Prevalence of Diabetic Neuropathy and Foot Ulceration Identification

Prevalence of Diabetic Neuropathy and Foot Ulceration: Identification of Potential Risk Factors -A Population-Based Study in North Hellas Ch. Manes, MD, N. Papazoglou, MD, E. Sossidou, K. Soulis, MD, D. Milarakis, A. Satsoglou and A. Sakallerou Wounds 14(1): 11 -15, 2002

Results from Hellas • • N=821 Mean age: 59. 5 ± 7. 96 yrs Diagnosis of neuropathy: NSS, NDS, VPT Type 2: n=781, Type 1: n=41 • Prevalence of neuropathy: 33. 5% – Men: 35. 2% – Women: 32. 6% • Painful symptoms: 31. 3% • FU: 4. 75%, PVD: 12. 7% Manes et al, Wounds 14(1): 11 -15, 2002

Περιφερική νευροπάθειαεπισκόπηση N. Katsilambros et al. , Atlas of the Diabetic Foot, 2003, Wiley, UK

Diabetologia 1998, 41: 416 -423

Reversal of diabetic somatic neuropathy by whole PT in rats Orloff MJ et al, Surgery 108: 179 -90

Steno-2: treatment conditions Conventional group • Aim: to modify CV risk factors to conventional targets: • • • Systolic BP < 160 Diastolic BP < 95 Hb. A 1 c < 7. 5% Fasting serum total cholesterol: 250 mg/dl Fasting serum triglycerides: 195 mg/dl Aspirin for those with known ischaemia Intensive group • Aim: to modify CV risk factors to strict targets: • • Slide No. 40 • • Steno-2: N Engl J Med 2003; 348: 383– 93 Steno-2: Lancet 1999; 353: 617– 22 Systolic BP < 140 Diastolic BP < 85 Hb. A 1 c < 6. 5% Fasting serum total cholesterol 190 mg/dl Fasting serum triglycerides 150 mg/dl Aspirin for those with known ischaemia or peripheral vascular disease Automatic treatment with ACE inhibitor

Slide No. 41 • A ne ut ur on op om at ic hy in Re t ep hr N CV D Relative risk reduction for intensive vs conventional treatment (%) op op a at th y hy Steno-2: relative risk reduction with intensive treatment * p < 0. 05 ** p < 0. 01 * ** • Adapted from: N Engl J Med 2003; 348: 383– 93 * **

Συμπτωματική θεραπεία Τρικυκλικά Φάρμακο Amitriptyline Imipramine SSRIs Paroxetin Citalopram SNRIs Duloxetin Venlafaxin Αντιεπιληπτικά Carbamazepine Gabapentin Pregabalin Topiramate Λακοσαμίδη Οπιοειδή Tramadol Codein CR Εμπορικό όνομα Saroten (25, 75 mg) Anafranil (10, 25, 75 mg) Δόση (mg/d) 25 -150 NNT 2. 7 (2. 1 -3. 9) Seroxat (20 mg) Seropram (20 mg) 40 40 - Cymbalta (60 mg) Efexor (75, 150 mg) - 60 75 -300 Tegretol (200 mg) Neurontin (300 -800 mg) Lyrica (25 -300 mg) Topamac (25 -200 mg) Lacosamide (200 -600 mg) 200 -400 900 -1800 150 -600 25 -400 400 -600 1. 9 (1. 4 -2. 8) 2. 7 (2. 2 -3. 4) 3. 7 9 50 -400 10 -60 7. 8 - - - ADA Statement, Diabetes Care 2005, 28: 956

Συμπτωματική θεραπεία Τρικυκλικά Φάρμακο Amitriptyline Imipramine SSRIs Paroxetin Citalopram SNRIs Venlafaxin Duloxetin Αντιεπιληπτικά Carbamazepine Gabapentin Pregabalin Topiramate Λακοσαμίδη Οπιοειδή Tramadol Codein CR Εμπορικό όνομα Saroten (25, 75 mg) Anafranil (10, 25, 75 mg) Δόση (mg/d) 25 -150 NNT 2. 7 (2. 1 -3. 9) Seroxat (20 mg) Seropram (20 mg) 40 40 - Efexor (75, 150 mg) Cymbalta (60 mg) 75 -300 60 - Tegretol (200 mg) Neurontin (300 -800 mg) Lyrica (25 -300 mg) Topamac (25 -200 mg) Lacosamide (200 -600 mg) 200 -400 900 -1800 150 -600 25 -400 400 -600 1. 9 (1. 4 -2. 8) 2. 7 (2. 2 -3. 4) 3. 7 9 50 -400 10 -60 7. 8 - - ADA Statement, Diabetes Care 2005, 28: 956

NNT και ΝΝΗ για ασθενείς με ΕΔΠΝ Vinik & Casselini Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2013: 6 57– 78 69

BMJ 2014; 349: g 4658 doi: 10. 1136/bmj. g 4658 (Published 31 July 2014) Ioanna Eleftheriadou , Nicholas Tentolouris , Edward B Jude

Ποσοστό ανταπόκρισης ασθενών 52, 7% Διαβητική νευροπάθεια % ασθενών Total Symptom score (TSS): relative improvement at 3 weeks vs baseline ITT analysis of 4 phase II-III plus meta-analysis 90 * 80 88. 3 70 60 50 * 63. 6 a-lipoic acid 49. 7 40 30 20 10 * p<0, 05 vs placebo 44. 4 43. 6 43. 2 37. 7 6. 7 n=77 n=81 ALADIN I n=338 n=165 ALADIN III n=60 SYDNEY 52. 7 n=241 n=236 NATHAN II placebo 36. 9 n=716 n=542 Meta-Analysis D Ziegler et al Treatment of symptomatic diabetic polyneuropathy with the antioxidant a-lipoic acid a meta-analysis 2004 Diabetes UK Diabetic Medicine, 21, 114– 121

Μείωση σημείων στην κλίμακα Neuropathy Impairment Score of the Lower Limbs (NIS-LL) Σχετικές διαφορές ομάδας άλφα-λιποϊκού οξέος 600 mg vs placebo την 3 εβδομάδα χορήγησης Άλγος από τσίμπημα βελόνας στο μεγάλο δάκτυλο ποδιού OR (95% CI) Αίσθηση πίεσης-αφής OR (95% CI) Αντανακλαστικά αχίλλειου τένοντα OR (95% CI) ALADIN I 1. 32 (0. 61, 2. 86) 1. 78 (0. 87, 3. 65) 1. 38 (0. 49, 3. 91) ALADIN III 1. 12 (0. 75, 1. 68) 1. 22 (0. 82, 1. 82) 1. 08 (0. 69, 1. 68) SYDNEY 2. 56 (1. 13, 5. 80) 1. 17 (0. 49, 2. 79) 5. 07 (1. 36, 18. 88) NATHAN II 1. 65 (1. 03, 2. 66) 0. 99 (0. 62, 1. 56) 1. 70 (0. 84, 3. 46) Meta-analysis 1. 57 (1. 21, 2. 05) 1. 35 (1. 05, 1. 75) 1. 69 (1. 22, 2. 35) Values >1 favour a-lipoic acid Values < 1 favour placebo D Ziegler et al Treatment of symptomatic diabetic polyneuropathy with the antioxidant a-lipoic acid a meta-analysis 2004 Diabetes UK Diabetic Medicine, 21, 114– 121

ΔΕΙΚΤΗΣ ΣΥΜΠΤΩΜΑΤΩΝ ΝΕΥΡΟΠΑΘΕΙΑΣ (NSS) • NSS: Mean ± SD at both Study Visits. Minimum value=0 (no neuropathic symptoms), Maximum value=10 (the most severe neuropathic symptoms). Base: Total sample (N=30). Mean difference 2. 7, pvalue<0. 001

ΕΡΩΤΗΜΑΤΟΛΟΓΙΟ ΚΑΤΑΓΡΑΦΗΣ ΤΟΥ ΠΟΝΟΥ ΤΗΣ ΠΕΡΙΦΕΡΙΚΗΣ ΝΕΥΡΟΠΑΘΕΙΑΣ (SPNSQ) • Subjective Peripheral Neuropathy Screen Questionnaire Score: Mean ± SD at both Study Visits. Minimum value=0 (no neuropathic symptoms), Maximum value=15 (the most severe neuropathic symptoms). Base: Total sample (N=30). Mean difference 4. 9 , p-value<0. 001

ΕΡΩΤΗΜΑΤΟΛΟΓΙΟ DN 4 • DN 4 Questionnaire Score: Mean ± SD at both Study Visits. Minimum value=0 (no neuropathic pain), Maximum value=10 (the most severe neuropathic pain). Base: Total sample (N=30). Mean difference 3. 6 , p-value<0. 001

SHEEHAN DISABILITY SCALE (SDS)

PATIENT GLOBAL IMPRESSIONIMPROVEMENT (PGI-I)