Prevalence and Determinants of Diabetic Peripheral Neuropathy/Foot Syndrome in a rural population of North India

Background Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Objectives The study aimed to assess prevalence of DPN in patients of type 2 DM from rural North India and associated risk factors. Methods A facility based cross sectional study was carried out among type 2 diabetic patients attending NCD clinic of a secondary care hospital in rural North India. A questionnaire which included socio-demographic details, clinical and laboratory parameters, and the Michigan Neuropathy Screening Instrument (MNSI) for detecting peripheral neuropathy, was administered to 100 consecutive patients. Statistical Package for Social Sciences (SPSS) version 25.0 was used for entering and analyzing data. Bivariate analysis was performed for determining the factors signicantly associated with presence of DPN. Results The prevalence of DPN was 42.0%. Male gender, advancing age( ≥ 60 years), longer duration of diabetes (>10 years ), smoking, physical inactivity, obesity, uncontrolled blood pressure, poor A glycaemic control and altered lipid prole were found to be signicantly associated with the presence of DPN. Conclusion Prevalence of DPN among type 2 diabetics from rural north India is alarmingly high. There is need of essential screening of all diabetic patients by their primary care provider for early detection of DPN particularly in rural India.


Introduction
Diabetes mellitus is a major public health problem with rising prevalence worldwide and in the year 2018, approximately 415 million people were known to have diabetes. This estimate is expected to increase to 642 million of the population by 2040 [1]. Further, it is the 6th leading cause of death overall [2], attributing to 5 million deaths globally in 2017. According to recent estimates, 69.2 million people are affected with diabetes in India [1].
Along with the raising prevalence of diabetes, an increase in its complications is also expected. Diabetes along with its complications is expected to result in increasing morbidity, mortality, and health expenditure due to the requirement of specialized care [3].
Diabetic foot is one of the most signi cant and devastating complication of diabetes and is de ned as a group of syndromes in which neuropathy, ischemia and infection lead to tissue breakdown, and possible amputation [4]. Around 15% of diabetic patients will develop foot ulcers in their lifetime and this is known to precede amputation in 85% of the cases [5]. Every 20 seconds a lower limb is lost to diabetes in the world and it is the most common cause of non-traumatic lower limb amputation [6]. It is estimated that approximately 45,000 lower limbs are amputated every year in India and the vast majority of these are probably preventable [5].
Prevention of diabetic foot ulceration is critical to reduce the associated high morbidity and mortality rates, and the danger of amputation. A number of contributory factors work together to cause foot ulceration in patients with diabetes. These include peripheral neuropathy; mechanical stress and peripheral vascular disease [7].Since its development, it became imperatively important to diagnose Diabetic Peripheral Neuropathy (DPN) as early as possible in order to prevent amputations, disability and improve the quality of life [8].
Regular comprehensive foot examination, patient education on foot care like simple hygienic practices, provision of appropriate footwear, and prompt treatment of minor injuries and a multi-disciplinary team approach can decrease ulcer occurrence by 50% and amputations by up to 85% [3], [9].
Identi cation of diabetics with peripheral neuropathy and its associated factors is the key to reduce further complications and to have baseline information to initiate appropriate interventions. There is a dearth of community-based studies particularly from rural settings of India, which assessed the prevalence of diabetic foot and its associated risk factors among diabetics. Hence the present study was planned to nd the prevalence of diabetic peripheral neuropathy (DPN) and its associated risk factors in a rural secondary care setting of North India. Community Medicine under guidance of a faculty receives patients from Naraingarh and its nearby blocks which are rural in nature and caters a population of about 100,000 population. The aim of the hospital is to provide good quality health care that is easily accessible, affordable, and culturally acceptable, and to serve as a model for training post-graduates in community medicine and family medicine. Average general outpatient department (OPD) attendance of the clinic, including new and revisits, is around 100 per day.

Study population and Sample size
All cases of type 2 diabetes as per World Health organization's criteria diagnosed for at least six months of duration constituted the study population. Those with cognitive impairment and obvious disability that could affect the functions of the nervous system affect independent self-care behavior, and those who had undergone amputations of the lower limbs were excluded from the study.
According to a previous study done by George H et al. [10] from Southern India, the prevalence of peripheral neuropathy among people with diabetes was reported to be 47%. Thus, at con dence interval of 95% and 80% power with 10% precision on prevalence of 47%, sample size of 96 subjects was obtained. However, a total of 100 consecutive patients who were eligible and giving consent would be enrolled in the study.

Study tools
All the enrolled patients of type 2 DM were administered a semi-structured questionnaire developed by the investigators. The rst part of the questionnaire consisted data on socio-demographic details, history of diabetes mellitus including treatment details and associated risk factors for development of diabetic foot including dietary habits, physical activity, tobacco use and alcohol consumption, anthropometric details (height, weight, waist circumference, BMI), associated co-morbidities such as hypertension and dyslipidemia and laboratory parameters to assess Glycaemic control status such as FBS and HBA1C levels. The second part of the questionnaire assessed peripheral neuropathy by Michigan Neuropathy Screening Instrument (MNSI) [11], a simple and validated screening tool for diabetic peripheral neuropathy (DPN). The MNSI is designed to be used in an outpatient setting by primary care or other providers. It consists of two steps, the history questionnaire, and the physical assessment. The history questionnaire assesses the presence of neuropathic symptoms. This part consists of 15 items, (13) items assessed symptoms of DPN, item number (4) assessed peripheral vascular disease (PVD), and item number (10) assessed general asthenia. The score ranges from 0 to 13 points and a score that is ≥ 7 indicates the presence of neuropathic symptoms. The second part of the MNSI is a brief physical examination involving 1) inspection of the feet for deformities, dry skin, hair or nail abnormalities, callous, or infection; 2) semi-quantitative assessment of vibration sensation at the dorsum of the great toe; 3) grading of ankle re exes; and 4) mono lament testing. Patients screening positive on the clinical portion of the MNSI (greater than or equal to 2.5 points on a 10-point scale) were considered to have peripheral neuropathy and were considered as having high risk feet. The physical assessment was performed by one of the investigators who was trained in performing it.
The subjects found to be having foot problems were classi ed according to The International Working Group on Diabetic Foot (IWGDF) Risk Classi cation System. [12] Health education regarding foot care practices was imparted to all subjects. Subjects found to be in category 1 or 2 were managed at the health facility and subjects with category 3 risk were referred to department of endocrinology, PGIMER, Chandigarh.

Statistical analysis
The collected data was tabulated and analyzed using software SPSS (Statistical Package for Social Sciences) V. 18.0 for windows. The data was cross checked for data entry errors. Findings were described in terms of proportions and their 95% con dence intervals. Continuous data were summarized using mean, and standard deviation or median and inter quartile range depending on skewness of data. Chi-square test was applied to nd the association and p-value < 0.05 was considered statistically signi cant.

Ethical considerations
The study did not involve any potential risks to the participants. The participants were screened for peripheral neuropathy through a non-invasive screening instrument and the screening helped in its timely diagnosis and management so as to prevent patients from developing diabetic foot ulcers and amputation and help in improving their quality of life. The data collected from the participants were kept con dential, and the study protocol was approved from Institute Ethical Committee (IEC), PGIMER, Chandigarh (Vide letter No. PGI/IEC/233/18).

Results
The study included a total of 100 consecutive type 2 diabetic patients aged from 31 to 85 years with a mean age of 59.76 years (SD = 19.82) attending the NCD clinic. More than half (58.0%) of the participants were females, 41.0% were unemployed/retired and 73.0% were found to be physically inactive. The mean BMI of study participants were 33.2 kg/m 2 (SD = 7.63). The mean duration of diabetes was 9.24 years, almost half of participants were having diabetes for more than 10 years and only 34.0% were having controlled diabetes.
Microvascular complications in the form of retinopathy and nephropathy were present in 6.0 and 12.0%, respectively. The majority (56.0%) of study subjects were having dyslipidemia and. Moreover, 24.0% and 78.0% were having cardiovascular disease and uncontrolled blood pressure, respectively (Table 1). had a score of 2.5 or above on physical assessment.
The history questionnaire of the MNSI assessment showed that most of the participants had at least one symptom of the DPN. The most frequently reported symptoms in DPN patients were numbness and pain with walking which was present in 81.0 and 74.0% of study participants, respectively while, the least reported symptoms were history of one or more toes amputation and loss of sensation in legs/feet while walking which was present in 3.0 and 16.0% of patients, respectively (Table 2).

Discussion
About 42.0% of diabetic patients were found to be suffering from peripheral neuropathy. This was similar to the ndings of other studies on diabetic peripheral neuropathy (DPN) [10], [13][14][15][16].However, this was in contrast to the ndings of Kaewput et al. [17] and Perrin et al. [18] in which prevalence ranged from 3.0% to 16.6%. The possible reasons for this variation could be different study settings and different classi cation used to diagnose DPN in these studies. The prevalence of DPN found in present study was lower as compared to study conducted by Yang Q et al. [19] and Qin L et al. [20] in which prevalence of DPN was close to 71.0% and 80.0% respectively due to the similar reason as they used Neuropathy symptom score (NSS) and Neuropathy disability score (NDS) to assess DPN in their study population. High prevalence of DPN is a matter of concern for clinicians and public health specialists working with diabetic patients as this may lead to ulceration, amputation, life-long disability, and poor quality of life [21]. DPN can also increase the risks of future cardiovascular events and associated mortality [22].
In the present study, it was found that prevalence of DPN was signi cantly higher among males than females. This was similar to the results of some other studies [15], [17], but different from the ndings of Sendi RA et al. [14] who observed no gender difference in DPN prevalence. The higher prevalence of DPN among males could be due to the fact that health seeking behavior among women is poor in most of the developing countries, hence lesser chances of being detected, especially in rural areas.
Being older was found to be signi cantly associated with DPN. This was in line with the observations of other authors [14], [15], [20]. As age advances, nerve function deteriorates, even in absence of DM. With increasing life expectancy, the population of elderly is bound to increase due to demographic transition and prevalence of non-communicable diseases is also on rise as a result of epidemiological transition happening in India. Their concurrent occurrence complicated by complications of NCDs like diabetes is worrisome.
The prevalence of DPN was also found to be higher among DM patients who were having diabetes for more than 10 years. This was in line with results of previous studies [13], [14], [17], [20]. As the duration of DM increases, the risk of complications advances and this accelerates if the glycemic control is also poor. This was supported by the ndings of the present study in which patients with poor glycemic control were found to have higher prevalence of DPN, similar to ndings by other studies [10], [14], [15], [20], [23].
Smoking was also found to be associated with DPN with higher percentage of smokers having DPN compared to non-smokers. This was similar to the ndings of study by Van der Velde et al. [23] in which smoking was found to be associated with reduced nerve function. Smoking causes atherosclerosis, elevates blood pressure, and causes nerve injury due to in ammation which collectively leads to impaired nerve functioning.
Uncontrolled blood pressure and dyslipidemia were found to be more prevalent in diabetic patients suffering from DPN. This was similar to ndings from other studies [14], [15]. In another study, DPN was found to be associated with elevation of systolic blood pressure and problems in management of hypertension among patients with type 2 DM [24]. This nding needs further exploration as exact mechanism behind co-existence of DPN and uncontrolled blood pressure is still not completely known. The cause-effect studies could help in better understanding of this interaction.
Obesity was another modi able factor which was found to be associated with DPN in present study. This was in line with ndings of other studies conducted globally [15].DPN originating among DM patients can not solely be attributed to increased blood sugar level, but to complex interplay of increasing age, deranged lipid pro le, obesity, and hypertension [25]. participants in a language familiar to them. Anonymity and discretion of the information given by the patients were maintained with utmost care and a written informed consent was obtained from the participants Disclosure of potential con icts of interest The authors declare that they have no competing interests.