Introduction: Dysbiosis of gut microbiota impairs the homeostasis of immune and metabolic systems. Although previous studies have revealed the correlation between gut microbiota and various diseases, the function between gut microbiota and diabetic nephropathy (DN) has not been discovered distinctly. In this study, we tried to investigate the profile and function of gut microbiota in DN. Methods: A total of 100 people were enrolled in this study. Twenty were healthy people, 20 were diabetes patients, and 60 were DN patients. The DN patients were divided into three stages including stage III, IV, and V. We conducted taxonomic analyses in different groups. The distributions of phyla, classes, orders, families, and genera in different groups and samples were investigated. We also evaluated the correlations between clinical parameters and gut microbiota in 60 DN patients. Results: The gut microbiota in the healthy group, diabetes group, and DN group had 1764 operational taxonomic units (OTUs) in total. The healthy group had 1034 OTUs, the diabetes group had 899 OTUs, and the DN group had 1602 OTUs. The diversity of gut microbiota in the stage III DN group was smaller than that in the other groups. 24-h urinary protein was positively correlated with Alistipes and Subdoligranulum, cholesterol was positively correlated with Bacteroides and Lachnoclostridium, and estimated glomerular filtration rate was negatively correlated with Ruminococcus torques group. Discussion: The gut microbiota might play an important role in the development and pathogenesis of DN. A change in gut microbiota diversity is correlated with disease progression. Some kinds of gut microbiota including Alistipes, Bacteroides, Subdoligranulum, Lachnoclostridium, and Ruminococcus torques group might be detrimental factors in DN.

Visceral adiposity index (VAI) is a reliable indicator of visceral adiposity. However, no stu-dies have evaluated the association between VAI and DKD in US adults with diabetes. Theref-ore, this study aimed to explore the relationship between them and whether VAI is a good pr-edictor of DKD in US adults with diabetes. Our cross-sectional study included 2508 participan-ts with diabetes who were eligible for the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Univariate and multivariate logistic regression were used to an-alyze the association between VAI level and DKD. Three models were used to control for pot-ential confounding factors, and subgroup analysis was performed for further verification. A tot-al of 2508 diabetic patients were enrolled, of whom 945 (37.68%) were diagnosed with DKD. Overall, the VAI was 3.36 ± 0.18 in the DKD group and 2.76 ± 0.11 in the control group. VAI was positively correlated with DKD (OR = 1.050, 95% CI 1.049, 1.050) after fully adjusting for co-nfounding factors. Compared with participants in the lowest tertile of VAI, participants in the highest tertile of VAI had a significantly increased risk of DKD by 35.9% (OR = 1.359, 95% CI 1.355, 1.362). Through subgroup analysis, we found that VAI was positively correlated with the occurrence of DKD in all age subgroups, male(OR = 1.043, 95% CI 1.010, 1.080), participants wit-hout cardiovascular disease(OR = 1.038, 95% CI 1.011, 1.069), hypertension (OR = 1.054, 95% CI 1.021, 1.090), unmarried participants (OR = 1.153, 95% CI 1.036, 1.294), PIR < 1.30(OR = 1.049, 95% CI 1.010, 1.094), PIR ≧ 3 (OR = 1.085, 95% CI 1.021, 1.160), BMI ≧ 30 kg/m² (OR = 1.050, 95% CI 1.016, 1.091), former smokers (OR = 1.060, 95% CI 1.011, 1.117), never exercised (OR = 1.033, 95% CI 1.004, 1.067), non-Hispanic white population (OR = 1.055, 95% CI 1.010, 1.106) and non-Hipanic black population (OR = 1.129, 95% CI 1.033, 1.258). Our results suggest that elevated VAI levels are closely associated with the development of DKD in diabetic patients. VAI may be a simpl-e and cost-effective index to predict the occurrence of DKD. This needs to be verified in furt-her prospective investigations.

Mitochondrial homeostasis imbalance plays an important role in the development of diabetic kidney disease (DKD). Kaempferol is a key bioactive compound widely present in the rhizomes of Kaempferia L. and vegetables. Its anti-inflammatory and antioxidant properties have gained increasing attention in treating various metabolic diseases. This study investigated whether kaempferol could improve mitochondrial structure and function by regulating mitochondrial dynamics and mitophagy in DKD. A DKD rat model was established via unilateral nephrectomy and streptozotocin injection. Renal function, histopathology, and inflammatory factors were assessed, along with fibrosis, apoptosis, mitochondrial dynamics, and mitophagy-related proteins. Meanwhile, an AGEs-induced HK-2 cell injury model was used to evaluate autophagic flux and mitochondrial function and morphology through ad-mCherry-GFP-LC3B transduction, JC-1 staining, and MitoTracker probes. In vivo results showed that kaempferol exhibited significant anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in DKD rats. Moreover, kaempferol demonstrated good safety by alleviating hepatic fibrosis. It also restored mitochondrial dynamics by promoting the upregulation of mitochondrial fusion proteins (Mfn1, OPA1) and the downregulation of fission proteins (Drp1, Fis1). In addition, kaempferol enhanced mitochondrial biogenesis by upregulating PGC-1α and TFAM. Notably, kaempferol reactivated mitophagy, as evidenced by increased levels of PINK1, Parkin, LC3, Beclin1, and ATG5, along with a reduction in p62 levels. In vitro, kaempferol further demonstrated its antioxidative potential by increasing SOD levels and decreasing MDA levels. Additionally, it promoted autophagic induction and facilitated the fusion of autophagosomes with lysosomes. These combined effects led to the restoration of mitochondrial membrane potential and structural integrity, while reducing ROS production and enhancing ATP generation. In conclusion, kaempferol promotes mitochondrial fusion, restores mitophagy, enhances autophagy flux, and facilitates mitochondrial clearance, showing the potential to mitigate kidney injury and slow disease progression in DKD.

Previous studies have emphasized the independent effects of anthropometric indices—including body mass index (BMI), A Body Shape Index (ABSI), waist-to-height ratio (WHtR), body roundness index (BRI), and Conicity Index—on mortality. However, their combined impact, especially in diabetic populations with distinct obesity patterns, has been less frequently explored. This study investigates both the independent and combined effects of these anthropometric indices on mortality in diabetic Americans and compares their individual and combined diagnostic value. A nationally representative cohort study was conducted using NHANES data (2005–2018), including 6,572 diabetic adults. Weighted Cox proportional hazards models and restricted cubic splines were applied to evaluate the independent and combined associations of anthropometric indices (BMI, ABSI, WHtR, BRI, and Conicity Index) with all-cause mortality. The weighted receiver operating characteristic (ROC) curve was used to assess the diagnostic value of individual anthropometric indices and their combinations in predicting mortality. Among all the anthropometric indices, ABSI exhibited the strongest independent association with all-cause mortality, outperforming other measures such as BMI, WHtR, BRI, and Conicity Index. A clear linear relationship was identified, with higher ABSI tertiles consistently linked to an increased risk of mortality. Notably, within each BMI tertile, ABSI effectively differentiated mortality risk, particularly in the highest tertile. Furthermore, ABSI demonstrated the highest predictive performance among individual metrics (weighted AUC = 0.653) and showed further improvement when combined with BMI (weighted AUC = 0.669). BMI and ABSI collectively provide a comprehensive evaluation of mortality risk in diabetic populations, capturing the synergistic effects of general and central obesity. These findings highlight the importance of integrating BMI and ABSI into risk assessments to identify high-risk individuals and guide targeted interventions for reducing mortality.

Diabetic kidney disease (DKD), a prevalent microvascular complication of diabetes, is a leading cause of end-stage renal disease (ESRD). Emerging evidence implicates ferroptosis in DKD pathogenesis. Qing-Re-Xiao-Zheng-(Yi-Qi) Formula (QRXZYQF), a traditional Chinese medicine with a 30-year clinical application history, exhibits multifaceted pharmacological benefits. But its potential role in DKD has yet to be fully investigated. This study investigates whether QRXZYQF alleviates podocyte injury and mitigates DKD progression by modulating ferroptosis through AMP-activated protein kinase (AMPK) pathway activation. We induced DKD in male sprague dawley (SD) rats by performing left unilateral nephrectomy followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg). Rats received QRXZYQF (12/24 g/kg), metformin (100 mg/kg), and valsartan (8 mg/kg) for 16 weeks. Renal function, blood glucose, lipid profiles, 24-hour urinary protein (24 h-UTP), oxidative stress markers glutathione (GSH) and malondialdehyde (MDA), and histopathology were assessed. In vitro, high-glucose-cultured conditionally immortalized mouse podocytes (MPC-5) cells were analyzed for cell viability assays, ferroptosis markers, mitochondrial integrity, and AMPK signaling. Additionally, we used short hairpin RNA (shRNA) to suppress AMPK expression to confirm whether QRXZYQF exerts protective effects on DKD via AMPK-mediated ferroptosis signaling. QRXZYQF improved body weight, glucose-lipid metabolism, and renal function in DKD rats, and alleviated kidney tissue pathology, renal fibrosis and mitochondrial damage. Furthermore, QRXZYQF upregulated the expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while downregulating acyl CoA synthase long-chain family member 4 (ACSL4) expression, and attenuated oxidative stress. Moreover, AMPK silencing partially reversed QRXZYQF's protective effects, confirming AMPK-dependent ferroptosis inhibition. QRXZYQF attenuates DKD progression by activating AMPK signaling, thereby suppressing podocyte ferroptosis. These findings underscore its potential as a therapeutic agent for DKD.

Introduction: Qing-Re-Xiao-Zheng-Yi-Qi Formula is an effective prescription in diabetic kidney disease treatment, we have confirmed the efficacy of Qing-Re-Xiao-Zheng therapy in diabetic kidney disease through clinical trials. In this study, we investigated the mechanisms of Qing-Re-Xiao-Zheng-Yi-Qi Formula in the treatment of diabetic kidney disease.Methods: We used Vanquish UHPLC^TM to analyze the chemical profiling of Qing-Re-Xiao-Zheng-Yi-Qi Formula freeze-dried powder. We constructed diabetic kidney disease rat models induced by unilateral nephrectomy and high-dose streptozocin injection. We examined blood urea nitrogen, serum creatinine, serum glucose, total cholesterol, triglyceride, serum total protein, albumin, alanine aminotransferase, aspartate aminotransferase and 24 h urinary total protein in diabetic kidney disease rats. The renal pathological changes were observed by HE, Masson, PAS stanning and transmission electron microscopy. The levels of fibrosis-related proteins and mitophagy-related proteins were detected by western blot analysis. We also conducted an immunofluorescence co-localization analysis on podocytes to further investigate the effect of Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment on mitophagy.Results: A total of 27 constituents in Qing-Re-Xiao-Zheng-Yi-Qi Formula were tentatively identified. We found PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could raise body weight and reduce renal index, reduce proteinuria, improve glycolipid metabolic disorders, ameliorate renal fibrosis, and reduce the expression of Col Ⅳ and TGF-β1 in diabetic kidney disease rats. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could also increase the expression of nephrin, activate mitophagy and protect podocytes in diabetic kidney disease rats and high glucose cultured podocytes.Conclusion: PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease, and Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could not only ameliorate pathological damage, but also promote mitophagy to protect podocytes in diabetic kidney disease.