A Growing Microvascular Burden Dr Amanullah Khan Medical

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

Overview: Diabetes in Pakistan • Pakistan among top 10 nations for harboring diabetics. 1 • Prevalence of T 2 DM 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 4 th most populous country with diabetic patients 2 1 -Diabetes Atlas- IDF -2012 2 - Wild S. Diabetes Care 27: 1047– 1053, 2004

Association of Diabetes Mellitus with Micro & Macrovascular Complications Microvascular Complications Macrovascular Complications Risk of complications and Hb. A 1 c Diabetic Retinopathy Leading cause of blindness in working-age adults Diabetic Nephropathy Leading cause of end-stage renal disease Relative risk in % 15 Stroke 13 Retinopathy Nephropathy 11 Neuropathy Microalbuminuria 25% of all ischemic strokes are due to diabetes alone or with hypertension Heart Disease 9 Leading cause of mortality in patients with Type 2 diabetes 7 5 3 Diabetic Neuropathy Leading cause of diabetic foot syndrome and non-traumatic lower-extremity amputations Peripheral Vascular Disease 1 6 7 8 9 10 Hb. A 1 c (%) 11 12 Leading cause of non-traumatic lower-extremity amputations Endocrinol Metab Clin 1996; 25: 243 - 254 (DCC Trial) 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.

Epidemiology of Diabetic Foot Syndrome (DFS) • DFS encompasses multiple pathologies, including • 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 • • • diabetic neuropathy peripheral vascular disease Charcot neuroarthropathy foot ulceration osteomyelitis and the potentially preventable endpoint, amputation 1 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

is the first large study designed to estimate the burden of DFS in T 2 DM patients attending General Practitioner’s clinics August 2010 - March 2011

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

Study Objectives Primary: • To estimate the prevalence of DFS in established T 2 DM patients Secondary: • To document patient profile of and categorize them according to risk classification • To determine the Hb. A 1 C levels

Study Duration & Patient Recruitment – Overall study duration: • 7 months (Aug 10 - Mar 11) – Recruitment period: • 1 month per investigator – Patient recruitment: • • 10 consecutive T 2 DM patients per investigator Age > 18 years Male and Female patients Given written informed consent

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

Risk-Classification of Diabetes Foot complications Category Risk Profile 0 Sensation 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 3 Previous ulcer or amputation (Screening for the diabetic foot – How & Why; International Working Group on the Diabetic Foot)

Study Results

Characteristics of All Patients at Consultation (n=230) Characteristics Age yrs (mean + S. D) 53. 8 ± 9. 9 Male 40. 9% Female 59. 1% BMI (mean + S. D) 29 ± 5 BP Systolic mm. Hg (mean + S. D) 135. 1 ± 18. 9 BP Diastolic mm. Hg (mean + S. D) 86. 2 ± 10. 2 Duration of Diabetes yrs (mean + S. D) 7. 9 ± 5. 5 Current FBS mg/d. L (mean + S. D) 160. 6 ± 60. 2 Current Hb. A 1 c (%) (mean + S. D) 8. 8 ± 2. 0

Results – Foot Examination • 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

Ankle Brachial Pressure Index: ABPI On ABPI assessment 41% (94/230) patients had impaired values (< 0. 9) Mean ABPI - 0. 98 (± 0. 13) L R Mean ABPI - 0. 97 (± 0. 13)

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

n= 32 Hb. A 1 c Distribution (All Patients) & Risk of DFS N= 230 Patients (%) Hb. A 1 c Distribution in DFS Patients RR 1 1. 5 2 2. 5 Endocrinol Metab Clin 1996; 25: 243 - 254 (DCC Trial) 4

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 Previous Hx. of diabetic foot ulcer Current ulceration Amputation Gangrene N=230 % 15 20 3 1 6. 5 8. 7 1. 3 0. 4

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 Hb. A 1 c levels. • Data indicates that these patients have poor glycaemic control (mean Hb. A 1 c 9. 4%) • Foot examination is essential to identify DFS

Thank you

BACKUP

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 Hb. A 1 c levels • Data indicates that these patients have poor glycaemic control (mean Hb. A 1 c 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

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

Associated Risk Factors of All Patients at Consultation Associated Risk Factors n (%) Current Smoker 23 10. 3 Past Smoker 45 19. 6 Hypertension 128 55. 7 Nephropathy 24 10. 4 Coronary Artery Disease 29 12. 6 Peripheral Artery Disease 10 4. 3 Stroke 10 4. 3

Background Diabetic Treatment of All Patients at Consultation Treatment n % OADs 148 64. 3 Metformin 196 85. 2 Sulphonylurea 154 66. 9 Alpha Glucosidase Inhibitor 9 3. 9 TZDs 36 15. 7 Monotherapy 31 20. 9 Two OADs 93 62. 8 > Two OADs 24 16. 2 Insulin 79 34% Both 72 31. 3%

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

Findings on assessment for DFS in diabetic patients (N=230) Parameters n (%) Physical examination of feet Dryness of skin Cracked skin Discoloration/Pigmentation Ingrown toe nails Infection Callus Blister Muscle wasting Neurological Assessment Sensation absent on monofilament examination Pinprick sensation absent Ankle reflexes absent Vibration absent 91 71 36 24 23 21 13 22 39. 6 30. 9 15. 7 10. 4 10. 0 9. 1 5. 7 9. 6 50 23 35 37 21. 7 10. 9 15. 2 16. 5

Three most common associated risk factors reported by patients in both the groups Coronary Artery Disease 19. 6% (45/230) Hypertension 55. 7% (128/230) Past Hx of smoking 19. 6% (45/230)

Findings on assessment for DFS in diabetic patients (N=230) Parameters n (%) Vascular Assessment Varied temperature gradient Foot pulses (by palpation) absent Impaired ABPI (<0. 9) Extreme findings Previous Hx. of diabetic foot ulcer Current ulceration Amputation Gangrene Deformity 38 28 94 15 20 3 1 11 16. 5 12. 2 40. 9 6. 5 8. 7 1. 3 0. 4 4. 8

Associated Risk Factors in Both Groups * signifies statistically significant difference, p <0. 05.

Distribution of patients with DFS across Hb. A 1 c levels (N=32) Hb. A 1 c levels (%) n (%) Odds ratio p value <7 6 (18. 8) - - 7. 1 – 8. 0 3 (9. 4) 1. 69 0. 48 8. 1 – 9. 0 4 (12. 5) 1. 40 0. 62 9. 1 – 10. 0 6 (18. 8) 0. 64 0. 48 >10 13 (40. 6) 0. 44 0. 12 Reference category for Odds Ratio, Hb. A 1 c <7. 0%

Comparison of treatment between patients with diabetic foot syndrome & normal feet Treatment DFS (n=32) Normal feet (n=198) 19 (59. 4) 129 (65. 2) Monotherapy 4 (21. 1) 27 (20. 9) Two OADs 12(63. 2) 81 (62. 8) >2 OADs 3 (15. 8) 21 (16. 3) 0 (0. 0) 7 (3. 5) 13 (40. 6) 59 (29. 8) OADs only Insulin only OADs + insulin

Ankle Brachial Pressure Index: ABPI • 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