|Year : 2010 | Volume
| Issue : 2 | Page : 51-57
Prevalence and risk factors for severity of diabetic neuropathy in type 2 diabetes mellitus
Padmaja Kumari Rani1, Rajiv Raman1, Sudhir R Rachapalli2, Swakshyar Saumya Pal1, Vaitheeswaran Kulothungan2, Tarun Sharma1
1 Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
2 Department of Preventive Ophthalmology, Sankara Nethralaya, Chennai, Tamil Nadu, India
|Date of Web Publication||28-Mar-2012|
Principal Investigator and Director, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, 18 College Road, Chennai - 600 006, Tamil Nadu
Purpose: To estimate the prevalence of diabetic neuropathy (severity wise) and associated risk factors in a population having type 2 diabetes mellitus. Materials and Methods: A population-based sample of 1401 persons with diabetes (identified as per the WHO criteria) underwent comprehensive eye examination including stereoscopic digital photography (45° four field) for diabetic retinopathy grading. Vibration perception threshold (VPT) measurements were done to assess neuropathy (cut off ≥ 20 V). Severity of neuropathy was graded into three groups based on VPT score as mild (20-24.99 V), moderate (25-38.99 V), and severe (≥39 V). Univariate and multivariate analyses were done to find out the independent risk factors for severity of diabetic neuropathy. Results: In the overall group, the prevalence of diabetic neuropathy was 18.84% (95% CI: 16.79-20.88). The prevalence of mild diabetic neuropathy was 5.9% (95% CI: 4.68-7.15), moderate diabetic neuropathy was 7.9% (95% CI: 6.50-9.33), and severe diabetic neuropathy was 5% (95% CI: 3.86-6.14). Increasing age per year (P < 0.0001) was a statistically significant risk factor for all - mild, moderate, and severe - types of diabetic neuropathy. For severe diabetic neuropathy, other significant risk factors were duration of diabetes mellitus (P = 0.027), macroalbuminuria (P = 0.001), and presence of diabetic retinopathy (P = 0.020). Conclusions: The results suggested that every fifth individual in a population of type 2 diabetes is likely to have diabetic neuropathy. Nearly 13% had neuropathy of moderate and severe category, making this group vulnerable for complications such as foot ulceration or lower limb amputation.
Keywords: Diabetic neuropathy, prevalence, risk factors, type 2 diabetes mellitus
|How to cite this article:|
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
|How to cite this URL:|
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 [serial online] 2010 [cited 2013 May 22];64:51-7. Available from: http://www.indianjmedsci.org/text.asp?2010/64/2/51/94400
| ¤ Introduction|| |
Diabetic neuropathy is an important microvascular complication of diabetes mellitus. It is a major contributor to foot ulceration and lower limb amputation in persons with diabetes.  As the population of diabetes is increasing worldwide, the prevalence of diabetes-related microvascular complications is also on the rise. Duration of diabetes mellitus is an important risk factor for all diabetes-related microvascular complications such as neuropathy, retinopathy, and nephropathy. Up to 7.5% of patients with non-insulin-dependent diabetes mellitus (NIDDM) have clinical neuropathy at the time of diagnosis and this rate increases to 50% among patients who have had diabetes for 25 years. 
Various screening modalities for diabetic neuropathy include recording of symptoms or signs, nerve conduction studies, quantitative sensory testing, and autonomic testing.  Quantitative assessment of vibration perception threshold (VPT) is a widely applied tool in the screening for, and staging of, diabetic sensory neuropathy, particularly in epidemiological studies. , Values of VPT of more than 25 V are associated with a 6-10-fold risk of developing a foot ulcer.  These findings suggest the role of "severity" of diabetic neuropathy in the etiology of its complications. However, there is paucity of population-based data from India regarding the prevalence based on the severity of diabetic neuropathy and the influencing risk factors.  The present population study was done to assess the prevalence of severity of diabetic neuropathy (mild, moderate, and severe) in type 2 diabetes mellitus and report the risk factors that influence it.
| ¤ Materials and Methods|| |
Study subjects were recruited from the Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS). The study design and research methodology of SN-DREAMS 1 is described in detail elsewhere. 
The study area was Chennai metropolis with a population of 4.3 million, distributed in 155 divisions of 10 zones. As a sample, a total of 5999 people from the general population aged >40 years were enumerated; multistage random sampling was stratified on the basis of economic criteria. Of the 5999 subjects enumerated, 1414 persons identified with diabetes as per the WHO criteria  (both known and newly diagnosed) were analyzed for the study (96.20% response rate for first fasting blood sugar estimation, 85.60% response rate for base hospital examination, 8.7% turned out as nondiabetic after second blood sugar, and 0.78% of retinal images were ungradable). A total of 1401 subjects underwent diabetic neuropathy assessment. The study was approved by the Institutional Review Board, and informed consent was obtained from the subjects as per the Helsinki declaration.
Procedures pertaining to the present study are described below.
Diabetic neuropathy assessment
Diabetic neuropathy assessment was done by measuring VPT using sensitometer. The VPT was measured by a single observer by placing biothesiometer probe perpendicular to the distal plantar surface of the great toe of both legs. The VPT was measured at a voltage level when patient felt the first vibration sensation. The mean VPT measure of three readings of both legs was considered for the analysis. The upper limit of mean ± 2 SD VPT of healthy controls without diabetes (n = 136) in the age group between 40 and 81 years (mean age 53.22 ± 9.63 years) was 18.53 V. Diabetic neuropathy was considered as present if the VPT value was >20 V. The severity of neuropathy was graded into 3 levels: mild neuropathy (VPT score, 20-24.99 V), moderate neuropathy (VPT score, 25-38.99 V), and severe neuropathy (VPT score, >39 V). 
Diabetic retinopathy grading
All patients had their fundi photographed by means of 45° four-field stereoscopic digital photography. The diagnosis of diabetic retinopathy was based on the modified Klein classification.  For those who showed evidence of any retinopathy, additional 30° seven-field stereo digital pairs were taken. All photographs were graded by two independent observers in a masked fashion; the grading agreement was high (k = 0.83).
Non- sight threatening diabetic retinopathy
Non-sight threatening diabetic retinopathy included cases of mild or moderate non-proliferative diabetic retinopathy. 
Sight threatening diabetic retinopathy
Sight-threatening diabetic retinopathy (referable diabetic retinopathy) was defined as severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, and clinically significant macular edema. 
The patient was considered normoalbuminuric if Albumin Creatinine Ratio (ACR) was less than 30 mg/g, microalbuminuric if the ACR was between 30 and 300 mg/g, and macroalbuminuric if the ACR was above 300 mg/g. 
Statistical analyses were performed using the statistical software (SPSS for Windows, ver. 13.0 SPSS Science, Chicago, IL, USA). The results were expressed as mean ± SD if the variables were continuous and as percentage if the variables were categorical. Student's t-test for comparing continuous variables and χ2 test to compare proportions amongst groups were used. Both univariate and multivariate logistic regression analyses were performed to study the effect of various risk factors using neuropathy as a dependent variable. From the univariate analysis, variables with P values ≤0.1 were included in the multivariate logistic regression analysis to derive at the parsimonious model. P value of ≤0.05 was considered significant.
| ¤ Results|| |
The mean age of the total study population (N = 1401) was 56.3 ± 10 years; 746 (53.2%) were men. [Table 1] shows the prevalence of diabetic neuropathy (severity wise) in the study population. In the overall group, the prevalence of diabetic neuropathy was 18.84% (95% CI: 16.79-20.88); the prevalence was significantly higher in persons with known diabetes than in those with newly detected diabetes (19.77 vs. 14.40, P = 0.05). The prevalence of mild diabetic neuropathy was 5.9% (95% CI: 4.68-7.15), moderate diabetic neuropathy was 7.9% (95% CI: 6.50-9.33), and severe diabetic neuropathy was 5% (95% CI: 3.86-6.14). The prevalence of severe diabetic neuropathy was significantly high in persons with known diabetes than in those with newly detected diabetes (5.53 vs. 2.47, P = 0.04).
[Table 2] summarizes the univariate analysis of risk factors influencing the severity of diabetic neuropathy. Significant risk factors common to all the three neuropathy groups were: advancing age (P < 0.0001), longer duration of diabetes mellitus (P < 0.0001), use of insulin (P = 0.006), high systolic blood pressures (P = 0.008), presence of macroalbuminuria (P < 0.0001), and presence of diabetic retinopathy (P < 0.0001). [Figure 1] shows the increasing odds ratio (OR) for all types of diabetic neuropathy in relation to the increasing duration of diabetes mellitus. The OR for severe neuropathy in persons with diabetes of more than 15 years was 6.02 (95% CI: 3.22-11.25), which was much higher than in those with diabetes duration of less than 5 years.
|Table 2: Univariate analysis of risk factors for severity of diabetic neuropathy|
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[Table 3] shows the multivariate analysis of risk factors influencing the severity of diabetic neuropathy. Increasing age per year (P < 0.0001) was a statistically significant risk factor for all types of diabetic neuropathy - mild, moderate, and severe. For severe diabetic neuropathy, other significant factors were duration of diabetes mellitus (P = 0.027), macroalbuminuria (P = 0.001), and presence of diabetic retinopathy (P = 0.020).
|Table 3: Multivariate analysis of risk factors for severity of diabetic neuropathy|
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| ¤ Discussion|| |
The prevalence of diabetic neuropathy, as assessed by VPT, in this population-based study was around 19%. This suggested that every fifth individual in the population having diabetes mellitus, particularly among known diabetics, has a chance of developing this microvascular complication. In the literature, the reported prevalence of neuropathy varies widely from 8.3 to 45%. ,,,,, This variability could be due to variation in the population studied, type of diabetes, and the criteria used to assess diabetic neuropathy. A quantitative technique such as VPT that was used in this study provides several advantages: It is easier to administer, takes less time, and involves lower cost.
The risk of foot ulceration and lower limb amputation increases in those with VPT of more than 25 V. This study demonstrated that the prevalence of combined moderate and severe neuropathy (>25 V) was about 13% across the population of diabetes. This risk of severe neuropathy was much higher in persons with known diabetes compared to those with newly detected diabetes (5.5% vs. 2.5%). Likewise, the overall prevalence of neuropathy was also more in the group of individuals with known diabetes than in those with newly detected diabetes (19.8% vs. 14.4). Others have reported prevalence of neuropathy in newly detected cases as ranging from 3.6 to 19.1%. ,,,,,,,
This study has identified increasing age as a risk factor for all types of neuropathy - mild, moderate, and severe. However, longer duration of diabetes, macroalbuminuria, and diabetic retinopathy were related to only severe type of neuropathy. Several other reports have also identified age as significant risk factor for diabetic neuropathy. ,,,,,,,, Similarly, others have also observed that longer duration of diabetes increased the chance of neuropathy. ,,,,,,,,
One important observation from this study was that the risk of neuropathy was around fivefold in the presence of macroalbuminuria. Therefore, microvascular complications such as diabetic nephropathy and diabetic neuropathy go hand in hand in persons with diabetes. 
The limitation of the present study is the use of a single measurement (biothesiometry) for diagnosing neuropathy; however, other diagnostic measures such as nerve conduction studies and neuropathy symptom score estimations are somewhat cumbersome in large epidemiological studies. Another limitation is the point estimation of risk factors which cannot prove a causal association. This is a known inherent weakness of a cross-sectional study.
The merits of the present study are the following. This was a well-conducted large epidemiology study of individuals with type 2 diabetes mellitus using standard diagnostic techniques. The study is unique in the sense that it estimated the prevalence rates of neuropathy, severity wise; therefore, the findings would have the necessary clinical impact and inspire resource mobilization for treatment.
| ¤ Acknowledgement|| |
We acknowledge the support of RD Tata Trust, Mumbai, for this project.
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[Table 1], [Table 2], [Table 3]