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.
The aim of the study was to investigate the association of single nucleotide polymorphisms, haplogroups, and copy number in the D-loop region of mitochondrial DNA (mtDNA) with the genetic susceptibility to gestational diabetes mellitus (GDM) and postpartum abnormal glucose metabolism (AGM).
This was a case–control study in which peripheral blood samples were collected from 500 GDM patients and 500 normal pregnant women from 14 to 20 weeks of pregnancy. The sequence of the D-loop region of mtDNA was detected by Sanger sequencing, and the copy number of mtDNA was detected by qPCR.
Analysis of SNPs in the D-loop region of mtDNA showed that 249d was a risk factor and 309+C and 16193+C were protective factors for GDM. The mtDNA haplogroups R9 and M* were a risk factor and protective factor for GDM, respectively. Compared to the group with normal postpartum glucose tolerance, the haplogroups M7b and N9a were associated with an increased risk of AGM. The whole blood mtDNA copy number was lower in the GDM group than in the control group and was also lower in the postpartum AGM group than in the postpartum normal group. The plasma free mtDNA copy number was higher in the GDM group than in the control group, and higher in the postpartum AGM group than in the normal postpartum group.
Mitochondrial genomic variants are associated with the risk of GDM and postpartum AGM, and may provide some etiologic evidence for GDM and postpartum AGM.
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.
Lower limb muscle strength is often reduced in patients with type 2 diabetes and is associated with a lower quality of life and poorer walking ability. Diabetic peripheral neuropathy (DPN) may contribute to muscle weakness, though evidence is inconsistent. No meta-analysis has specifically examined the effect of DPN on lower limb muscle strength. This study aimed to review the literature and assess whether lower limb muscle strength is reduced in individuals with DPN compared to those without DPN.
MEDLINE, Embase, and CENTRAL were searched for cohort and case-control studies on the association between DPN and lower limb muscle strength in individuals with type 2 diabetes. We pooled mean differences and standard deviations using random effects models. We evaluated the risk of bias in the included studies using the Quality in Prognosis Studies tool and determined the certainty of the evidence using the Grading of Recommendations Assessmet, Development and Evaluation (GRADE) approach.
Overall, 25 studies for qualitative synthesis and 23 (2,798 participants) for meta-analysis were selected. The methodological quality demonstrated a moderate risk of bias in 72% of the included studies. There was low-certainty evidence of an association between DPN and lower extremity muscle strength (standardized mean difference -0.46, 95% CI −0.65 to −0.27).
Patients with type 2 diabetes and DPN may have lower muscle strength than those without DPN. Moreover, they should be informed of the risk of muscle weakness. Further research is needed to identify factors contributing to lower extremity weakness in DPN and determine which muscle groups are most susceptible.
Depressive tendencies associated with difficulty in the treatment of type 1 diabetes (T1D) could hinder appropriate intervention. Factors related to depressive tendencies in Japan remain unclear, though recent advances in medication may have affected them.
Three hundred and fifty-two Japanese patients with T1D registered in the Juntendo-Aso Type 1 Diabetes (JAT-1) Cohort Study were divided into two groups based on depressive tendencies assessed with the Beck Depression Inventory-II score. We compared background characteristics of the patients between the groups and also analyzed additional clinical factors and quality of life scores.
The patients with a Beck Depression Inventory-II score ≧14 (35.5%) are classified as having depressive tendencies. Compared to the individuals without depressive characteristics, those with depressive tendencies had significantly higher proportions of females, welfare recipients, and shift workers; a higher proportion of individuals with microvascular complications; higher diastolic pressure; eating out or taking out food more frequently for dinner; lower protein intake; and higher scores in the total score of diabetes-related problem domains and Pittsburgh Sleep Quality Index. Multiple regression analysis revealed that diastolic blood pressure, welfare recipient status, total score of diabetes-related problem domains (PAID), and Pittsburgh Sleep Quality Index were significantly associated factors with BDI-II score, and the PAID score showed the strongest association.
This study revealed that diabetes-specific psychological burden, evaluated with the PAID score, is strongly associated with depressive tendencies. Routine use of the PAID could support the strategies to prevent depression in people with type 1 diabetes by identifying those at risk.
High 1-h plasma glucose levels have an increased risk of type 2 diabetes. To determine the pathophysiological features in participants with normal glucose tolerance (NGT) with 1-h hyperglycemia (HG), we investigated the variability in the glucagon and insulin secretions after oral glucose loading and nutrient survey.
A 75-g oral glucose tolerance test (OGTT) was performed in Japanese Americans (aged 40–75 years), enrolled in medical surveys conducted in 2015. We recruited only participants with NGT defined as fasting glucose values <110 mg/dL and 2-h glucose levels <140 mg/dL. We evaluated homeostatic model assessment for insulin resistance (HOMA-IR), insulin sensitivity index (MATSUDA-Index), insulin, and glucagon (GCG) secretions during the 75-g OGTT and compared them between 1-h serum glucose values: <155 mg/dL (1-h non-hyperglycemia: NHG, n = 76) and 1-h serum glucose values: ≥155 mg/dL (HG, n = 41). We also conducted a dietary intake survey to determine the association between 1-h serum glucose and nutritional intake in the usual diet.
The HG group demonstrated significant insulin resistance compared to the NHG group. Two-h GCG levels were significantly lower in the HG group. Additionally, low vegetable fat intake was significantly associated with 1-h HG after adjusting for sex, age, and body mass index.
Insulin resistance is already present in the HG group. Vegetable fat intake may be associated with glucose metabolism regardless of clinical background.
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