9 HbA1c in Intensive vs Conventional Treatment (DCCT study) 11n: 1441A1C%10Mean glucose : 23155 mg/dL9.09Quantitative HbA1c (%)87.0715530 mg/dL651234567891984Study Time in Years
10 Results of DCCT Report (DCCT Report in NEJM 329:977-86, 1993) Retinopathy 發生率減少 76%Nephropathy發生率減少 56%Neuropathy 發生率減少 60%PS. Type I and Type II DM 有相同結果。
11 DCCT HbA1c levels and the risk of complications in type 1 diabetes Improved glycemic control following intensive diabetes therapy delayed the onset and slowed the progression of diabetic retinopathy, nephropathy and neuropathy in patients with type 1 diabetes. :DCCT. Diabetes 1995;44:968–83.
13 ADA recommendations for Diabetes care quality (2005) Perform the A1C test at least 2 times per year in stable patients.Achieve A1C < 7.0% as goal of glycemic control.Lower A1C is associated with lower risk of cardiovascular diseases.A1C < 6.0% can be considered in individual patients.
18 NIH Guidelines for A1C Test 1.Specific measurement of HbA1c.2.Narrow non-diabetic range (4.0%-6.0%).3.Highly precise measurement (<2% CV)4.Removal of interferences.5.Hemoglobin variant detected when present.6.NGSP certified method and calibrator.7.Within ± 0.5% HbA1c bias from the referencevalue.
21 Correlation of eAG With HbA1c AG (mg/dl) = 28.7 x HbA1c – 46.7R2 = 0.84P <eAG (mg/dl)The overall results of the ADAG study are shown here. There was a highly significant correlation between average glucose and A1C. The regression equation is shown here. The R-squared was 0.84, meaning that 84% of the variance in one measure is explained by the variance of the other, with the R or correlation coefficient being 0.91.HbA1c (%)Diabetes Care 2008;31:1-6ADAG:A1C derived average glucoseeAG : Estimated Average Glucose
22 How does HbA1c relate to (eAG)? 1. eAg is a mean value of 7-8 points blood glucosedetermination in 24 hrs.2. The relationship between eAG and HbA1c was:eAG(mg/dl)= (28.7*HbA1c)-46.7, r2=0.843. Only post-lunch and bedtime single glucose valueshowed relationships to HbA1c4. Single fasting glucose value was underestimatedthe level of HbA1c
23 ADAG Study: “Translation” of HbA1c into eAG Blood glucoseHbA1c (%) (mg/dl) (mmol/l)We can use the ADAG results to “translate” A1C into average glucose, with values shown here.Diabetes Care 2008;31:1-6
24 Consensus Statement IFCC, EASD, IDF, ADA ,Sept 2007) HbA1c assay to be standardized worldwide using the new IFCC standard and expressed as:% as currently used (DCCT values)mmol HbA1c/mol HbA (IFCC units )eAG in mmol/l or mg/dLThis paved the way for reporting both HbA1c and eAG on lab reportsThere is a complicated “back-story” to all this that involves the potential a few years ago that the DCCT-standardized A1C as we know it might have gone away. This actually did not come to pass, in part because ADA and other international diabetes groups forged an agreement with the International Federation of Clinical Chemists in 2007 to:Standardized HbA1c assays worldwide using a new IFCC standard and expressed as:% as currently used (DCCT values)IFCC units in mmol HBA1c/mol HbAeAG in mmol/l or mg/dL (if ADAG study meets its data acceptability goals…which it did)This paved the way for reporting both HbA1c (in %) and eAG (in mg/dl or mmol/l, depending on country) on lab reportsDiabetes Care and Diabetologia, 2007
29 ADA recommendations for Diabetes care quality (2005) Perform the A1C test at least 2 times per year in stable patients.Achieve A1C < 7.0% as goal of glycemic control.Lower A1C is associated with lower risk of cardiovascular diseases.A1C < 6.0% can be considered in individual patients.
33 ADA recommendation: Real-time results. Better outcomes. Use A1C point-of-care testing for timely decisions on therapy changes .Feedback from A1C number real time may result in a 1% reduction in their A1C.
34 測定糖化血紅素的方法 陽離子交換層析法(Cation exchange HPLC) 親和力層析法(Boronate affinity HPLC)免疫比濁法(Immuno-turbidity assay)直接酵素法 (Direct enzymatic method)毛細管電泳法(Capillary electrophoresis)Interference by Hb variants was method dependent
51 (International Federation of Clinical Chemistry) IFCC Standardization(International Federation of Clinical Chemistry)The IFCC WG was formed in 1994 with its aim to establish a Global Reference System for HbA1c.Specific aims were:(a) To define the heterogenous HbA1C(b) To prepare pure HbA0 and HbA1C(c) To develop a Reference Method(d) To establish a Reference Laboratory Network(e) To prepare secondary reference calibratorsand controls
52 Difference between IFCC and NGSP(2001) NGSP %HbA1cIFCC %HbA1cDifference %HbA1c42.11.953.21.864.31.775.41.686.497.51.5108.61.4119.71.31210.7
53 The relationship between the IFCC and NGSP 2004
54 The IFCC Reference System Definition of the analyte: glycated and non- glycated N-terminal peptides of the beta-chainPrimary Reference Material:mixtures of pure HbA1c and pure HbA0Reference Method: HPLC and thenMass spectrometry / Capillary electrophoresisTraceability :calibrators and/or control materials must be "traceable" to the IFCC Reference Method
55 HbA1c reporting的共識宣告 The IFCC results are accuracy-based NGSP results can be directly related to diabetes care goals.Although the IFCC/NGSP correlation is excellent, the absolute numbers are different.The IFCC number scale can not be related to clinical outcomes without conversion to DCCT (NGSP) -aligned numbers.HbA1c result can be expressed in IFCC units, derived NGSP units, and eAG.
62 HbA1c in G-6P.D deficiency blood HbA1c(%) G-6P.D IU/gmHb SexM.M.M.M.F.F.F.F.Normal range:4.0～5.7%HbA1c in G-6P.D deficiency blood
63 Distribution of HbA1c in G-6PD def. group Group n Mean Min Max.NormalG-6PD def
64 QA Activity in HbA1c test in Taiwan 1.使用NGSP/IFCC認證過的檢測方法2.Tracible to DCCT /IFCC value 的校正3. CV< 3% and Bias < 0.5 A1C%4. 鑑別變異型Hb/G-6-P.D.等干擾因素
65 Conclusion 1. Reference range of HbA1c is 4.0 ~6.0 % 2.HbA1c 6.5% is a New Diagnostic Criteria forDiabetes3.Achieve A1C < 7.0% or < 6.5% as goal of goodglycemic control.4.“Translation” of HbA1c into eAG in laboratoryreport.5.Real time report of HbA1c have good outcome6.Traceability to NGSP unit(%) in Taiwan