Journal of Diabetes Investigation最新文献

Dear Editor,

Ye et al.¹, in their study entitled ‘Inhibition of the LINC00707/miR-223-3p/FKBP5 axis has a protective effect on diabetic kidney disease,’ explores the LINC00707/miR-223-3p/FKBP5 pathway in diabetic nephropathy, revealing useful understanding of LINC00707 silencing's protective actions on kidney filtering cells during hyperglycemia. Employing mannitol comparisons and SOD assessments reinforces methodology. However, several aspects could enhance the study's impact.

First, their protocol utilized only 30 mmol/L glucose across 48 h. Examining varied sugar concentrations (5–40 mmol/L) would establish response boundaries². Specifying the delivery approach (single dose vs progressive elevation) might better simulate actual patient sugar levels³.

Second, the study measures MDA and SOD activity, showing reduced oxidative stress after LINC00707 silencing. Adding markers like reduced glutathione or HO-1 activity would provide a fuller picture of redox dynamics⁴. This could confirm whether oxidative stress drives or follows podocyte injury.

Third, the clinical cohort is stratified by albuminuria. Including eGFR-based staging would link LINC00707 levels to renal function decline⁵. This could strengthen its potential as a biomarker.

Additionally, there is a discrepancy in the reporting of LDL-C significance. In table 1, the P-value for LDL-C is reported as 0.236 (non-significant), but it is labeled as significant in the text. This inconsistency should be addressed to ensure the accuracy of the data interpretation.

These suggestions aim to build on the study's robust foundation. Addressing them could deepen its mechanistic and clinical contributions.

The authors declare no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.

There is no original data for this letter to the editor.

Dear Editor,

This study¹ offers valuable insights into cordycepin's role in diabetic nephropathy (DN), particularly its modulation of ferroptosis via SLC7A11/GPX4. However, three critical concerns warrant attention to strengthen clinical applicability and mechanistic depth. First, the exclusive use of high-glucose (HG)-treated MPC5 cells and streptozotocin (STZ)-induced diabetic mice limits translational relevance. STZ models mimic type 1 diabetes, while DN predominantly complicates type 2 diabetes (T2D), which involves insulin resistance and heterogeneous renal pathology not captured here². Human podocytes or patient-derived cells would better reflect DN pathophysiology. Second, the SLC7A11/GPX4 axis is presented in isolation, neglecting crosstalk with established DN pathways like nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 regulates GPX4 and ferroptosis in DN but was unexplored³. Validating interactions using Nrf2 inhibitors (e.g., ML385) could clarify the mechanistic hierarchy. Third, the cordycepin dose (400 mg/kg in mice) raises safety concerns. This far exceeds typical human-equivalent doses (~3–6 mg/kg) and lacks supporting toxicity data⁴. Dose–response studies in T2D models (e.g., db/db mice) and renal/hepatic safety assays are essential.

To address these gaps, future work should prioritize human cell lines, incorporate T2D models, and probe Nrf2-SLC7A11/GPX4 crosstalk. Additionally, lower cordycepin doses with toxicity profiling would enhance therapeutic feasibility. These steps may bridge mechanistic findings to clinical practice, aligning with precision medicine approaches for DN⁵.

The author declares no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Approval date of registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.

This article is linked to https://doi.org/10.1111/jdi.14407.

There is no original data for this letter to the editor.

Dear Editor,

We read the article “The cholesterol-HDL-glucose (CHG) index and traditional adiposity markers in predicting diabetic retinopathy and nephropathy”¹ by Çatak et al. with great interest. The study addresses an important clinical question by evaluating novel metabolic indices in relation to microvascular complications in long-standing type 2 diabetes, and the suggestion that CHG may serve as a composite marker of metabolic risk is noteworthy. However, several methodological issues limit the validity and generalizability of the authors' conclusions.

The cross-sectional design of the study fundamentally restricts causal inference. Although significant associations are reported between CHG and both diabetic nephropathy (DN) and retinopathy (DR), the temporal relationship between metabolic dysfunction and complication onset remains unclear. For instance, elevated CHG may be a consequence of advanced microvascular disease—such as dyslipidemia secondary to nephropathy—rather than a causative factor. The results presented in tables 1 and 2 (pages 3–4) demonstrate associations but do not establish predictive utility. A prospective cohort design with serial measurements of metabolic indices and complication status would be necessary to infer predictive value and establish temporality².

Furthermore, the regression models used to identify independent predictors of DN and DR did not adjust for several established confounders. Although age, sex, diabetes duration, and HbA1c were included, other critical variables such as blood pressure control, use of antihypertensive or lipid-lowering medications, and smoking status were omitted. Table 1 indicates a significantly higher prevalence of hypertension in the DN group (81% vs 64.5%, P = 0.026), yet hypertension was not considered in the multivariable model predicting DN (page 4). This omission may have led to overestimation of the effect of CHG³. Future analyses must incorporate these clinically relevant confounders to ensure that the associations attributed to CHG are independent of conventional risk factors.

In summary, while the study proposes CHG as a promising metabolic index for microvascular complications, the cross-sectional design and insufficient adjustment for confounders undermine the robustness of its conclusions. We recommend that future research adopt longitudinal designs and more comprehensive statistical models to validate the role of CHG in risk stratification and to support its potential integration into clinical practice.

The authors declare no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.