Diabetic peripheral neuropathy and diabetic nephropathy; a close relationship, even with good glycaemic control

Aims: To investigate if the Toronto Clinical Scoring System (TCS) for diabetic peripheral neuropathy (DPN) can predict early diabetic nephropathy (albuminuria) (DN) in well-controlled patients with type 2 diabetes (T2D).

Methods: In this cross-sectional study, 122 T2D patients (HbA1c <7%, eGFR >90 ml/min/1.73 m2) were enrolled.  DPN was studied using TCS (neuropathy severity was categorized as 0–5: no DPN; 6–8: mild DPN; 9–11: moderate DPN; and ≥12: severe DPN) and DN using the urinary albumin-to-creatinine ratio (UACR). DN was categorized as normo- (UACR <30 mg/g), micro- (UACR 30–300 mg/ g), and macroalbuminuria (UACR >300 mg/g). Patients were divided into two groups: no DN: UACR <30mg/g and early DN: UACR ≥30 mg/g (both micro- and macroalbuminuria).

Results: Patients with DPN (n=98) or DN (n=50) were older and with higher systolic blood pressure. Progressive and significant increases in DN prevalence were identified per DPN category. DN was present in 42% of patients without DPN, in 59% of patients with mild DPN (n=27), 65% of those with moderate DPN (n=34), and 72% in the severe DPN group (n=29). Patients without DPN had the lowest median UACR, with a narrower interquartile range, while patients with mild, moderate, and severe DPN presented increasingly higher median UACR levels (respectively UACR medians: no DPN 12 mg/g, mild DPN 57 mg/g, moderate DPN 91 mg/g, severe DPN 116 mg/g). A Spearman correlation revealed a positive linear relationship between TCS and UACR (ρ=0 29, p=0 0012).

Conclusions: DPN is significantly associated with early DN in well-controlled T2DM patients.

Comments: In this simple cross-sectional study, the authors observed a significant association between DPN and early DN. Although the data presented is interesting, it’s quite risky to talk about DPN as a “predictor” of DN, as described in the title and the text. First, because of some limitations, such as the DPN assessment (as measured only by TCS), the lack of adjustment of the association for clinical variables including medications, or the cross-sectional design of the study (which prevents the authors from identifying the causality between the two complications). Second, in literature there is evidence that DN and DPN may occur independently or there may be a bidirectional relationship between the two complications. However, the study highlights an interesting aspect: microvascular complication could be present also in patients with good glycaemic control and normal eGFR and the presence of one of these complications increased the likelihood of having more than one. In fact, there are many other factors involved in their pathogenesis, like genetic susceptibility, dyslipidemia or hypertension (KDIGO CKD Work Group Kidney Int. 2024;105:S117-S314). Even the sympathovagal imbalance, caused by cardiovascular autonomic neuropathy, can interfere with renal function (Herat LY et al JACC Basic Transl Sci. 2020;5:169-179) and it would have been interesting to obtain this data in the population studied. Anyway, routine DPN assessment, in particular using very simple tools like TCS, should be performed as frequently as we request UACR samples. Of course, prospective studies could clarify the causal relationships between the two complications and if early intervention in patients with DPN can attenuate or delay DN.

Marika Menduni

Reference. Zaki SM, El Karsh D, Moallem GA, Sembawa AHA, Alsubhani MSO, Sindi AMW, Alafif MKO, Mulla FWA. Early Neuropathy as a Predictor of Subclinical Diabetic Nephropathy in Well-Controlled Type 2 Diabetic Patients: A Cross-Sectional Study. J Diabetes Res. 2025 Nov 10;2025:3736035. doi: 10.1155/jdr/3736035. PMID: 41255512; PMCID: PMC12623091.

🔗 https://onlinelibrary.wiley.com/doi/10.1155/jdr/3736035