The complex relationship between diabetic polyneuropathy and circadian BP rhythm

Aims: To study the relationship between the progression of diabetic polyneuropathy (DPN) and impaired circadian blood pressure (BP) variability.

Methods: 154 patients with diabetes (139 with T2DM and 15 with T1DM), who were hospitalized for hyperglycaemic control, were recruited. Biochemical tests and screening for complications were performed. Signs and symptoms of DPN were evaluated as well as nerve conduction studies (NCS) to measure compound muscle (CMAP) and sensory nerve action potential (SNAP), and conduction velocities of tibial and peroneal nerves. Then patients were classified according to the Baba classification (stage 0-IV based on the number and degree of abnormalities in SNAP and CMAP) and to the clinical staging of the Diabetic Neuropathy Study Group in Japan (presence of ≥2 out of 3 abnormalities among: 1. bilateral numbness, pain or abnormal sensation in the feet attributable to DPN; 2. decreased/absent bilateral ankle reflexes; 3. decreased bilateral vibratory sensation in the medial malleoli).

Holter electrocardiography and 24-h free-acting BP measurement were performed. Patients were classified as extreme-dippers, non-dippers, dippers and risers according to a decrease of nocturnal BP by ≥20%, 10–20%, 0–10% and ≤0%, respectively. All patients underwent coefficient of variance of the R-R interval (CVRR testing) and 24-h heart rate variability (HRV) data were analysed using the power spectrum analysis method to quantify sympathetic and parasympathetic nerve activity. Clinical staging for DPN, BP monitoring and HRV data were compared.

Results: As the severity of DPN progressed, the degree of nocturnal BP reduction decreased (for systolic BP p=0.003 and for diastolic BP p=0.004) and the percentage of patients with riser-type circadian BP pattern increased (for both systolic and diastolic BP p<0.001). In the multivariate logistic regression analysis, the severity of DPN and urinary albumin excretion were independently associated with the percentage of patients with riser-type BP profile.

Conclusions: Patients with progressive DPN showed impaired circadian BP variability and the progression of DPN was associated with riser-type circadian BP variability.

Comments: In this accurate study, the authors strengthen the relationship among DPN, circadian BP rhythm and nocturnal hypertension. Although the link between autonomic neuropathy and non-dipping has been well explored, the topic is still of great interest because of the increased cardiovascular risk that changes in BP variation entail. In particular, patients with renal impairment often have abnormal circadian BP variation but the association found between DPN and abnormal circadian BP pattern seems to be independent of known factors such as urinary albumin content, BMI, insulin therapy and RAAS inhibitor status. Moreover, impairment of day-night BP variation is already present in early stages of DPN.

Certainly, the choice of DPN classification not used internationally (i.e., the Baba classification, also not widely used in clinical practice for its complexity and the need for a clinical staging) and of HVR for the autonomic evaluation (instead of the cardiovascular reflex tests) can be considered study limitations. Further studies would allow us to clarify these results and understand the relationship between DPN, BP variability and nephropathy. However, the suggestion of DPN as a possible independent marker of the prognostic-significant BP rising condition is of interest.

Marika Menduni

Reference: Yamagami D, Deguchi T, Arimura A, Nishio Y. Relationship between the progression of diabetic polyneuropathy and impaired circadian blood pressure variability. J Diabetes Investig. 2024 Dec 18. doi: 10.1111/jdi.14282. Epub ahead of print. PMID: 39696835.

🔗 https://onlinelibrary.wiley.com/doi/10.1111/jdi.14282