecting an aging and pro-inflammatory status, was significantly associated with DR. The variation in the IgG glycome deserves more attention in diabetic complications.

Low serum levels of bone turnover markers are associated with the presence and severity of diabetic retinopathy in patients with type 2 diabetes mellitus.

BACKGROUND: Accumulating evidence demonstrates an association of type 2 diabetes mellitus (T2DM) and its microvascular complications with increased fracture risk. In this study, we aimed to evaluate the relationships between serum concentrations of bone turnover markers and the presence and/or severity of diabetic retinopathy (DR) among patients with T2DM. METHODS: A total of 285 patients with T2DM comprising 168 patients without DR and 117 patients with DR were enrolled in the cross-sectional study. In the latter group, patients were further divided into patients of mild and severe DR stages. The biochemical parameters and bone turnover markers were determined in all participants. RESULTS: This study found that serum levels of procollagen type 1 N-terminal propeptide (P1NP), a bone formation marker, and the bone resorption marker serum ß-cross-linked C-telopeptide of type I collagen (ß-CTX) were more decreased in diabetic patients with DR than in those without DR, with differences remaining significant (P < .05) in multivariate linear regression models after adjustments for multiple confounding factors. Osteocalcin and ß-CTX levels were further reduced along with the severity of DR among participants with DR. Moreover, multivariate logistic regression analysis revealed that lower serum levels of P1NP and ß-CTX were associated with higher odds for the presence of DR, while ß-CTX was associated with the severity of DR. CONCLUSION: Our results suggest that the development of DR might be involved in the progression of T2DM-induced deficits in bone formation and resorption or vice versa. Follow-up studies and further research are necessary to validate the associations and elucidate the underlying mechanisms.

Urinary C-peptide/creatinine ratio: A useful biomarker of insulin resistance and refined classification of type 2 diabetes mellitus.

BACKGROUND: The urinary C-peptide/creatinine ratio (UCPCR) is low in patients with type 1 diabetes mellitus, but it has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We aimed to measure the UCPCRs in patients with T2DM and explore the relationships among UCPCR, insulin resistance (IR), and chronic vascular complications of diabetes. METHODS: A cross-sectional study was performed of 1299 Chinese hospitalized patients with T2DM. Binary logistic regression was used to evaluate the relationships between the chronic vascular complications of diabetes and UCPCR. K-means analysis was used to allocate participants to subgroups with five to six variables (age at diagnosis, body mass index [BMI], glycosylated hemoglobin, homoeostasis model assessment 2-estimated beta-cell function (HOMA2-B), and HOMA2-insulin resistance (HOMA2-IR), with or without UCPCR). RESULTS: UCPCR positively correlated with HOMA2-IR (r = 0.448, P < .001). After adjustment for sex, age, duration of diabetes, and other cardiovascular risk factors, UCPCR was positively associated with diabetic kidney disease (DKD) (odds ratio [OR] = 1.198, 95% CI 1.019-1.408, P = .029) and coronary heart disease (CHD) (OR = 1.312, 95% CI 1.079-1.594, P = .006). When UCPCR was added, cluster analysis using the six variables identified five subgroups of T2DM, characterized by differing age at diagnosis, BMI, beta-cell function, IR, and prevalence of vascular complications. CONCLUSIONS: UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.

Design and validation of a scoring model for differential diagnosis of diabetic nephropathy and nondiabetic renal diseases in type 2 diabetic patients.

BACKGROUND: We aim to design a scoring model for differential diagnosis between diabetic nephropathy (DN) and nondiabetic renal disease (NDRD) in type 2 diabetic patients through a combination of clinical variables. METHODS: A total of 170 patients with type 2 diabetes who underwent kidney biopsies were included and divided into three groups according to pathological findings: DN group (n = 46), MIX group (DN + NDRD, n = 54), NDRD group (n = 70). Clinical characteristics and laboratory data were collected and compared among groups. Variables with a significant statistical difference between DN and NDRD patients were analyzed by logistic regression to predict the presence of NDRD; then a scoring model was established based on the regression coefficient and further validated in an independent cohort of 67 patients prospectively. RESULTS: On biopsy, 72.9% of patients had NDRD, and the most common pathological type was membranous nephropathy. The established scoring model for predicting NDRD included five predictors: age, systolic blood pressure, hemoglobin, duration of diabetes, and absence of diabetic retinopathy. The model demonstrated good discrimination and calibration (area under curve [AUC] 0.863, 95% CI, 0.800-0.925; Hosmer-Lemeshow [H-L] P = .062). Furthermore, high prediction accuracy (AUC = 0.900; 95% CI, 0.815-0.985) in the validation cohort proved the stability of the model. CONCLUSIONS: We present a simple, robust scoring model for predicting the presence of NDRD with high accuracy (0.85) for the first time. This decision support tool provides a noninvasive method for differential diagnosis of DN and NDRD, which may help clinicians assess the risk-benefit ratio of kidney biopsy for type 2 diabetic patients with renal impairment.

Interstitial eosinophilic infiltration in diabetic nephropathy is indicative of poor prognosis, with no therapy benefit from steroid.

BACKGROUND: Studies suggested that eosinophils in diabetes might be associated with severity of diabetic nephropathy (DN). In a retrospective study of 102 Chinese patients with biopsy-proven DN, we aimed to evaluate relationships of both blood and renal eosinophils (Eos) to the severity of DN and check whether Eos can serve as an indicator of prognosis as well as the therapeutic effect of steroids. METHODS: One hundred and two patients diagnosed with DN were enrolled. Demographical and clinical data and histopathological scores were associated. Interstitial eosinophilic aggregates (IEA) were defined as the presence of ≥10 Eos in at least one high-power field. End-stage renal disease was defined as the end point. RESULTS: We observed that log2 (blood eosinophil counts) correlated with neutrophil counts, proteinuria, and tubulointerstitial inflammatory cell infiltration. IEA was observed in 33.3% of the DN patients and was associated with decreased estimated glomerular filtration rate, higher proteinuria, hematuria, higher HbA1c, increased blood eosinophil counts, tubular injury, tubulointerstitial chronicity, and interstitial inflammation. IEA was associated with worse renal prognosis (hazard ratio [HR] 2.424, P = 0.008). Consistently, urine eosinophil cationic protein (ECP) (ng/mgCr) was associated with renal injury and poor renal prognosis (HR 1.173, P = 0.020). Patients with IEA were more likely to be treated with steroid/immunosuppressants (47.1% vs 14.7%, P = 0.001) but did not show renal benefit. CONCLUSIONS: It suggested that both blood and renal infiltrated eosinophils were prevalent in DN and associated with severity of DN. IEA in renal pathology showed better fit in correlation with renal prognosis. Treatment with steroid/immunosuppressants showed no significant improvement regarding renal prognosis.

Implications of immunoglobulin G deposit in glomeruli in Chinese patients with diabetic nephropathy.

BACKGROUND: In the current study, we explored the associations of glomerular immunoglobulin G (IgG) deposit and further investigated the pattern of IgG subclass deposition in the renal biopsy specimens from patients with diabetic nephropathy (DN). METHODS: A total of 170 inpatients with type 2 diabetes mellitus and biopsy-proven DN who were followed up for at least 1 year were retrospectively recruited. Renal outcomes were defined by DN progression (end-stage renal disease [ESRD] or ≥ 50% reduction in estimated glomerular filtration rate [eGFR] from baseline). Additionally, 38 renal biopsy specimens of patients with renal IgG deposit underwent the immunofluorescence IgG1-4 staining. RESULTS: The median follow-up period was 22 months. During follow-up, 38.23% (65) of patients progressed to ESRD, and 6.47% (11) of patients had an eGFR decline ≥50%. The multivariate Cox analysis demonstrated that the glomerular IgG deposit (hazard ratio, 1.835; 95% CI, 1.013-3.324, P = .045) was still significantly associated with DN progression when adjusted for the important clinical variables and pathological findings. In addition, a logistic regression showed that the glomerular IgG deposit was independently associated with glomerular basement membrane (GBM) thickness (odds ratio [OR], 1.276; 95% CI, 1.046-1.558; P = .016), Kimmelstiel-Wilson nodules formation (OR, 3.822; 95% CI, 1.052-13.881; P = .042), and C3 deposit in the glomeruli (OR, 124.883; 95% CI, 20.754-751.472; P < .001). The IgG subclass staining showed that IgG1 deposit along the GBM tended to be dominant (28/38) in IgG (+) patients with DN. CONCLUSIONS: The glomerular IgG deposit affected glomerular structure and emerged as an independent risk factor for the renal clinical outcomes. In addition, IgG1 predominantly deposited along the GBM among the DN patients with IgG (+), which might be involved in the renal injury and progression of DN.

Effect of gender on transition of normo- to microalbuminuria under angiotensin receptor blocker therapy in diabetes.

Highlights In normoalbuminuric diabetic patients at low cardiovascular risk, the risk of transition from normo- to microalbuminuria is lower in women, despite the nonprotective effects of the angiotensin receptor blocker olmesartan. Additional methods of assessment of albuminuria in clinical studies (eg, measurements of albumin and creatinine excretion rate) should be implemented or the actually accepted higher urine albumin creatinine ratio (UACR) cutoff values for microalbuminuria in women reconsidered.