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 was0.65 ± 0.78 years, and the mean BMI was 26.17 ± 4.4 kg/m2.

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The meanFPG, 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 fromeastern (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 < 6 with a DNS score of ? 1. The prevalence rates ofDPN based on the NDS and biothesiometry were 6.5% and 5.1%, respectively (Table1).

A significant correlation was observed between NDSand VPT values (r = 0.54, P = 0.01).

Patients in the DPN (n = 38, 9.2%) groupwere significantly older and had a greater duration of prediabetes than thosein the non-DPN group (n = 376, 90.8%).

The HbA1c value was also significantlyhigher in the DPN group than in the non-DPN group (6.1% vs 5.9%, P = 0.01)(Table 2).Factors associated with DPN: Univariate analysis revealed age, duration ofprediabetes, HbA1c, hypertension, and smoking as significant predictors of DPN.

In the multivariate logistic regression model after adjustment for theconfounding factors, only age (OR: 1.11; 95% CI: 1.06–1.15, P = < 0.

001),smoking (OR: 3.01; 95% CI: 1.01–9.20, P = 0.04), and hypertension (OR: 3.34;95% CI: 1.43–7.

77, P = 0.005) were independently associated with DPN (Table 3).  2.

          DiscussionOur study reports on the prevalence of andfactors associated with DPN in patients with prediabetes. To our knowledge,this is the first major report on the prevalence of DPN in prediabetes amongIndians. The results of our study indicate old age, smoking, and hypertensionas the major predictors of DPN. The findings of our study are in line with theobservations noted in previous studies. Dyck et al. reported a prevalence of12.6% for neuropathy diagnosed based on abnormal nerve conduction studies(NCS).11 Zeigler et al.

reported a 13% prevalence of neuropathy,defined as Michigan Neuropathy Screening Instrument score of > 2, inpatients with prediabetes.12 Another study reported a 15.6%prevalence of neuropathy using abnormal vibratory perception and thermaldiscrimination thresholds as the diagnostic criteria.

22 However, alow rate of neuropathy has also been reported in a few studies.23, 24Differences in the diagnostic criteria, screening techniques, participantcharacteristics, genetic and ethnic factors, and subjective nature of screeningtests could explain the variation in the frequency of DPN noted among differentstudies. In general, studiesemploying NCS have reported a higher prevalence than other diagnosticmodalities.Biothesiometry is a commonly used screeningtechnique for DPN in epidemiological studies because of its ease, highspecificity, capability to predict risk of foot ulceration, and low cost.25,26 However, it has a low sensitivity because it detects only large-fiberdysfunction, whereas small-fiber neuropathy is typically more common in earlyDPN.

27 Hence, a combination of a validated screening examinationscore such as NDS with VPT can yield a higher sensitivity for detecting DPNthan biothesiometry alone, as the results of our study indicate. Although NCSis still considered to be the gold standard for the diagnosis of DPN, it isdifficult to employ for large-scale epidemiological purposes, and small-fiberneuropathy might be missed by NCS.28, 29 A combination of anklereflex and vibration sense has been shown to have a high sensitivity in thediagnosis of DPN.30 In addition, several studies have shown thecapability of NDS to accurately diagnose patients with DPN.31, 32Hence, we believe that the indicators of the neuropathy employed in our studyare valid.We found that age, smoking, and hypertension areindependent and significant factors correlated with DPN. This is in accordanceto findings from previous studies.

In a previous study, age was independentlyassociated with DPN among participants with prediabetes, diabetes, andnormoglycemia.24 Hypertension and smoking were independent riskfactors for the development of neuropathy in patients without neuropathy atbaseline in the EuroDIAb study.33 Factors other than hyperglycemiacould also be involved in the pathogenesis of neuropathy in prediabetes.34Evidence 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 markersfrequently associated with metabolic syndrome are thought to contribute toneuropathy.

34-36 Similarly, oxidative low-density lipoproteinparticles have been shown to induce direct toxicity to the neuronal cells. 37DPN is a major contributory factor to increasedmorbidity and lower-limb complications associated with T2D.38-41 Inaddition, individuals with impaired glucose metabolism who have neuropathy arenearly four times more likely to have retinopathy and two times more likely tohave albuminuria.42 Autonomic neuropathy in prediabetes has beenlinked with increased risk of cardiovascular mortality.

43, 44 Hence,the early diagnosis of DPN in the prediabetes stage play an important role inpreventing complications such as foot ulceration/amputation and in initiatingintervention strategies directed toward better glycemic control, cardiovascularprotection, and patient education. This is particularly relevant in a countrylike India with a high burden of T2D and prediabetes.The strengths of our study are the large samplesize, use of the OGTT for the accurate diagnosis of IGT, and use of acombination of a validated examination score and VPT for the diagnosis of DPN.However, our study also has several limitations. First, it is a cross-sectionalstudy conducted in a tertiary care center.

Population-based epidemiologicalstudies are required to confirm our findings. Second, NCS was not performed inthe patients to confirm the diagnosis of DPN. However, we believe the resultswould not be much different if NCS had been performed.