Prevalence of alterations in nerve conduction velocity in pediatric patients with type 1 diabetes

Incluido en la revista Ocronos. Vol. VII. Nº 4–Abril 2024. Pág. Inicial: Vol. VII; nº 4: 528.2

Autor principal (primer firmante): Alejandra Rodríguez-Ramos

Fecha recepción: 11 de abril, 2024

Fecha aceptación: 16 de abril, 2024

Ref.: Ocronos. 2024;7(4): 528.2

https://doi.org/10.58842/RXCU2640

Alejandra Rodríguez-Ramos 1, Leonor Hinojosa-Amaya 1, Karla Hernández-Trejo 1, Harold Ozuna-Díaz, Omar Israel Campos-Villareal,Marisela Mendoza-Garza 1

1 Department of Pediatrics, University Hospital “Dr. José E. González” Universidad Autónoma de Nuevo León , Monterrey, Mexico

Publica TFG cuadrado 1200 x 1200

Running Title: NERVE CONDUCTION VELOCITY ALTERATIONS

Abstract

Purpose: Peripheral neuropathy is one of the most frequent microvascular complications of type 1 diabetes, its main risk factors are poor glycemic control and evolution time of the disease; its early detection can prevent serious sequelae. We sought to evaluate the prevalence of diabetic neuropathy in patients with type 1 diabetes through nerve conduction velocity and its association with metabolic control.

Methods: An observational, retrospective, cross-sectional study was carried out, recruiting patients aged 0-18 years with a diagnosis of type 1 diabetes mellitus, the inclusion criteria were patients without comorbidities and who had routine studies including HbA1c, HDL, cholesterol, triglycerides, TSH, T4L and microalbuminuria as well as nerve conduction velocity testing in the lower limbs.

Results: 53 patients with a diagnosis of type 1 diabetes mellitus were recruited, of whom 30 (56.6%) were male. The mean age at diagnosis was 6 years ±3.36, and the mean time of evolution was 6.42 years (1-13 years). 25 (47.2%) had an abnormal nerve conduction assessment; of these, 13 (24.5%) showed alteration in the motor component, 2 (3.8%) in the sensitive component and 10(18.9%) in both. Only 11 (20.8%) reported symptoms. No relationship was found between the lack of glycemic control or the time of evolution with the presence of neuropathy.

Conclusions: There is a high prevalence of diabetic neuropathy in our pediatric population, most of whom were asymptomatic. Since no relationship was found with the time of evolution, the best method of prevention is the performance of timely screening tests.

Keywords: Diabetes Mellitus, Type 1, Diabetic Neuropathies, Pediatrics

Introduction

Diabetes Mellitus is considered a pathology of heterogeneous etiology characterized mainly by chronic hyperglycemia, as well as other metabolic abnormalities caused by defects in insulin secretion and action. 1) Type 1 diabetes is defined as a chronic autoimmune disease in which the pancreas ceases insulin production, it is estimated that there are 10-20 million cases worldwide and its incidence has been increasing considerably; even though the incidence is estimated to be low in the North American region, Mexico is in second place after the United States, with figures tending to increase during the last two decades. 2)

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During the period 2000-2010, weekly epidemiological reports from the Mexican Institute of Social Security (IMSS) reported an increase in incidence from 3.4 to 6.2 per 100,000 pediatric beneficiaries, and later, another study covering the period 2000-2018 reported a decrease to 2.83 per 100,000 pediatric beneficiaries in 2018.3) However, there are few existing studies on the prevalence or incidence of type 1 diabetes in Mexico. 4) A patient with type 1 diabetes needs a strict and self-administered management that includes the use of insulin, capillary glycemia monitoring, physical activity and balanced diet, however, many patients do not have access to all the necessary resources; and even if they have them to carry out the treatment properly, it represents a great challenge for both the patient and the family, which often leads to poor metabolic control with the subsequent appearance of complications; these include neuropathy, retinopathy, nephropathy, as well as macrovascular pathologies as well as macrovascular pathologies including atherosclerosis, which leads to a deterioration in the patient’s quality of life, as well as an increase in the economic cost of the disease. 1,3)

Diabetic neuropathy is defined as the presence of symptoms and/or signs of peripheral nerve dysfunction in patients with diabetes, after excluding other causes. 5) It affects different parts of the nervous system, so the clinical manifestations are very varied, with chronic distal symmetric polyneuropathy and autonomic neuropathy being among the most common; however, unlike in adult patients, in children and adolescents it is not possible to identify early signs and symptoms of peripheral neuropathy; in addition, in them the clinical examination is less sensitive and specific, so nerve conduction velocity is considered the gold standard for the detection of subclinical diabetic neuropathy. 6) When used in children and adolescents with type 1 diabetes, abnormalities can be found in up to 28-58% of the cases. 7)

Nerve conduction velocity is the electrodiagnostic test that yields the most information about the function of myelinated sensory and motor nerve fibers; either demyelinating or axonal neuropathy can be diagnosed through this study, referring to a demyelinating pathology when there is a prolongation of latency and decrease in conduction velocity above 40% of normal, while axonal degeneration is measured by the degree of reduction of action potential amplitudes to distal stimulation and Dyck’s criteria can be used to define the severity of diabetic peripheral neuropathy. 1,8)

Among the main disadvantages is that it is an uncomfortable study and difficult to access for most patients, which leads to an underestimation of the incidence of this pathology in children and adolescents with type 1 diabetes. 9) Other types of studies have been attempted for the detection of peripheral neuropathy, measuring the perception of vibrotactile stimulus with a biotensiometer, without conclusive results since there are no standardized cut-off points. 6,10)

Although hyperglycemia is considered the main risk factor, other factors such as duration, early onset, family history of diabetes mellitus complications, among others, also play a role; however, only the duration of diabetes and poor glycemic control have been confirmed in some studies as factors for developing diabetic neuropathy. 6,11,12)

Pediatric patients are more susceptible to present complications due to type 1 diabetes, in relation to poor glycemic control, susceptibility, social environment; implying a higher economic cost in addition to the psychological repercussions presented in them by decreasing their quality of life. In Mexico there are few studies aimed at observing the frequency of diabetic neuropathy in pediatric patients with type 1 diabetes, since the vast majority are performed in adults with type 2 diabetes, which cannot be extrapolated to the pediatric population, we sought to determine the prevalence of diabetic neuropathy in children and adolescents with type 1 diabetes by means of nerve conduction velocities and the relationship between patients’ glycemic control and the presence of peripheral neuropathy.

Materials and methods

This was an observational, descriptive, and cross-sectional study, carried out on children and adolescents with type 1 diabetes between 0 and 18 years of age who belong to the «Regalando Vida» (Giving Life) program of the Mexican Diabetes Association in Monterrey, Nuevo Leon, Mexico and who attend the Pediatrics Department of the University Hospital «Dr. José Eleuterio Gonzalez» from the Universidad Autónoma de Nuevo León (U.A.N.L). No sample size calculation was performed since all patients meeting the inclusion criteria in the department were included during the period July-September 2022.

Inclusion Criteria

  • Patients from 0 to 18 years old with a diagnosis of type 1 diabetes.
  • To Have complete control laboratory tests
  • To have a nerve conduction velocity study.

Exclusion criteria

  • Patient with type 1 diabetes older than 18 years of age at the time of recruitment.
  • Patient or family member/guardian who does not wish to participate.
  • Patient with presence of diagnosed psychiatric illnesses.
  • Diagnosis of any other neurological disease.
  • Patients with neuropathy of a cause other than type 1 diabetes.

Elimination Criteria

  • Patients who wish to leave the study.
  • Patient with incomplete clinical record

Procedure

Patients who met the inclusion criteria were verbally invited to participate, application of informed consent form was carried out in both parents as well as the patient, patients were included and their clinical record reviewed; information was obtained on sociodemographic, clinical variables (age, weight, height, Body Mass Index) as well as information about metabolic control studies routinely performed annually (glycosylated hemoglobin, lipid profile, TSH and Free T4), as well as nerve conduction studies.

Statistical Analysis

In descriptive statistics, frequencies and percentages were reported for categorical variables. For quantitative variables, measures of central tendency and dispersion (mean/median; standard deviation/interquartile range) were reported. For inferential statistics, the sample distribution was evaluated using the Kolmogorov-Smirnov test. To compare categorical variables, Pearson’s Chi-square test was used. Variables found to be statistically significant on X2 test were subjected to Spearman’s correlation test between categorical variables. A value of P<0.05 was considered significant. A database with alphanumeric characteristics was obtained in Microsoft Office Excel software to be later analyzed with The SPSS version 24.0 statistical package.

Results

A total of 53 patients were recruited, excluding one because he had a cognitive deficit and 27 because they did not have a complete evaluation (laboratory and/or nerve conduction studies). The average age of the group studied was 12 years ±3.48. 30 patients (56.6%) belonged to the male sex. The mean age at which Diabetes Mellitus was diagnosed was 6 years ±3.36. Regarding Body Mass Index, the average was 20kg/m2 ± 4.05, with ranges from 12.98kg/m2 to 22.69kg/m2. The mean years of disease evolution was 6.4 years ± 3.19 with a range from 1 to 12 years. 25 patients (47.2%) obtained an abnormal neuronal conduction assessment; 13 (24.5%) patients presented abnormal results in the motor component, 2 (3.8%) presented alterations in the sensitive component and 10 (18.9%) presented alterations in both the motor and sensitive component. Of the total number of patients identified with alterations in nerve conduction velocity, 76% (19) had mild neuropathy and 24% (6) had moderate neuropathy. No patients with severe neuropathy were reported.

Regarding the laboratory tests studied, 68% (36) of the patients had glycosylated hemoglobin levels above the established target according to the recommendations of the American Diabetes Association. 13) Regarding microalbuminuria assessment, normal values were reported in 96% (51) of the patients. Cholesterol values were within the range in 56.6% (30), high values in 11.3% (6) and borderline values in 32.1% (17).14) Other results of laboratory studies can be seen in table 1. As for the bivariate analysis between clinical examinations and nerve conduction velocity, no association was demonstrated between poor glycemic control or metabolic dyscontrol and the presence of diabetic neuropathy. These results can be seen in table 2

Regarding the motor component, the results and description can be seen in figure 1 and 2, in these figures the mean and median are lower in those who obtained normal results compared to those with abnormalities. Similarly, regarding the descriptive analysis of the amplitudes of the motor component, the figures 3 and 4 present the result found, in which it can be observed that, for each motor nerve, a slightly higher range was observed in those who obtained normal results compared to those who had some alteration. Having evaluated the neurological properties of the motor nerves under study, it was described and illustrate the conduction velocities that resulted from this evaluation in this group of patients, obtaining the data in figure 5.

To study the factors involved in the presentation of conduction disturbances, the means of age were compared between the groups that presented results with alterations in conduction velocities versus those that did not, and it was observed in the analysis of variance that there was no association between patient age, age at diagnosis or years of evolution of type 1 Diabetes Mellitus.

In the evaluation between the risk factors with the development of motor conduction alteration, no statistically significant results were found either, the results can be seen in table 3.

Regarding the sensitive component, the results and description can be seen in figure 6 and 8. Having evaluated the neurological properties of the sensory nerves under study, we describe and illustrate the conduction velocities that resulted from this evaluation in this group of patients, obtaining the data in figure 8.

In the descriptive analysis of the conduction velocities of the sensitive component studied, the results were observed as shown in the table 4.

Discussion

According to the results obtained, we can identify that in this population studied there is a slight predominance towards the male sex, which is similar to what has been observed in the literature where it is reported that the incidence is similar between both sexes with a predominance towards the male sex in some populations. In addition, the mean age at diagnosis of the disease was 6 years, like the data already known, which reflects that there are no significant differences in the characteristics of the patients in the different populations studied. 11,12) Regarding the main objective of the study, it was found that there is a high prevalence of alterations in nerve conduction velocity, which is considered the gold standard for the identification of diabetic neuropathy in pediatric patients, reporting that 47% of the patients studied had some degree of alteration. Of this percentage, 24.5% presented abnormal results in the motor component, 18.9% presented alterations in both the motor and sensitive components and 3.8% showed purely sensitive alterations.

In a study conducted by Ghaemi et al. 15), the presence of diabetic neuropathy was evidenced by alterations in nerve conduction velocity in 24% of the patients studied, of which only 25% presented any symptoms; however, the prevalence reported varies depending on the region and the population studied, observing wide ranges from 28% to 58%.

Therefore, the results obtained in this study are of great importance since there is no previous literature that reports the prevalence of diabetic neuropathy in pediatric patients in our region either by means of quantitative sensitivity studies or by nerve conduction velocity.

Although Mexico is one of the countries with the highest incidence of type 1 diabetes and diabetic neuropathy is one of the main complications that greatly affect the quality of life of patients, there are no reports in our country about the incidence of these present complications, much less the predominance of sensory or motor involvement, as well as its association with other risk factors.

Of the patients who presented an abnormal nerve conduction velocity, only 20% showed symptoms compatible with diabetic neuropathy, among which lower limb paresthesia and mild pain predominated; however, one of the limitations of this study is the subjectivity of these symptoms since they present with great variability in terms of clinical presentation and complexity, without having a scale or way of assessing their severity to make a comparison between the degree of alteration in the nerve conduction velocity and the severity of the symptoms. In addition, since this was a transversal study, it was not possible to perform a detailed physical examination for neurological assessment in this group of patients, as it would have allowed us if we had conducted a prospective, longitudinal study.

Due to the relativity in the presence or not of symptoms, in some regions that do not have access to electrophysiological studies, sensitivity tests for tactile and vibration perception threshold are used as a screening method for the detection of neuropathy in early stages, however, their performance and interpretation depends on the cooperation of the patients, which can be complicated in the pediatric population.

According to the latest recommendations of the American Diabetes Association, a physical examination including inspection of the lower limbs, palpation of pulses, determination of proprioception, vibration, and sensation along with an assessment of neuropathic pain symptoms is recommended at the onset of puberty or at age 10 years (whichever comes first) once more than 5 years have passed since diagnosis. 13)

With these results, we can highlight the importance of conducting more studies to determine the prevalence of this pathology in different populations and the associated risk factors in order to update the protocols and guidelines already established, and to standardize access and early performance of nerve conduction velocities in all patients diagnosed with type 1 diabetes both at the time of debut and on a routine basis, since we can observe that most of the patients who presented alterations in this study were totally asymptomatic, with neuropathy being an incidental diagnosis at the time of intentionally searching for it by means of electrophysiological studies, and that, if we base ourselves only on the presence or absence of symptoms, it could be detected late.

Regarding the analysis of the laboratory results that were studied, we can observe that most of the patients were within the normal ranges for their age for each of the studies, except for the glycosylated hemoglobin where it was observed that most of the patients (67%) presented a value above 7.5%, which shows the lack of glycemic control that these patients have in spite of being patients and families belonging to an association where courses and classes are given to contribute to the education of these patients. These were considered because previous studies have demonstrated the association of poor metabolic control with the presence of diabetic neuropathy. Sajic et al. 16), demonstrated a statistically significant relationship between the abnormal HbA1c level and the appearance of neuropathy; as well as Ji Na et al. 17) , observed a correlation between hyperlipidemia and diabetic neuropathy; however, most of these studies include adolescent and adult patients with type 1 diabetes of long duration and making the diagnosis through quantitative sensitivity tests, which differs in the case of our study population.

In our case, when analyzing the contingency tables, no relationship was observed between abnormal metabolic control results and the presence of diabetic peripheral neuropathy. Although 80% of the patients presenting an alteration in nerve conduction velocity showed elevated HbA1c levels, up to 57.1% of the patients without diabetic neuropathy also reported HbA1c above the normal value, which is why we were unable to establish a direct relationship between these two variables, presenting a p 0.088.

This could be related to what was previously commented, since the studies that have been carried out to demonstrate the presence of diabetic neuropathy and its association with metabolic dyscontrol include patients of greater age and time of evolution, in which a relationship between these variables has been evidenced. In a study carried out by Hajas G et al. 11), they conducted a 10-year follow-up of patients with type 1 diabetes aged 3-28 years who underwent electrophysiological evaluation for the detection of diabetic neuropathy, observing an increase in the prevalence of this pathology from 24.2% at the time of the first evaluation to 62.9% 10 years later and relating it to poor glycemic control.

Subsequently, when evaluating the relationship between the time of evolution of diabetes and the presence or absence of neuropathy, unlike what is known from other studies, it was found that there is no statistically significant difference between these variables, with a mean of 6.4 years of evolution. However, the range of time of evolution since the detection of diabetes varied widely, ranging from 1 to 13 years. This is of great importance because, although no statistical association was found, our results differ from the general recommendations to start screening at 5 years after diagnosis, as they show that some patients present electrophysiological alterations within the first months after diagnosis.

Due to the aforementioned, these results help us to understand that the annual follow-up by means of laboratory studies without further investigation in a complete neurological physical examination, direct interrogation of the symptoms and above all the early performance of electrophysiological studies, is not enough and the patient cannot be established as out of risk of complications when having blood studies within the normal range, since as we can observe in the case of our patients, most of them presented an adequate metabolic control and even so, 47% of these patients already showed changes compatible with diabetic neuropathy.

This study is of great interest as it can be a starting point for further research in this area, either to assess the prevalence in other regions with a different population characteristic, or even within the same population to visualize the changes observed over time and with the control or lack of control of the same underlying pathology.

It was shown a high prevalence of diabetic peripheral neuropathy in the pediatric population with type 1 diabetes, with the motor component being more predominant and presenting mostly in a subclinical form. This initiates a watershed in what was already known about the pathology and its complications since we can demonstrate the importance of performing timely detection tests, in this case the nerve conduction velocity for an intentional search of its alterations so that, in this way, we can improve the living conditions of our patient.

Although we have not found a relationship at this time between metabolic dyscontrol and the presence of neuropathy, we must emphasize the importance of maintaining glycosylated hemoglobin levels within the normal range, since this is one of the main risk factors for developing not only nervous disorders but also the multiple macro and microvascular complications caused by diabetes, we would recommend a detailed neurological physical examination and electrophysiological studies from the time of diagnosis and on a routine basis in order to detect incipient changes and thus perform targeted interventions to prevent their progression

Ethical statement

The study was performed according to the Helsinki Declaration Institutional Review Board (IRB), written informed consent was obtained.

Conflicts of interest

The authors have nothing to disclose.

Acknowledgments

None

Anexos – Prevalence of alterations in nerve conduction velocity in pediatric patients with type 1 diabetes.pdf

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