1. A Growing Microvascular Burden Dr. Amanullah Khan Medical Director sanofi-aventis Pakistan limited

2. Overview: Diabetes in Pakistan Pakistan among top 10 nations for harboring diabetics. 1 Prevalence of T2DM in Pakistan is high - 7.6 to 11% 1 6.6 mio. people with diabetes are between 20-79 years (IDF-2012) 1 Pakistan will have 13.9 mio. diabetics by 2020, making it the 4th most populous country with diabetic patients 2 1-Diabetes Atlas- IDF -2012 2- Wild S. Diabetes Care 27:1047–1053, 2004

3. 3 Harris MI. Clin Invest Med 1995;18:231–239; Nelson RG et al. Adv Nephrol Necker Hosp 1995;24:145–156; WHO. 2002;Fact Sheet N° 138. Microvascular Complications Macrovascular Complications Diabetic Retinopathy Leading cause of blindness in working-age adults Diabetic Nephropathy Leading cause of end-stage renal disease Heart Disease Leading cause of mortality in patients with Type 2 diabetes Peripheral Vascular Disease Leading cause of non-traumatic lower-extremity amputations Diabetic Neuropathy Leading cause of diabetic foot syndrome and non-traumatic lower-extremity amputations Stroke 25% of all ischemic strokes are due to diabetes alone or with hypertension Association of Diabetes Mellitus with Micro & Macrovascular Complications Endocrinol Metab Clin 1996;25:243 - 254 (DCC Trial) Risk of complications and HbA1c HbA1c (%) Relative risk in % 1 3 5 7 9 11 13 15 6789101112 Retinopathy Nephropathy Microalbuminuria Neuropathy

4. Epidemiology of Diabetic Foot Syndrome (DFS) DFS encompasses multiple pathologies, including diabetic neuropathy peripheral vascular disease Charcot neuroarthropathy foot ulceration osteomyelitis and the potentially preventable endpoint, amputation 1 Lifetime risk of a person with diabetes developing a foot ulcer is 25% 2 Studies from Pakistan show 1 prevalence of diabetic foot ulceration - 4 to 10% & amputation rate following foot ulceration - 8 to 21% Scant and isolated data available on DFS in Type-2 diabetics of Pakistan 1. Basit A, Hydrie ZI, Rubina Ahmedani MYH, Masood Q. J Coll Physicians Surg Pak 2004; 14(2)79-83. 2. Ince P, Abbas ZG, Lutale JK, et al. Diabetes Care 2008;31:964–967

5. is the first large study designed to estimate the burden of DFS in T2DM patients attending General Practitioner’s clinics August 2010- March 2011

6. Investigators Hyderabad: Amir Saleem But Merajuddin Nizami Sialkot: Qamar Hameed Qurieshi Lahore: Asif Mahmood Qadri Bakhtawer Ali Syed Manzoor-ul-Haq Saeed Ahmed Sohail Ahmed Zafar Iqbal Bhatti Gujrat Abdul Sattar Major Sarfaraz 08 cities across Pakistan 25 investigators nationwide Karachi: Khalid Farooq Ramiz Ali Riasat.A. Khan Shakir Hussain Shahid Akhtar Tajwer Anees V.M Lohana Multan Saeed Ahmed Safder Khan Zaheer Abbas Faisalabad Altaf-ur-rehman Azeem Imtiaz Jami Muhammad Arif Gujranwala: Mohammad Shafique

7. Study Objectives Primary: To estimate the prevalence of DFS in established T2DM patients Secondary: To document patient profile of and categorize them according to risk classification To determine the HbA1C levels

8. Study Duration & Patient Recruitment –Overall study duration: 7 months (Aug 10 - Mar 11) –Recruitment period: 1 month per investigator –Patient recruitment: 10 consecutive T2DM patients per investigator Age > 18 years Male and Female patients Given written informed consent

9. Definition of DFS A patient suffering from DFS is defined as a person with current ulcer or/and gangrene or/and healed ulcer or/and lower limb amputation

10. Risk-Classification of Diabetes Foot complications CategoryRisk Profile 0Sensation intact 1 Diminished sensation Blood supply intact no foot deformities such as hammer or claw toes 2 Diminished sensation Blood supply compromised or foot deformity such as hammer or claw toes 3Previous ulcer or amputation (Screening for the diabetic foot – How & Why; International Working Group on the Diabetic Foot)

12. Characteristics of All Patients at Consultation Characteristics (n=230) Age yrs (mean + S.D)53.8 ± 9.9 Male40.9% Female59.1% BMI (mean + S.D)29 ± 5 BP Systolic mmHg (mean + S.D) 135.1 ± 18.9 BP Diastolic mmHg (mean + S.D)86.2 ± 10.2 Duration of Diabetes yrs (mean + S.D)7.9 ± 5.5 Current FBS mg/dL (mean + S.D) 160.6 ± 60.2 Current HbA1c (%) (mean + S.D) 8.8 ± 2.0

13. The most common findings observed on foot examination were –dryness of skin 39.6% (91/230) –cracked skin 30.9% (71/230) –discoloration/pigmentation 15.7% (36/230) 8.7% (20/230) had a foot ulcer at the time of examination Six percent had history of previous foot ulcer Results – Foot Examination

14. Ankle Brachial Pressure Index: ABPI On ABPI assessment 41% (94/230) patients had impaired values (< 0.9) Mean ABPI - 0.98 (± 0.13) Mean ABPI - 0.97 (± 0.13) L R

15. Categorization of patients based on international consensus on diabetic foot risk classification Risk Categories N=230

16. Endocrinol Metab Clin 1996;25:243 - 254 (DCC Trial) RR11.522.54 Patients (%) n= 32 HbA1c Distribution in DFS Patients N= 230 HbA1c Distribution (All Patients) & Risk of DFS

17. DFS Prevalence The prevalence of DFS in this population was (C.I 10.0%-18.9%) 13.9% There were 32 patients with manifestation of DFS 198 patients with normal feet Extreme findings N=230 % Previous Hx. of diabetic foot ulcer156.5 Current ulceration208.7 Amputation31.3 Gangrene10.4

18. Conclusions Prevalence of DFS was 13.9 % in a relatively young population (mean age 54 years) One third (75/230) patients were at high risk of DFS based on ADA risk classification Extreme degree of foot complication (category 3) which includes ulcers and amputation was found in 13.9% DFS is prevalent across all HbA1c levels. Data indicates that these patients have poor glycaemic control (mean HbA1c 9.4%) Foot examination is essential to identify DFS

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21. Conclusion Prevalence of DFS was 13.9 % in a relatively young population (mean age 54 years) One third (75/230) of the patients were at high risk of DFS based on ADA risk classification Extreme degree of foot complication (category 3) which includes ulcers and amputation was found in 13.9% DFS is prevalent across all HbA1c levels Data indicates that these patients have poor glycaemic control (mean HbA1c 9.4%) Patients with DFS were more likely to be past smokers with a history of CAD and stroke Prescribed treatment for patients with DFS was not different from those with normal feet

22. Conclusion The current burden is further aggravated by the high proportion of population at risk of DFS, a significant minority of which is prone to high risk of “extreme degree of foot infections The association of poor knowledge about DFS with poor foot care has already been noted, but a point of further concern is the low rate of prescription of insulin in patients with DFS in Pakistan This implies low awareness of appropriate treatment options even in healthcare providers dealing with patients’ routine care Considering the poor glycemic control, associated risk factors of DFS and existing treatment in the population, there’s a need for early diagnosis and optimization of treatment for the management of not only diabetes but also foot complications in this population

23. Associated Risk Factors of All Patients at Consultation Associated Risk Factors n (%) Current Smoker2310.3 Past Smoker4519.6 Hypertension12855.7 Nephropathy2410.4 Coronary Artery Disease2912.6 Peripheral Artery Disease104.3 Stroke104.3

24. Background Diabetic Treatment of All Patients at Consultation Treatment n % OADs 14864.3 Metformin 19685.2 Sulphonylurea 15466.9 Alpha Glucosidase Inhibitor 93.9 TZDs 3615.7 Monotherapy 3120.9 Two OADs 9362.8 > Two OADs 2416.2 Insulin 7934% Both 7231.3%

25. Treatment N = 202 n=4 n=29 n=163 Percentage (%) Therapy

26. Findings on assessment for DFS in diabetic patients (N=230) Parametersn(%) Physical examination of feet Dryness of skin9139.6 Cracked skin7130.9 Discoloration/Pigmentation3615.7 Ingrown toe nails2410.4 Infection2310.0 Callus219.1 Blister135.7 Muscle wasting229.6 Neurological Assessment Sensation absent on monofilament examination5021.7 Pinprick sensation absent2310.9 Ankle reflexes absent3515.2 Vibration absent3716.5

27. Three most common associated risk factors reported by patients in both the groups Hypertension 55.7% (128/230) Past Hx of smoking 19.6% (45/230) Coronary Artery Disease 19.6% (45/230)

28. Parametersn(%) Vascular Assessment Varied temperature gradient3816.5 Foot pulses (by palpation) absent2812.2 Impaired ABPI (<0.9)9440.9 Extreme findings Previous Hx. of diabetic foot ulcer156.5 Current ulceration208.7 Amputation31.3 Gangrene10.4 Deformity114.8 Findings on assessment for DFS in diabetic patients (N=230)

29. Associated Risk Factors in Both Groups * signifies statistically significant difference, p <0.05.

30. HbA1c levels (%)n (%)Odds ratiop value <76 (18.8)-- 7.1 – 8.03 (9.4)1.690.48 8.1 – 9.04 (12.5)1.400.62 9.1 – 10.06 (18.8)0.640.48 >1013 (40.6)0.440.12 Distribution of patients with DFS across HbA1c levels (N=32) Reference category for Odds Ratio, HbA1c <7.0%

31. Comparison of treatment between patients with diabetic foot syndrome & normal feet TreatmentDFS (n=32)Normal feet (n=198) OADs only19 (59.4)129 (65.2) Monotherapy4 (21.1)27 (20.9) Two OADs12(63.2)81 (62.8) >2 OADs3 (15.8)21 (16.3) Insulin only0 (0.0)7 (3.5) OADs + insulin13 (40.6)59 (29.8)

32. The ABPI is the ratio of the blood pressure in the lower legs to the blood pressure in the arms. Compared to the arm, lower blood pressure in the leg is a symptom of blocked arteries (peripheral vascular disease) ABPI calculation: –Divide ankle systolic blood pressure by brachial artery systolic blood pressure. –An ABPI >0.9 is normal <0.8 is associated with claudication <0.4 is commonly associated with ischemic rest pain and tissue necrosis. ABPI= Ankle systolic blood pressure Brachial systolic pressure Ankle Brachial Pressure Index: ABPI