Scholarly article on topic 'The prevalence and management strategies for peripheral artery disease associated with diabetes mellitus in the Arab world'

The prevalence and management strategies for peripheral artery disease associated with diabetes mellitus in the Arab world Academic research paper on "Clinical medicine"

CC BY-NC-ND
0
0
Share paper
OECD Field of science
Keywords
{"داء السكري" / "مرض الشرايين الطرفية" / "انخفاض التروية بالأطراف" / الغرغرينة / "مؤشر الضغط العضدي الكاحلي" / "Ankle brachial pressure index" / "Diabetes mellitus" / Gangrene / "Lower limb ischaemia" / "Peripheral artery disease"}

Abstract of research paper on Clinical medicine, author of scientific article — Salman Y. Guraya, N.J.M. London

Abstract A growing body of published literature has indicated that diabetes mellitus (DM) is a global health epidemic. There is a staggering upsurge of the prevalence of DM and its associated complications across the globe. Peripheral artery disease (PAD) is a devastating long-term complication of DM. Although there is an exponential increase in the prevalence of diabetes in the Arab world, there are few reports that contain scant data that do not reflect the real magnitude of challenges to health-care agencies. Major risk factors for PAD include smoking, type 2 DM (T2DM), hypertension, hyperlipidaemia, hyperhomocysteinaemia, and advancing age. PAD is an age-dependent disorder that is under-diagnosed, under-estimated, and sub-optimally treated. Diagnosing PAD is challenging in patients with DM because, despite the presence of severe tissue loss, it may remain asymptomatic because of associated neuropathy. PAD is considered to be a strong predictor of future cardiovascular events. The purpose of this review is to provide data regarding the existing prevalence of DM and diabetes-induced PAD with special focus on the Arab world. Subsequently, deep insight regarding the diagnostic modalities and management guidelines is provided. There is a dramatic rise in the prevalence of diabetes-induced PAD that leads to significant morbidity and a marked reduction in the quality of life. Early identification of individuals with risk factors can help to minimize the onset of PAD in patients with DM, thus preventing limb and life-threatening complications. This review argues for more nationally representative surveillance data in the Arab world regarding the impact of DM on PAD.

Academic research paper on topic "The prevalence and management strategies for peripheral artery disease associated with diabetes mellitus in the Arab world"

Journal of Taibah University Medical Sciences (2016) ■(■), 1—7

Taibah University Journal of Taibah University Medical Sciences

www.sciencedirect.com

Review Article

The prevalence and management strategies for peripheral artery disease associated with diabetes mellitus in the Arab world

Salman Y. Guraya, FRCS a'* and N.J.M. London, FRCSb

a College of Medicine, Taibah University, Almadinah Almunawwarah, KSA

b Leicester Medical School, Department of Medical Education, University of Leicester, Maurice Shock Medical Sciences Building, Leicester, UK

Received 17 November 2015; revised 23 December 2015; accepted 23 December 2015; Available online ■ ■

jj*j ^ill t^j£mJl ílj úc Sjjuàxjl AjjiäjJI jjjlajll úx Jjljjx JJc lxj t^j£mll ílj jUqjl ^AÎx Ijcl^aJ Ú lx£ tAjxllc Ajiä^ö

AjàjLll ÚJJIJ.11

jJJ*Jj .¡JUJI

AJÜIA SJ\J^ Jj^j ú* ^jll ^^cj . JjjLll ^Jxll ^Jc SjxJxll Olicl^xll ¿x ^Jc ÁJjlá jjjlâJ ¿í V] t^jj*]l ^JUJI ^i ÍIJ jluojl

Ajlcjll ^JIM^JJX l^^^ IJJ ^""ll '^'lj J^JJl ^aja^ 11 V A aJ* ^jljljj

túJ^JJll AjàjLll újjlj.11 ^^IjxV AMJJJII ÓjjU^ ll Jxljc Jx. .AJÄ^ÄII újAjll ^liJjlj ^jll ^ ^lijjlj t^jUll ^J*ll úx ^J^.11 íljj

^^Ijxí ^JJJJ lx£ . jxxll ^i ^jaSllj t^jll ^i ÚJ'"iJ'"Jxj^ll ^liJjlj '^jUj .Síli^j l^^^cj cl^Aâjjj 'lg ' a* ' ^j lx ljJl¿j jx*Jlj Ajajkll újjlj.11

^Jxâ tljj^ ljJ^J ^j^mll ^^jxl AJJLJI újjlj.11 ^^Ijxí U ^j^ .J JJxjj ^^Ijcí ÚjJj J^j ^^jjxll Ú V] 'A ^ . l JjJ^ ôljaâ Jj^j úx ^^jll AjájLll újjlj.ll ^^Ijxí Jj^j j""*-j lx£ .AjájLll ^l^acVl

ûJA úx .J.'âJ.i^ll ^i Ajjxjll AjcjVlj ^Jâll ^^IjxV ljJ Ij^Jx

újjlj.ll ^^Ijxí jl.Jjlj ílj Üj^ ^ljljj jjájj jA AjjäjJI A*a.Ijx1I

lx£ .^JJ*JI ^HAJI üjJ ^-Jc ^^lÀ. jj£jj úc A^Jljll Ajâj^all

Aj^j^jill ^Jl^xllj 'U ^j^ .ill Ó^J^ Üj^ A ajAA^IJAII

^Ijxí jl.Jjl ^i IjjjS lclijjl úí ¿^^xll úxj .^^«JJ ^i J^ J^jcl ^J] újjJü ^JJj ^jll J*Vl '^J^mll íIJ úc A^ljJl AjijLll ^ ",Vl "ll ^J«JJI ú] .Sl-j^ll Ajcjj ^í ^j^lx ^^li^jlj A^^ll

^^Ijxí JjlâJ ^i Jcl.J úí ú^^J 'SjjL^ ll Jxljc úx újjl«j újill

t^j^ mll úx ^jlJll ^j*JI úx újjl«j újill ^^Jxll J*c AJiJ^L1l 0jjlj.ll

ÚJJ^IJJI ^jJâjj .Slj^ ll JJ^J ^JJI ^licl^x]lj c_âlj^^l ^^Ij^í ^^ ^ïliïl^j

^Jc ^J^ Mill í|j jjülj Üj^ ^JJ*JI ú^jll ^J"'' x ^Jc Üljljü jSjx íl.j]

.AjijLll újjlj.ll ^^ljxí

* Corresponding address: College of Medicine, Taibah University Almadinah Almunawwarah, KSA.

E-mail: salmanguraya@gmail.com (S.Y. Guraya) Peer review under responsibility of Taibah University.

Production and hosting by Elsevier

AJJJJJI —^^ ÍAjSjkll ÚJJIJÜI i^j^i '1 ^L^IÜI

Abstract

A growing body of published literature has indicated that diabetes mellitus (DM) is a global health epidemic. There is a staggering upsurge of the prevalence of DM and its associated complications across the globe. Peripheral artery disease (PAD) is a devastating long-term complication of DM. Although there is an exponential increase in the prevalence of diabetes in the Arab world, there are few reports that contain scant data that do not reflect the real magnitude of challenges to health-care agencies. Major risk factors for PAD include smoking, type 2 DM (T2DM), hypertension, hyperlipidaemia, hyper-homocysteinaemia, and advancing age. PAD is an age-dependent disorder that is under-diagnosed, under-estimated, and sub-optimally treated. Diagnosing PAD is challenging in patients with DM because, despite the presence of severe tissue loss, it may remain asymptomatic because of associated neuropathy. PAD is considered to be a strong predictor of future cardiovascular events. The purpose of this review is to provide data regarding the existing prevalence of DM and diabetes-induced PAD with special focus on the Arab world. Subsequently, deep insight regarding the diagnostic modalities and management guidelines is provided. There is a dramatic rise in the prevalence of diabetes-induced PAD that leads to significant morbidity and a marked reduction in the quality of life. Early identification of individuals with risk factors can help to minimize the onset of PAD in patients with DM, thus preventing limb and life-threatening complications. This review argues for more nationally

1658-3612 © 2016 The Authors.

Production and hosting by Elsevier Ltd on behalf of Taibah University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). http://dx.doi.org/10.1016/j.jtumed.2015.12.003

2 S.Y. Guraya and N.J.M. London

representative surveillance data in the Arab world regarding the impact of DM on PAD.

Keywords: Ankle brachial pressure index; Diabetes mellitus; Gangrene; Lower limb ischaemia; Peripheral artery disease

© 2016 The Authors.

Production and hosting by Elsevier Ltd on behalf of Taibah University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Diabetes mellitus (DM) is a major health challenge that explains a significant contribution to morbidity and premature mortality worldwide.1 The projected number of global diabetic patients is estimated to rise from 135 million in 1995 to 300 million in 2025.2 The number of people with undiagnosed T2DM is rapidly increasing, and there is a proportionately increased risk of developing complications in this group, many of whom have unidentified disease.3

In congruence with the global prevalence of DM, the Asia Pacific region is considered to be on the brink of an epidemic of DM.4 Several studies have reported a high prevalence of DM in various countries of the Middle East region such as Bahrain (25.7%),5 the Kingdom of Saudi Arabia (KSA) (23.7%),6 the Al Ain region of the United Arab Emirates (l7.1%),7 and Jordan (16.9%).8 DM is a growing health problem in the Middle East region including KSA.9 In 1982, Bacchus RA published the first estimated prevalence of 2.5% of DM in KSA.10 This report showed that the prevalence of DM begins to rise at 35 years with a peak at 45—54 years. In 1987, Fatani et al. reported a prevalence of 4.3% in the rural areas,11 followed by a subsequently reported prevalence of 9.7% by El-Hazmi MA et al., in 1996.12 Another survey showed that "the age adjusted prevalence of DM was significantly higher in urban populations (males 12%, 95% CI = 11—13 and females 14%, 95% CI = 13—15) than in rural populations (males 7%, 95% CI = 7—8 and females 7.7%, 95% CI = 7—9), which is among the highest in the world".13 Later, in 2004, Nozha et al. showed an estimated prevalence of DM in KSA of 23.7%.6 A changing lifestyle,14 increased

longevity,15,16 lack of physical activity,17 change in dietary habits, and increasing urbanization18 are major reasons for this upsurge in the prevalence of DM in KSA in particular and in the Middle East in general.

A survey-based research study was conducted on the adult Qatari population to explore the prevalence of diagnosed and undiagnosed diabetes and pre-diabetes and to determine the associated risk factors of DM.16 "The identified risk factors were significantly higher in the diabetic adult Qatari population: central obesity (p < 0.001), hypertension (p < 0.001), triglyceride (p < 0.001), high-density lipoprotein (p = 0.003), metabolic syndrome (p < 0.001), heart diseases (p < 0.001)".16 According to the International Diabetes Federation Report published in 2014, KSA was ranked 4th among the top five

Middle Eastern and North African countries, with 3.6 million diabetics in the adjusted age group ranging from 20 to 79 years.19 T2DM affects nearly all systems of the body, which leads to a range of complex and chronic illnesses such as diabetic nephropathy,20 diabetic peripheral neuropathy (DPN),21 otopathy,22 PAD,23 retinopathy,24 coronary artery disease,25 diabetic foot and trophic ulcers,26 gallstones27 and colorectal malignancy.28—30

The rising prevalence of DM and its associated complications, particularly PAD, poses a great burden to the health care system.31,32 PAD refers to the atherosclerotic narrowing of the abdominal aorta, iliac and lower extremity arteries, presenting varying degrees of ischaemia, leading to intermittent claudication (IC), ulceration, gangrene or limb loss.33 Therefore, from a community health perspective, it is imperative to identify the pathogenesis and management strategies of DM-induced PAD.34 There are very few publications regarding DM and PAD in the Arab world. This review's objective is to provide a comprehensive critique of the current published literature with a focus on comparing the current situation in the Arab world with the rest of the world. The existing deficiencies and gaps in the literature are identified, and future directions and challenges for research are outlined.

Search design

A literature search was conducted through the MED-LINE, EBSCO CINAHL, and ISI Web of Knowledge databases for English language articles by connecting MeSH terms "Diabetes mellitus" AND "Diabetic foot ulcers" AND "Arab world" OR "Peripheral arterial disease" in Endnote X 7, which retrieved 1742 citations. The further selection and exclusion of studies is outlined in Figure 1.

The burden of peripheral vascular disease

More than 202 million people have PAD worldwide, with approximately 70% residing in low-to middle-income countries.35 There is an estimated increase of 3—7% in the prevalence of PAD that is positively correlated with advancing age.36 "Although it was believed that the prevalence of PAD is common in men, the prevalence of PAD in women is at least equal, if not higher".37 Approximately 100,000 people are diagnosed annually with PAD in the UK and carry high chances of developing cardiovascular complications.38 From the Arabian perspective, Alsheikh et al. conducted a cross-sectional study on all respective 45-year and older Saudi patients, who attended the primary health care centre at King Khalid University Hospital Riyadh.39 Of 471 patients, the prevalence of PAD was 11.7% (95% CI: 8.9—14.9%), and 92.7% were asymptomatic. Patients with PAD were identified to have a range of risk factors including T2DM, hypertension, hyperlipidaemia, smoking, cerebrovascular accidents, and coronary artery disease. Another study conducted a 1-year follow-up study to determine the incidence of foot disorders such as PAD, DPN, foot ulcer, gangrene, and amputation, among 556 Saudi diabetic pa-tients.40 The 1-year cumulative incidence of PAD, peripheral

1742 articles were retrieved from the selected database

After analysis, 890 studies were excluded prior to 2007

852 retrieved records were further explored by reviewing titles of studies in the reference list

An additional 834 studies were excluded that did not fulfil the inclusion criteria after reviewing their abstracts

Finally, 18 studies were finalized, which fulfil the inclusion criteria

Figure 1: Flow diagram showing the search design for the selection of publications regarding diabetes mellitus and peripheral vascular disease in the Arab world.

neuropathy, foot ulcer, and gangrene was reported to be 6.3, 9.2, 3.6, and 16.7%, respectively.

The diabetic foot, resulting from either PAD or diabetic peripheral neuropathy, represents 1 in 5 hospitalizations among diabetics.41 The treatment costs of these foot complications consume approximately 25% of the hospital costs of total diabetes care.42 This finding places a huge burden on the financial and administrative resources of health-care sectors across the globe. Wang et al., in their cross-sectional study, explored the prevalence and correlates of lower extremity amputation in the Saudi population with diabetic foot ulcers due to PAD and DPN.43 From a group of 91 participants, the investigators found a 29.7% prevalence of lower extremity amputation. The odds ratio for amputation was 2.42 (95% confidence interval [CI] = 0.70-8.45; p for trend = 0.03) for ulcer size and 0.22 (95% CI = 0.06-0.87; p for trend = 0.03) for high-density lipoprotein cholesterol. The overall prevalence of lower limb amputation in this study was found to be significantly higher than the previously reported data.

Diabetes mellitus as a leading risk factor for peripheral artery disease

Smoking, T2DM, hypertension, hyperlipidaemia, hyper-homocysteinaemia, and advancing age are the major risk factors for PAD.44-46 Obesity is another leading risk factor for T2DM as well as PAD.32 Positive correlations have been reported between obesity and DM in Iraq,47 United Arab Emirates,48 Egypt,49 Jordan,50 and Iran.51 The estimated risk in the diabetic patients of developing PAD is two to four times higher, and the risk of amputation is 15

times greater than in the non-diabetic population.52 Unfortunately, after amputation, the patients' mortality rate remains as high as 50% at 2 years. Longer diabetes duration, insulin use, and low haemoglobin levels have been reported to be associated with a higher prevalence of diabetic foot complications.53 Both PAD and neuropathy increase the risk of foot complications 10-fold compared with the non-diabetic population. In contrast, a prospective cohort study could not find a significant correlation between the duration of DM and the development of foot complications.44

Alzahrani et al. investigated the correlation between risk factors and the prevalence of PAD in 598 Saudi diabetic patients.54 This study reported PAD prevalence of 23.1%. "Hypertension (OR (odds ratio) = 2.13, 95% CI: 1.293.52), obesity (OR = 1.75, 95% CI: 1.13-2.73) and longer duration of diabetes (OR for >20 years vs 2-4 years = 3.30, 95% CI: 1.66-6.58) were independently and significantly associated with a higher prevalence of PAD". This study reported a higher prevalence of DM-induced PAD than the published range of 20-30%.33,55 These findings emphasize the importance of identifying individuals with significant risk factors in an attempt to prevent the onset of PAD among patients with diabetes in KSA.56

Diagnostic modalities for peripheral artery disease

The cardinal features of lower limb ischaemia are IC, resting pain, and gangrene. The initial presentation of PAD is IC,57 and the symptoms of IC remain unchanged in the majority of people. When patients seek medical

S.Y. Guraya and N.J.M. London

consultation, physicians often struggle to differentiate claudication from other common conditions such as hip arthritis and spinal stenosis. As many as 20% of patients will develop a progressive disease with more severe symptoms that leads to critical limb ischaemia.36 The strategies commonly employed to diagnose PAD include a detailed medical history, physical examination, and diagnostic tests. Undoubtedly, the most accurate clinical examinations for diagnosing PAD are unilateral absent or abnormal pedal pulses, changes in colour, cold foot, and bruit in the femoral artery.58 Traditionally, the clinical staging for grading the severity of PAD is categorized according to the Fontaine or Rutherford classification, as shown in Table 1.59 The non-invasive tools to confirm PAD include the ankle brachial pressure index (ABPI), pulse volume recording, Doppler flowmetry, and Doppler ultrasound. A treadmill test can provide an objective measure of walking capacity.60,61 The values of ABPI can determine the severity of lower limb ischaemia. A brief clinical interpretation of ABPI is outlined in Table 2.62

Colour scanning combines B mode ultrasound with Doppler scanning to locate the narrowed segment in addition to evaluation of the size of the blockage.63 Digital subtraction angiography (DSA), computerised tomography angiogram (CTA), and magnetic resonance angiogram (MRA) can provide comprehensive information regarding the location and size of obstruction as well as the architectural details of the arterial skeleton.64 CTA and MRA are usually reserved for those who are being considered for angioplasty or arterial reconstruction surgery.65

Management of peripheral artery disease and diabetes mellitus

The International Working Group on the Diabetic Foot Guidance on the Diagnosis, Prognosis and Management of Peripheral Artery Disease in Patients with Foot Ulcers in Diabetes has provided the following recommendations66:

1. Examine patients with T2DM annually for the presence of PAD including at least a detailed history and palpation of foot pulses.

2. Evaluate patients with T2DM annually for the presence of PAD by Doppler waveforms and ABPI. A value of ABPI <0.9 is considered abnormal.

Table 2: Clinical interpretation of ABPI to assess the severity of lower limb ischaemia affected by diabetes mellitus.

Ankle brachial Interpretation

pressure index

>1.4 Equivocal due to

non-compressible/calcified arteries

1.0—1.4 Normal; PAD disease

can be excluded in a large number of patients 0.9 Borderline; discussion

with a specialist is advisable; <0.9 Abnormal: Diagnostic of PAD

<0.4 Critical limb ischaemia

3. Consider urgent vascular imaging and limb revascular-isation in diabetic patients with foot ulcers showing toe pressure <30 mmHg or transcutaneous oxygen pressure <25 mmHg.

4. Consider vascular imaging and revascularisation in all diabetic patients with a foot ulcer and PAD, regardless of the findings of clinical and non-invasive tests, when the ulcer does not improve within 6 weeks of non-surgical therapy.

5. Consider urgent vascular imaging and revascularisation in patients with a non-healing ulcer with either an ankle pressure <50 mm Hg or ABPI <0.5.

6. "Limb revascularisation should be aimed to restore direct flow to at least one of the foot arteries, preferably the artery that supplies the anatomical region of the wound, with the aim of achieving a minimum skin perfusion pressure >40 mmHg; a toe pressure >30 mmHg".

7. The literature is deeply divided regarding a standard surgical approach that can be offered for revascularisa-tion. A multidisciplinary strategy coupled with the level of surgical expertise, morphological distribution of PAD, autogenous vein or prosthesis, and patient co-morbidities play key roles in decision-making.

8. Avoid considering revascularisation in patients in which the risk-to-benefit ratio for the probability of success is not optimal.

9. All patients with T2DM and PAD should be provided with an aggressive cardiovascular risk management therapy that includes advice for the cessation of smoking, therapies for DM and hypertension, and a prescription for a statin and low-dose aspirin or clopidogrel.

The guidelines provided by the American Heart Association and American College of Cardiology Foundation recommend the control of risk factors such as DM, smoking, hypertension and hyperlipidaemia, in addition to the use of antiplatelet drugs, angiotensin converting enzyme inhibitors and statins.67 Lifestyle changes geared towards more physical activity and a fat-free diet play major roles in preventing PAD. The Scandinavian Simvastatin Survival Study has observed that Simvastatin reduces the incidence of new claudication in patients with myocardial infarction or angina and leads to a longer pain-free walking time.68 Currently, aspirin is recommended as a first-line antiplatelet drug. However, in the case of repeated events of ischaemia, despite

Table 1: Classifications for the clinical staging of peripheral arterial disease.62

Fontaine classification Rutherford classification

Stage Symptoms Grade Category Symptoms

I Asymptomatic 0 0 Asymptomatic

II Intermittent I 1 Mild claudication

claudication I 2 Moderate

claudication

I 3 Severe claudication

III Ischaemic II 4 Ischaemic rest pain

resting pain

IV Ulceration III 5 Minor tissue loss

or gangrene III 6 Major tissue loss

Source: European Stroke Association.59

antiplatelet therapy, replacing aspirin with clopidogrel or an anticoagulant or adding another antiplatelet drug may be considered.69 A combination of the suggested therapies has been reported to be successful in delivering the optimal risk factor management in patients with symptomatic PAD.70 Such conservative non-surgical strategies may reduce, if not eliminate, atherothrombotic events and will improve the quality of life with a better outcome.

Conclusion

There is a dramatic rise in the prevalence of DM and accompanying complications worldwide. This diabetes epidemic is a threat and burden to health-care systems and has created significant public health challenges in the Arab world including KSA. There is a proportionate rise in the prevalence of diabetes-induced PAD, an age-dependent disorder that is difficult to treat, which is caused by factors similar to that of coronary artery and cerebrovascular disease. PAD is associated with significant morbidity and a marked reduction in the quality of life. The early identification of individuals with risk factors can help to prevent the onset of PAD in patients with DM. Lifestyle changes, cessation of smoking, control of DM and hyperlipidaemia as well as the use of aspirin or clopidogrel and a statin should be instituted in an attempt to arrest the progression of PAD. In patients with PAD with critical ischaemia, endovascular revascularisation or bypass surgery should be considered. A national level concerted multidisciplinary approach, together with guideline-directed therapies, can minimize the complications of PAD. These actions would help the diabetic population improve their quality of life and minimise their risk of both loss of limb and loss of life.

Conflict of interest

The authors have no conflict of interest to declare.

Author contributions

SYG conceived the concept of this research, conducted the literature review and wrote the initial draft. NJL revised and reviewed the initial write-up. Both authors approved the final manuscript.

References

1. Alberti K, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120(16): 1640-1645.

2. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21(9): 1414-1431.

3. Franse LV, Di Bari M, Shorr RI, Resnick HE, Van Eijk JT, Bauer DC, et al. Type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the health, aging, and

body composition study. Diabetes Care 2001; 24(12): 2065— 2070.

4. Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetes Med 1997; 14(S5): S7—S85.

5. Hamadeh R. Noncommunicable diseases among the Bahraini population: a review. East Mediterr Health J 2000; 6(5—6): 1091 — 1097.

6. Al-Nozha MM, Al-Maatouq MA, Al-Mazrou YY, Al-Harthi SS. Diabetes mellitus in Saudi Arabia. Saudi Med J 2004; 25(11): 1603—1610.

7. Saadi H, Carruthers SG, Nagelkerke N, Al-Maskari F, Afandi B, Reed R, et al. Prevalence of diabetes mellitus and its complications in a population-based sample in Al Ain, United Arab Emirates. Diabetes Res Clin Pract 2007; 78(3): 369—377.

8. Ajlouni K, Khader YS, Batieha A, Ajlouni H, El-Khateeb M. An increase in prevalence of diabetes mellitus in Jordan over 10 years. J Diabetes Complicat 2008; 22(5): 317—324.

9. Alqurashi KA, Aljabri KS, Bokhari SA. Prevalence of diabetes mellitus in a Saudi community. Ann Saudi Med 2011; 31(1): 19.

10. Bacchus R, Bell J, Madkour M, Kilshaw B. The prevalence of diabetes mellitus in male Saudi Arabs. Diabetologia 1982; 23(4): 330—332.

11. Fatani HH, Mira SA, El-Zubier AG. Prevalence of diabetes mellitus in rural Saudi Arabia. Diabetes Care 1987; 10(2): 180— 183.

12. El-Hazmi M, Warsy A, Al-Swailem A, Al-Swailem A, Sulaimani R, Al-Meshari A. Diabetes mellitus and impaired glucose tolerance in Saudi Arabia. Ann Saudi Med 1996; 16(4): 381—385.

13. Al-Nuaim A. Prevalence of glucose intolerance in urban and rural communities in Saudi Arabia. Diabet Med 1997; 14(7): 595—602.

14. Khan MA, Al Kanhal MA. Dietary energy and protein requirements for Saudi Arabia: a methodological approach. East Mediterr Health J 1998; 4(1): 68—75.

15. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94(3): 311—321.

16. Bener A, Zirie M, Janahi IM, Al-Hamaq AO, Musallam M, Wareham NJ. Prevalence of diagnosed and undiagnosed diabetes mellitus and its risk factors in a population-based study of Qatar. Diabetes Res Clin Pract 2009; 84(1): 99—106.

17. Al-Nozha MM, Al-Hazzaa HM, Arafah MR, Al-Khadra A, Al-Mazrou YY, Al-Maatouq MA, et al. Prevalence of physical activity and inactivity among Saudis aged 30—70 years: a population-based cross-sectional study. Saudi Med J 2007; 28(4): 559—568.

18. Heymann DL. The world health report 2007: a safer future: global public health security in the 21st century. World Health Organization; 2007.

19. Guariguata L, Whiting D, Hambleton I, Beagley J, Linnenkamp U, Shaw J. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103(2): 137—149.

20. Bharti AK, Agrawal A, Agrawal S. Advanced glycation end products in progressive course of diabetic nephropathy: exploring interactive associations. Int J Pharm Sci Res 2015; 6(2): 521.

21. Edwards JF, Casellini CM, Parson HK, Obrosova IG, Yorek M, Vinik AI. Role of peroxynitrite in the development of diabetic peripheral neuropathy. Diabetes Care 2015; 38(7): e100—e101.

22. zum Gottesberge A-MM, Massing T, Sasse A, Palma S, Hansen S. Zucker diabetic fatty rats, a model for type 2 diabetes, develop an inner ear dysfunction that can be attenuated by losartan treatment. Cell Tissue Res 2015: 1—9.

S.Y. Guraya and N.J.M. London

23. Stein RA, Rockman CB, Guo Y, Adelman MA, Riles T, Hiatt WR, et al. Association between physical activity and peripheral artery disease and carotid artery stenosis in a self-referred population of 3 million adults. Arterioscler, Thromb, Vasc Biol 2015; 35(1): 206-212.

24. Raja SS, Vasuki S. Screening diabetic retinopathy in developing countries using retinal images. Appl Med Inf 2015; 36(1): 13-22.

25. Armstrong MJ, Sigal RJ, Arena R, Hauer TL, Austford LD, Aggarwal S, et al. Cardiac rehabilitation completion is associated with reduced mortality in patients with diabetes and coronary artery disease. Diabetologia 2015; 58(4): 691-698.

26. Prakash SS, Prabha C. The influence of peripheral neuropathy and peripheral vascular disease in the outcome of diabetic foot management—a prospective study. Int J Med Res Health Sci 2015; 4(2): 258-264.

27. Guraya SY. Reappraisal of the management of cholelithiasis in diabetics. Saudi Med J 2005; 26(11): 1691 — 1694.

28. Guraya SY. The association of type 2 diabetes mellitus and the risk of colorectal cancer; a meta analysis and systematic review. World J Gastroenterol 2015; 21(19): 1626—1631.

29. Guraya SY, Murshid KR. Malignant duodenocolic fistula. Various therapeutic surgical modalities. Saudi Med J 2004; 25(8): 1111 — 1114.

30. Guraya SY, Al Naami M, Al Tuwaijri T, Arafah M. Malignant melanoma of the small bowel with unknown primary: a case report. J Ayub Med Coll Abbottabad 2007; 19(1): 63—65.

31. Badran M, Laher I. Type II diabetes mellitus in Arabic-speaking countries. Int J Endocrinol 2012; 2012: 1 — 11.

32. Zabetian A, Keli HM, Echouffo-Tcheugui JB, Narayan KV, Ali MK. Diabetes in the middle East and north Africa. Diabetes Res Clin Pract 2013; 101(2): 106—122.

33. American Diabetes Association. Peripheral arterial disease in people with diabetes. J Am Podiatric Med Assoc 2005; 95(3): 309—319.

34. Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Yousef M, Sabico SL, et al. Diabetes mellitus type 2 and other chronic non-communicable diseases in the central region, Saudi Arabia (Riyadh cohort 2): a decade of an epidemic. BMC Med 2011; 9(1): 76.

35. Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013; 382(9901): 1329—1340.

36. Layden J, Michaels J, Bermingham S, Higgins B. Diagnosis and management of lower limb peripheral arterial disease: summary of NICE guidance. BMJ 2012: 345.

37. Barochiner J, Aparicio LS, Waisman GD. Challenges associated with peripheral arterial disease in women. Vasc Health Risk Manag 2014; 10: 115.

38. Belch J, Stansby G, Shearman C, Brittenden J, Dugdill S, Fowkes G, et al. Peripheral arterial disease-a cardiovascular time bomb: achieving best practice. South Afr J Diabetes Vasc Dis 2008; 5(2): 83—86.

39. Al-Sheikh SO, Aljabri BA, Al-Ansary LA, Al-Khayal LA, Al-Salman MM, Al-Omran MA. Prevalence of and risk factors for peripheral arterial disease in Saudi Arabia. A pilot cross-sectional study. Saudi Med J 2007; 28(3): 412—414.

40. Alzahrani HA, Wang D, Alzahrani AH, Hu FB. Incidence of diabetic foot disorders in patients with diabetes in Jeddah, Saudi Arabia. Int J Diabetes Dev Ctries 2015: 1—8.

41. Al-Maskari F, El-Sadig M. Prevalence of risk factors for diabetic foot complications. BMC Fam Pract 2007; 8(1): 59.

42. Songer TJ. The role of cost—effectiveness analysis and health insurance in diabetes care. Diabetes Res Clin Pract 2001; 54: 7—11.

43. Wang DD, Jamjoom RA, Alzahrani AH, Hu FB, Alzahrani HA. Prevalence and correlates of lower-extremity

amputation in patients with diabetic foot ulcer in Jeddah, Saudi Arabia. Int J Low Extrem Wounds 2015.

1534734615601542.

44. Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Davignon DR, Smith DG. A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study. Diabetes Care 1999; 22(7): 1036-1042.

45. Khan AS, Isik M, Set T, Akturk Z, Avsar UA. 5-year trend of myocardial infarction, hypertension, stroke and diabetes mellitus in gender and different age groups in Erzurum, Turkey. J Taibah Univ Med Sci 2014; 9(3): 198-205.

46. El Hadidy M, Abdul-Aziz MY, Mokhtar A-RA, El Ata MMA, El Gwad SSA. Helicobacter Pylori infection and vascular complications in patients with type 2 diabetes mellitus. J Taibah Univ Med Sci 2009; 4(1): 62-72.

47. Mansour AA, Al-Jazairi MI. Predictors of incident diabetes mellitus in Basrah, Iraq. Ann Nutr Metab 2007; 51(3): 277-280.

48. Baynouna LM, Revel AD, Nagelkerke N, Jaber TM, Omar AO, Ahmed NM, et al. Associations of cardiovascular risk factors in Al Ain-United Arab Emirates. Cardiovasc Dia-betol 2009; 8(1): 21.

49. Lfotouh A, Soliman L, Mansour E, Farghaly M, El Dawaiaty A. Central obesity among adults in Egypt: prevalence and associated morbidity. East Mediterr Health J 2008; 14(1): 57-68.

50. Walke H, Mokdad AH, Zindah M, Belbeisi A. Obesity and diabetes in Jordan: findings from the behavioral risk factor surveillance system, 2004. Prev Chronic Dis 2008; 5(1): 1.

51. Esteghamati A, Ashraf H, Khalilzadeh O, Rshidi A, Mohammad K, Asgari F, et al. Trends of diabetes according to body mass index levels in Iran: results of the national surveys of risk factors of non-communicable diseases (1999-2007). Diabet Med 2010; 27(11): 1233-1240.

52. Hinchliffe R, Andros G, Apelqvist J, Bakker K, Fiedrichs S, Lammer J, et al. A systematic review of the effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral arterial disease. Diabetes/Metab Res Rev 2012; 28(S1): 179-217.

53. Hu Y, Bakhotmah BA, Alzahrani OH, Wang D, Hu FB, Alzahrani HA. Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. Diabetes Res Clin Pract 2014; 106(2): 286-294.

54. Alzahrani HA, Wang D, Bakhotmah BA, Hu FB. Risk factors for peripheral artery disease among patients with diabetes in Saudi Arabia. Vasc Med 2014. 1358863X14526948.

55. Lange S, Diehm C, Darius H, Haberl R, Allenberg J, Pittrow D, et al. High prevalence of peripheral arterial disease and low treatment rates in elderly primary care patients with diabetes. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc 2004; 112(10): 566-573.

56. Elhadd TA, Al-Amoudi AA, Alzahrani AS. Epidemiology, clinical and complications profile of diabetes in Saudi Arabia: a review. Ann Saudi Med 2007; 27(4): 241.

57. O'Donnell M, Reid J, Lau L, Hannon R, Lee B. Optimal management of peripheral arterial disease for the non-specialist. Ulster Med J 2011; 80(1): 33.

58. Mitchell M, Mohler E, Carpenter J. Overview of acute arterial occlusion of the extremities (acute limb ischemia). Waltham, MA: UpToDate; 2014 [Accessed 13.06.14].

59. Tendera M, Aboyans V, Bartelink M-L, Baumgartner I, Clement D, Collet J-P, et al. ESC guidelines on the diagnosis and treatment of peripheral artery diseases. Revista Española de Cardiología (English Edition) 2012; 2(65): 172.

60. Brownrigg J, Schaper N, Hinchliffe R. Diagnosis and assessment of peripheral arterial disease in the diabetic foot. Diabetes Med 2015; 32(6): 738-747.

61. Gray C, Goodman P, Cullen P, Badger SA, O'Malley K, O'Donohoe MK, et al. Screening for peripheral arterial disease

and carotid artery disease in patients with abdominal aortic aneurysm. Angiology 2015. 0003319715590299.

62. Aerden D, Denecker N, Keymeulen B, Van den Brande P. Ankle-brachial pressure index: a mixed blessing. Diabet Foot J 2011; 14(4).

63. Walker CM, Bunch FT, Cavros NG, Dippel EJ. Multidisci-plinary approach to the diagnosis and management of patients with peripheral arterial disease. Clin Interv Aging 2015; 10: 1147.

64. Anzidei M, Lucatelli P, Napoli A, Jens S, Saba L, Cartocci G, et al. CT angiography and magnetic resonance angiography findings after surgical and interventional radiology treatment of peripheral arterial obstructive disease. J Cardiovasc Comput Tomogr 2015; 9(3): 165-182.

65. Nambiar V, Sohn S, Almekhlafi M, Chang H, Mishra S, Qazi E, et al. CTA collateral status and response to recanali-zation in patients with acute ischemic stroke. Am J Neuroradiol 2014; 35(5): 884-890.

66. Hinchliffe R, Brownrigg J, Apelqvist J, Boyko E, Fitridge R, Mills J, et al. IWGDF guidance on the diagnosis, prognosis and management of peripheral artery disease in patients with foot ulcers in diabetes. Diabetes/Metabolism Res Rev 2015. http:// dx.doi.org/10.1002/dmrr.2698.

67. Smith SC, Bonow RO, Creager MA, Gibbons RJ, Hiratzka LF, Lloyd-Jones DM, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 Update: a Guideline from the American Heart Association and American College of Cardiology Foundation (vol. 124, pg 2458, 2011). Circulation 2015; 131(15): E408—E.

68. Khan S, Flather M, Mister R, Delahunty N, Fowkes G, Bradbury A, et al. Characteristics and treatments of patients with peripheral arterial disease referred to UK vascular clinics: results of a prospective registry. Eur J Vasc Endovascular Surg 2007; 33(4): 442—450.

69. Gilchrist I, Morrow D, Scirica B, Creager M, Bhatt D, He P, et al. Statin intensity and outcome in patients with peripheral artery disease: insights from the TRA2P-TIMI 50 trial. J Am Coll Cardiol 2015; 65(10_S).

70. Armstrong EJ, Chen DC, Westin GG, Singh S, McCoach CE, Bang H, et al. Adherence to guideline-recommended therapy is associated with decreased major adverse cardiovascular events and major adverse limb events among patients with peripheral arterial disease. J Am Heart Assoc 2014; 3(2): e000697.