Slowing of Peripheral Nerve Conduction Velocity in Children and Adolescents With Type 1 Diabetes Is Predicted by Glucose Fluctuations

Abstract

Nerve conduction velocity (NCV) abnormalities are the forerunners of diabetic peripheral neuropathy (DPN). Therefore, this study aimed to analyze the effect of glucose profile quality on NCV in children and young adults with type 1 diabetes. Fifty-three children age 5 to 23 years with type 1 diabetes were recruited to participate in the study, which was conducted prospectively at the Children's Hospital of Eastern Switzerland from 2016 to 2022. Glycemic targets were recorded, and a cross-sectional nerve conduction study analyzing the peroneal, tibial, median motor, and median sensory nerves was performed. Data were compared with those of a control group of 50 healthy children. In the age- and height-matched diabetes subgroup aged 10-16 years, all four nerves showed significantly slower NCV, most pronounced for the peroneal nerve. Because height has a retarding effect on peroneal NCV, NCV was adjusted for height (dNCV). Peroneal dNCV correlated negatively with long-term glycated hemoglobin and highly significantly with glucose variability. Because high glucose variability clearly increases the risk of neuropathy, together with but also independently of the mean glucose level, this aspect of glycemic control should be given more attention in the care of individuals with diabetes.

Article highlights: There is a strong need for the better identification of early subclinical manifestations of microvascular complications, such as diabetic peripheral neuropathy, in young individuals with diabetes. To identify peripheral neuropathy and contributing factors at an asymptomatic disease stage, and to exclude height as a known modifying factor, we performed association studies of height-adjusted nerve conduction velocity. We identified high glucose variability, especially the SD of mean glucose, as an unexpectedly strong predictor of slowed nerve conduction velocity. More attention should be paid to the goal of low glucose variability in the care of individuals with diabetes.

Graphical abstract

Figure 1

A–D: Box plots for the NCV of the age- and height-matched control and diabetes subgroups age 10 to 16 years in four nerves (n.) analyzed: peroneal (A), tibial (B), motor median (C), and sensory median (D). The significance level of the Wilcoxon test is specified above the box plots, in which the box represents 50% of the data, respectively, the interquartile range (IQR); whiskers show the most extreme observed values that still fall within 1.5 times of the IQR; points represent the more extreme values.

Figure 2

A–D: Scatter plots relating the residual of the dNCV on the y-axis to the following glycemic targets on the x-axis: HbA_1c (n = 53) (A) and, for individuals wearing a CMG device >70% of the time (n = 33), glucose variables TIR (B), CV (C), and glucose SD (D). The Pearson correlation factor (R) was calculated for each graph, shown in the upper-left corner of each panel. For conversion of HbA_1c presented in percentage to mmol/mol, please use https://www.diabetes.co.uk/hba1c-units-converter.html.

Figure 3

A: Scatter plot of the residual of the dNCV on the y-axis to age at disease onset on the x-axis. B: Scatter plot relates dNCS to duration of diabetes. In both panels, the dots are colored according to three levels of the glucose SD: <3 mmol/L (black dots), 3–6 mmol/L (green dots), and >6 mmol/L (orange dots).