The prevalence and clinical characteristics of diabetic neuropathy in ...

The prevalence and clinicalcharacteristics of diabeticneuropathy in Korea: Results from a population-based study of type 2 diabeticpatients in Korea by Korean Diabetes Association DiabeticNeuropathy Study GroupJong Chul Won, MD, PhDDepartment of Internal Medicine, Cardiovascular andMetabolic Disease Center, Inje University,Sanggye Paik Hospital, Inje University Schoolof Medicine, Seoul

• In the West bare feetare a sign of humilityand poverty. Christ andthe Apostles,Franciscan friars, andsaints are all depicted inart without footwear.• Eastern nationscustomarily perform allacts of religious worshipwith bare feet.• In antiquity bare feetwere also sign ofmourning.

•Diabetes was associated with 2-3 foldsincreased risk of being unable to domobility-related task 1,2• The severity of diabetic peripheralneuropathy (DPN) was predictive of thedecreased QoL 31. Gregg EW, Diabetes Care, 2000• DPN and its Cx are reported to2. Volpato S, Diabetes Care, 2002account for nearly 27% of direct medical3. Currie CJ, Diabetologia, 2006costs of diabetes 4 4. Daousi C, Diabet Med, 2004

Foot disease in patients with diabetesFoot amputation rate (2003) Foot ulcer rate (2003)50.040.047.8100.080.091.030.060.020.040.010.04.720.011.70.0non-diabeticdiabetic0.0non-diabeticdiabeticPer population of 100,000Analysis of the medical records sampled from the health insurance data regarding claims with footamputation (Z894-899), ulcer of lower limb (L97), gangrene (R02), insulin-dependent diabetes (E10), noninsulindependent diabetes (E11), malnutrition related diabetes (E12), other specified diabetes (E13) orunspecified diabetes (E14) as principal or secondary diagnosis between Dec 1994 and Dec 2002.KDA Diabetes in Korea, 2007

Total medical cost in patients withdiabetic foot diseaseFoot amputation (2003) Foot ulcer (2003)Mean annual total medical costper person (1,000 KRW)14,00012,00010,0008,0006,0004,0002,0000579DM (-)outpatient6,097DM (-)hospitalization1,309DM (+)outpatient11,931DM (+)hospitalization10,0008,0006,0004,0002,0000550DM (-)outpatient4,538DM (-)hospitalization1,757DM (+)outpatient7,907DM (+)hospitalizationKDA Diabetes in Korea, 2007

12Prevalence and Clinical Characteristicsof DPN in KoreaClinical Implications of DPN in Korea

DISCLOSUREAnalysis of data from the results of “Study for evaluation of painand QOL in patients with DPN in Korea”, which enrolled 4,000diabetic patients from 40 hospitals throughout Korea during 2009~ 2010.– [당뇨병성 신솟경병증환자에숷서의 통증의 정도 및 삶의 질에숷 관한 연구]– Sponsored by Pfizer Korea inc.Announcement of results– Final meeting of research group, 10-Sept, 2010– Preliminary results were presented and discussed at 8 th IDFmeeting at Busan in 2010 (by Dr. JH Kim).

Prevalence and ClinicalCharacteristics of DPN in Korea

Prevalence of diabetic neuropathy in patients withdiabetes from cross-sectional research studies inKorea (1957~1994)Study site and year Neuropathy diagnosis Subjects, n Prevalence, %Seoul, 1957~1977 NA 5,601 32.7Seoul, 1963 ~ 1973 NA 1,332 22.9Nationwide, 1976 NA 3,076 28.9Kwangju, 1976 ~ 1981 NA 779 14.1Seoul, 1981~1983 Symptoms, signs, NCV 300 54.5Seoul, 1982 Symptoms, signs, NCV 224 45.5Seoul, 1990 Symptoms, signs, NCV 837 48.9Seoul, 1993 Symptoms, signs, NCV 1,301 39.0Seoul, 1994 Symptoms, signs, NCV 668 19.0Seoul, 1994 Symptoms, signs, NCV 235 37.5Taegu, 1999 Symptoms, signs, NCV 1,270 47.6NA, not available; NCV, nerve conduction velocityKim SY, J Korean Diabetes Assoc 1979; Han DH, J Korean Diabetes Assoc 1974; Son SK, J KoreanDiabetes Assoc 1976; Lee TH, J Korean Diabetes Assoc 1981; Lee HC, J Korean Diabetes Assoc1984; Lee MK, J Korean Diabetes Assoc 1983; Hong YS, J Korean Diabetes Assoc 1990; Kim SM, JKorean Diabetes Assoc 1993; Park JY, J Korean Diabetes Assoc 1993

Study for evaluation of pain and QOL inpatients with DPN in KoreaObjectives– Evaluation of impact of DPN on the disease burden and QOLof diabetic patientsMethods– For nationwide survey, we investigated 4,000 patientsthroughout 40 hospitals by questionnaires, clinicalexamination and review of medical records.– Measures of patients-reported outcomes: Brief Pain Inventory(BPI)-Short Form (SF), Medical Outcomes Study (MOS) –Sleep, EuroQOL-5 dimensions (EQ-5D).– Diagnosis of DPN: Known DPN (typical symptoms, sensorymotornerve test including neurologic or electrophysiologicalexamination) or MNSI (2>) and positive 10-g monofilamenttest.MNSI, Michigan Neuropathy Screening Instrument.

Prevalence of DPNN = 3,339Non-DPNDPN33.5%66.5%Firstly diagnosed DPNDPN:Previously diagnosed by symptomDPN:Previously diagnosed by signDPN:Previously diagnosed by symptom and sign6.3%4.8%27.2%8.3%14.1%

Clinical characteristics of DPN in Korea (1)(n, %) DPN (1,338, 33.5) Non-DPN (2,661, 66.5)Age (yr) 62.7 ± 10.7* 59.4 ± 11.3Women (n,%) 745 (55.7)* 1315 (49.4)Duration of diabetes (yrs) 11.8 ± 8.0* 8.4 ± 7.1Current smoker (%) 16.7 17.4Diabetes treatment (%)Diet and exerciseOHAInsulinCombination of OHAs and insulin9.6*52.5*12.9*25.0*15.065.66.912.4BMI (kg/m 2 ) 25.4 ± 3.1 23.6 ± 3.1Data are mean ± SD. * P < 0.05 vs Non-DPN. OHA, oral hypoglycemic agent; BMI, body mass index.

Clinical characteristics of DPN in Korea (2)(n, %) DPN (1,338, 33.5) Non-DPN (2,661, 66.5)Systolic BP (mm Hg) 127.5 ± 15.5 127.0 ± 14.4Diastolic BP (mm Hg) 74.5 ± 10.3 75.3 ± 9.8Fasting plasma glucose (mmol/L) 7.9 ± 3.1 7.9 ± 2.7A1C (%) 7.8 ± 2.4 7.6 ± 2.9Total cholesterol (mmol/L) 4.4 ± 1.1 4.4 ± 1.1Triglyceride (mmol/L) 1.6 ± 1.0 1.7 ± 1.2HDL-cholesterol (mmol/L) 1.2 ± 0.4 1.2 ± 0.3LDL-cholesterol (mmol/L) 2.4 ± 0.9* 2.6 ± 0.9Data are mean ± SD. * P < 0.05 vs Non-DPN. BP, blood pressure; A1C, hemoglobin A1 C ; HDL, high density lipoprotein;LDL, low density lipoprotein.

Clinical characteristics of DPN in Korea (3)(n, %) DPN (1,338, 33.5) Non-DPN (2,661, 66.5)Hypertension (%) 65.7* 50.8Dyslipidemia (%) 52.6* 46.9Any retinopathy (%) 31.8* 15.6Nephropathy (%) 22.5* 12.3History of CVDs (%) 12.0* 6.8History of CVAs (%) 6.4* 4.0History of PADs (%) 7.3* 1.5Foot ulcer or amputation (%) 3.1* 0.3MNSI scores 3.1 ± 2.2* 1.5 ± 1.5Abnormal site of monofilament test (n)Rt. FootLt. foot1.8 ± 2.6*1.8 ± 2.6*0.3 ± 1.00.3 ± 1.0Data are mean ± SD. * P < 0.05 vs non-DPN.; CVD, cardiovascular disease; CVA, cerebrovascular accident; PAD,peripheral arterial disease; MNSI, Michigan Neuropathy Screening Instrument.

Prevalence of DPN according to theduration of diabetes (yrs)DPNNon-DPN100.00%80.00%60.00%78.5%68.5%54.7%40.00%20.00%21.5%31.5%45.3%0.00%< 5 5 -1 0 ≥ 10

Prevalence of DPN stratified by age (yrs)(A) and glycemic status (A1C, %) (B)A.60.0%50.0%40.0%30.0%20.0%10.0%0.0%P for trend < 0.05< 50 (n = 650) 50 ~ 59 (n = 1,193) 60 ~ 69 (n = 1,314) ≥ 70 (n = 842)B.40.0%30.0%P for trend < 0.0520.0%10.0%0.0%< 7.0 (n = 1,576) 7.0 ~ 9.0 (n = 1,813) ≥ 9.0 (n = 610)

Temporal prevalence (%) of diabetic complicationsaccording to quartile of duration of diabetes (yrs)60.050.0Neuropathy Retinopathy Nephropathy Any macroangiopathyAll P for trend < 0.0540.030.020.010.00.0Q1 (< 3.6, n = 1,033) Q2 (3.7 ~ 7.7, n = 960) Q3 (7.8 ~ 13.6, n = 969) Q4 (≥ 13.7, n = 1036)

ORs of risk factorsassociated with DPN (1)• With multivariate logisticregression analysis• Log-transformed ODs( 95% CI)A1C, hemoglobin A1C; CVD,cardiovascular disease; CVA,cerebrovascular accident; PAD, peripheralarterial disease; MNSI, MichiganNeuropathy Screening Instrument.

ORs of risk factors associated with DPN (2)Variables OR (95% CI) P valueAge (yr) 1.014 (1.004, 1.024) 0.0038Diabetes duration (≥ 10 yrs vs 5 yrs) 1.449(1.126, 1.864) 0.0039Retinopathy 1.826(1.454, 2.292)

Comparison of MNSI score between inpatients with DPN and Non-DPNMNSI 설문 문항 DPN Non-DPN1. 발 또는 다리에숷 저린 감이 있습솚니까? 868(64.87) 954(35.85)2. 발 또는 다리에숷 화끈거리는 통증을 느낀 적이 있습솚니까? 454(33.93) 392(14.73)3. 발에숷 무엇이 닿을 때 과민하게 느낍니까? 252(18.83) 198(7.44)4. 발 또는 다리에숷 갑자기 쥐가 납니까? 617(46.11) 890(33.45)5. 발 또는 다리에숷 찌르는 듯한 느낌을 받은 적이 있습솚니까? 547(40.88) 469(17.62)6. 이불이 피부에숷 닿을 때 아쇾픔을 느낍니까? 82(6.13) 58(2.18)7. 목욕할 때 뜨거운 물과 차가운 물을 구분할 수 있습솚니까? 51(3.81) 42(1.58)8. 발에숷 까진 상처가 생긴 적이 있습솚니까? 162(12.11) 144(5.41)9. 의사로부터 '당뇨병성 신솟경병증' 이라고 진단된 적이 있습솚니까? 171(12.78) 31(1.16)10. 다리나 발에숷 마비가 있습솚니까? 221(16.52) 142(5.34)11. 다리나 발의 증상이 밤에숷 더 심솣해집니까? 478(35.72) 392(14.73)12. 걸을 때 다리가 아쇾픕니까? 493(36.85) 461(17.32)13. 걸을 때 발에숷 감각을 느낄 수 있습솚니까? 104(7.77) 109(4.10)14. 발의 피부가 건조해서 자주 갈라집니까? 490(36.62) 731(27.47)15. 발이나 발가락을 자르는 수술셶을 받은 적이 있습솚니까? 39(2.91) 9(0.34)Mean score ± SD 3.13±2.19 1.50±1.54N (%). All P < 0.05 between DPN and Non-DPN. DPN, diabetic peripheral neuropathy; MNSI, Michigan NeuropathyScreening Instrument. A “no” response on items 7 and 13 counts as 1 point. Item #4 is a measure of impairedcirculation and item #10 is a measure of general aesthenia and are not included in scoring.

Comparison of MNSI symptom distributionbetween 2005 and 2010 surveyResponder (%)1. 발 또는 다리에숷 저린 감이 있습솚니까?2. 발 또는 다리에숷 화끈거리는 통증을 느낀 적이 있습솚니까?3. 발에숷 무엇이 닿을 때 과민하게 느낍니까?4. 발 또는 다리에숷 갑자기 쥐가 납니까?5. 발 또는 다리에숷 찌르는 듯한 느낌을 받은 적이 있습솚니까?6. 이불이 피부에숷 닿을 때 아쇾픔을 느낍니까?7. 목욕할 때 뜨거운 물과 차가운 물을 구분할 수 있습솚니까?8. 발에숷 까진 상처가 생긴 적이 있습솚니까?9. 의사로부터 '당뇨병성 신솟경병증' 이라고 진단된 적이 있습솚니까?10. 다리나 발에숷 마비가 있습솚니까?11. 다리나 발의 증상이 밤에숷 더 심솣해집니까?12. 걸을 때 다리가 아쇾픕니까?13. 걸을 때 발에숷 감각을 느낄 수 있습솚니까?14. 발의 피부가 건조해서 자주 갈라집니까?15. 발이나 발가락을 자르는 수술셶을 받은 적이 있습솚니까?2005, n = 472 2010, n = 13380 20 40 600 20 40 60A “no” response on items 7 and 13 counts as 1 point. Item #4 is a measure of impaired circulation and item #10 is a measureof general aesthenia and are not included in scoring. MNSI, Michigan Neuropathy Screening Instrument

Distribution of MNSI clinical scoreDPN (n = 1,338) Non-DPN (n = 2661)100.0%80.0%60.0%40.0%20.0%0.0%≤ 2.0 ≥ 3, < 5 ≥ 5, < 7 ≥ 7At each level, all P < 0.05 between DPN and Non-DPN. Scores with 0.5 increments were rounded up to the next integer.DPN, diabetic peripheral neuropathy; MNSI, Michigan Neuropathy Score Instrument.

DPN: treatmentTreatment (+) Treatment (-)30.2%69.8%local preparationSSRIopiodiSSNRITCAsgamma-linoleic acidanti-convulsant drugalpha-lipoic acid0.0% 20.0% 40.0% 60.0%20.1% patients receivedmore than one medication.DPN patients with treatmenthad longer duration ofdiabetes, more insulin use,and more retinopathy,nephropathy andhypertension.However, mean number ofsite unable to feel themonofilament was higher inDPN patients withouttreatment than those withtreatment (P < 0.001).

Clinical Implications of DPN inKorea

BPI-SF (1): Pain severityNon-DPNDPNPain severity indexCurrent painWorst painAverage pain0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5All measures are P < 0.05 between DPN and Non-DPN. 0 (no pain) to 10 (worst possible pain) numericrating scales. Korean January 19, 2006, The University of Texas MD Anderson cancer center, Charles S.Cleeland, PhD.

BPI-SF (2): Pain interferenceNon-DPNDPNPain interference indexEnjoyment of lifeSleepRelationshipNormal WorkWalkingMoodGeneral activity0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5All measures are P < 0.05 between DPN and Non-DPN. 0 (no pain) to 10 (worst possible pain) numericrating scales.

MOS-sleep scale• 당신솟이 필요한 만큼 충분히 많이 잠을 잤습솚니까?• 낮에숷 완전히 잠이 깬 상태로 있기 어숦려웠습솚니까?• 잠 자는 동안숀 깨고 다시 잠들기 어숦려웠습솚니까?• 잠들기가 어숦려웠습솚니까?• 숨셷이 차서 또는 머리가 아쇾파 잠을 깨숲습솚니까?• 아쇾침에숷 일어숦났을 때 잘 쉬솆숲다고 느낄 만큼 충분한 수면을취했습솚니까?Quantity of sleep/OptimalsleepSomnolenceSleep maintenanceSleep disturbanceAwaken short of breath orheadacheSleep adequacyHays, RD, The Medical Outcomes Study approach, Duke University Press, 1992

MOS-sleep scaleNon-DPNDPNQuality of sleep/Optimal sleepSomnolenceSleep maintenance SnoringSleep disturbanceAwaken short of breath or headacheSleep adequacy0 10 20 30 40 50 60 70 80 90 100All measures are P < 0.05 between DPN and Non-DPN. Numeric rating score (1, always; 6, never)transformed to 0 ~ 100.Hays, RD, The Medical Outcomes Study approach, Duke University Press, 1992

EQ-5D descriptive system: 5 dimensionsNon-DPNDPNAnxiety/DepressionPain/DiscomfortUsual activitySelf-careMobility0.0 10.0 20.0 30.0 40.0 50.0Percentages of respondents reporting more than “some problem”. Each question has three levelsindicating “no problem (or 1),” “some problems (or 2),” and “severe problems (or 3),” respectively. EQ-5D, EuroQoL-5 Dimensions.EuroQol Group, Health Policy, 1990All measures are P < 0.05 between DPN and Non-DPN

EQ-5D index: Korean ScoringNon-DPNP < 0.05DPN0.0 0.2 0.4 0.6 0.8 1.0Korean version, © 1990 EuroQol Group. These weights lie on a scale on which full health has avalue of 1 and dead a value of 0.EQ-5D, EuroQoL-5 Dimensions.Kang EJ, Value Health, 2009

Patients awareness of DPNAwarenessYes No12.6%87.4%27.2%Education27.8%Foot care72.8%72.2%

SummaryMore than one third of patients with type 2 diabetes were DPN.DPN patients had high prevalence of diabetes-relatedcomplications and co-morbidity.Risk factors associated with DPN were age, duration of diabetes,diabetic complications (retinopathy, CVD, and PAD), and comorbidities(hypertension and dyslipidemia).High prevalence but low proper management and awareness oftheir own DPN deserves attention from clinicians to ensure bettermanagement of diabetes in Korea.Further analysis: Clinical implications of painful-DPN, QOL issue,and disease burden.

Investigators and study centersincluded in this analysis:강남 세브란스솔병원강남성심솣병원강릉아쇾산병원강북삼성병원경상대병원계명대병원고대구로병원고대안숀암숇병원길병원노원을지병원대구가톨릭병원대전을지병원동서신솟의학병원부산대병원부산백병원부천세종병원분당서울대병원분당제생병원분당차병원삼성서울병원충북대병원안숀철우홍은경심솣명셳박철영함종렬김혜순셴최경묵김신솟곤박이병민경완이지현박강서정인경김인주박정현김종화임수김용현김수경이명솞오태근상계백병원상계백병원서울성모병원서울아쇾산병원성가병원순셴천향서울병원순셴천향부천병원순셴천향천안숀병원여의도성모병원영남대병원예수병원울산대부속셏병원원주기독병원의정부성모병원이대목동병원전북대병원중앙숋대병원 (용산)중앙숋대병원 (흑석동)춘천성심솣병원화순셴전남대병원고경수원종철차봉연이우제김성래변동원정찬희김상진권혁상원규장송셗선경김영일정춘희손셑태서오지영박태선안숀지현김재택류옥현강호철

AcknowledgementFully acknowledged the participating investigators and steering members ofKorean Diabetic Neuropathy Study Group. Special thank to professor Ki JunSong (Department of Health statistics, Yonsei University, School of Medicine,Seoul, Korea) for statistical analysis.

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