Shandong Ye

Objective: To investigate the association between iron metabolism disorders and diabetic kidney disease (DKD) and to evaluate the potential of urinary ferritin as an early marker of tubular injury in diabetic patients. Methods: This study utilized data from 1,306 diabetic patients and 1,306 propensity score-matched non-diabetic controls from the NHANES (2017–March 2020) dataset. Diabetic participants were classified into Non-DKD (n = 923) and DKD (n = 383) groups based on the urinary albumin-to-creatinine ratio (UACR). Binary logistic regression and restricted cubic spline models were used to evaluate the association between iron metabolism indicators and DKD risk. Additionally, renal tissue samples from 12 patients (6 with T2DM and 6 non-diabetic controls) undergoing nephrectomy were analyzed for iron accumulation and tubular injury markers. Clinical data from 35 T2DM patients (with and without DKD) and 20 matched healthy controls were included to assess urinary ferritin and tubular injury markers. Finally, 120 T1DM patients were stratified by disease duration to assess correlations between urinary ferritin and renal injury biomarkers. Results: Decreased serum iron (OR = 0.962, P = 0.037) and increased serum ferritin (OR = 1.001, P = 0.024) were identified as independent risk factors for DKD. Diabetic patients exhibited higher renal iron, urinary ferritin, and tubular injury markers, with significant correlations between renal iron and urinary ferritin levels. Urinary ferritin levels also increased with T1DM duration, significantly correlating with tubular injury markers. Conclusion: Impaired iron metabolism, characterized by low serum iron and high serum ferritin, is an independent risk factor for DKD. Urinary ferritin may serve as a biomarker of early tubular injury in diabetic patients, even in the absence of albuminuria.

Objective: This study aims to explore the link between iron deficiency anemia (IDA) and diabetic kidney disease (DKD) and assess the safety of iron supplementation. It also investigates key mechanisms and molecules involved in iron deficiency's role in disease development.Methods: A retrospective analysis was conducted on 1,398 T2DM patients using propensity score matching to identify risk factors for DKD. Mendelian randomization (MR) was used to explore causal relationships between IDA, iron supplementation, liver iron content, and DKD. The GSE27999 dataset was analyzed to examine how an iron‐deficient diet affects kidney‐related gene expression. Key pathways and molecules were identified through GSEA, GO/KEGG, and PPI analysis.Results: Retrospective data showed a correlation between hemoglobin levels and DKD risk. Logistic regression confirmed that IDA increased DKD risk independently of other factors. MR revealed a causal link between IDA and DKD, with no significant effect from iron supplementation. GSE27999 analysis identified 580 differentially expressed genes, enriched in pathways like cytokine signaling, oxidative biology, and small molecule transport. PPI analysis highlighted 10 key hub genes, including Cyp2d26 and Fgf4.Conclusion: IDA increases susceptibility to DKD, possibly through oxidative stress and altered small molecule transport. However, iron supplementation does not appear to increase the risk of DKD.

Objective: To evaluate the efficacy of combined therapy of compound betamethasone periocular injection and oral mycophenolate mofetil (MMF) in treating active thyroid‐associated ophthalmopathy (TAO). Methods: A retrospective study was conducted on 17 patients with active TAO treated with compound betamethasone periocular injection combined with oral MMF from February 2022 to August 2023, involving a total of 31 eyes. Results: In one eye, the Clinical Activity Score (CAS) decreased by less than two points, while in the remaining eyes, the CAS decreased by two points or more. Patients exhibited decreased proptosis, a reduction in average extraocular muscle thickness, and improvement in diplopia in six cases. Subgroup analysis indicated that this regimen showed no significant difference in efficacy for patients treated with radioactive iodine therapy or oral methimazole medication at baseline. Conclusion: Combined therapy of compound betamethasone periocular injection and oral MMF is an effective approach for treating active TAO.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization. We report two patients with Grave’s disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge. GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.

Purpose: Given the importance of metformin, reasonable utilization is essential. We designed a cross-sectional survey on physicians’ attitude and clinical application of metformin in Anhui Province, China. Methods: The survey was distributed via an electronic questionnaire among endocrinologists and general practitioners. Seven representative questions were used to evaluate professional levels. Results: Among the 477 valid responses, 72.75% of the respondents preferred to prescribe metformin extended-release, while only 34.38% of them would prescribe metformin extended-release at the correct frequency. More than half of the respondents thought that estimated glomerular filtration rate ˂ 45 mL/min/1.73 m² should be the contraindication of metformin prescription. Less than 10% of the physicians selected correct responses for two questions regarding metformin usage and contrast agent. Physicians with higher levels of hospital grades, education background and professional titles as well as working in general hospitals and in the Department of Endocrinology achieved high scores (P˂0.05). Logistic regression showed that department was an independent predictor for high scores. Conclusion: Physicians, especially non-endocrinologists, are not at a professional level for prescribing metformin. Physicians should be highly vigilant in terms of standardized prescription for metformin. The guidelines or consensuses about diabetes care for physicians should be promoted.

Background: Metformin is used as a first-line drug for the treatment of type 2 diabetes. Epithelial–mesenchymal transition (EMT) plays a significant role in the development of renal tubular damage in diabetic kidney disease. However, the underlying mechanisms of EMT in diabetic kidney disease are unclear and how to inhibit this process remains to be explored. Methods: C57 mice were randomly divided into four groups, including the normal control group (NC group), the Type 2 diabetes group (T2DM group), the metformin group (MET group), and glibenclamide group (GLIB). Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), urinary albumin, RBP, PCX, and creatinine were measured. Renal pathology was observed with HE staining. Molecular mechanism of VDR expression are regulated by metformin through wound healing assay, and Western blot analysis of VDR, Ecad, and SMA in HK2 cells. Results: In animal experiments, compared with the NC group, the T2DM group showed decreased body weight, increased levels of FBG, HbA1c, UAlb/UCR, URBP/UCR, and UPCX/UCR, decreased levels of VDR protein and mRNA expression in renal tissues (P < 0.05), and significantly increased renal pathological damage in mice in the T2DM group. Compared with the T2DM group, mice in the GLIB and MET groups had higher body weight and lower FBG, HbA1c, UAlb/UCR, URBP/UCR, and UPCX/UCR (P < 0.05). In addition, renal pathological damage was significantly reduced in the MET group compared to the GLIB group. In HK2 cells, high glucose promoted the reduction of VDR and the development of EMT compared to the NC group. In addition, we found that Metformin can up-regulate VDR and inhibit EMT. Conclusion: Our study shows that the renoprotective effect of metformin is independent of glycemic control and metformin is involved in the progression of EMT by regulating VDR expression.