What features of neuropathy make patients aware of their disease?
Norina A. Gâvan1, Cosmina I. Bondor2, Bogdan Florea3, Etta J. Vinik4, Aaron I. Vinik4, Ioan A. Veresiu5
1 Society of Diabetic Neuropathy, Cluj-Napoca, Romania
2 Iuliu Hațieganu University of Medicine and Pharmacy Cluj-Napoca, Department of Medical Informatics and Biostatistics, Cluj-Napoca, Romania
3 Podiatrie SRL, Medical center for foot care, Cluj-Napoca, Romania
4 Eastern Virginia Medical School, Norfolk, Virginia, USA
5 Iuliu Hațieganu University of Medicine and Pharmacy Cluj-Napoca, Department of Diabetes, Nutrition and Metabolic Diseases, Cluj-Napoca, Romania 
Given the subjective nature of symptoms and the differences in recognizing the features of diabetic neuropathy (DN), patients can be unaware of their difficult to understand condition even if healthcare providers have discussed and explained the diagnosis of DN.  The objective of our study was to explore what features of DN patients aware of DN. 
This cross-sectional survey was conducted in 2016, in which 47 healthcare providers from 21 Romanian cities distributed the linguistically translated Romanian Norfolk Quality of Life (QoL-DN) questionnaire to patients with diabetes from their clinics who participated in 2012 in a previously reported screening study in Romania. Patients were evaluated for DN with the Michigan Neuropathy Screening Instrument (MNSI) and MNSI questionnaire. Only patients who give their informed consent to Norfolk QOL-DN and MNSI were included. 
Those patients (1484) who had the MNSI combined score ≥ 3.5 were determined to have DN and resulted in 2 study groups:  Group A, 357 (24.1%) responded “no” to the question “Do you have neuropathy” while Group B, 1127, (75.9%) responded “yes” to the question. Two groups (C and D) with MNSI combined scores less than 3.5 were determined not to have DN by MNSI. Group C (75) responded “yes” to the question, “Do you have neuropathy” and group D (325) responded “no” to the question.  The DN frequency in the study group was 78% (patients with MNSI>3.5). Analysis of scores between groups showed significant differences between Total QOL-DN (Total: A= 22.71±1.01, B=37.53±0.76, p<0.001). Multivariate logistic models evaluated the association between symptoms, Norfolk QOL-DN subdomain scores and probability of patients’ awareness of their DN Table 1.
Multivariate logistic models evaluated the association between the symptoms, Norfolk QOL-DN subdomain scores and the probability of patients to be aware of their DN (Table 1). 
Table 1. Multivariate logistic models evaluating the association between the symptoms, Norfolk QOL-DN subdomain scores and the probability of having neuropathy (Forward LR method)
Independent variable	OR	95% CI	p
Group A compare with group B
With numbness	2.03	1.39-2.97	<0.001+
With pins and needles	1.85	1.28-2.66	0.001+
With unusual sensations	1.67	1.11-2.50	0.014+
With superficial pain	1.67	1.26-2.18	<0.001+
Physical functioning/large fibers neuropathy score	1.03	1.01-1.04	0.002+
Autonomic neuropathy score	1.13	1.05-1.22	0.001*
Small fiber score	1.24	1.14-1.35	<0.001+
Group C compare with group D			
With numbness	2.03	1.39-2.97	<0.001**
With numbness	2.03	1.39-2.97	<0.001**
With numbness	2.03	1.39-2.97	<0.001**
* = higher likelihood to be in group A; + = higher likelihood to be in group B; ** = higher likelihood to be in group C; ++ = higher likelihood to be in group D;
OR, odds ratio; CI, confidence interval
OBS. Only significant variables are presented.
Conclusion.
Numbness, pins and needles, unusual sensations are the most prominent predictors of perception of neuropathy and QOL-DN subdomains are able to detect neuropathy even in the absence of positive MNSI scores and in those who deny the presence of neuropathy (Group D). There appears to be a threshold of doubling of numbness and pins and needles (OR 2.03 and 1.85), which alerts patients to the presence of neuropathy.