Prevalence and associated factors of painful diabetic peripheral neuropathy among diabetic patients on follow up at Jimma University Medical Center

Abstract

Background

Despite having significant impact on the patient’s quality of life, painful diabetic peripheral neuropathy (PDPN) is usually underdiagnosed. Screening for PDPN in patients with diabetes is needed in order to get timely identification and management. Hence, the purpose of this study was to assess the prevalence and determinants of PDPN among diabetes patients attending outpatient at Jimma University Medical Center from September 1 November 10, 2019.

Methods

Hospital based cross-sectional study was conducted and douleur neuropathique-4 was used to identify the presence of PDPN. Data were collected using pretested structured questionnaire and entered into EPI data 3.1 and exported to SPSS version 20 for analysis. Both bivariate and multivariate binary logistic regression was employed to identify factors associated with PDPN. Variable having a p value of <0.25 in the bivariate model were considered as candidates for multivariable regression. Adjusted odds ratios were calculated at 95%CI and considered significant with a p value of <0.05.

Results

A total of 366 diabetic patients were enrolled into the study and their mean duration of diabetes was 6.8 ± 5.3 years. The study finding showed that the prevalence of PDPN was 14.5%. According to the multivariate logistic regression analysis smoking [current smoker(AOR = 6.17; 95%CI:2.25,16.86),former smoker(AOR = 3.22;95%CI:1.29,8.03)],diabetes duration[5 to 10 years (AOR = 3.32;95%CI:1.29,8.53), ≥ 10 years (AOR = 8.86;95% CI: 3.49,22.5)] and comorbid hypertension [AOR = 2.54; 95%CI:1.17,5.49] were independent predictors of PDPN among study participants.

Conclusion

The overall prevalence of PDPN in this study was 14.5% and it was significantly associated with smoking, comorbid hypertension and diabetes duration of above 5 years. Early detection and appropriate interventions are important for high risk patients identified in the current study.

Introduction

Diabetes is one of the leading causes of peripheral neuropathy, that can affect neuronal function throughout the body [1]. Peripheral neuropathies present with painful or painless symptoms and many patients experience both [2]. Painful diabetic peripheral neuropathy (PDPN) is a common type of diabetic neuropathy and is the most common cause of neuropathic pain [3]. It is defined as pain arising as direct consequence of a lesion or disease affecting the somatosensory system [4]. Of all the distressing symptoms of diabetic peripheral neuropathy(DPN), pain is the most prominent and most frequent reason for seeking medical attention [5].

The prevalence of PDPN ranges from 10% to 20% among patients with diabetes mellitus (DM) and from 40% to 50% among with diabetic neuropathies [6–8] and its prevalence is about 20% in patients with type 2 DM and 5% in those with type 1DM [9]. Up to 50% of patients with DPN experience painful symptoms. In the US, an estimated 15% to 30% of people with DM have PDPN [10].

Painful diabetic peripheral neuropathy has a great impact on the patient’s quality of life and it is widely underdiagnosed with a consequent delay in management. Affected patients are usually unaware that the pain is related to diabetes, and do not report it to their clinician [11]. PDPN is characterized by insidious onset of pain, which is described as shooting, burning or aching and responds poorly to conventional analgesics. It can be severe, chronic, and disabling leading to substantial functional, psychological and social limitations. Furthermore, it causes depression, higher healthcare costs, loss of productivity, anxiety and sleep disorders [12–14].

The origin of pain in the PDPN is not fully explored. Factors, such as chronic hyperglycemia seems to play a key role in its development, as it induces ionic dysregulation and hypoxia in peripheral neurons, specifically at the level of nociceptors [15]. Previous studies have shown that older age, longer duration of diabetes, being female and the presence of DPN increase the risk for PDPN [16–18]. While several studies have assessed the prevalence of DPN, many didn’t report the prevalence of PDPN. Screening patients at high risk for PDPN using validated tools helps timely identification and management [19]. To date, there is no data regarding prevalence and factors related to PDPN among diabetic patients on follow up at Jimma University medical center. So, the aim of this study tried to fill this gap.

Methods and materials

Study area, design and period

The study was conducted on diabetic patients who have a follow-up at Jimma University Medical Center (JUMC) diabetic clinic. It is one of the teaching and referral hospitals in the Southwestern part of the country, providing services for approximately 15 million people in the catchment area. An institution based cross-sectional study was conducted and the study period was from September 1 to November 10, 2019.

Population

The source population consists of all adult diabetic patients who were under regular follow up clinic of JUMC, while the study population was those diabetes patients attending chronic illnesses clinic fulfilling eligibility criteria and willing to participate.

Eligibility criteria

Participants of age ≥ 18 years were included, whereas participants who were seriously ill, gestational diabetes, had other type of neuropathic pain of non-diabetic origin (pain associated with cancer, post-herpetic neuralgia etc.), with psychiatric disorder and HIV infection were excluded.

Sample size calculation and sampling technique

The sample size was determined by using the single population proportion formula:

$$\mathrm{n}\frac{=\left(z\raisebox{1ex}{$\alpha $}\!\left/ \!\raisebox{-1ex}{$2$}\right.\right)2p\left(1-p\right)}{d2}$$

Where n = required sample size

Z = Percentiles of the standard normal distribution corresponding to 95% confidence level assumption.

$z\raisebox{1ex}{$\alpha $}\!\left/ \!\raisebox{-1ex}{$2$}\right.$= Coefficient at level of significance = 1.96

p = prevalence of PDPN (by assuming 50%)

d = Margin of error = 0.05

Accordingly ‘n’ were calculated to be 384. Because the total number of diabetic patients on follow-up (N) were 2500, which was less than 10,000, I employed a population correction formula for a finite population.

$$n_f=\frac{n}{1+\frac{n}{N}}⟶\frac{384}{1+\frac{384}{2500}}⟶n_f=333$$

Where:

n = sample size

N = total population (2500)

nf = final sample size

By taking into consideration 10% non-response rate, the final sample size was 366.

Systematic random sampling technique was used to select study participants using the monthly client flow-up record of the hospital.

Data collection tool and procedure

The data collection tool was adapted from WHO step wise approach for surveillance of chronic disease risk factors [20] and from different scientific related literatures. The data were collected using pretested structured questionnaire by face to face interview, participant record reviews and physical examination. The questionnaire contains socio-demographic characteristics, Douleur Neuropathique-4, behavioral and clinical variables.

Clinical variables were taken from patient chart review and anthropometric measurements were measured. Body weight was measured to an accuracy of 0.1 kg by using portable weight scale machine by participants being barefoot and wearing light indoor clothing. Height was measured by meter, standing upright on a flat surface by stadiometer and body mass index (BMI) was calculated as kg/m².

Douleur neuropathique-4 (DN4) was used to assess presence of PDPN. The DN4 questionnaire is a validated screening tool to assess PDPN [21] and it can distinguish between nociceptive and neuropathic pain [22]. It consists of both interview questions and brief physical examination. The first 7 part of the DN4 is analysis of the patient’s sensory description of their pain and the final 3 items are physical assessment of sensory function. For each question, answering “Yes” scores 1, a “No” response scores 0. The total score ranges from 0 to 10. The test is considered positive for a score ≥ 4/10 with sensitivity and specificity of 82.9% and 89.9% respectively [9, 23].

Data collection was performed by trained three medical interns and two BSC nurses with the supervision of principal investigator.

Operational definition

Seriously ill = Patients who were unable to communicate and abnormal conscious.

Painful diabetic peripheral neuropathy: was present if Douleur Neuropathique-4 was ≥4/10.

Controlled blood sugar: Fasting blood sugar <130 mg/dl.

Uncontrolled blood sugar: Fasting blood sugar >130 mg/dl.

Diabetes patient: Known diabetic patient on follow up who had medical record number at JUMC.

Diabetes duration: the duration of DM was calculated as age at data collection minus age at onset of DM.

Data quality assurance

Data quality was assured through training of data collectors and close supervision during data collection. Two days’ training was given to the data collectors on ways of approaching respondents, on the data-collection tool and how to ask questions. Pretest on 5% of the sample population was conducted at Shenen Gibe Hospital Diabetic Clinic. After analyzing pretest results, necessary adjustments were made. The collected data were checked on daily basis for accuracy and completeness by principal investigator. Incomplete checklists were returned back to the data collector for completion. Codes were given to the data collection tool so that any identified errors were traced back via the codes given.

Statistical analyses

The collected data were checked for its completeness and then entered to Epi data version 3.1 then exported to SPSS version 20.0 for analysis. Descriptive statistics such as percentages, frequencies, means, and standard deviations were computed. Bivariate and multivariate logistic regression models were used to determine association between the dependent and independent variables. Variables with p value of < 0.25 on bivariate logistic regression were considered as candidates for multivariate regression. Finally, variables which had independent association with outcome variable on multivariate analysis were determined on basis of AOR, with 95% CI and a p value of ≤0.05. Moreover, model fitness was checked using the Hosmer–Lemeshow test, with p > 0.05.

Results

A total of 366 patients were enrolled into the study. The mean age of the respondents was 50.1 ± 14.28 years and almost one third (30.9%) of participants were farmers. Almost half (51.6%) of participants were rural dwellers (Table 1).

Table 1.

Socio-demographic characteristics of patients with diabetes mellitus at JUMC 2019, Jimma, Ethiopia

Variables	Category	Number	Percentage
Sex	male	203	55.5
	female	163	44.5
Age	<39 years	91	24.9
	40 to 59 years	181	49.5
	>60 years	94	25.7
Marital status	married	283	77.3
	single	66	18
	others*	17	4.6
Religion	muslim	161	44
	orthodox	146	39.9
	protestants	46	12.6
	others†	13	3.6
Educational status	illiterate	108	29.5
	primary	165	45.1
	secondary	45	12.3
	college and above	48	13.1
Occupational status	house wife	108	29.5
	farmer	113	30.9
	employer	78	21.3
	Private worker	51	13.9
	Others ‡	16	4.4
Residence	Urban	177	48.4
	Rural	189	51.6
Family history of DM	Yes	87	23.8
	No	279	76.2
Average monthly income (ETB)	< 1000	96	26.2
	1000 to 1999	40	10.9
	2000 to 2999	95	26
	>3000	135	36.9

*widowed, divorced, † catholic, Wakefata, ‡ retired, unemployed

Clinical and behavioral characteristics of participants

More than three fourth (80.1%) of participants were type 2 diabetes mellitus and majority of them were in normal BMI category. The mean duration of diabetes was 6.8 ± 5.3 years. Near to three fourth of the participants had controlled fasting blood sugar (≤130 mg/dl) (Table 2).

Table 2.

Clinical and behavioral characteristics of patients with diabetes mellitus at JUMC 2019, Jimma, Ethiopia

Variables	Category	Number	Percentage
Type of DM	1	73	19.9
	2	293	80.1
Duration of DM	<5 years	197	53.8
	5–10 years	90	24.6
	> 10 years	79	21.6
Comorbid HTN	yes	117	32
	no	249	68
Treatment regimen	noninsulin	244	66.7
	insulin	99	27
	both	23	6.3
BMI (kg/m2)	< 18.5	30	8.2
	18.5 to 24.99	230	62.8
	25 to 29.99	84	23
	≥ 30	22	6
Alcohol intake	current	44	12
	former	31	8.5
	never	291	79.5
Smoking	current	54	14.8
	former	68	18.6
	never	244	66.7
Physical exercise	active	179	48.9
	inactive	187	51.1
Other comorbidity*	Yes	42	11.5
	No	324	88.5
Fasting blood sugar (mg/dl)	<130	263	71.9
	>130	103	28.1

*22 chronic kidney disease, 11 congestive heart failure, 7 Asthma, 2 cancer

Prevalence of painful diabetic peripheral neuropathy

In this study, the DN4 scores were used for defining prevalence of PDPN for each study subject. It was then defined as a score of ≥4 out of 10 DN4 screening questionnaire. Accordingly the prevalence of PDPN was 14.5% [95%CI:10.9–18].

Factors independently associated with painful diabetic peripheral neuropathy

Diabetic patients who were currently active smokers were 6.17 times more likely to develop PDPN as compared with those who never smoker [AOR = 6.17; 95%CI: 2.25, 16.86]. Likewise, former smokers were 3.22 times more likely to develop PDPN as compared with those who never smoker [AOR = 3.22; 95%CI: 1.29, 8.03]. The other factor identified was diabetic duration. Participants of 5 to 10 years duration of DM were 3.32 times more likely to develop PDPN as compared with those who with less than 5 years duration of DM [AOR = 3.32;95% CI: 1.29,8.53]. Those participants of greater than 10 years duration were 8.86 times more likely to develop PDPN as compared with those with shorter diabetic history less than 5 years [AOR = 8.86;95% CI: 3.49,22.5] after controlling for other variables. Finally, diabetic patients with comorbid hypertension were 2.54 times more likely to develop PDPN compared to their counter parts [AOR = 2.54; 95%CI: 1.17, 5.49] (Table 3).

Table 3.

Multivariate logistic regression analysis of factors associated with PDPN among diabetes outpatients at JUMC, 2019

Variables	Category	PDPN		Bivariate Analysis		Multivariate analysis
		Yes	No	P- value	COR (95%CI)	P value	AOR (95%CI)
Age (Years)	< 39	8	83	1	1	1	**
	40–59	20	161	.564	1.28[.54, 3.05]	.055	.33[.11,1.02]
	≥ 60	25	69	.002	3.75[1.59, 8.86]	.214	.45[.12,1.58]
Educational level	illiterate	25	83	.070	2.59[.92, 7.24]	.713	**
	primary	17	148	.982	.98[.34, 2.83] 2.66]	.297	**
	secondary	6	39	.664	1.32[.374, 4.68] 2.68]	.537	**
	College and above	5	43	1	1	1	1
Type of DM	1	5	68	1	1	1	1
	2	48	245	.045	2.66[1.02, 6.95]	.184	**
Smoking	current	14	40	≤0.001	3.92[1.83, 8.39]]	≤0.001*	6.17[2.25,16.86]
	former	19	49	≤0.001	4.34[2.15, 8.74]	0.012*	3.22[1.29, 8.03]
	never	20	224	1	1	1	1
Physical Exercise	active	16	163	1	1	1	1
	inactive	37	150	.004	2.51[1.34, 4.70]	.088	**
Comorbid HTN	yes	31	86	≤0.001	3.71[2.04, 6.77]	.017*	2.54[1.17, 5.49]
	no	22	227	1	1	1	1
BMI(Kg/m2)	18.5 to 24.9	24	206	1	1	1	1
	<18.5	6	24	.130	2.14[.79, 5.77]	.069	**
	25 to 29.9	18	66	.013	2.34[1.19, 4.58]	.261	**
	≥30	5	17	.094	2.52[.85, 7.45]	.108	**
Duration of DM (years)	<5	10	187	1	1	1	1
	5 to 10	13	77	.009	3.15[1.32, 7.50]	.013*	3.32[1.29, 8.53]
	≥10	30	49	≤0.001	11.44[5.23, 25.01]	≤0.001*	8.86[3.49, 22.5]

* value statistically significant; **value not statistically significant; 1-reference

Discussion

This study was intended to assess the prevalence and associated factors of PDPN. In the present study, the prevalence of PDPN among diabetic patients attending JUMC was 14.5% [95%CI: 10.9–18]. This study result was in line with several studies conducted so far across the world. This includes study done in Morocco 15.3% [24], in Turkey 16.% [25], in Brazil 16.7% [26] and 14% in Belgium [11]. However, the current finding was lower than study conducted in Saudi Arabia 65.3% [18], in UK 34% [17], in South Africa 30.3% [16], in Libya 42.2% [27] and in Japan 22.1% [28]. The possible explanation for those discrepancies could be due to difference in sample size used, diagnostic criteria, study population, study duration and health care infrastructure. For instance, study in Libya recruited only diabetes duration of greater than 5 years and used self-report leeds assessment of neuropathic symptoms and signs pain scale to study PDPN.

On the other hand, the current finding was higher than study conducted in USA and France which reported the prevalence of PDPN 8.8% and 8% respectively [29, 30].The possible explanations for those discrepancy were due to different methods used to screen PDPN, health seeking behavior and study setting.

The present study revealed that the likelihood of PDPN was higher among patients with diabetic duration of greater than 5 years. This finding has been confirmed by other studies [18, 26, 27, 31–33]. Although the precise mechanisms is unclear, this relation can be explained by longer duration of diabetes is associated with chronic hyper glycaemia which causes activation of multiple biochemical pathways which induces oxidative stress in neurons and leads to nerve ischemia and damage [34].

Another finding in the current study was comorbid hypertension which was identified as an independent predictor of PDPN. This association was in agreement with previous studies [31, 35–37]. The association between hypertension and PDPN can be explained with studies in rodents which showed that the additive effect of hypertension on diabetic neuropathy damages Schwann cells and myelin sheaths around axons [38].

Finally, in agreement with other reports, this study showed that smoking habit was found to be significantly associated with PDPN [15, 17, 27, 33, 39]. The association between smoking and PDPN can be explained by the fact that smoking is associated with oxidative stress, systemic inflammation, endothelial dysfunction and from its direct toxic effect on the neurons [40].

Limitation of the study

The duration of diabetes as measured in this study might not reflect the true duration of the disease, because the time since diagnosis and actual diabetes onset might precede diagnosis type 2 DM. Another limitation is the cross-sectional nature of the study which does not confirm the definitive cause and effect relation. Finally, the patient-recall bias may be affect the performance of DN4 symptom score.

Conclusion

In this study, there was 14.5% prevalence of PDPN. It was significantly associated with smoking habit, comorbid HTN and DM duration of above 5 years. Early detection and appropriate interventions are important for high risk patients.

Abbreviations

AOR

Adjusted odds ratio

BMI

Body mass index

CI

Confidence interval

COR

Crude odds ratio

DM

Diabetes mellitus

DN4

Douleur Neuropathique-4

DPN

Diabetic peripheral neuropathy

FBS

Fasting blood sugar

JUMC

Jimma University Medical Center

Htn

Hypertension

PDPN

Painful diabetic peripheral neuropathy

Funding

No funding was available for this work.

Compliance with ethical standards

Ethical approval and consent to participate

Ethical clearance was obtained from Jimma University Institutional Review Board. Oral informed consent was obtained from the study participants to start data collection. Information was recorded anonymously and their confidentiality was assured throughout the study period.

Competing interests

The authors of this study declare that has no competing interests.