Commentary on “Prognostic value of longitudinal HbA1c variability in predicting the development of diabetic sensorimotor polyneuropathy among patients with type 2 diabetes mellitus: A prospective cohort observational study”

Dear Editor,

We read with great interest the article titled “Prognostic Value of Longitudinal HbA1c Variability in Predicting the Development of Diabetic Sensorimotor Polyneuropathy Among Patients with Type 2 Diabetes Mellitus: A Prospective Cohort Observational Study” by Lai et al.¹ The study identifies average real variability (HbA1c ARV) as the most predictive measure of HbA1c variability for anticipating new cases of diabetic sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes mellitus. The authors' meticulous investigation of HbA1c variability in the context of DSPN risk adds substantial value to the growing body of literature on glycemic control. However, we believe that addressing the following methodological aspects would enhance the robustness of the findings and provide broader clinical insights.

While the study convincingly establishes the predictive value of HbA1c ARV, the lack of additional laboratory parameters limits its scope. Biomarkers such as thyroid and liver function tests, vitamin B12, zinc, copper, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) have been implicated in diabetic complications and could potentially provide further insights into DSPN risk². The absence of these markers leaves room for residual confounding, especially in a multifactorial condition like DSPN, where inflammation and micronutrient deficiencies play critical roles.

The article does not detail the concurrent use of other medications, such as lipid-lowering therapies, antihypertensives, and antibiotics, which could significantly influence the development or progression of neuropathy³. For example, statins have been linked to myopathy and neuropathy in specific populations, while the anti-inflammatory properties of some drugs might modulate DSPN risk. A more comprehensive medication profile would strengthen the causal attributions made in this study.

Comorbidities such as psychological disorders, autoimmune diseases, and thyroid dysfunctions were not adequately accounted for. Each of these conditions has been independently associated with neuropathy⁴. Their exclusion not only limits the generalizability of the findings but may also lead to overestimation of the role of HbA1c variability.

Socioeconomic determinants, including urban vs rural residency, educational attainment, and income, were overlooked. Additionally, lifestyle factors such as physical activity levels, alcohol consumption, and dietary habits could significantly modify the risk of DSPN. These factors are particularly relevant in assessing glycemic variability, as they influence both HbA1c levels and overall diabetes management.

The study does not report on insulin resistance or vitamin D status—both key players in the pathogenesis of neuropathy. Insulin resistance is a central mechanism in type 2 diabetes mellitus and has been closely linked with microvascular complications. Similarly, vitamin D deficiency is increasingly recognized as a risk factor for neuropathy and could serve as a modifiable target for intervention.

The methodology lacks specific details regarding the nerve conduction studies (NCS) and other diagnostic tools used. Standardization of these measures is critical for reproducibility and comparison with other studies. Providing this information would bolster confidence in the validity of the findings.

The authors excluded patients with advanced diabetic kidney disease (DKD) but noted a higher prevalence of DSPN in those with moderate kidney dysfunction. Given the complex interplay between DKD and neuropathy, further exploration into the role of HbA1c variability in advanced DKD populations is warranted.

Despite its limitations, this study offers valuable evidence linking HbA1c variability to the risk of DSPN in type 2 diabetes mellitus patients. Addressing the highlighted areas in future research will enhance our understanding of this relationship and provide a more comprehensive framework for clinical application. We commend the authors for their contributions to this critical field and hope our suggestions will pave the way for even more impactful studies.

No funding was received for this manuscript.

The authors declare no conflict of interest.

The authors have nothing to report.