|Year : 2012 | Volume
| Issue : 3 | Page : 105-109
Peripheral arterial disease in patients with type 2 diabetes mellitus in South India: The urban vs rural divide
Bhavana Sosale1, Y. J. V. Reddy1, M. V. Nagbhushana1, Aravind Sosale2, Edward B. Jude3
1 Department of Medicine, PES Institute of Medical Sciences and Research, Kuppam, Chittor, Andhra Pradesh, India
2 Diacon Hospital, Bangalore, Karnataka, India
3 Tameside Hospital, Manchester, United Kingdom
|Date of Web Publication||21-May-2014|
Dr. Aravind Sosale
Diacon Hospital, 360, 19th Main, 1st Block, Bangalore - 560 010, Karnataka
Source of Support: None, Conflict of Interest: None
Background and Aims: Peripheral arterial disease (PAD) is a marker for macrovascular disease and a risk factor for lower limb amputations, in patients with diabetes. The extent and impact of PAD in the rural population in India has not been well studied. The aim of this study was to screen for asymptomatic PAD using ankle brachial index (ABI) in order to characterize and compare risk factors associated with it and to look for the presence of ischemic heart disease (IHD) in rural and urban populations.
Materials and Methods: This was an observational, cross-sectional study involving type 2 diabetic patients attending the diabetes clinic in an urban and rural hospital, in South India. Two hundred rural (R) and 400 urban (U) patients were screened for PAD over a period of1 year. An ABI ≤0.9 or >1.3 was considered abnormal. Patients with known PAD and or claudication were excluded as the aim was to look for PAD in asymptomatic patients. Anthropometric measurements and investigations were carried out. Risk factors were analyzed and P values and odds ratio (OR) were calculated.
Results: 17.8% of patients had an ABI suggestive of PAD (R 20% vs U 16.8%). 63.6% were male. Known risk factors of PAD were identified and included dyslipidemia (85%; R 92.5% vs U 80.6%; OR 1.61), obesity (84.1%; R 85% vs U 83.6%; OR 0.75), hypertension (59.8%; R 47.5% vs U 67.2%; OR 1.26), and age >50 years (64.5%; R 55% vs U 70%; OR1.24). Except for smoking (22.4%; R 32.5% vs U 16.4%; OR 1.03), none of the other risk factors were different between groups. Mean duration of type 2 diabetes mellitus (T2DM) was 7.95±7.50 (R 4.66±5.22 vs U 9.61±7.93; P<0.001). Electrocardiogram (ECG) changes consistent with IHD were found in 25.3% of patients with PAD (R 20% vs U 28.3%; OR 3.06; confidence interval (CI) 1.81-5.18; P=0.001).
Conclusion: Our study demonstrates that one in six asymptomatic South Indians with T2DM have PAD. One in four patients with PAD had ECG changes of IHD which was statistically significant. Based on the odds ratio, the rural patients with PAD had two and a half times higher risk of IHD, even though there was no statistically significant difference in cardiovascular risk factors, age, sex, and mean hemoglobin A1c (HbA1c) in both groups. Prevalence of PAD with a lower duration of DM and higher strength of association with IHD noted in the asymptomatic rural population in our study is a cause for concern.
Keywords: Ankle brachial index, coronary artery disease, peripheral arterial disease, rural vs urban
|How to cite this article:|
Sosale B, Reddy Y, Nagbhushana MV, Sosale A, Jude EB. Peripheral arterial disease in patients with type 2 diabetes mellitus in South India: The urban vs rural divide. J Acad Med Sci 2012;2:105-9
|How to cite this URL:|
Sosale B, Reddy Y, Nagbhushana MV, Sosale A, Jude EB. Peripheral arterial disease in patients with type 2 diabetes mellitus in South India: The urban vs rural divide. J Acad Med Sci [serial online] 2012 [cited 2021 Apr 14];2:105-9. Available from: http://www.e-jams.org/text.asp?2012/2/3/105/132951
| Introduction|| |
The World Health Organization (WHO) estimates that between 2000 and 2030, the number of people with diabetes will increase by 114%. ,, Conservative estimates based on population growth and ageing and rate of urbanization in Asia show that India will have highest numbers of people with diabetes (79.4 million) by 2030. ,
Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. Cardiovascular disease (CVD) is the major cause of morbidity and mortality for individuals with diabetes, and the largest contributor to the direct and indirect costs of diabetes. 
It is well established that peripheral arterial disease (PAD) is a marker for CVD and that the risk is greater with more advanced PAD. ,,,,,, The risk factors that favor the development of peripheral artery disease (i.e., hyperlipidemia, smoking, hypertension (HTN), diabetes) are similar to those that promote the development of coronary atherosclerosis. ,,,,,,
ABI involves measuring the systolic blood pressures in the ankles (dorsalis pedis or posterior tibial arteries) and arms (brachial artery) using a hand-held Doppler and then calculating a ratio. Simple to perform, it is a noninvasive, quantitative measurement of the patency of lower extremity arterial system. It has been validated against angiographically conﬁrmed disease and found to be 95% sensitive and almost 100% speciﬁc. 
Studies regarding the prevalence of PAD in patients with type 2 diabetes in the rural population, which constitutes 72.2% of the Indian population as per the 2001 census, are lacking. Hence, we do not have comparative data between the rural and urban population. We carried out the present study to assess prevalence of PAD in rural and urban patients with type 2 diabetes by measuring ankle brachial index (ABI) and to correlate PAD with cardiovascular risk factors. We also sought to evaluate the relationship between PAD and CVD in both groups.
| Materials and Methods|| |
This was a prospective observational, cross-sectional study that included all patients attending the diabetes outpatient department (OPD) at P. E. S. Institue of Medical Sciences and Research (PESIMSR), Kuppam and Diacon Hospital, Bangalore from March 2011 to March 2012. All patients included in the rural population come from agricultural background and hold government issued 'free treatment medical cards' given for people with low economic group. All these patients are treated free of cost in specialized diabetes clinic run by the institution. Patients with known ischemic heart disease (IHD) and/PAD or those who were symptomatic for the same, that is, those with angina/claudication were excluded. Each patient gave a written informed consent to participate in the study and the institutions' ethics and review board approved the study protocol.
There were 200 type two diabetes mellitus (T2DM) patients included in the rural group and 400 T2DM in the urban group in the age group of 18-90 years. A detailed history was taken regarding the duration of diabetes, medication history, and history of CVD risk factors like HTN, smoking, obesity, and dyslipidemia. Family history of diabetes and history of macro- and microvascular complications were noted.
All patients underwent a complete physical examination that included height, weight, BMI, waist/hip ratio, blood pressure (supine, standing, sitting), and a systemic examination. Indirect and direct ophthalmoscopy was performed in all patients after complete dilatation of the pupil by a qualified retinologist and findings reported.
All were subjected to a comprehensive foot examination  that included inspection, palpation of dorsalis pedis and posterior tibial pulses, presence/absence of patellar and Achilles reﬂexes and determination of proprioception, vibration, and monoﬁlament sensation.
The ABI of all patients included in this study was measured using Hedeco computerized ABI measuring tool. Bilateral brachial and posterior tibial pressures were measured in supine position after 15 min of rest and an ABI ≤0.9 or >1.3 (on one/both sides) was considered abnormal.
All patients were subjected to the following investigations: Fasting blood sugar (FBS), postprandial blood sugar (PPBS), hemoglobin A1c (HbA1C), total count (TC), differential count (DC), Hb%, lipid profile, renal function tests, electrocardiogram (ECG), and urine routine.
Patients with both PAD and ECG changes consistent with IHD were subjected to a treadmill test (TMT) for confirmation of IHD.
Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented on mean±standard deviation (SD) (min-max) and results on categorical measurements are presented in number (%). Significance is assessed at 5% level of significance.
Chi-square/Fisher'sexact test has been used to find the significance of study parameters on categorical scale between two or more groups and 95% confidence interval (CI) has been computed to find the significant features. Odds ratio (OR) has been used to assess the strength association between study variables. The statistical software namely Statistical Analysis Software (SAS) 9.2, Statistical Package for Social Sciences (SPSS) 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0, and R environment ver. 2.11.1 were used for analysis of the data.
| Results|| |
Our study population comprised of 600 T2DM patients with a mean age of 53.21±11.37 years, 56.2% were male and the mean duration of diabetes was 7.95±7.50 years.
17.8% of patients had an ABI suggestive of PAD. In the rural group 40 patients (20%) had PAD and in the urban the number was found to be 67 (16.8%). The baseline data and cardiovascular risk factors of patients with PAD in both groups are depicted below [Table 1].
There was no statistically significant difference in the P values with respect to the parameters given in both groups when patients with and without PAD were compared.
On comparison of the duration of diabetes in both groups with PAD, we found that patients in the rural group had a significantly shorter duration of diabetes compared to their urban counterparts. It was found to be 4.66±5.22 years in the rural group and 9.61±7.93 years in the urban with a P<0.001 [Figure 1].
The patients with electrocardiogram (ECG) changes consistent with ischemic heart disease (IHD) and a positive treadmill test (TMT) comprised of 20 and 28.4% of the rural and urban population with PAD, respectively. The results are represented below [Figure 2] and [Table 2].
| Discussion|| |
There is substantial evidence that the majority of cases of PAD go undetected in routine clinical practice. , As a result, there is considerable interest in detection of PAD through routine screening. ,,,, Detection of asymptomatic PAD has value because it identifies patients at increased risk of atherosclerosis at other sites and most importantly coronary artery disease (CAD). Thus, patients with asymptomatic PAD, most often detected by ABI, should be aggressively treated with risk factor reduction (e.g., aspirin, lipid lowering, and blood pressure control). In addition to protecting against coronary disease and stroke, lipid lowering may also slow progression of the PAD (as measured by angiography). ,, PAD is linked strongly and apparently independently with CVD morbidity and mortality; perhaps more strongly than prior myocardial infarction (MI). PAD is less emphasized and less systematically evaluated than other atherosclerotic conditions or risk factors such as hyperlipidemia and HTN. 
Patients with asymptomatic PAD constitute about 20-50% of those with PAD as per the 2005 American Heart Association (AHA) guidelines on PAD.  A study by McDermott et al., in 2006 clearly clarifies the point that asymptomatic patients with PAD fare badly when compared to symptomatic patients with PAD. These results indicate that clinicians should not equate lack of exertional leg symptoms with a "benign" form of PAD.  This is due to pathways involved in pain perception. Patients who are free of pain despite major disease in one site (as with major asymptomatic PAD) are more likely to be free of pain when disease arises in another vascular bed, as suggested by an increase in total MI, but no trend towards increased angina. 
In this study of 600 T2DM patients, 17.8%, one in six patients from south Indians with T2DM had asymptomatic PAD. A higher percentage of rural patients, that is, 20% had PAD as opposed to 16.8% in the urban group. Previous studies in India like the population based Chennai Urban Population Study (CUPS)  have found the prevalence of PAD to be 6.3%. Hospital based studies from north India by Agrawal et al.,  (n=4400) and by Madhu and Kant,  (n=364) found the prevalence of PAD in diabetics to be 18.1 and 13.73%, respectively.
In our study, among the patients with PAD, 63.6% were male. This was in concordance with other studies by Leibson et al.,  and Li et al.,  where men were found to have higher rates of PAD. Gender differences between the rural and urban groups were not studied.
In CUPS,  higher systolic blood pressure predicted PAD. In the studies by Agrawal et al.,  and Agrawal et al.,  a significant correlation was found between age and prevalence of PAD. In our study, we did not find any correlation between the cardiovascular risk factors and PAD. There were also no significant differences in the CV risk factors and glycemic control between the urban and rural group, even though the patients in the rural group had a higher rate of smoking.
As per the American Diabetes Association (ADA) 2012 consensus statement on PAD, those with a duration of diabetes >10 years have a higher risk for PAD.  In this study, patients with a shorter duration of diabetes were found to have PAD. 32.5% of those with PAD had diabetes for <2 years and 72.5%, that is, almost three-fourth of the patients had diabetes for <5 years in the rural group. The mean duration of diabetes in those with PAD in the rural group was found to be 4.66±5.22 years with a statistically significant P < 0.001. This was as opposed to the urban group, where the mean duration of diabetes in patients with PAD was found to be 9.61±7.93 years which was in concordance with other studies by Agarwal et al.,  and Agrawal et al.,  which had found a significant correlation between longer duration of diabetes and prevalence of PAD. This difference could perhaps be attributed to the asymptomatic nature of type 2 diabetes and lack of awareness leading to a late diagnosis in the rural group. Propensity to earlier vascular disease due to a lean but unhealthy phenotype resulting from fetal malnutrition, or even unknown factors which have yet to be identified can also be the contributing factors which has to be explored in future longitudinal studies.
The prevalence of CAD in PAD patients ranges from 14 to 90%, which clearly reflects differences in sensitivity of the detection technique for CAD. CAD is present in 19 to 47% of PAD patients in studies using clinical history plus ECG; in 62-63% using stress tests; and in 90% of subjects when angiography is used. 
In our study, one in four patients with PAD (24.2%) had ECG changes consistent with IHD, confirmed by TMT. This was similar to the finding that PAD is associated with worse cardiovascular mortality and morbidity in studies like the Cardiovascular Health Study  and The Strong Heart Study.  In a study by Agrawal et al.,  the prevalence of PAD in patients with type 2 diabetes was found to be 52.38%. This included both symptomatic and asymptomatic patients. However, in the CUPS,  prevalence of CAD was not found to be higher in patients with PAD compared to the no PAD group.
This group of patients with IHD comprised of 20% of the rural and 28.4% of the urban patients with PAD, numbers significant in both groups. Based on the OR, rural patients with PAD had two and a half times higher strength of association between PAD and IHD, when compared to their urban counterparts (6.42 vs 2.67).
With 72.2% of the Indian population considered 'rural' and prevalence of diabetes increasing, prevalence of PAD with a lower duration of DM and higher strength of association with IHD noted in the asymptomatic rural population in our study is a cause for concern. This puts at risk a large population of patients with diabetes, asymptomatic for PAD/IHD susceptible to complications. It not only adds to the mortality and morbidity, but also can substantially increase health care costs in our rural population.
The limitations of this study are: (1) A normal ECG does not mean 'no CAD'. However, TMT was only done in patients with an abnormal ECG due to financial constraints. (2) In this study ABI >1.3 was considered abnormal. It is known that in patients with diabetes this can be falsely positive due to peripheral arterial calcification. Pulse wave measurements or the toe pressures need to be calculated to confirm PAD in this subset which has not been done. We need larger studies to confirm our results in order to aid in formulating a screening and prevention strategy to improve public health in our country.
| References|| |
|1.||Ramachandran A, Ma RC, Snehalatha C. Diabetes in Asia. Lancet 2010; 375:408-18. |
|2.||Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53. |
|3.||Sicree R, Shaw J, Zimmet P. Prevalence and projections. In: Gan D, editor. Diabetes Atlas. 3 rd ed. Brussels: International Diabetes Federation; 2006. p. 16-104. |
|4.||American Diabetes Association. Executive summary: Standards of medical care in diabetes - 2012. Diabetes Care 2012;35:S4-10. |
|5.||Vogt MT, McKenna M, Wolfson SK, Kuller LH. The relationship between ankle brachial index, other atherosclerotic disease, diabetes, smoking and mortality in older men and women. Atherosclerosis 1993;101:191-202. |
|6.||Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381-6. |
|7.||Doobay AV, Anand SS. Sensitivity and specificity of the ankle-brachial index to predict future cardiovascular outcomes: A systematic review. Arterioscler Thromb Vasc Biol 2005;25:1463-9. |
|8.||Steg PG, Bhatt DL, Wilson PW, D'Agostino R Sr, Ohman EM, Röther J, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 2007;297:1197-206. |
|9.||O'Hare AM, Katz R, Shlipak MG, Cushman M, Newman AB. Mortality and cardiovascular risk across the ankle-arm index spectrum: Results from the Cardiovascular Health Study. Circulation 2006;113:388-93. |
|10.||Criqui MH, Ninomiya JK, Wingard DL, Ji M, Fronek A. Progression of peripheral arterial disease predicts cardiovascular disease morbidity and mortality. J Am Coll Cardiol 2008;52:1736-42. |
|11.||Feringa HH, Karagiannis SE, Schouten O, Vidakovic R, van Waning VH, Boersma E, et al. Prognostic significance of declining ankle-brachial index values in patients with suspected or known peripheral arterial disease. Eur J Vasc Endovasc Surg 2007;34:206-13. |
|12.||Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: Results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation 2004;110:738-43. |
|13.||Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-24. |
|14.||Smith SC Jr, Milani RV, Arnett DK, Crouse JR 3 rd , McDermott MM, Ridker PM, et al. American Heart Association. Atherosclerotic Vascular Disease Conference: Writing Group II: Risk factors. Circulation 2004;109:2613-6. |
|15.||Murabito JM, D'Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation 1997;96:44-9. |
|16.||Zelis R, Mason DT, Braunwald E, Levy RI. Effects of hyperlipoproteinemias and their treatment on the peripheral circulation. J Clin Invest 1970;49:1007-15. |
|17.||Couch NP. On the arterial consequences of smoking. J Vasc Surg 1986;3:807-12. |
|18.||Al-Delaimy WK, Merchant AT, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Effect of type 2 diabetes and its duration on the risk of peripheral arterial disease among men. Am J Med 2004;116:236-40. |
|19.||American Diabetes Association. Peripheral arterial disease in people with diabetes, Diabetes Care 2003;26:3333-41. |
|20.||Schep G, Bender MH, van de Tempel G, Wijn PF, de Vries WR, Eikelboom BC. Detection and treatment of claudication due to functional iliac obstruction in top endurance athletes: A prospective study. Lancet 2002;359:466-73. |
|21.||Reeder BA, Liu L, Horlick L. Sociodemographic variation in the prevalence of cardiovascular disease. Can J Cardiol 1996;12:271-7. |
|22.||Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45:S5-67. |
|23.||Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: Morbidity and mortality implications. Circulation 2006;114:688-99. |
|24.||Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006;113:e463-654. |
|25.||McDermott MM, Guralnik JM, Ferrucci L, Tian L, Liu K, Liao Y, et al. Asymptomatic peripheral arterial disease is associated with more adverse lower extremity characteristics than intermittent claudication. Circulation 2008;117:2484-91. |
|26.||Premalatha G, Shanthirani S, Deepa R, Markovitz J, Mohan V. Prevalence and risk factors of peripheral vascular disease in a selected South Indian population: The Chennai Urban Population Study. Diabetes Care 2000;23:1295-300. |
|27.||Agrawal RP, Ranka M, Beniwal R. Prevalence of micro and macro vascular complications in type 2 diabetes and their risk factors. Int J Diabetes Dev Ctries 2004;24:11-6. |
|28.||Madhu SV, Kant S. Preclinical evaluation of atherosclerosis. Int J Diabetes Dev Ctries 2006;26:105-11. |
|29.||Leibson CL, Ransom JE, Olson W, Zimmerman BR, O'fallon WM, Palumbo PJ. Peripheral arterial disease, diabetes and mortality. Diabetes Care 2004;27:2843-9. |
|30.||Li J, Hasimu B, Yu J, Wang J, Hu D. Prevalence of peripheral vascular disease and risk factors for low and high ankle brachial index in Chinese type 2 diabetics, J Health Sci 2006;52:97-102. |
|31.||Agarwal AK, Singh M, Arya V, Garg U, Singh VP, Jain V. Prevalence of peripheral arterial disease in type 2 diabetes mellitus and its correlation with coronary artery disease and its risk factors. J Assoc Physicians India 2012;60:28-32. |
|32.||Resnick HE, Lindsay RS, McDermott MM, Devereux RB, Jones KL, Fabsitz RR, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: The Strong Heart Study. Circulation 2004;109:733-9. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]