The independently associated with DPN (Table 3). 2. Discussion

The participants’ mean age was 45.3 ± 11.1 years,
and the male-to-female ratio was 0.95:1. The mean duration of prediabetes was
0.65 ± 0.78 years, and the mean BMI was 26.17 ± 4.4 kg/m2. The mean
FPG, 2-hr OGTT PG, and HbA1c was 105.4 ± 11.2 mg/dl, 158.1 ± 27.48, and 5.9 ± 0.4%.
Geographically, the study group predominantly comprised participants from
eastern (54.8% of participants) and southern India (41.3%).

Prevalence of DPN: Overall, 38 patients were detected to have DPN,
rendering a prevalence of 9.2%. A total of 1.7% of patients had NDS ? 6.
Meanwhile, 4.8% of patients had an NDS ? 3 and 2, in
patients with prediabetes.12 Another study reported a 15.6%
prevalence of neuropathy using abnormal vibratory perception and thermal
discrimination thresholds as the diagnostic criteria.22 However, a
low rate of neuropathy has also been reported in a few studies.23, 24
Differences in the diagnostic criteria, screening techniques, participant
characteristics, genetic and ethnic factors, and subjective nature of screening
tests could explain the variation in the frequency of DPN noted among different
studies. In general, studies
employing NCS have reported a higher prevalence than other diagnostic
modalities.

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Biothesiometry is a commonly used screening
technique for DPN in epidemiological studies because of its ease, high
specificity, capability to predict risk of foot ulceration, and low cost.25,
26 However, it has a low sensitivity because it detects only large-fiber
dysfunction, whereas small-fiber neuropathy is typically more common in early
DPN.27 Hence, a combination of a validated screening examination
score such as NDS with VPT can yield a higher sensitivity for detecting DPN
than biothesiometry alone, as the results of our study indicate. Although NCS
is still considered to be the gold standard for the diagnosis of DPN, it is
difficult to employ for large-scale epidemiological purposes, and small-fiber
neuropathy might be missed by NCS.28, 29 A combination of ankle
reflex and vibration sense has been shown to have a high sensitivity in the
diagnosis of DPN.30 In addition, several studies have shown the
capability of NDS to accurately diagnose patients with DPN.31, 32
Hence, we believe that the indicators of the neuropathy employed in our study
are valid.

We found that age, smoking, and hypertension are
independent and significant factors correlated with DPN. This is in accordance
to findings from previous studies. In a previous study, age was independently
associated with DPN among participants with prediabetes, diabetes, and
normoglycemia.24 Hypertension and smoking were independent risk
factors for the development of neuropathy in patients without neuropathy at
baseline in the EuroDIAb study.33 Factors other than hyperglycemia
could also be involved in the pathogenesis of neuropathy in prediabetes.34
Evidence points to the involvement of components of the metabolic syndrome,
specifically obesity, hypertension, and dyslipidemia in the pathogenesis.
Oxidative stress, endothelial perturbation, and elevated inflammatory markers
frequently associated with metabolic syndrome are thought to contribute to
neuropathy.34-36 Similarly, oxidative low-density lipoprotein
particles have been shown to induce direct toxicity to the neuronal cells. 37

DPN is a major contributory factor to increased
morbidity and lower-limb complications associated with T2D.38-41 In
addition, individuals with impaired glucose metabolism who have neuropathy are
nearly four times more likely to have retinopathy and two times more likely to
have albuminuria.42 Autonomic neuropathy in prediabetes has been
linked with increased risk of cardiovascular mortality.43, 44 Hence,
the early diagnosis of DPN in the prediabetes stage play an important role in
preventing complications such as foot ulceration/amputation and in initiating
intervention strategies directed toward better glycemic control, cardiovascular
protection, and patient education. This is particularly relevant in a country
like India with a high burden of T2D and prediabetes.

The strengths of our study are the large sample
size, use of the OGTT for the accurate diagnosis of IGT, and use of a
combination of a validated examination score and VPT for the diagnosis of DPN.
However, our study also has several limitations. First, it is a cross-sectional
study conducted in a tertiary care center. Population-based epidemiological
studies are required to confirm our findings. Second, NCS was not performed in
the patients to confirm the diagnosis of DPN. However, we believe the results
would not be much different if NCS had been performed.