Abstract
Dear Editor,
We read with great interest the study by Vaishali et al, which investigated the associations between glycated hemoglobin (HbA1c), fructosamine, and estimated glomerular filtration rate (eGFR) across chronic kidney disease (CKD) stages in individuals with type 2 diabetes mellitus (T2DM). 1 The authors’ stage-stratified approach and use of both short- and long-term glycemic markers provide valuable insights into the complexity of diabetes monitoring in progressive renal dysfunction.
One area of concern is the statistical interpretation of weak correlations and their clinical implications. For instance, the reported Spearman correlation between fructosamine and eGFR in CKD stage 3 (r = –0.392, P = .001) appears quantitatively stronger than the correlations in other stages; however, the study does not elaborate on potential threshold effects or nonlinearities. Clinically, this may obscure whether a distinct glycemic profile emerges in moderate CKD, which could influence treatment decisions. 2 Incorporating non-parametric trend analyses or spline models may help clarify these stage-dependent shifts.
The use of fructosamine as a supplementary glycemic index is a noteworthy inclusion, particularly given the limitations of HbA1c in advanced renal disease. However, the interpretation of fructosamine trends across CKD stages appears uniform, without accounting for serum albumin levels or nutritional status. Given that hypoalbuminemia is prevalent in later CKD stages and directly impacts fructosamine concentrations, 3 the lack of albumin adjustment may restrict the clinical validity of this marker in advanced diseases. Clinicians relying on fructosamine alone for therapeutic decisions may inadvertently misclassify glycemic control in hypoalbuminemic states.
Additionally, the multivariable regression results yielded wide confidence intervals for key predictors, such as HbA1c in CKD stage 3 (β = 47.6, 95% CI: –25.9 to 121.2), suggesting considerable imprecision. While the authors acknowledge this uncertainty, the potential influence of diabetes duration and comorbidities on the reliability of glycemic markers has not been fully investigated. From a clinical perspective, failing to integrate these factors into interpretive algorithms may reduce the translational utility of biomarker-based risk stratification in real-world settings. 4
This study commendably disaggregated CKD into 5 stages, offering granular insights often lacking in diabetes-nephropathy research. However, the absence of a composite glycemic burden index that integrates glycemic variability, anemia status, and renal clearance limits the ability to guide longitudinal care. 5 Introducing a multivariable risk-adjusted scoring system could enhance the prediction of renal decline and inform marker prioritization at various disease stages.
We commend the authors for addressing the nuanced interplay between glycemic indices and renal function across distinct chronic kidney disease (CKD) stages. Their findings reinforce that neither glycated hemoglobin nor fructosamine alone serves as a universally reliable marker for type 2 diabetes mellitus with coexisting CKD. A context-sensitive combination strategy, adapted to renal function, hematologic parameters, and short- and long-term glycemic fluctuations, may offer a more clinically robust framework for optimizing therapeutic decisions and enhancing patient safety.
Footnotes
Consent to Participate
Not applicable, as no patient data were collected or analyzed in this study.
Author Contributions
Shyam Sundar Sah: Conceptualization, Methodology, Writing—Original Draft, Writing—Review & Editing. Abhishek Kumbhalwar: Validation, Supervision, Project Administration, Writing—Original Draft, Writing—Review & Editing.
Data Availability Statement
Not applicable, as no data were generated or analyzed in this study.
Clinical Trial Registration Details/Number
Not applicable, as this study does not report a clinical trial.
Generative AI Use Statement
Paperpal and ChatGPT 5, were utilized solely for language, grammar, and stylistic refinement. These tools had no role in the conceptualization, data analysis, interpretation of results, or substantive content development of this manuscript. All intellectual contributions, data analysis, and scientific interpretations remain the sole work of the authors. The final content was critically reviewed and edited to ensure accuracy and originality. The authors take full responsibility for the accuracy, originality, and integrity of the work presented.