혈당조절의모니터링 국립중앙의료원내과 조영중
Agenda 혈당조절의중요성 Assessment of long-term glycemic control Assessment of short-term glycemic control 요약
혈당조절의중요성 Assessment of long-term glycemic control Assessment of short-term glycemic control 요약
혈당조절의중요성 : 미세혈관합병증의감소 A1C DCCT 9.1 7.3% Kumamoto 9+ 7.2% UKPDS 7.9 7% 망막병증 47% 신증 54% 신경병증 60% 69% 17-29% 70% 24-33% 개선 - 심혈관질환 NS - 16% (NS) DCCT Research Group. N Engl J Med 1993;329:977-86; Ohkubo Y et al. Diabetes Res Clin Pract 1995;28:103-17; UKPDS 33: Lancet 1998;352:837-53.
Summary of Major Clinical Trials 연구 A1C 미세혈관합병증 UKPDS 9 7.9 7 DCCT/EDIC* 9.0 7.1 ACCORD 7.5 6.4 ADVANCE 7.3 6.5 VADT 8.4 6.9 본시험 Adapted from Bergenstal RM, Bailey C, Kendall DM. Am J Med 2010;123:374e9-e18; UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-65; Holman RR. N Engl J Med 2008;359(15):1577-89; DCCT Research Group. N Engl J Med 1993;329;977-86; Nathan DM et al. N Engl J Med 2005;353:2643-53. Gerstein HC et al. N Engl J Med 2008;358:2545-59. Patel A et al. N Engl J Med 2008;358:2560-72; Duckworth W et al. N Engl J Med 2009;360:129-39. 장기추적관찰 * In T1DM
Summary of Major Clinical Trials 연구 A1C 미세혈관합병증심혈관질환사망률 UKPDS 9 7.9 7 DCCT/EDIC* 9.0 7.1 ACCORD 7.5 6.4 ADVANCE 7.3 6.5 VADT 8.4 6.9 본시험 Adapted from Bergenstal RM, Bailey C, Kendall DM. Am J Med 2010;123:374e9-e18; UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-65; Holman RR. N Engl J Med 2008;359(15):1577-89; DCCT Research Group. N Engl J Med 1993;329;977-86; Nathan DM et al. N Engl J Med 2005;353:2643-53.; Gerstein HC et al. N Engl J Med 2008;358:2545-59; Patel A et al. N Engl J Med 2008;358:2560-72; Duckworth W et al. N Engl J Med 2009;360:129-39. 장기추적관찰 * In T1DM
성인의혈당목표 DCCT 로부터 ACCORD 까지의교훈 A1C 목표는 7% 이하 미세혈관합병증위험이유의하게감소 단기연구들에서는심혈관질환위험을감소시키지않음 모든원인에의한사망에유의한증가없음 ( 메타 - 분석 ) 환자에따라서는더낮은 A1C 목표가적절할수있음 당뇨병유병기간이짧은환자, 예상수명이긴환자, 동반질환이적은환자 목표혈당도달을안전하게이룰수있는환자 목표 A1C 를덜엄격하게정하는것이적절한경우 : 중증저혈당병력 합병증이진행된오래된당뇨병또는동반질환이많은환자 예상수명이짧은환자 집중치료에도목표달성이어려운환자 Skyler JS. Diabetes Care 2009;32(1):187-92; ADA Standards of Medical Care in Diabetes. Diabetes Care 2011;34(Suppl 1).
혈당조절의평가 Assessment of long-term glycemic control : HbA1c - standard method for assessing long-term control - over the previous 2-3 months - 50% of HbA1c value preceding month - 합병증의발생과밀접한관련성이있다 Short-term glycemic control : Self-monitoring of blood glucose (SMBG) HbA1c, SMBG : complementary
혈당조절의중요성 Assessment of long-term glycemic control Assessment of short-term glycemic control 요약
당화혈색소의측정 High-performance liquid chromatography (HPLC) assay 를이용해서측정. 전체혈색소에대한백분율 (%) 로표시. 금식이필요없고, 최근의생활습관변화와관계없이안정된결과를보임. Hemoglobinopathies, hemolysis, blood loss 등과같이 RBC turnover 에영향을주는요인이있는경우에는측정치에 변화가생긴다. : 환자의임상상황과당화혈색소결과가부합되지않는경우에는 위의상황을고려해야한다.
진단기준으로서의당화혈색소 일중변동이 2% 이하로공복혈당 (6-11%) 이나당부하후 2 시간혈당 (14-17%) 에비해안정적 미국에서 1994 년 National glycohemoglobin standardization program (NGSP) 이발족된후, 2007 년에는미국의 99% 이상에서표준화가 이루어짐 (HPLC 방법 ) 1995 년유럽의 International Federation of Clinical Chemistry Working group (IFCC) 에서당화혈색소의표준화를위한새로운 체계를제시 HbA1c 만을측정하는방법 2007 년 ADA, EASD, IDF, IFCC 가참여하여 IFCC 측정방법을권고, 검사결과는 IFCC 단위 (mmol/mol), NGSP 단위 (%), HbA1c-derived average glucose value 를함께표기하도록함
진단기준으로서의당화혈색소 국제전문가위원회 (International Expert Committee) 는당화혈색소 6.5% 이상이면당뇨병으로진단할수있다고하였고, 2010 년 ADA 가 이를수용하여당뇨병진단기준으로추가 당화혈색소는 NGSP 에의해인증되고 DCCT 방법으로표준화된방법으로측정되어야한다.
Linear regression of A1C at the end of month 3 and calculated AG during the preceding 3 months. Diabetes Care 31:1473-1478, 2008
Correlation of A1c with average glucose 평균혈장혈당 (mg/dl) HbA1c (%) 5 97 (76-120) 6 126 (100-152) 7 154 (123-185) 8 183 (147-217) 9 212 (170-249) 10 240 (193-282) 11 269 (217-314) 12 298 (240-347) ADA 에서는당화혈색소와함께추정평균혈당 (eag) 을함께보고하도록권장 Data in parentheses are 95% Cis. Linear regression eag (mg/dl) = 28.7 X HbA1c 46.7. Diabetes Care 31:1473-1478, 2008
권고안 ( 당뇨병학회진료지침, 2011 ) 당뇨병환자에서혈당조절상태의평가는당화혈색소로한다. 일반적으로당화혈색소는 3 개월마다측정하나환자의상태에 따라의사가결정할수있다. 치료수단의변경시당화혈색소를기준으로사용하여치료의적합성을판단할수있다.
ADA Recommendations (2012) 치료목표를달성한경우에는최소한연 2 회당화혈색소를검사 치료목표를달성하지못한경우거나, 치료방법이변경된경우에는 3 개월마다검사 Diabetes Care 35(suppl 1):S16-18,2012 개별환자의임상상황, 사용중인치료방법, 임상의의 판단등에의해측정간격을결정한다.
Assessment of glycemic control : others 당화혈색소치를신뢰할수없는경우 Fructosamine assay (measuring glycated albumin) 를이용 - over the prior 2 weeks - 포도당에의한단백질의변화를반영 - 측정방법의표준화가안되어있고, - 측정치와합병증과의관계가아직은불분명 1,5-anhydroglucitol (1,5-AG) - 단기간인 24 시간동안의혈당상태를반영
혈당조절의중요성 Assessment of long-term glycemic control Assessment of short-term glycemic control 요약
자가혈당측정 (SMBG)
채혈, 측정검체에따른혈당의차이 동맥혈 > 모세혈관혈 > 정맥혈의순 : 공복시에는비슷, 동맥과정맥의차이 - 10 mg/dl 전후 식후에는 20-50 mg/dl 정도차이가있다. 혈장 (plasma) 이전혈 (whole blood) 보다 12-15% 정도높다. 자가혈당측정 (SMBG) 은모세혈관혈을이용한다. : 주로전혈을이용하여측정하나대부분의자가혈당측정기는 정맥혈장포도당농도로보정하여결과를표시
자가혈당측정 장점 - 검사의편리함 - 결과를바로확인할수있다 임상에서널리이용 개별적인치료에따른반응이나치료목표에도달했는지를알려주는중요한요소 임상영양요법, 운동요법, 약물치료의정도를조절하는지표 the standard of care in diabetes management
혈당측정기사용시주의점 1 년에한번이상검사실에서측정한값과비교하여오차를관리 혈당측정기의국제표준 (www.iso.org) : 4 mmol/l (72 mg/dl) 미만에서 95% 의결과가 15 mg/dl 이내, 그이상에서는 20% 이내로보고되어야한다. 기기간에서로 10% 정도의오차범위를가지고있다. accuracy of SMBG : instrument and user dependent 자가혈당측정의정확성을높이기위해주기적으로정확한사용법에 대한교육을하고, 의료진에의한평가가이루어져야한다. 혈당측정기에대한보험급여 (X) 검사지 (O) : type 1 DM 의경우만
소모품보험급여기준 1) 인슐린투여 2) - c-peptide 0.6 ng/ml 이하 - 경구포도당섭취자극 ( 또는글루카곤주사, 식사후등 ) 후 1.8 ng/ml 이하 - 24시간소변 c-peptide 수치가 30 ug/24hr 미만 - anti-gad antibody 등췌도또는인슐린등에대한자가항체양성인경우
혈당측정기 GlucoDr. Plus+ Accu-Chek Active ONE TOUCH SureStep
혈당측정기의사용 ONE TOUCH SureStep
혈당측정기의사용 ONE TOUCH SureStep
혈당측정기의사용 ONE TOUCH SureStep
혈당측정기의정도관리 ONE TOUCH SureStep HIGH LOW
자가혈당측정의유용성 Type 1 DM (O) : SMBG is a component of effective therapy Insulin-treated type 2 DM (O) Non-insulin treated type 2 DM (?) : Optimal frequency and timing of SMBG is unclear. Evidence on the effectiveness of SMBG is less clear cut.
Murata GH et al. Diabetes Care 2003;26(6):1758-63.
3 개군공개형무작위배정시험 총 453 환자 : 등록시평균 A1C 7.5% SMBG (with or without intervention) vs. no-smbg 일차결과 12 개월후의 A1C BMJ 2007;335(7611):132. Epub 2007 Jun 25.
BMJ 2007;335(7611):132. Epub 2007 Jun 25.
0.25%
Continuous blood glucose monitoring (CGM) Sensor Transmitter Receiver International Diabetes Center
CGM sensor : Measuring glucose in Interstitial Fluid Target Tissue G G G G G G G Time Lag Value Difference G G G Passive Diffusion International Diabetes Center
Current Real-time Continuous Glucose Monitoring (CGM) Technology Sensor and Sensor Delivery Unit Transmitter and Receiver Seven PLUS (DexCom) Commercially available in US and Europe 7-day sensor Calibrated with One Touch Ultra by cable or manual entry with any meter Wireless transmission of data from transmitter to receiver Cable download to PC Data can be blinded to the patient Guardian RT (Medtronic) Commercially available in US, Europe, China 3-day sensor (6 day Europe) Calibrated with any meter by manual entry or wireless with linked meter (UltraLink) Wireless transmission of data from transmitter to receiver Cable with upload to Medtronic website Data cannot be blinded Freestyle Navigator (Abbott) Commercially available in US, and Europe 5-day sensor Calibrated with integrated Freestyle meter Wireless transmission of data from transmitter to receiver Wireless download to PC Data can be blinded to the patient
Glucose monitoring (ADA Guideline, 2012) SMBG should be carried out three or more times daily for patients using multiple insulin injections or insulin pump therapy. (B) For patients using less-frequent insulin injections, noninsulin therapies, or medical nutrition therapy (MNT) alone, SMBG may be useful as a guide to management. (E) To achieve postprandial glucose targets, postprandial SMBG may be appropriate. (E) When prescribing SMBG, ensure that patients receive initial instruction in, and routine follow-up evaluation of, SMBG technique and their ability to use data to adjust therapy. (E) Continuous glucose monitoring (CGM) in conjunction with intensive insulin regimens can be a useful tool to lower A1C in selected adults (age 25 years) with type 1 diabetes. (A)
Glucose monitoring (ADA Guideline, 2012) Although the evidence for A1C-lowering is less strong in children, teens, and younger adults, CGM may be helpful in these groups. Success correlates with adherence to ongoing use of the device. (C) CGM may be a supplemental tool to SMBG in those with hypoglycemia unawareness and/or frequent hypoglycemic episodes. (E)
자가혈당측정 (KDA 진료지침, 2011) 1. 자가혈당측정은제2형당뇨병환자의중요한자가관리수단이므로모든환자에서스스로측정할수있도록교육을실시한다. [A] 2. 자가혈당측정기의측정정확도를유지하기위하여 1년에 1회이상검사실에서측정한혈당치와비교하여오차범위내에서측정되도록자가혈당측정기를관리하는것을권장한다. [E] 3. 자가혈당측정은최소한공복과식후 2시간혈당 ( 식사개시후 2시간째 ) 을포함하여측정하도록권장한다. [E] 4. 자가혈당측정의횟수는환자의혈당조절정도에따라달라지지만, 임상영양치료, 운동요법, 경구혈당강하제치료, 2회이내의인슐린치료를하는제2형당뇨병환자에서매일최소 1회이상의자가혈당측정을권고하며, 다회인슐린치료를필요로하는제1형당뇨병및제2형당뇨병환자에서매일최소 3회이상의자가혈당측정을고려한다. [E]
요약 합병증을예방하고관련질환의이환율과사망률을낮추기위해서엄격한혈당조절은필수적이다. 적절한방법을통해개별환자의혈당조절을모니터링하고평가하는것이필요하다. 당화혈색소와자가혈당측정은상호보완적으로장 단기혈당조절에대한정보를제공해준다. 측정간격과측정횟수는개별환자의임상상황에맞게임상의가판단해야한다.
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