Diabetic Neuropathy: A Study of its Association with Various Risk Factors in Type 2 Diabetic Patients.

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1 International Journal of Current Medical And Applied Sciences, 2015, July, 7(2), ORIGINAL RESEARCH ARTICLE Diabetic Neuropathy: A Study of its Association with Various Risk Factors in Type 2 Diabetic Patients. Shaikh Shahabuddin 1,Daimi Sayed Badar 2 & Khan Moizuddin M. 3 1 Associate Professor, Department of Physiology, SMBT Institute of Medical Sciences & Research Centre, Nandi Hills, Nashik, [MS],India. 2 Assistant Professor, Department of Physiology, JIIU s Indian Institute of Medical Science and Research Warudi, Jalna [MS],India. 3 Associate Professor, Dept. of Physiology, MGM s Medical College, Aurangabad, [MS],India Abstract: The aim of the present work was to study the association of various risk factors in relation to presence of signs and symptoms of Diabetic Peripheral Neuropathy (DPN) in type II Diabetics. The study was conducted at MGM Medical College and Hospital, Aurangabad among the diabetic patient presenting in Diabetic clinic in MGM Hospital. In present study, Age > than 65 years, duration of diabetes more than 10 years, raised Glycosylated hemoglobin and presence of other diabetic complication have shown significant Association with Clinical neuropathy hence taller, older diabetics and/or who have diabetes of long duration or raised glycosylated hemoglobin or show evidence of any diabetic complications, should be examined and investigated for evidence of neuropathy. Based on our study we also recommend routine evaluation for neuropathy of all diabetic patients from the time when they are first diagnosed as diabetics. Keywords: Diabetes mellitus, Neuropathy, Complications. Introduction: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs leading to nephropathy, retinopathy, angiopathy and neuropathy (1). Earlier studies have shown that Peripheral neuropathy is a complication in approximately 50% of patients with diabetes, and up to 50% of patients with peripheral neuropathy may not have symptoms (2-4). An internationally agreed simple definition of Diabetic Peripheral Neuropathy (DPN) for clinical practice is "the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes". DPN affects sensory, motor, and autonomic nerve fibers diffusely leading to progressive degeneration and nerve fiber loss (5). Peripheral neuropathy causes clinically significant morbidities, such as pain, loss of sensation, foot ulcers, gangrene and amputations. The development and progression of Diabetic Neuropathy is still a matter of intense research. It is generally accepted as a multi factorial process and many hypotheses have been proposed. Like any other complication of DM, DPN is caused by multiple mechanisms both metabolic and vascular (6). Risk factors for the development of peripheral neuropathy (PN) include diabetes duration, degree of hyperglycemia, hyperlipidemia, hypertension, and height (3). Retinopathy and nephropathy are highly associated with PN, occurring in 55% and 32% of type 2 diabetic patients, respectively (4). Address for correspondence: Dr. Khan Mo i zuddi n M Associate Professor Department of Physiology, MGM s Medical College, Aurangabad [MS], India. drmoizkhan@rediffmail.com How to cite this article: Shaikh Shahabuddin, Daimi Sayed Badar & Khan Moizuddin M ; Diabetic Neuropathy: A study of its association with various risk factors in Type 2 Diabetic Patients.; International Journal of current Medical and Applied sciences; 2015, 7(2), Access this Article Online Quick Response Code Website: Subject: Medical Sciences IJCMAAS,E-ISSN: ,P-ISSN: Page 143

2 Shai kh Shah a buddi n, D a i mi Saye d Bad ar & Khan Mo i zuddi n M. The aim of the present work is to study the association of various risk factors in relation to presence of signs and symptoms of DPN in type II Diabetics. In this study clinical characteristics and hematological tests are compared between group of diabetics who showed signs and symptoms of diabetic neuropathy with group of diabetics who do not have any sign or symptom of diabetic neuropathy. Materials and Methods: This is a Hospital-based Cross-sectional study. The study was conducted at MGM Medical College and Hospital, Aurangabad after approval by the institutional ethical committee and informed written consent was taken from all the subjects. Purposive sampling was done among the diabetic patient presenting in Diabetic clinic in MGM Hospital. The study population for the present study was 180, divided into two groups as follows: Group-1 (n=90): Patients with Type 2 diabetes who on clinical evaluation and monofilament testing do not ful fill minimal criteria for diagnosis of Diabetic Polyneuropathy. Group-2 (n=90): Patients with diabetes who on clinical evaluation were diagnosed as having Diabetic Polyneuropathy. All the subjects of our study were enrolled and assigned to one of the above two groups after verifying their compliance with appropriate inclusion and exclusion criteria. In order to ensure the closest possible match between the two groups, equal numbers of subjects were included. A total of 45 males and 45 females in each group were selected. Clinical Assessment: The subjects of the two groups under study were evaluated clinically by physicians. A questionnaire was completed to obtain demographic data, medical history including drugs, and lifestyle factors. Clinical complications of diabetes Retinopathy, Nephropathy and Peripheral arterial disease were defined as per history of physician diagnosed disease. Cardiovascular disease (CVD) was defined as either a history of physician-diagnosed CVD (e.g. previous myocardial infarction, angina, coronary-artery bypass grafting) or ischemic changes detected on a 12-lead electrocardiogram. Clinical neuropathy was diagnosed in patients of DM using the Michigan Neuropathy Screening Instrument (MNSI). Neuropathy is defined as seven or more positive responses on the MNSI questionnaire or a score >2 on the MNSI examination, thresholds defined by prior validation studies (7, 8). Statistical Analysis: All the data obtained was compiled into excel sheet and analyzed using Statistical Package for Social Sciences version 17.0 (SPSS Inc., Chicago, IL, USA). The analysis for males and females were done separately. Comparison between the groups with respect to blood tests, presence of other diabetic complications was done. Association of risk factors (categorical variables) with incidence of neuropathy was established using chi square test. Results: In this study, a comparison of clinical characteristics and hemato logical tests of type 2 DM patients was done in between those who did not show any sign and symptoms of Neuropathy (Group 1) and those who have clinical Neuropathy (Group 2). Table 1: Comparison of Duration of Diabetes in the groups: Males Group Obsn Mean Std. Err SD 95% Conf. Interval P < Females Group Obsn Mean Std. Err SD 95% Conf. Interval P < As shown in Table 1, the Duration of diabetes since diagnosis showed highly significant difference when compared between the two groups in both males and females. In males the duration of diabetes was 5.64 ± 3.40 (mean ±SD) years in group 1 and ± 5.02 years in group 2. While in females the duration of diabetes was 5.49 ± 3.89 (mean ± SD) years in group 1 and 8.64 ±6.38 years in group 2. Table 2: Comparison of Hematological tests in the groups: Table 2 shows the comparison of hematological finding between the two groups. Both the fasting blood glucose level and the glycosylated hemoglobin were significantly higher in group 2 as compared to group 1 in both male and female participants. Interestingly in males, the serum total cholesterol and Serum Triglyceride levels were higher in group 1 as compared to group 2 though the difference was statistically not significant while in females the levels were higher in group 2 as compared to group 1 and the difference was statistically significant. Logic 2015, IJCMAAS, E-ISSN: ,P-ISSN: Page 144

3 Logic 2015, IJCMAAS, E-ISSN: ,P-ISSN: V ariab le Se x Gr o up Mean SD Mi n Ma x P-v alue FB G M < F < HbA 1C ( %) Total Cho Sr Trig M < F < M < F < M F Table 3: Comparison of Diabetic Complication in the groups Diab. Complication/ Sex Group No. of +ve Percentage P -value Associated conditions Participants Retinopathy M F Nephropathy M F Coronary Artery M Disease Peripheral Vascular Disease F M F Hypertension M F When prevalence of other diabetic complications and associated medical conditions was compared between the two groups, as shown in table 3, we found, in males, retinopathy was prevalent in 60% of the group 2 participants as compared to only % of the group 1 participants the difference being statistically highly significant. While in females the difference was not significant with group 2 prevalence being % and group 1 prevalence being 31.11%. The difference in prevalence of nephropathy in the two groups was statistically significant with 42.22% and 37.78% prevalence in group 2 in males and females respectively and 17.78% prevalence in both males and females in group 1. Similarly the prevalence of CAD, PVD and Hypertension was higher in both male and female participants of group 2 as compared to group 1 though the difference was not statistically significant except in prevalence of PVD in females where the difference in prevalence between group 2 and group 1 was statistically significant. Table 4: Association of Clinical Neuropath y and its risk factors: We further analyzed the association of various risk factors in relation to our two study groups. The data is as shown in table 4. Out of the total 45 male participants in group 1, 57.78% were less than 50 years old, 28.89% were between 51 to 65 years old and only 13.33% were more than 65 years old. In comparison out of the total 45 male participants in group 2, 28.89% were less than 50 years old, 44.44% were between 51 to 65 years old and 26.67% were more than 65 years old thus there was significant difference in the two groups. International Journal of Current Medical And Applied Sciences [IJCMAAS], Volume : 7, Issue:2.

4 Shai kh Shah a buddi n, D a i mi Saye d Bad ar & Khan Mo i zuddi n M. Variable Male No. Of Participants (%) Female No. Of Participants (%) Group 1 Group 2 Group 1 Group 2 AGE (Years) (57.78 %) 13 (28.89 %) 28 (62.22 %) 16 (35.56 %) (28.89%) 20 (44.44%) 13 (28.89 %) 16 (35.56 %) > 65 6 (13.33% ) 12 (26.67 %) 4 (8.89 %) 13 (28.89 %) P Value DURATION (Years) (44.44 %) 9 (20 %) 25 (55.56 %) 16 (35.56 %) (51.11 %) 14 (31.11 %) 17 (37.78 %) 11 (24.44 %) > 10 2 (4.44 %) 22 (48.89 %) 3 (6.67 %) 18 (40 %) P Value < HbA1C (Percentage) P Value Other Complications P Value (73.33 %) 22 (48.89 %) 30 (66.67 %) 17 (37.78%) > 8 12 (26.67 %) 23 (51.11 %) 15 (33.33 %) 28 (62.22 %) Absent 22 (48.89 %) 7 (15.56 %) 24 (53.33 %) 17 (37.78%) Present 23 (51.11 %) 38 (84.44 %) 21 (46.67 %) 28 (62.22 %) Similarly the difference in the duration of diabetes since diagnosis also showed significant difference with 48.89% males and 40% females of group 2 having duration of diabetes of more than 10 years in comparison to only 4.44% males and 6.67% females of group 1 have duration of diabetes more than 10 years. HbA1C value of 8 % also showed significant difference in the groups with 51.11% male and 62.22% females of group 2 having HbA1C value more than 8% in comparison to 26.67% males and 46.67% females of group 1 having Value more than 8%. The association of prevalence of other complication or associated condition also showed significant difference in the groups with 84.44% males and 62.22% females in group 2 having at least one other diabetic complication or associated hypertension in comparison to 51.11% males and 46.67% females in group 1 having at least one other diabetic complication or associated hypertension. Discussion: In this study, a well-defined group of patients with Type 2 diabetes mellitus has been studied. In our study the diabetic subjects were divided into two group, diabetics without clinical neuropathy (Group 1) and diabetics with clinical neuropathy (Group 2). As shown in Table 4, in our study age more than 65 years was significantly associated with clinical neuropathy in both males and females with 26.67% male and 28.89% female diabetics having clinical neuropathy being in that age group as compared to 13.33% male and 8.89% female diabetic participants without clinical neuropathy in that age group. Age is an established risk factor for development of neuropathy in diabetics and many studies have shown steady increase in incidence of neuropathy with increase in age (3,4,6). As expected the mean duration of diabetes since diagnosis and Glycosylated hemoglobin were higher in both male and female diabetics with clinical neuropathy as compared to diabetics without clinical neuropathy (Table 1-3). Both duration of diabetes and Glycosylated hemoglobin are established independent factor for development of neuropathy and other complications of diabetes (9). When duration of diabetes since diagnosis was analyzed, we found duration more than 10 years was significantly associated with clinical neuropathy in both genders with 48.89% male and 40% female diabetic participants with clinical neuropathy had duration of diabetes since diagnosis more than ten years as compared to 4.44% male and 6.67% female diabetic participants without clinical neuropathy had duration of diabetes since diagnosis more than ten years. Interestingly 20% male and 35.56% female diabetic participants with clinical neuropathy were with duration of diabetes ranging from newly diagnosed to 5 years as compared to 44.44% male and 55.56% female diabetic participants without clinical neuropathy in that group. In an earlier study 7.5 percent of patients with Type 2 diabetes had clinical neuropathy at the time of diagnosis (10). In another study of patients with Type 2 diabetes it was found that 15.2 percent had abnormalities in nerve conduction velocity at the time of diagnosis, but only 2.3 percent had clinical signs of polyneuropathy (11). After five years of follow-up, changes in neurophysiologic measurements in this group were slight and were associated with poor glycemic control (12). Significantly high number of cases of diabetics with duration up to 5 years having clinical neuropathy in our study as compared to earlier studies may be an indication of less awareness and delayed consultation with physician in our population. Similarly there was significant association of HbA1C level with incidence of clinical neuropathy amongst the participants. The American Diabetes Association recommends a target glycated hemoglobin concentration as the goal for optimum glycaemic control. Each 1 % reduction in glycated hemoglobin was associated with reductions in risk of 45 % for the progression of diabetic retinopathy, 21 % for any end point related to Logic 2015, IJCMAAS, E-ISSN: ,P-ISSN: Page 146

5 Logic 2015, IJCMAAS, E-ISSN: ,P-ISSN: diabetes, 21 % for deaths related to diabetes, 14 % for myocardial infarction, and 37 % for micro-vascular complications (13, 14). As seen in table 4 the presence of at least one of the above complication is strongly associated with incidence of clinical neuropathy with 84.44% of male participants with clinical neuropathy having at least one other complication as compared to only 51.11% in participants without clinical neuropathy while in females it is 62.22% as compared to 46.67%. Our results show that the prevalence of other complications like Retinopathy, Nephropathy, CAD, PVD and Hypertension was higher in both male and female participants who already had clinical neuropathy. Considerable earlier evidence indicates that diabetic micro-vascular diseases are associated with neuropathy (4,9,15). Retinopathy and nephropathy in particular are highly associated with DPN, occurring in 55% and 32% of Type 2 diabetic patients with DPN, respectively (4).We found similar association of presence of other diabetic complication with diabetic neuropathy. Conclusion: In the study population, age more than 65 years, duration of diabetes more than 10 years, raised Glycosylated hemoglobin and presence of other diabetic complication have shown significant association with Clinical neuropathy. Based on the above findings it is recommended that, elderly diabetics and/or who have diabetes of long duration or raised glycosylated hemoglobin or show evidence of any diabetic complications, should be examined and investigated for evidence of neuropathy. Considering the significant prevalence of clinical neuropathy in diabetics with duration of to less than five years in our study population, it is recommended that all diabetic patients should be evaluated routinely for neuropathy right from the time of their first diagnosis as diabetics. References: 1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes care [Internet] ;34 Suppl 1:S62 9. Available_from: d= &tool=pmcentrez&rendertype. 2. American Diabetes Association. Standards of medical care in diabetes Diabetes care [Internet] Jan [cited 2012 Mar 12];35 Suppl 1:S Available_from: 3. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005; 28: Dyck PJ, Kratz KM, Karnes JL, 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(4): Dyck P.J. and Giannini C. Pathologic alterations in the diabetic neuropathies of humans: a review. J NeuropatholExp Neuro. 1996; 55: Cameron NE, Cotter MA. Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes. 1997; 46 Suppl 2:S Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene DA. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care. 1994; 17: DCCT Research Group. Factors in development of diabetic neuropathy: Baseline analysis of neuropathy in feasibility phase of Diabetes Control and Complications Trial Diabetes.1988 Apr; 37(4): Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH, EURODIAB Prospective Complications Study Group. Vascular risk factors and diabetic neuropathy. N Engl J Med 2005; 352: Partanen J, Niskanen L, Lehtinen J, Mervaala E, Siitonen O, Uusitupa M. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. The New England journal of medicine [Internet] Jul 13; 333(2): Lehtinen JM, Uusitupa M, Siitonen O, Pyörälä K. Prevalence of neuropathy in newly diagnosed NIDDM and nondiabetic control subjects. Diabetes. 1989; 38: Lehtinen JM, Niskanen L, Hyvönen K, Siitonen O, Uusitupa M. Nerve function and its determinants in patients with newly-diagnosed Type 2 (non-insulindependent) diabetes mellitus and in control subjects a 5-year follow- up. Diabetologia. 1993; 36: DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin dependent diabetes mellitus. N Engl J Med. 1993; 329: Stratton, Irene M., Amanda I. Adler, H. Andrew W. Neil, David R. Matthews, Susan E. Manley, et.al. Association of glycaemia with macrovascular and microvascular complications of Type 2 diabetes (UKPDS 35): prospective observational study. 2000; Bmj: 321(7258) Dyck PJ, Davies JL, Wilson DM, Service FJ, Iii LJ, Peter C. O brien. Risk Factors for Severity of Diabetic Polyneuropathy. Diabetes care. 1999; 22(9): International Journal of Current Medical And Applied Sciences [IJCMAAS], Volume : 7, Issue:2.