Glucose Fluctuation Linked to Slowed Nerve Conduction Velocity in Youth With T1D

Glucose variability, especially the standard deviation (SD) of mean glucose, was strongly predictive of reduced nerve conduction velocity (NCV) in children and young adults with type 1 diabetes (T1D) in a study published in the journal Diabetes.

The findings, which investigators described as surprising, suggest that high glucose variability may be an early subclinical manifestation of diabetic peripheral neuropathy (DPN) and other microvascular complications that may impact quality of life. Therefore, glucose variability warrants more attention in the management of patients with T1D, according to the authors of the study.

“Because of the increasing incidence of type 1 diabetes worldwide, incompletely understood pathogenesis, and missing causal therapy for DPN, we conducted this study to learn more about the prevalence of and risk factors for DPN,” the authors wrote. “We used NCV as the most sensitive and objective screening tool for DPN and looked for clinical signs and symptoms.”

Illustration of neurons | Image credit: Igor - stock.adobe.com

The prospective study included 53 children aged 5 to 23 years who were recruited at the Children’s Hospital of Eastern Switzerland from 2016 to 2022. Researchers recorded glycemic targets and conducted a cross-sectional analysis of peroneal, tibial, median motor, and median sensory nerves in the cohort. A control group of 50 healthy children served as a comparator.

When compared with age- and height-matched healthy children, the T1D subgroup aged 10 to 16 years showed a significant reduction in NCV across the 4 nerves that were assessed. The most notable difference between the T1D and control groups was seen in the peroneal nerve, which the researchers then focused on when performing regression analyses of the entire diabetes group. The findings related to this nerve were adjusted for height (dNCV), which has a known slowing effect on peroneal NCV.

Peroneal dNCV was negatively associated with mean hemoglobin A_1C (HbA_1C) (R = –0.37; P = .001) and mean glucose in the preceding 3 months (R = –0.42; P = .016), as well as concomitantly measured HbA_1C (R = –0.22; P = .022). However, dNCV was not significantly associated with time in range.

Glucose SD was also highly statistically significantly associated with dNCV in the entire diabetes group (R = –0.32; P = .0013). A multiple regression model was used to investigate this finding further using the variables NCV, glucose SD, and height, and glucose SD and height explained 60% of the variability of peroneal NCV in the model. Overall, NCV and glucose SD showed a negative association, with a lesser association in taller patients than shorter patients.

“The slowing of NCV was not associated with clinical symptoms, but as a possible sign of DPN, a reduced vibration perception threshold was found in 57% of individuals with diabetes,” the authors wrote. “Our data align with previous findings that symptoms of neuropathy are rare in children and adolescents, despite its pathogenesis having already developed.”

While reduced NCV is not the same as DPN, the authors noted that it represents a functional limitation in the definition of “preneuropathy.”

“In conclusion, more attention should be paid to glucose variability in the care of individuals with diabetes because the particularly robust correlation for glucose SD supports the finding that glucose variability is an independent risk factor for DPN,” the authors concluded.

Reference

Oberhauser SS, l'Allemand D, Willems EP, et al. The slowing of peripheral nerve conduction velocity in children and adolescents with type 1 diabetes is predicted by glucose fluctuations. Diabetes. Published online September 12, 2023. doi:10.2337/db23-0063