HbA1C

HbA1C

            It is a quantitative and reliable measure of glycemic control over an extended time period. Measurement of glycated proteins (primarily hemoglobin and serum protein) can, with a single measurement, quantify average glycemia over weeks and months.

            Glycated hemoglobin, especially A1c is a term used to describe and series of stable minor hemoglobin components formed slowly and nonenzymatically from hemoglobin and glucose. When plasma glucose is consistently elevated, there is an increase in nonenzymetic glycation of hemoglobin; this alteration reflects the glycemic history over the previous 2-3 months because erythrocytes have an average lifespan of 120 days. The rate of formation of A1c is directly proportional to the ambient glucose concentration and the A1c test has become the preferred standard for assessing glycemic control. This test has been shown to predict the risk for the development of many chronic complications in diabetes.

            Optimal use of the A1c test for assessing glycemia required for standardization of A1c test assay. Manufacture of A1c test assay methods are awarded a “certificate of traceability to the DCCT reference method” if their assay method passes rigorous testing criteria for precision and accuracy. The ADA recommends that laboratories use only A1c test assay methods that have passed certification testing. The reference factor is only used to standardize the A1c assay and cannot be used by the clinical laboratory for measuring A1c values.

            A1c testing should be performed routinely in all patients with diabetes, I to document the degree of glycemic control at initial assessment and then as part of continuing care. Because the A1c test reflects mean glycemia over the preceding 2-3 months, measurement approximately every 3 months is required to determine whether a patients metabolic control has reached and been maintained with in the target range.

            For any individual patient the frequency of A1c testing should be dependent on the treatment regimen used and on the judgment of the clinician.

            It is recommended that A1c testing be done at least twice a year in patients who are meeting treatment goals (and who have stable glycemic control) and more frequently (i.e. quarterly) in patients whose therapy has changed, and those who are not meeting glycemic goals and in those who are newly diagnosed with diabetes. Proper interpretation of A1c test results requires to understand the relationship between test results and average blood glucose, kinetics of the A1c test and specific assay limitations. Depending on the assay methodology, hemoglobinopatheis, anemias and uremia may interfere with the A1c results.

            A1c test values range from normal in a small percentage of patients whose average blood glucose levels are in or close to the normal range to markedly elevated values (eg. >9.5%) in some patients, reflecting an extreme degree of hyperglycemia. The ADA recommends the goal of therapy for most patients should be an A1c <7% and the physicians should reevaluate and in most cases, significantly change the treatment regimen in patients with A1c test results consistently above this goal.

Role of A1c in Diagnosing Diabetes

            Use of A1c values for screening and identification of IGT and diabetes. There are significant problems with using A1c as a diagnostic tool, much as false positive and false negative results related to hemoglobinpathy and altered red cell survival and the imperfect correlation between A1c and 2 hr plasma glucose, the traditional gold standard test. Its use is not recommended for screening purpose. The diagnosis of diabetes is considered cut points to diagnose diabetes with the new globally standardized A1c test. The target for glycemic control (as reflected by A1c) must be individualized and the goals of therapy considered after a number of medical, social and life style issues, including the patients age, ability to understand and implement a complex treatment regime, presence and severity of diabetes complications. Ability to recognize hypoglycemic symptoms, presence of other medical conditions or treatment that might alter the response to therapy, occupation and level of support from family and friends.

            The ADA established suggested glycemic goals based on premise that glycemic control predicts development of diabetes related complication. For more patients, the target A1c should be <7% but the goals should be individualized based on age, comorbidity and history of hypoglycemia.

Glycemic Targets

	Normal	Diabetes
Pre meal Plasma Glucose	<100	<130
Post prandial plasma glucose	<140	<180
A1c	4-6%	<7%

Rationale for the use of HbA1c to Diagnose DM

            If chronic hyperglycemia is implicated in causation of diabetes specific complication, then HbA1c can measure long term glycemic exposure should provide a better marker for presence and severity of disease than single measure of glucose concentration.  There is a strong correlation between HbA1c and retinopathy HbA1c is related more intimately to risk of complications than single or episodic measure of glucose levels, may reveal as a better biochemical marker of diabetes and should be considered as a diagnostic tool.

            HbA1c cut point for diagnosis. Retinopathy increased at HbA1c values starting between 6-7%. Substantial increase in prevalence of moderate retinopathy at HbA1c levels >6.5% supports the threshold level of glycemia that results in retinopathy most characteristic of DM.

            Falsely increase in HbA1c: increase renal threshold, uremia, chronic alcoholism, lead poisoning, hypertriglyceridemia, iron deficiency, post splenectomy, hyperblirubinemia, and opiate poisoning and G6 PD deficiency.

            False decrease in HbA1c: decrease threshold, blood loss, hemolytic anemia and vitamin C and vitamin E deficiency

Limitation of HbA1c as means of diagnosing diabetes

1. Cost
2. Patients condition that preclude HbA1c testing

Hb traits – Hbs, Hbc, HbF, HbE

3. Conditions that change RBC turnover
1. Hemolytic anemia
2. Chronic malaria
3. Major blood loss
4. Blood transfusion
4. HbA1c levels appears to increase with age
5. Racial variability might be present
6. HbA1c doesnot provide information about glycemic variability
7. HbA1c do not differentiate among fasting, preprandial and post prandial glycemia.

HbA1c Recommendations

For diagnosis of diabetes

1. The HbA1c assay is an accurate, precise measure of chronic glycemic levels and correlates well with the risk of diabetic complications.
2. HbA1c assay has several advantages over laboratory measures of glucose.
3. Diabetes should be diagnosed with HbA1c >6.5% diagnosis should be confirmed with a repeat HbA1c test confirmation is not required in symptomatic subjects with plasma glucose >200mg/dl
4. If HbA1c testing is not possible previously recommended diagnostic methods are acceptable.,
5. HbA1c testing is indicated in children in whom diabetes is suspected, but the classic symptoms and causal plasma glucose >200mg/dl are not found.

For identification of those at high risk for diabetes

1. As for diagnosis of diabetes the HbA1c assay has several advantages over laboratory measures of glucose in identifying individuals at high risk for developing diabetes.
2.  Those with HbA1c levels below the threshold for diabetes, but >6% should receive demonstrably effective preventive intervention.

Note:

            HbA1c should be measured between two and four times a year for assessing overall long term glucose control A1c testing should be performed routinely in all patients with diabetes, I to document the degree of glycemic control at initial assessment, then as part of continuing care. Since the A1c test reflects a mean glycemia over the preceding 2 – 3 months measurement ~ every 3 months is required to determine whether a patients metabolic control has reached and been maintained within the target range.

REFERENCE:

            Therapy for DM and Related Disorders, ADA