THE FORGOTTEN COMPLICATION M. Pfeifer

Transcription

1 Diabetic Neuropathy THE FORGOTTEN COMPLICATION M. Pfeifer P 1

2 The Burden of Diabetic Peripheral Neuropathy Most common peripheral neuropathy in the developed nations Major contributor to the hospital rate of diabetic patients Results in 50-70% of all non-traumatic lower extremity amputations in the USA P 2

3 Prevalence of Neuropathy in Diabetes At time of diagnosis % 25 years after diagnosis % Overall % Similar prevalence in T2DM versus T1DM but more common in men (height) P 3

4 Diagnosis of Diabetic Neuropathy A clinical diagnosis of exclusion Characteristic (but not pathognomonic) clinical presentation(s) Other etiologies must be excluded by clinical and laboratory investigations P 4

5 Types of Diabetic Neuropathy Focal diabetic neuropathies Ischemic etiology Entrapment etiology Diffuse diabetic neuropathies Distal symmetrical polyneuropathy Autonomic neuropathies P 5

6 Ischemic Focal Neuropathies Characteristics Acute ischemic event Sudden onset Asymmetrical distribution Self-limited course Examples Mononeuropathies Plexopathies Femoral neuropathy Radiculopathies Cranial neuropathies P 6

7 Ischemic Focal Neuropathy: Mononeuropathy Cranial Third Nerve Palsy Involvement of the 3 rd Cranial Nerve (oculomotor nerve) Upper eyelid weakness Unable to constrict iris Diplopia due to lack of normal alignment of eyes (severe cases) --- down and out P 7

8 Entrapment Focal Neuropathies Characteristics Nerve entrapment in a specific bodily compartment Gradual onset Usually asymmetrical distribution but may be symmetrical Often a progressive course (unless etiology of the entrapment is eliminated) Examples Carpal tunnel syndrome Ulnar entrapment Tarsal tunnel syndrome P 8

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10 Diffuse Neuropathies Characteristics Structural, vascular, metabolic and autoimmune abnormalities Insidious onset Symmetrical distribution Progressive course Examples Distal symmetrical polyneuropathy Autonomic neuropathies P 10

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12 Abnormal Vasa Nervorum Abnormal PKCβ Activity Poor Metabolic Control Nerve Ischemia Abnormal Morphometry/Fx Development of Neural Autoantibodies Nerve Function Confirmed Clinical Neuropathy Ulceration Amputation Pain

13 Abnormal Vasa Nervorum Abnormal PKCβ Activity Poor Metabolic Control Abnormal Fatty Acid Metabolism Nerve Ischemia Abnormal Morphometry/Fx Development of Neural Autoantibodies Nerve Function Confirmed Clinical Neuropathy Ulceration Amputation Pain

14 Abnormal Vasa Nervorum Abnormal PKCβ Activity Poor Metabolic Control Abnormal Fatty Acid Metabolism Hyperglycemia Polyol Activity Z-2 Gene Polymorphism Nerve Ischemia Nitric Oxide Synthase Activity Abnormal Morphometry/Fx Development of Neural Autoantibodies Nerve Function Confirmed Clinical Neuropathy Ulceration Amputation Pain

15 Abnormal Vasa Nervorum Abnormal PKCβ Activity Poor Metabolic Control Abnormal Fatty Acid Metabolism Hyperglycemia Nerve Ischemia Polyol Activity Z-2 Gene Polymorphism Nitric Oxide Synthase Activity Abnormal Morphometry/Fx Development of Neural Autoantibodies Myoinositol Uptake Nerve Myoinositol Nerve Function Confirmed Clinical Neuropathy

16 Abnormal Vasa Nervorum Abnormal PKCβ Activity Poor Metabolic Control Abnormal Fatty Acid Metabolism Hyperglycemia Polyol Activity Myoinositol Uptake Glycosylation Nerve Proteins Z-2 Gene Polymorphism Nerve Myoinositol Axonal Transport Nerve Ischemia Nitric Oxide Synthase Activity Abnormal Morphometry/Fx Development of Neural Autoantibodies Nerve Function Confirmed Clinical Neuropathy Ulceration Amputation Pain

17 Abnormal Vasa Nervorum Abnormal PKCβ Activity Poor Metabolic Control Abnormal Fatty Acid Metabolism Hyperglycemia Polyol Activity Myoinositol Uptake Glycosylation Nerve Proteins Z-2 Gene Polymorphism Nerve Myoinositol Axonal Transport Nerve Ischemia Nitric Oxide Synthase Activity Abnormal Morphometry/Fx Development of Neural Autoantibodies Nerve Function Confirmed Clinical Neuropathy Ulceration Amputation Pain

18 P 18 DSP May Lead to Foot Ulceration

19 Why worry about DSP unless you can do something? Slowing the Progression of Distal Symmetrical Polyneuropathy (DSP) Prevention of outcomes of DSP (e.g. ulceration amputation) Symptomatic treatment (e.g. pain) P 19

20 General Risk Factors for the Development or Progression of DSP Non-Modifiable Older age Longer duration of diabetes Genetic factors Z-2 allele HLA-DR 3/4 phenotype Height Modifiable Poor glucose control Hypertension Smoking Hypertriglyceridemia (Heavy alcohol use) P 20

21 Determination of Neuropathy in Large Glycemic Related Trials TYPE OF DM T1DM T2DM TRIAL (year) + EFFECT OF IMPROVED GLYCEMIA Determination of Neuropathy Holman ( 83) Yes Vib The Oslo Study ( 86) Yes MNCV DCCT ( 93) Yes Clin Confirmed Reichard ( 93) Yes NCV Linn ( 96) Yes Unknown UKPDS ( 98) Yes Vib pos; RR-Var neg VA Cooperative Study ( 99) Yes PE pos; Testing neg Gaede ( 03) Yes ANS pos; Vib neg Veterans Complication Study ( 09) No PE only ACCORD ( 10) Yes MNSI, Reflex, Monofil pos; Vib neg P 21

22 DCCT Showed Intensive Therapy was Associated with a 60% Reduction in Neuropathy DCCT Definition of Confirmed Clinical Neuropathy: Peripheral Sensorimotor neuropathy on physical exam by a DCCT trained neurologist plus either abnormal nerve conduction velocity in two different peripheral nerves or unequivocal abnormal autonomic test results P 22

23 In EDIC (DCCT Follow-Up) the Prevalence of Neuropathy Remains Reduced after Years % P 23

24 Genomic Profile and Neuropathy Aldose reductase ALR2 gene polymorphism Aldose reductase polymorphism is associated with 3-20x greater prevalence of microvascular complications (nephropathy, neuropathy and retinopathy) Z-2 allele is associated with 2-3X greater prevalence of microvascular complications 20 year duration of diabetes Z+2 allele = 14% risk of DM neuropathy Z-2 allele = 38% risk of DM neuropathy Prevalence of Z-2 allele is approximately 30% P 24

25 Why worry about DSP unless you can do something? Slowing the Progression of Distal Symmetrical Polyneuropathy (DSP) Prevention of outcomes of DSP (e.g. ulceration amputation) Symptomatic treatment (e.g. pain) P 25

26 Avoidance of Further Complications Routine assessment Appropriate type of exercise Proper footwear Education P 26

27 Routine Assessment: Feet Exams Foot appearance (each visit) Foot structure (each visit) Vascular status (pulses at each visit) Neurosensory evaluation (annually) P 27

28 Reminder Poster on the Wall of the Exam Room can Speed up the Office Visit and Serve as a Reminder to both HCP and Patient P 28

29 Foot Appearance Often Reveals Dry Cracked Skin or Fungal Infection Use a natural lanolin foot cream to provide moisture (not a petroleum-based ointment) P 29

30 Examination of Shoes As Well As Feet may Reveal Additional Sources of Problems P 30

31 P 31 Common Abnormal Foot Structures

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33 Vascular and Neurosensory Routine Exams Vascular status Pulses each visit Detailed exam as needed Neurosensory evaluation (annually) Michigan Neuropathy Scale (MNSI) Deep tendon reflexes 128 Hz tuning fork Monofilaments P 33

34 Michigan Neuropathy Screening Instrument (MNSI) An instrument designed to screen for the presence of diabetic neuropathy minutes It includes both a self-assessment of symptoms (15 questions) and a brief physical examination (inspection, vibration (tuning fork) & ankle reflexes) The MNSI is designed to be used in an outpatient setting Survey Instruments MNSI Download Fill out form Free P 34

35 P 35 Abnormal Achilles Deep Tendon Reflexes Provides Information that more extensive Gait and Motor Nerve Function Testing may Be Indicated

36 P 36 Test the Ability of the Patient to Feel the Vibration of a 128 Hz Tuning Fork Against the Base of the Great Toe Nail

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39 Importance of the Presence of Insensate Feet The presence of an insensate foot is defined as the inability to feel 128 Hz tuning fork vibration at the base of the great toe nail and/or the inability to feel the 5.07 (10 gram) monofilament anywhere on the foot Insensate feet are at 60% risk of developing a foot ulcer in the next three years --- this rate is increased if there is any foot deformity Medicare and most third party insurance companies will pay for 80% of one pair of custom footwear for patients with insensate feet annually Custom footwear will decrease the rate ulceration from 60% to 20% over the next three years P 39

40 Avoidance of Further Complications Routine assessment Appropriate type of exercise Proper footwear Education P 40

41 Appropriate Type of Exercise No neuropathy Routine health care considerations Education about proper foot care & footwear Neuropathy present but not insensate feet Special footwear (extra-depth; well fitting; extra padding; therapeutic socks) Avoid exercise which may traumatize the foot Cardiac stress test prior to initiation Insensate feet No exercise which may put the foot at risk Consider formal nuclear medicine stress test P 41

42 Avoidance of Further Complications Routine assessment Appropriate type of exercise Proper footwear Education P 42

43 P 43 Mechanical Stresses of High Heels

44 Educate the Patient Daily foot care Wash feet daily & dry carefully Examination of feet (especially between the toes) and shoes Look for changes in skin color Feel for elevated skin temperature Proper foot and nail care When cutting nails cut straight across Proper lubrication P 44

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47 Educate the Patient Appropriate type of exercise Proper footwear Comfortable and well fitting Therapeutic socks Appropriate shoes Avoidance of temperature extremes without proper insulation Visit with diabetes educator Books, films & pamphlets P 47

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51 Why worry about DSP unless you can do something? Slowing the Progression of Distal Symmetrical Polyneuropathy (DSP) Prevention of outcomes of DSP (e.g. ulceration amputation) Symptomatic treatment (e.g. pain) P 51

52 TREATMENT ALGORITHM FOR PAINFUL DIABETIC NEUROPATHY Bilateral Painful Feet Non-DSP Etiologies

53 ETIOLOGY OF PAIN IN 117 CONSEQUENTIVE DIABETIC PATIENTS REFERRED FOR PAINFUL DSP Spinal Stenosis 4% Tarsal Tunnel Syndrome 4% Femoral Neuropathy 7% Peripheral Vascular Disease 11% Reflex Sympathetic Dystrophy 3% Miscellaneous 6% Distal Symmetrical Polyneuropathy 65%

54 TREATMENT ALGORITHM FOR PAINFUL DIABETIC NEUROPATHY Bilateral Painful Feet Non-DSP Etiologies DSP Most Likely Etiology Acute Painful Neuropathy Treat Acute Painful Neuropathy

55 Acute Painful Diabetic Neuropathy Typical Characteristics Known duration of diabetes is relatively short (less than 2 years) Sudden onset Often after a rapid improvement in glucose control Pain duration less than 12 months Self-limiting Proposed etiology: Endoneurial swelling Treatments Simple OTC analgesics Education and reassurance P 55

56 TREATMENT ALGORITHM FOR PAINFUL DIABETIC NEUROPATHY Bilateral Painful Feet Non-DSP Etiologies DSP Most Likely Etiology Chronic Painful Neuropathy Improve Glucose Control Acute Painful Neuropathy Treat Acute Painful Neuropathy

57 Chronic Painful Diabetic Neuropathy Typical characteristics Known duration of diabetes is intermediate (~ 5-15 yrs) Gradual onset Not related to a precipitating event Pain duration more than 12 months May persist for years Relapses occur Proposed etiology: Structural, metabolic and muscular Treatments Improve glycemic control Education and reassurance Treat specific type of pain P 57

58 TREATMENT ALGORITHM FOR PAINFUL DIABETIC NEUROPATHY Bilateral Painful Feet Non-DSP Etiologies DSP Most Likely Etiology Chronic Painful Neuropathy Improve Glucose Control Acute Painful Neuropathy Treat Acute Painful Neuropathy Determine Type & Severity of Pain Dysesthesia Paresthesia Muscle Pain Treat if Symptoms Severity Warrants Treat Muscular Pain

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60 Muscular Pain Physical exam Tightly contracted foot extensors (cocked back toe deformity --- hammer toe deformity) Tightly contracted gastrocnemius muscles Descriptors Dull Aches Night Cramps Deep Aches Band-Like Sensation Drawing Sensation Therapy Daily stretching exercises Spasms Like A Tooth Ache Proper footwear Metatarsal bars Custom shoes Avoid high heels Short term use of muscle relaxants & OTC analgesics P 60

61 Dysesthesia and Paresthesia Dysesthesia descriptors Burning Sensation Like A Sun Burn Skin Tingling Painful Sensation When Something Touches Me That Usually Would Not Hurt --- Such As Bed sheets Or Stockings Paresthesia descriptors Pins & Needles Shooting Pains Numb But Achy Like Feet In Ice Water Electric-Like Knife-Like Lancinating Pain There are three drugs approved for the treatment of painful (dysesthesia and paresthesia) diabetic neuropathy P 61

62 TREATMENT ALGORITHM FOR PAINFUL DIABETIC NEUROPATHY Bilateral Painful Feet Non-DSP Etiologies DSP Most Likely Etiology Chronic Painful Neuropathy Improve Glucose Control Acute Painful Neuropathy Treat Acute Painful Neuropathy Determine Type & Severity of Pain Dysesthesia Paresthesia Muscle Pain Treat if Symptoms Severity Warrants Treat Muscular Pain Reevaluate q6w; Adjust Meds D/C Meds (usually within 12 mos); Retreat if reoccurrence

63 Summary Diabetic Neuropathy Important medical and public health problem involving both T1DM & T2DM Includes well defined clinical syndromes Distal symmetrical polyneuropathy is the most common Most cases are asymptomatic Diagnosis of exclusion Therapy is directed toward slowing the progression/prevention, avoiding complications from neuropathy and appropriate symptomatic treatment of painful diabetic neuropathy P 63

64 Conclusion WITH PROPER CONCERN & DELIGENCE, THE QUALITY OF LIFE, TREATMENT MODALITIES, AND LIFE STYLE OF DIABETIC PATIENTS CAN BE IMPROVED BY ADDRESSING THE FORGOTTEN COMPLICATION : DIABETIC NEUROPATHY P 64