| A1c (glycohemoglobin)… |
| A1c provides an accurate and reliable method to routinely assess the relative level of diabetes control, level of mean blood glucose (MBG), effectiveness of treatment, and risk for development of possible acute and/or long-term chronic complications typically associated with sub-optimal diabetes control. Routine monitoring of A1c can improve patient compliance when used as part of a comprehensive treatment plan. A1c is an important test for individuals with all types of diabetes or those at risk for developing diabetes. |
| Lowering A1c levels helps prevent, and/or reduce complications… |
| The Diabetes Control & Complications Trials (DCCT) demonstrated that lowering A1c levels helps prevent, and/or reduce diabetes complications. A1c has been determined to be an important test for all individuals with all forms of diabetes, or those suspected of having diabetes. A1c directly relates the average glucose concentration (mean blood glucose) in the body over the life span of the circulating red blood cell (RBC)1. The A1c test (when performed using an analytical method with CV's under 2.0%) is considered a very reliable indicator of the level of individual diabetes control during the past 90 days and can serve as an excellent indicator of the potential risk for developing possible long-term complications typically associated with diabetes mellitus. In addition, the A1c can be useful in identifying un-diagnosed cases of diabetes mellitus (DM) and/or impaired glucose tolerance (IGT). |
| * A1c can be monitored and may reflect meaningful glycemic changes during a 30 day period. A1c can be monitored and may reflect meaningful average glucose changes during a 30 day period. 30 day testing frequency may be appropriate during changes in therapy, infrequent BG monitoring or as indicated by your physician. While the A1c reaction is not considered reversible, the measured concentration of glucose bound to hemoglobin within the RBC may change relative to age and volume of the Red Blood Cells (erythrocytes). Kinetics (half-life) of the glycated protein (A1c) and erythrocyte (RBC) should be considered when determining monitoring frequency. The half-life of A1c is approximately +/- 34 days. The half-life of the circulating RBC is approximately 60 days. |
| How A1c Works… |
| A1c formation is proportional to the amount of available glucose. The attachment of the glucose and hemoglobin molecule is relatively irreversible, and it remains attached on the surface of the Red Blood Cell (RBC) for the life span of the RBC (G + Hb = glycated hemoglobin )2. |
| Why A1c is Clinically Important… |
| The clinical significance of A1c is well documented in such landmark diabetes clinical studies as the Diabetes Control & Complications Trial (DCCT), where a direct relationship of lowering A1c and mean blood glucose levels was linked to the prevention of chronic complications such as kidney, eye and nerve damage3. The DCCT demonstrated that individuals who maintained their A1c levels at or about the upper limit of normal reduced, delayed or prevented complications by as much as 76% for retinopathy (eye disease), 60% for neuropathy (nerve disease) and 35% for nephropathy (kidney disease) while reducing their risk for proteinuria by as much as 65%. |
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| Stylized Relative Risk For Developing Diabetes Complications4 |
| A1c provides a viable solution to meet the new NCQA/DQIP/and HEDIS 3.0 testing measures… |
| A recent quality care study in a large HMO documented that A1c levels were not documented in more than 56% of members 5. Current National Institutes of Health (NIH) estimates that less than 25% of individuals with diabetes have routine A1c tests performed. Medicare has recently established outcomes measurement requirements for beneficiaries with diabetes that include hemoglobin A1c testing for the purpose of evaluating improvement in their health care status6. (The American Diabetes Association (ADA) recommends monitoring A1c at least four times per year)7. |
| The DCCT Core Message and Type 1 Diabetes… |
| The core message of the DCCT was simple; "Control Matters". The standard of measurement for determining diabetes control was hemoglobin A1c measured by High Performance Liquid Chromatography (HPLC)8. |
| The Kumamoto Study and Type 2 Diabetes… |
| Other important studies that was conducted, about the time of the DCCT, was the Kumamoto and UK Prospective Studies which, concluded that "intensive control" in non-insulin dependent diabetes mellitus (Type 2) also matters in reducing and/or preventing complications typically associated with Type 2 diabetes9. |
| A1c and Mean Blood Glucose (MBG)… |
| The AccuBase A1c™ test results are measured by HPLC-Boronate Affinity which allow the determination of a calculated Mean Blood Glucose reported in mg/dl. This calculation is only possible using the HPLC analytical method and is based on the DCCT 7 point MBG equation. ( % A1c X 31.7 – 66.1 ) = MBG mg/dl. |
| The rate of glycation of all other hemoglobin's tests are different and can not be used to calculate mean blood glucose. Mean blood glucose values provide the patient and health care team with an important diabetes management tool. This statistically proven conversion method relates the patient’s most recent percent A1c level directly to their average glucose for the same reporting period. This value provides the patient with a measure that they can relate to in their self-management efforts. |
| Detection of hemoglobinopathies is important… |
| The AccuBase A1c™ Test Kit is the only at- home test kit that can detect, separate and identify hemoglobinopathies (variant hemoglobin's). To-date, over 400 structural variants have been described11. Many of these have clinical implications and represent significant clinical effects that include: Hemolytic Anemia, Cyanosis, Erythrocytosis and other abnormalities. |
| HPLC Analytical Reference (Gold Standard) Method… |
| The AccuBase A1c™ Test Kit uses the analytical reference method (HPLC) to measure A1c. The HPLC method was used in the DCCT to analyze over 75,000 samples during the 8 year landmark diabetes study. To-date over 1 million human A1c samples have been analyzed using this method. The College of American Pathologists (CAP) also use this method in their CAP Survey (accuracy-based glycohemoglobin survey)12. |
Features of the AccuBase A1c test Kit |
| 1. Narrow non-diabetic range (4.3% – 5.5%) 70 = 108 mg/dl |
| 2. Highly precise measurement (< 2% CV’s) 1.68 at 6.1 % and .68 at 9.5% |
| 3. Interference free method |
| 4. 30 day stability of sample after collection |
| Important Technical Features of the AccuBase A1c™
Analytical Method Include… |
No Refrigeration of test kits required |
| No drying time or pre-treatment or sample elution required – reduces technical errors |
| No false elevation – by carbamylation (uremia) or acetylated products of lysine |
| Excellent correlation of capillary method to traditional veni-puncture – (.989) |
| Sample stability (up to 30 days unrefrigerated) – allows remote collection |
| Meets diabetes screening sensitivity requirement of < 2.0% CV’s – highly precise |
| 2-year shelf life 30 day sample stability after sample collection |
| The HPLC Method Provides: |
| - Patient chromatogram print out (allowing visualization of total area peaks) |
| - Detects sample degradation (displaying abnormal or displaced peaks) |
| - Detects variant hemoglobin's |
| - Identifies out of range samples: < 3M or > 5M RBC’s (Important in anemia and other RBC abnormalities) |
A1c Assessment & Interpretation… |
| Interpretation of A1c is valuable in several different areas of overall diabetes management, and IGT and diabetes screening. |
| ° A reliable at-risk marker for assessing the possible development of complications. |
| ° An excellent means to assess, encourage and
reinforce individual patient compliance. ° An indicator for additional diagnostic tests such as microalbumin to be performed. ° A meaningful mean blood glucose (MBG) relationship. ° An useful method to judge the efficacy and effectiveness of intervention strategies. |
| Risk levels for developing possible diabetes complications associated with A1c levels: |
| Below normal levels:
levels <4.3 % (70 mg/dl) indicate an serious risk for acute hypoglycemia (low blood
sugar levels). High risk level for acute hypoglycemia. |
| Normal HPLC-BA non-diabetic
range: 4.3 – 5.5 % (70 – 108 mg/dl) While the normal range of a non-diabetic individual is in this range, individuals with diabetes should use extreme caution when maintaining A1c levels below 5.0% as this may represent a significant opportunity for hypoglycemia (especially in individuals that present with hypoglycemia unawareness). |
| Above normal levels: >5.6
% mg/dl (>109 mg/dl) The DCCT and other diabetes studies have concluded that there is an direct association with the risk for the possible development of complications with increasing levels of A1c. |
| Normal human glucose levels: 4.3 - 5.5 % (70 - 108 mg/dl) |
| Note: any elevation in mean blood glucose concentration above 5.5% (108 mg/dl) should be explained by a physician. |
| A1c level of 5.6 - 5.9%: The individual level of mean blood glucose has exceeded the normal upper limit of the assay range, indicating an abnormality in the expected normal human range. While this level is not recognized by the ADA as diagnostic of diabetes, it does signal a level that may be indicative of impaired glucose tolerance (IGT) and/or pre-diabetes. Anyone with an A1c in this range should seek medical attention to determine the cause of the elevation in mean blood glucose. This is an important early warning sign that could prevent an individual from becoming diabetic if caught early. Often, diet and/or exercise may reverse and/or reduce the A1c level back to within normal range. |
| An A1c Level of 6.0% (126 mg/dl) or greater: |
| An A1c level of 6.0% or greater represents a high risk for diabetes mellitus. It is recommended that the individual seek immediate medial attention to discuss the cause of the elevated glucose level. There are confounding factors that can cause elevation in blood glucose levels including use of steroids and other factors. Never-the-less, every effort should be taken to intervene in the progression of increased levels of A1c. The discussion should include a comprehensive personal history, diagnostic laboratory tests and physical examination. |
| Results Interpretation: Interpretation of Individual test results and setting of individual A1c goals should be jointly discussed between the physician and patient at routine office visits. The presence of hypoglycemia unawareness should be a serious consideration when setting individual A1c goals. A long-term history and graphic representation of current and past results will be retained by the testing laboratory database and will be printed along with the most recent HbA1c results. |
| Recommended ordering frequency of Hemoglobin A1c: According to the American Diabetes Association and the American Association of Clinical Endocrinologists, A1c should be routinely monitored in individuals with diabetes mellitus at least every 90 days. Ordering frequency of A1c may depend on the type of diabetes and intensity of treatment, (a decision made by the physician). The kinetic half-life of A1c is 30 days +/- 4. Given this sensitivity. A1c can be monitored every 30 days in cases where rapid changes in therapy may be implemented. |
| A1c testing should not replace or be a substitute for daily blood glucose monitoring or routine visits to the physician and/or diabetes health care team. Testing should not replace or be a substitute for daily blood glucose monitoring or routine visits to the physician and/or diabetes health care team. The AccuBase A1c Test Kit is designed to provide the physician and patient with an accurate and convenient method for the assessment of the average glucose concentration (mean blood glucose) in the body during the past 90 days. |
| Other important diagnostic tests, examinations and evaluations include: an annual dilated retinal examination, microalbumin (or 24 hour urine collection), monitoring for ketones, foot examination, thyroid evaluation, and other tests as recommended by your physician, the American Diabetes Association and/or your health care plan provider. |
| References: 1. C.M. Peterson and L. Jovanovic: A Primer for Glycosylated Hemoglobins, Helena Laboratories Q-4 DOI:2/84. 2,11. W. Tietz, Ph.D., W.B: Fundamentals of Clinical Chemistry; Edited by Norbert. Saunders Company: ISBN 0-7216-8866-7; pages: 401-421. 3. The DCCT Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications of insulin-dependent diabetes mellitus. N Engl J Med. 329: 977-86, 1993. 4. Document on file DTI: Jay Skyler, MD: University of Miami School of Medicine, Richard Eastman, MD., NIH (NIDDK), selected paper: Stylized report (DCCT follow-up): Spring, 1996. 5. . Anne L. Peters, M.D., Antonio P. Legorreta, M.D., MPH, R. Clifford Ossorio, M.D., Mayer B. Davidson, M.D.: Quality of Outpatient Care Provided to Diabetic Patients: A health maintenance organization experience: Diabetes Care, Vol 19, Number 6, June 1996. 6. Enhancement of Diabetes Policy in the Balanced Budget Act of 1997; HR Bill 15 & 58, Sec. 4105, C3, The Bureau of National Affairs, Inc., Washington, D.C. 20037: Special Supplement, p 116 of 528, American Diabetes Association 1997. 7. American Diabetes Association: Position Statement: Standards of care for patients with diabetes mellitus. Diabetes Care 1996. 8. Julio V. Santiago; Perspectives in Diabetes: Lessons from the Diabetes Control and Complications Trial. DIABETES, Vol 42, November 1993 P-1549-1554. 9. Y. Ohkubo Kumamoto, H. Araki,: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with NIDDM a randomized prospective 6-year study: Diabetes Research and Clinical Practice 1995: 28:103-117. 10. David M. Nathan, M.D., Daniel E. Singer, M.D., Katherine Hurxthal, R.N., John D. Goodson, M.D.: The Clinical Information Value Of The Glycosylated Hemoglobin Assay: The New England Journal Of Medicine Fef 1990. 12. Summing Up: CAP Today (Summer 1995), Richard A. Savage, MD, editor, Special Section: CAP Surveys Program (Glycosylated hemoglobin). 13. Randle R. Little, David E. Goldstein: Endocrine (Standardization of Glycohemoglobin Measurement), Analytical Chemistry, Vol. 57, No. 12, June 15, 1995: 393-396. 14. NIH Recommended Guidelines For Glycosylated Hemoglobin Testing: The New England Journal of Medicine, Vol. 323, No. 15, October 11, 1990: 1012-1025. 14. (Supp 1): S8-15, 1996. |
| References:
\ 1. American Diabetes Association, Standards of Medical Care for Patients With Diabetes Mellitus. Diabetes Care. 1998;21(supply 1):S23-S31 2. Goldstein DE. How Much Do You Know About Glycated Hemoglobin Testing? Clinical Diabetes. July/August 1995, p. 62. 3. The DCCT Research Group. The Effects Of Intensive Treatment Of Diabetes on The Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. N. Engl J Med. 1993;329:977-986.
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Product Summary
| To initiate the AccuBase A1c kit in your diabetes management program simply call DTI at: 1-888-872-2443 |
[ 16 ] W. Tietz, Ph.D., W.B: Fundamentals of Clinical Chemistry; Edited by Norbert. Saunders Company: ISBN 0-7216-8866-7; pages: 401-421
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