Glycemic variability is indeed associated with sural nerve conduction velocity in patients with type 2 diabetes

Aims: Recent evidence showed that glucose variability could be considered as an independent risk factor for diabetes complications. The aim of this work was to assess the possible association between CGM-derived glucose variability metrics with sensory nerve action potential (SNAP) and sensory conduction velocity (SCV) of the sural nerve obtained by the DPNCheck in outpatients with type 2 diabetes (T2D).

Methods: It is a retrospective, cross-sectional study conducted in outpatients with T2D using FreeStyle Libre Pro (FSL-pro) as a blinded CGM device. FSL-pro data of the middle 8 days were analysed considering all the glucose variability parameters. Diabetic neuropathy was assessed using DPNCheck, a new point-of-care device to detect SCV and SNAP of the sural nerve at the bedside in a quickly and reliable way with a sensitivity of 92% and a specificity of 82% compared with the gold standard nerve conduction study.

Results: 304 patients with T2D were included (mean age 68.8±9.3 years, 57.2% males, mean HbA1c 7.1±0.7%, mean disease duration 14.4±8.7 years). Using a simple linear regression analysis most CGM-derived glucose variability metrics were associated with SCV except for MAGE and LBGI and no significant associations were found with amplitude SNAP. HbA1c were significantly associated with both SCV and SNAP amplitude. With a multiple regression analysis after adjustment for several clinical parameters the significant associations between SCV and CGM-derived glucose variability parameters remained but these associations were not confirmed after adjustment for HbA1c. When considering subgroups with well-controlled and poorly-controlled HbA1c, after correction for HbA1c, most CGM-derived glucose variability parameters remained significantly associated with SCV in subgroup with well-controlled HbA1c values.

Conclusions: In this population of outpatients with T2D, several CGM-derived glucose variability metrics were significantly associated with SCV assessed using DPNCheck.

Comments. These findings are interesting in particular because glucose variability seems to be independently associated with nerve conduction velocity in patients with T2D and well controlled HbA1c. These results are in accord with literature data supporting a link between higher glucose variability and increased risk of DPN in patients with diabetes. Thus, reducing glucose variability may be another target to reach to prevent slowing SCV in particular in patients with well-controlled HbA1c.

Further longitudinal cohort studies are needed to confirm these findings with standardized protocols for CGM data collection and analysis.

Ilenia D’Ippolito

Reference. Morita M, Sada K, Hidaka S, Ogawa M, Shibata H. Glycemic variability is associated with sural nerve conduction velocity in outpatients with type 2 diabetes: Usefulness of a new point-of-care device for nerve conduction studies. J Diabetes Investig. 2024 Aug;15(8):1075-1083. doi: 10.1111/jdi.14211. Epub 2024 Apr 29. PMID: 38685597; PMCID: PMC11292385.

https://onlinelibrary.wiley.com/doi/10.1111/jdi.14211