4.1. Characteristics of the Study Cohort
In this study, we investigated the clinical manifestations and neurophysiological characteristics of a cohort of 61 patients diagnosed with type 2 diabetes according to the ADA’s standards (2019) at 103 Military Medical University Hospital. In terms of clinical and subclinical characteristics, our results showed that almost half of the patients had hypertension, and they had inadequate control of blood glucose, HbA1c, triglycerides, and cholesterol. Specifically, the average blood sugar level was 14.22 ± 4.96 mmol/L, and the average HbA1c level was 10.23 ± 2.84%. These findings are consistent with those of previous studies that have shown poor glucose control in patients with type 2 diabetes [12
presents the clinical manifestations of peripheral nerve damage in the studied cohort, with epidermal numbness (54.1%) and crude tactile reduction (52.5%) being the most common symptoms. The similarity of these results with those obtained by Kimura (2013) suggests that the nerve conduction rates are consistent across different populations [21
]. Most patients did not have movement disorders (95.1%) or impaired deep feelings (93.4%). Our study reports a higher rate of physical ability and entity compared to some previous studies, which could be attributed to differences in the means of assessing neuropathy [22
]. However, this difference is not statistically significant. This may be attributed to differences in the means of assessing neuropathy, highlighting the need for standardized assessment methods to obtain accurate results.
The study also examined differences in peripheral nerve parameters between age groups and genders. Interestingly, there were no significant differences in any of the measured parameters between age groups or between men and women. Similarly, Rubin et al. reported in his research that nerve conduction rates in infants are equal to that of adults [23
]. A recent systematic review of ultrasonography studies indicated that there was a weakly positive trend between age and tibial nerve CSA for both diabetic patients (r = 0.35, p
= 0.24) and diabetic patients with DPN (r = 0.27, p
= 0.34), though it was not statistically significant [24
When compared to other authors’ research, the study’s findings are consistent with previous studies that have reported similar changes in peripheral nerve parameters in response to various interventions or medical conditions. For instance, a study by McCorquodale and Smith (2019) reported decreased conduction velocities in the peroneal nerve following exposure to cold temperatures, which is similar to the present study’s findings [25
The study’s results, as presented in Table 2
, Table 3
and Table 4
, indicate several significant changes in the measured peripheral nerve parameters. The tibial nerve’s peripheral latent potential time increased, whereas the peroneal nerve’s peripheral latent potential time decreased. Additionally, the response amplitude of the tibial nerve increased, while the peroneal nerve’s response amplitude decreased. The conduction rate of both nerves decreased, with the peroneal nerve experiencing a greater reduction. However, there were no significant differences between the right and left sides in any of the measured parameters.
In 1997, Al-Sulaiman and colleagues conducted a study on electrophysiological results in 29 newly diagnosed diabetic patients. The study found that the latency time of the tibial nerve was 4.8 ± 1.02 ms, and the peroneal nerve was 6.0 ± 1.08 ms, which was more significant than the findings in our study. The difference in the results could be attributed to the fact that our study had a larger sample size, including 39 men and 22 women, and a broader range of disease duration [26
]. Another study conducted in 2002 by Muflih and colleagues examined 228 diabetic patients who were divided into two groups: those with insulin-dependent diabetes and those with non-insulin-dependent diabetes [27
]. The patients were further divided into subgroups based on their disease duration. The study measured seven nerves with potential time, velocity, and potential amplitude as parameters. Similarly to our results, the findings showed that potential time increased, neuropathic velocity decreased, and potential measures decreased in patients with diabetes for more than ten years compared to those with a shorter disease duration [27
]. The study also found that the potential TG, amplitude, and velocity were higher than our study. Moreover, the presence of lesions in diabetic patients can affect the patient’s pass-through parameters. In summary, the studies suggest that the duration of diabetes can have an impact on the electrophysiological results, and other factors such as gender, age, and the presence of lesions should also be considered when interpreting the findings [29
]. Muthuselvi et al. (2015) compared neurotransmitters in elderly diabetic patients to ordinary people, and found that the amplitude and velocity of the lower limb sensory nerve in diabetic patients decreased compared to the group without diabetes [30
]. This is consistent with our study results, which also noted a decrease in the speed of the lower limb sensory nerve in patients with type 2 diabetes. Similarly, a 2016 case-control study by Aruna and colleagues found that the tibial and peroneal nerves in diabetic patients had lower amplitude and velocity compared to healthy subjects, possibly due to the study population and longer duration of diabetes [31
4.2. Relationship between Indicators of Neurotransmitter, Nerve Damage Rate Clinical, and Biochemical Characteristics
indicates that patients with clinical signs of nerve damage were primarily observed in those who had diabetes for 5 to 10 years or more than 10 years. The group with the disease over 10 years had the highest percentage (8.19%) of patients with a severe burning sensation, while the reduction in crude touch was more pronounced in the 5–10 years disease group (22.95%) and the over 10 years disease group (21.31%). The movement disorder rate was 1.63% in the 5–10-year disease group and 3.27% in the over 10 years disease group. These findings suggest that the duration of diabetes has a significant association with the clinical manifestations of peripheral nerve damage. Other studies have reported similar findings. For instance, Partanen et al. (1995) found that the incidence of peripheral neuropathy was positively correlated with the duration of diabetes [32
]. In another study by Javed and colleagues (2015), the authors reported that the duration of diabetes was associated with an increased risk of developing neuropathic pain [33
In our study, all patients exhibited changes in neurotransmitter indexes, with 13 patients (21.31%) displaying no clinical symptoms of peripheral neuropathy, including one patient newly diagnosed with diabetes. Additionally, the difference in nerve damage rates between groups with disease duration less than 5 years, from 5 to 10 years, and over 10 years was not statistically significant. These findings suggest that nerve damage, as indicated by alterations in neurotransmitter levels, may occur prior to the onset of clinical symptoms, potentially even before a diabetes diagnosis. Pirart (1978) conducted a study of 4400 diabetic patients and found that the clinical symptoms of polyneuropathy detected at the time of diabetes diagnosis were only 7.5%. However, this rate increased to 40% after 20 years and 50% after 25 years of illness [34
]. Vinik (2013) stated that neuropathy caused by diabetes accounted for 90% of cases, and this complication was usually most evident after a year of diabetes diagnosis, with clinical manifestations of nerve impulse conduction in foot muscles as described by Terkidsen and Christensen (1971) [35
The group with a normal body mass index (BMI) ranging from 18.5 to 22.9 demonstrated the highest rate of nerve damage, with the right tibial nerve (32.78%), left tibial nerve (37.7%), right peroneal nerve (48.33%), left peroneal nerve (46.66%), and left superficial peroneal nerve (10.34%) all being affected. However, the difference in nerve damage rates among different body types was not statistically significant. There was also no significant difference in the neurotransmitter indexes of the tibial nerve, peroneal nerve, and right and left superficial peroneal nerve between patients with HbA1c levels ≤ 7.5% and those with levels > 7.5%. The study also found a positive correlation between diabetes duration, HbA1c levels, and abnormal neurotransmitter levels in the lower limbs. A significant difference was observed only in tibial nerve latency, peroneal nerve latency, and peroneal nerve velocity. In contrast, no significant difference was noted in the incidence rates of other injuries to the tibial, peroneal, and superficial peroneal nerves between patients with and without hypertension. These findings suggest that peripheral nerve damage is influenced by a complex interplay of multiple risk factors, and further research is required to fully comprehend the underlying mechanisms involved.
As shown in Table 8
, the incidence of nerve damage is significantly higher in patients with type 2 diabetes who have poor blood sugar control compared to those with good control. Additionally, the rate of nerve damage in patients with dyslipidemia was higher than in those without dyslipidemia. This is consistent with the findings in a study conducted in 1995 by Partanen and colleagues, in which inadequate blood sugar control was a major factor contributing to polyneuropathy in most patients [32
]. Furthermore, in 2014, Cho and their colleagues conducted a 6-year follow-up study to investigate the role of insulin resistance in neuropathy in Koreans with type 2 diabetes, and found that LDL cholesterol and triglyceride levels were also associated with the development of neuropathy [37
]. The development of peripheral neuropathy in diabetes is a complex pathogenic mechanism that includes many factors, such as hyperglycemia, duration of disease, age-related neural decline, and hypertension [38
]. Hyperglycemia, which is high blood sugar, can contribute to the development and progression of diabetic cardiomyopathy and peripheral neuropathy through various biochemical pathways. These pathways include the polyol pathway, the hexosamine pathway, activating excess or inappropriate protein kinase C isoforms, disturbances in Na/K pump function, and accumulation of end product metabolism. Each pathway can cause an imbalance in the cell’s mitochondrial redox state and lead to the excess formation of reactive oxygen species (ROS), which can cause oxidative stress in the cell. This stress can activate the poly (ADP-ribose) polymerase (PARP) pathway, which can affect the expression of genes involved in promoting inflammatory responses, microvascular deficits, and disorders of nerve function. [40
]. Hyperuricemia, which is high blood uric acid, and other metabolic changes can contribute to the faster onset and progression of both cardiomyopathy and diabetic peripheral neuropathy. Some evidence suggests that various toxins, including parathyroid hormone (PTH) and β2-microglobulin (elevated levels in patients with ESRD), may also play a role in the development of nerve urea blood.
also demonstrated that the rate of nerve damage was significantly higher in type 2 diabetic patients with reduced renal function, with a glomerular filtration rate of less than 60 mL/ph/1.73 m2
. According to Pop-Busui and their colleagues, peripheral neuropathy can be detected in the early stages of reduced renal function in type 1 diabetics and at the time of diagnosis in patients with type 2 diabetes [42
]. However, the entire mechanism of neurotoxicity in diabetic patients with renal failure is unclear. Older experimental evidence suggests that neurotoxicity related to the urea state may be due to an excitability change in membranes caused by an inhibitory effect of the axial Na/K pump, which will directly eliminate the contribution of the hyperpolar pump current to the membrane potential, leading to the accumulation of extracellular K+
causing depolarization. However, recent human evidence suggests that hyperkalemia, which is high blood potassium, rather than Na/K pump dysfunction, is a significant cause of urea depolarization and may be a contributing factor in the development of peripheral neuropathy [22
Overall, our study provides valuable insights into the characteristics of patients with type 2 diabetes in the studied cohort. However, our findings are limited by the relatively small sample size and the fact that the study was conducted at a single hospital. Future studies with larger and more diverse cohorts are needed to confirm and extend our findings.