World Rural Health Conference
Home Print this page Email this page Small font size Default font size Increase font size
Users Online: 3418
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents 
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 1891-1895  

A clinical study of the association and risk factors for lower limb neuropathy in patients with diabetic retinopathy


1 Department of Ophthalmology, Panel Consultant at Deenanath Mangeshkar Hospital and Research Centre, Pune, Maharashtra, India
2 Professor and Head, Department of Ophthalmology, Command Hospital Air Force, Bangalore, Karnataka, India
3 Associate Professor and Senior Advisor, Department of Ophthalmology, Command Hospital Air Force, Bangalore, Karnataka, India

Date of Submission07-Feb-2020
Date of Decision13-Mar-2020
Date of Acceptance30-Mar-2020
Date of Web Publication30-Apr-2020

Correspondence Address:
Dr. Mansur Ali Khan
Department of Ophthalmology, Command Hospital Air Force, Bangalore, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_231_20

Rights and Permissions
  Abstract 


Purpose: Association of peripheral neuropathy with diabetic retinopathy is known but the relationship of preclinical neuropathy with various grades of retinopathy is not well documented. This study evaluated the association of preclinical peripheral neuropathy using nerve conduction studies with various grades of retinopathy. Methods: Cases of diabetic retinopathy of various grades but asymptomatic for peripheral neuropathy underwent nerve conduction studies of the lower limbs using Caldwell machine and Sierra wave software. The risk factors for retinopathy and association of neuropathy with various grades of retinopathy were analyzed by bivariate and multivariate regression analysis. Results: The overall prevalence of neuropathy was 75.6% (sensory 58.54% and combined motor and sensory 17.1%) with increase in prevalence with increase in severity of retinopathy. Duration was positively associated with neuropathy (OR = 1.13, 95% CI = 1.02–1.24; P = 0.012); moderate nonproliferative diabetic retinopathy (NPDR) (OR = 5.60, P = 0.002), severe and very severe NPDR (OR = 5.8, P = 0.041), and PDR (OR = 16.05, P = 0.000) were significantly at higher risk for having neuropathy as compared to mild NPDR. Conclusion: Duration and severity of retinopathy are important risk factors for peripheral neuropathy. There is a high prevalence of peripheral neuropathy among diabetics with retinopathy especially with severe grades, when neuropathy is diagnosed using nerve conduction studies.

Keywords: Diabetes, nerve conduction, peripheral neuropathy, retinopathy


How to cite this article:
Joshi D, Khan MA, Singh A. A clinical study of the association and risk factors for lower limb neuropathy in patients with diabetic retinopathy. J Family Med Prim Care 2020;9:1891-5

How to cite this URL:
Joshi D, Khan MA, Singh A. A clinical study of the association and risk factors for lower limb neuropathy in patients with diabetic retinopathy. J Family Med Prim Care [serial online] 2020 [cited 2020 Jun 6];9:1891-5. Available from: http://www.jfmpc.com/text.asp?2020/9/4/1891/283424




  Introduction Top


With the rise in the incidence of diabetes worldwide, diabetic retinopathy has become one of the major causes of blindness.[1] The management of diabetic retinopathy is a complex and multipronged strategy which includes systemic glycemic control, laser treatment, intravitreal injections, and surgery.[2] The management can be delayed and sometimes confounded by coexisting systemic complications such as nephropathy and peripheral neuropathy.[3] The ocular fundus is unique as it facilitates visualization and grading of diabetic microangiopathy affecting the retinal vasculature. Since patients of type 2 diabetes are asymptomatic for prolonged periods with an undetected disease, fundus evaluation very often leads to the initial diagnosis of diabetes.[4] Similarly, the eye can be a pointer toward other microangiopathic complications and this association of retinopathy with nephropathy and neuropathy has been documented in several studies.[5],[6],[7] This is especially important in case of peripheral neuropathy which may be asymptomatic initially and difficult to detect clinically.[8],[9] Studies on the prevalence of peripheral neuropathy among diabetics have reported widely differing figures.[10],[11],[12] The prevalence of peripheral neuropathy is estimated to be between 6% and 51% among adults.[13] The difference is partly due to the different demographic population studied and also due to the different methods used to detect the neuropathy.[14] While clinicophysiological tests for peripheral neuropathy are easier to administer, nerve conduction studies are more objective and reproducible in standard labs.[15] It may also detect subclinical neuropathy at the asymptomatic stage. However, these tests are more expensive and not widely available. Considering the reported association between retinopathy and neuropathy, nerve conduction studies among diabetics who have already developed retinopathy may have a higher yield justifying the cost. The association of the various grades of retinopathy with neuropathy can guide the timing for carrying out these tests. This will help in instituting tighter control measures at an early stage to prevent complications of peripheral neuropathy. Therefore, this study was carried out for the detection of peripheral neuropathy among diabetics who had developed retinopathy but were undiagnosed and asymptomatic for peripheral neuropathy. This study also attempted to assess the other risk factors for neuropathy in this population subgroup and look for an association between the various severity grades of retinopathy and peripheral neuropathy.


  Methods Top


The study was done in a tertiary care multispecialty hospital with subjects being sampled from those reporting to the outpatient retina clinic of the Department of Ophthalmology between November 2014 and September 2016, by systematic random sampling. The study was carried out as per current guidelines of the Helsinki declaration. Institutional ethical committee clearance was taken prior to starting the study 19 Nov 2013. Patients with diabetic retinopathy of any grade and asymptomatic for peripheral neuropathy were included in the study. Retinopathy grading was done as per the Early Treatment of Diabetic Retinopathy (ETDRS) study criteria. Cases with coexistent retinopathy of cause other than diabetes, previous history of cerebrovascular accident, diagnosed neuropathy, peripheral vascular disease, and anemia were excluded from the study. A sample size of 234 was calculated taking an estimated prevalence of neuropathy of 15% among diabetics. For diagnosis and grading of diabetic retinopathy, all the enrolled patients underwent full ophthalmic examination including vision, slit-lamp examination, fundus biomicroscopy with 90 diopter lens, indirect ophthalmoscopy, color fundus photography, fundus fluorescein angiography, and optical coherence tomography. Best corrected vision was recorded by the ETDRS chart and vision recorded in Log MAR units. Informed consent was taken from all the patients and all of them also underwent blood and urine tests as a part of the treatment protocol for diabetic retinopathy including blood hemoglobin, urea, creatinine, lipid profile, glycosylated hemoglobin, and urine routine and microscopic examination. Nerve conduction studies were done at the Department of Neurology using Cadwell machine using Sierra wave software at surface temperature of 37.5°C and ambient temperature of 20°C to 24°C using surface electrodes. Motor and sensory nerves of both lower limbs were tested, peroneal and tibial nerve for motor and sural nerve for sensory. Sural nerve was tested with electrodes at the calf and lateral malleolus. For peroneal nerves, electrodes were placed at the head of fibula and ankle and for tibial nerve, near knee and ankle. The results were documented as neuropathy present or absent, sensory only, sensory and motor both, or motor only, based on the reference values for the lab. Data analysis was done using SPSS version 20. P value of 0.05 was taken as statistical significance. The Chi-square test was used for dichotomous qualitative data and unpaired t-test for quantitative data. The variables found to have significant association with neuropathy were then subjected to logistic regression analysis. Odds ratio and 95% confidence interval was calculated for those variables showing significant association with neuropathy after logistic regression analysis.


  Results Top


A total of 234 patients were enrolled in the study and all of them underwent full ophthalmology evaluation and nerve conduction studies as per the study protocol. The demographic profile and other characteristics are listed in [Table 1]. The mean age was 59.12 years with a male preponderance. The majority were type 2 diabetic (90%) on oral hypoglycemic drugs with an average duration of 7.51 years since diagnosis. Current HbA1C levels indicated poor control (HbA1C >7) in 66% of the patients as compared to 34% with good control (HbA1C <7). Proliferative diabetic retinopathy (PDR) accounted for the largest chunk (35.9%) as compared to mild, moderate, and severe and very severe nonproliferative diabetic retinopathy (NPDR). The overall prevalence of neuropathy was 75.6% with the majority having combined sensory and motor neuropathy (58.54%) as opposed to only sensory neuropathy (17.1%). The prevalence of both sensory and combined neuropathy was seen to increase progressively with increase in severity of retinopathy [Figure 1]. Duration of diabetes, HbA1C levels above 7, gender, and severity grades of retinopathy showed a significant association with the presence of retinopathy on bivariate analysis [Table 2]. When these risk factors were subjected to multivariate logistics regression analysis, gender, duration, and severity grades of diabetes were significantly associated with retinopathy, whereas the association with Hb A1C was not found to be significant [Table 3]. Females were found to be less likely to have neuropathy as compared to males with an odds ratio of 0.471. Duration was significantly and positively associated with neuropathy (OR = 1.13, 95% CI = 1.02–1.24; P = 0.012); moderate NPDR (OR = 5.60, P = 0.002), severe and very severe NPDR (OR = 5.8, P = 0.041), and PDR cases (OR = 16.05, P = 0.000) were significantly at higher risk of having neuropathy as compared to mild NPDR.
Table 1: Demographics of study sample in terms of age, gender, type of diabetes, treatment, duration and HbA1C levels

Click here to view
Figure 1: Prevalence of peripheral neuropathy in % in various grades of retinopathy

Click here to view
Table 2: Distribution of neuropathy in relation to age, gender, duration, retinopathy grades, Hb A1C levels, and presence of nephropathy

Click here to view
Table 3: Risk factors for neuropathy following logistic regression analysis

Click here to view



  Discussion Top


Retinopathy, nephropathy, and neuropathy are the comorbidities most commonly found in various population surveys on diabetics.[16],[17] In this study, we have evaluated the prevalence of subclinical neuropathy and the associated risk factors among diabetics with various grades of retinopathy. To the best of our knowledge, this is the largest study in this particular subgroup. Our study population consisted predominantly of type 2 diabetics, which reflects the higher prevalence of type 2 diabetics across diabetic care clinics in India.[18] The result of this study highlights the much higher prevalence of peripheral neuropathy in the presence of diabetic retinopathy than that reported in population studies, among patients who were asymptomatic for neuropathy. A higher prevalence of neuropathy in our studies can also be attributed to the diagnosis of neuropathy using nerve conduction. In the study by Venkatesh et al.[19] on patients with various grades of retinopathy, a higher yield was seen with nerve conduction as compared to clinical tests. An increased prevalence of neuropathy with increasing severity of retinopathy was seen in that study with a significant association with the presence of clinically significant macular edema (CSME). Although our study showed an increasing prevalence with increasing grades of retinopathy, statistically significant for moderate NPDR or worse, we did not see a significant association independently with CSME alone as noted by Venkatesh et al. Duration of diabetes was a significant determinant for neuropathy in this study similar to that reported by Feldman et al.,[20] Gill et al.,[21] and Ashok et al.[22] The role of tight control of hyperglycemia in preventing or delaying neuropathy has been well documented in various trials.[23],[24],[25] However, no significant association was seen between HbA1c levels and neuropathy in this study, probably because we have taken only the latest values and long-term average HBA1c measurements were not compared.[26] The association of neuropathy with male gender as seen in this study has been reported by several other studies as well.[24],[27],[28] This has been attributed to various factors such as health-seeking behavior, adherence to interventions and medications, smoking habit, obesity, etc., Since all of these factors were not matched or ruled out in our study, their role in influencing the association of male gender and neuropathy could not be assessed. Sensory neuropathy is usually the earliest to develop as reported in various epidemiological studies.[29],[30] The same is reflected in the higher proportion of sensory only neuropathy seen in this study among those with milder grades of retinopathy as compared to combined motor and sensory neuropathy in the higher grades.

The primary care physician is usually the first point of contact for newly detected diabetic patients as well as patients with several years of disease. Hence, the primary care physician must be made aware of the importance of early screening for neuropathy and especially so in a patient with known severe retinopathy. The ADA recommends that patients with type 1 diabetes for 5 or more years and all patients with type 2 diabetes should be assessed annually for distal symmetric polyneuropathy using medical history and simple clinical tests.[31] Beyond this, some patients may not notice or be forthcoming with history of diabetic peripheral neuropathy and its detection may be missed on office clinical tests. With this study, the authors emphasize on the need for referring a patient with known diabetic retinopathy for more sensitive tests like nerve conduction studies (NCS) so as to detect preclinical neuropathy earlier.

To summarize, male gender, longer duration of diabetes, and severity of retinopathy are important risk factors for peripheral neuropathy. Severity of diabetic retinopathy is a marker for peripheral neuropathy which may be asymptomatic. It is suggested that such cases should be referred early for neurological evaluation and nerve conduction studies. A tertiary care setting with a bias toward more severe cases of retinopathy is a limitation of this study. A larger study is suggested with the sample drawn from population of diabetics seen at the primary care level.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
International diabetes federation (IDF), IDF world atlas 6th ed 2013. http://www.idf.org/diabetes atlas World Health.  Back to cited text no. 1
    
2.
Stitt AW, Curtis TM, Chen M, Medina RJ, McKay GJ, Jenkins A, et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res 2016;51:156-86.  Back to cited text no. 2
    
3.
Tripathi BK, Srivastava AK. Diabetes mellitus: Complications and therapeutics Med Sci Monit 2006;12:130-47.  Back to cited text no. 3
    
4.
Linton D, Mitchell S. Physical examination of the eye: The fundus matters. J Nur Pra 2016;12:e371-2.  Back to cited text no. 4
    
5.
Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995;18:258-68.  Back to cited text no. 5
    
6.
Abdollahi A, Moghimi S, Tabasi A, Rajabi MT, Sabet B. Neuropathy and retinopathy in diabetes: Is there any association? Int J Ophthalmol 2009;2:57-60.  Back to cited text no. 6
    
7.
The DCCT Study Group. Progression of retinopathy with intensive versus conventional treatment in the diabetes control and complications trial. Diabetes control and complications trial research group. Ophthalmology 1995;102:647-61.  Back to cited text no. 7
    
8.
Duarte JM. Early diabetic neuropathy: A diagnostic challenge. EC Neurology 2017;5:204.  Back to cited text no. 8
    
9.
Braune HJ. Early detection of diabetic neuropathy: A neurophysiological study on 100 patients. Electromyogr Clin Neurophysiol 1997;37:399-407.  Back to cited text no. 9
    
10.
Janghorbani M, Rezvanian H, Kachooei A, Ghorbani A, Chitsaz A, Izadi F, et al. Peripheral neuropathy in type 2 diabetes mellitus in Isfahan, Iran: Prevalence and risk factors. Acta Neurol Scand 2006;114:384-91.  Back to cited text no. 10
    
11.
Mohmad AH, Sidig A, Gadour MOH, Hamad A, Aldar MM. Correlation between retinopathy, nephropathy and peripheral neuropathy among adult sudanese diabetic patients. Sudan J Med Sci 2011;6:27-32.  Back to cited text no. 11
    
12.
Rani PK, Raman R, Rachapalli SR, Pal SS, Kulothungan V, Sharma T. Prevalence and risk factors for severity of diabetic neuropathy in type 2 diabetes mellitus. Indian J Med Sci 2010;64:51-7.  Back to cited text no. 12
  [Full text]  
13.
Hicks CW, Selvin E. Epidemiology of peripheral neuropathy and lower extremity disease in diabetes. Curr Diab Rep 2019;19:86.  Back to cited text no. 13
    
14.
Tahrani AA, Altaf QA, Piya MK, Barnett AH. Peripheral and autonomic neuropathy in South Asians and White Caucasians with type 2 diabetes mellitus: Possible explanations for epidemiological differences. J Diabetes Res 2017;12:1-10.  Back to cited text no. 14
    
15.
Vinik AI, Kong X, Megerian JT, Gozani SN. Diabetic nerve conduction abnormalities in the primary care setting. Diabetes Technol Ther 2006;8:654-62.  Back to cited text no. 15
    
16.
Raman R, Gupta A, Krishna S, Kulothungan V, Sharma T. Prevalence and risk factors for diabetic microvascular complications in newly diagnosed type II diabetes mellitus. Sankara Nethralaya diabetic retinopathy epidemiology and molecular genetic study (SN-DREAMS, report 27). J Dia Comp 2012;26:123-8.  Back to cited text no. 16
    
17.
Gokhale VS, Chaudhari NC, Kakrani AL, Shah BP. High incidence of retinopathy in neuropathy proven diabetic patients: A cohort study Int J Med Public Health 2015;5:289-92.  Back to cited text no. 17
    
18.
Joshi SR, Das AK, Vijay VJ, Mohan V. Challenges in diabetes care in India: Sheer numbers, lack of awareness and inadequate control. J Assoc Physicians India 2008;56:443-50.  Back to cited text no. 18
    
19.
Venkatesh P, Tibrewal S, Bhowmik D, Tripathi M, Ramakrishnan S, Vashist N, et al. Tripathi prevalence of systemic co-morbidities in patients with various grades of diabetic retinopathy. Indian J Med Res 2014;140:77-83.  Back to cited text no. 19
[PUBMED]  [Full text]  
20.
Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers 2019;5:41.  Back to cited text no. 20
    
21.
Gill SK, Yadav SB, Bhatia E. A prospective study of prevalence and association of peripheral neuropathy in patients with newly diagnosed type 2 diabetes mellitus J Post Grad Med 2014;60:270-4.  Back to cited text no. 21
    
22.
Ashok S, Ramu M, Deepa R, Mohan V. Prevalence of neuropathy in type 2 diabetic patients attending a diabetes centre in south India. J Assoc Physicians India 2002;50:546-50.  Back to cited text no. 22
    
23.
Nathan DM, Cleary PA, Backlund JY. Epidemiology of diabetic interventions and complications (DCCT/EDIC) study research group. Intensive diabetic treatment and cardiovascular disease in patients with type 1 diabetes. N Eng J Med 2005;353:2643-53.  Back to cited text no. 23
    
24.
UK Prospective Diabetes Study Group. UK prospective diabetes study (UKPDS). Diabetologia 1991;34:877-90.  Back to cited text no. 24
    
25.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial. Lancet 2010;376:419.  Back to cited text no. 25
    
26.
Darivemula S, Nagoor K, Patan SK, Reddy NB, Deepthi CS, Chittooru CS. Prevalence and its associated determinants of Diabetic peripheral neuropathy (DPN) in individuals having type-2 diabetes mellitus in rural South India. Indian J Community Med 2019;44:88-91.  Back to cited text no. 26
[PUBMED]  [Full text]  
27.
Olamoyegun M, Ibraheem W, Iwuala S, Audu M, Kolawole B. Burden and pattern of micro vascular complications in type 2 diabetes in a tertiary health institution in Nigeria. Afr Health Sci 2015;15:1136-41.  Back to cited text no. 27
    
28.
Bruun C, Siersma V, Guassora AD, Holstein P, Fine Olivarius N. Amputations and foot ulcers in patients newly diagnosed with type 2 diabetes mellitus and observed for 19 years. The role of age, gender and co-morbidity. Diabetic Med 2013;30:964-72.  Back to cited text no. 28
    
29.
Tesfaye S, Stevens LK, Stephenson JM, Fuller JH, Plater M, Ionescu-Tirgoviste C, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycemic control and potential risk factors: The EURODIAB IDDM complications study. Diabetologia 1996;39:1377-84.  Back to cited text no. 29
    
30.
Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort the Rochester diabetic neuropathy study. Neurology 1993;43:817-24.  Back to cited text no. 30
    
31.
Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: A position statement by the American diabetes association. Diabetes Care 2017;40:136-54.  Back to cited text no. 31
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
   
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
  Methods
  Results
  Discussion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed107    
    Printed0    
    Emailed0    
    PDF Downloaded37    
    Comments [Add]    

Recommend this journal