Hemoglobin A1c: Glycated Hemoglobin (GHb)

Indicated at the time of initial diagnosis of DM, then:

--3-month interval testing in type I DM. --6-month interval testing in type II DM in pt's meeting treatment goals & having stable glycemic control. (Testing may be needed more frequently as required for glycemic control.) --Unstable or highly intensively managed pt's (eg, pregnant type I diabetic women) may be tested more frequently than every 3 months.

What is the formula for calculating the estimated average glucose (eAG)?

(28.7 x A1c) - 46.7 = eAG mg/dl

Contraindications for A1c measurement:

--Conditions with abnormal red cell turnover, such as anemias from hemolysis & iron deficiency. --Presence of hemoglobinopathy with normal red cell turnover (eg, sickle cell trait) requires a specialized A1c assay without interference from abnormal hemoglobins. --Pt's with > 10% Hb F will have lower than expected A1c results.

Use for the diagnosis of DM with A1c > or = 6.5%:

--Does not require fasting prior to test. --Does not require multiple blood draws or a prolonged time commitment. --Detects poor glycemic control in pt's who only check fasting or random glucose readings. --Detects more pt's with DM, at an earlier point in the disease. --Should be confirmed with repeat A1c testing.

Causes of misleading increases in A1c:

--High Hct. --Corticosteroid treatment. --Recent blood transfusion (blood preservative solutions contain high glucose levels). --Late pregnancy.

Laboratory/Diagnostic Pears:

--Point of care A1c assays are not sufficiently accurate at this time to use for diagnostic purposes (although generally adequate for follow up testing). --Formula for calculating the estimated average glucose (eAG): (28.7-A1c) - 46.7= eAG --A discrepancy between glucose readings & the A1c may indicate an undiagnosed underlying medical condition such as hemolobinopathy or erratic glycemic control. It is important to monitor glucose levels as well.

Overview:

--Since RBC's survive an average of 120 days, the measurement of GHb provides an index of a person's average blood glucose concentration (glycemia) during the preceding 2-3 months. --Normally, only 4-6% of Hgb is bound to glucose, while increased glycohemoglobin levels are seen in diabetes and other hypolycemic states. --In an attempt to standardize the clinical measurements, most assays now in use clinically measure A1c, or are calibrated to produce a result equivalent to such a measurement.

What is the diagnostic role of the A1c in the management of DM:

--The ADA position statement on the "Standards of Medical Care in Diabetes-2010" recommends that for all pt's with DM that the target A1c be no higher than 7%. --This level of control has been shown to reduce microvascular (retinopathy & nephropathy) & neuropathic complications of Type I & Type II DM. --The ADA additionally suggests that the general goal of A1c below or around 7% in the years soon after the diagnosis of DM is advisable to reduce the long-term macrovascular (cardiovascular) complications.

Causes of misleading decreases in A1c:

--chronic blood loss. --hemolytic anemias. --conditions that shorten red cell survival (eg, Hb SS, Hb CC, or Hb SC). --Renal failure (due to erythropoietin deficiency & consequent anemia). --Hb F > 10% of total Hb (typically found in children < or = 2, but may also be present in some adults). --Malnutrition & nutritional deficiencies (eg, folate, vitamin B12, vitamin B6). --Bone marrow failure.

What are some causes for the lab to reject the specimen?

--clotted specimen --unlabeled specimen --total Hgb < 7 g/dL or > 24 g/dL.

Essentials for the optimal treatment of DM:

--gauges the effectiveness of treatment over the preceding 2-3 months. --recommended ADA target for most diabetics is A1c < or = 7% to reduce microvascular and neuropathic complications of type I & type II diabetes (eg, neuropathy, nephropathy, & retinopathy).

ADA criteria to diagnose diabetes:

1. A1c > or = 6.5%. 2. Fasting blood glucose > or = 126 mg/dL; fasting is defined as no caloric intake for @ least 8 hours. 3. Secondary plasma glucose > or = 200 mg/dL after a 75 g oral glucose tolerance test. 4. A random (nonfasting) blood glucose level > or = 200 mg/dL when accompanied by classic signs of hyperglycemia (eg, polyuria, polydipsia, polyphagia, changes in vision).

Normal Values/findings of A1c:

A1c by age: < 6 y: 7.5-8.5% 6-12 y: <8% 13-19 y: < 7.5% >19 y: < 5.7%

Interpretative information:

A1c in adults > 19 years of age: < 5.7%= normal (absence of diabetes) 5.7-6.4%= increased risk of diabetes ("prediabetes") > or = 6.5% = diabetes

What is the A1c criteria to diagnose diabetes?

As of January 2010, the ADA recognizes an A1c > or = 6.5% as a criteria to diagnose DM.

What is glycated hemoglobin (GHb)?

Glycated hemoglobin (GHb), also called glycohemoglobins, are substances formed when glucose binds to hemoglobin, and occur in amounts proportional to the concentration of serum glucose.

Methodology:

High performance liquid chromatography (HPLC)/ boronate affinity The ADA recommends that laboratories only use a method that is National Glycohemoglobin Standardization Program (NGSP) certified & standardized to the Diabetes Control & Complications Trial (DCCT) assay.

Pt preparation/Specimen/collection:

Routine venipuncture; blood; fasting is not required.

What is the importance of Hgb A1c?

The measurement of A1c is important due to evidence showing tight glycemic control results in reduced incidence of neuropathy, and other long-term complications of DM.

What does the term "hemoglobin A1c" mean?

The term "hemoglobin A1c" is derived from the order of elution of glycated hemoglobin (GHb) when it is separated out by chromatographic techniques.