Lab Interpretation: High glycated hemoglobin (A1C) in nonpregnant adults

ALGORITHM — 

The evaluation of a high glycated hemoglobin (A1C) (calculator 1) depends on whether the A1C was measured as a screening test for type 2 diabetes or as part of the management of a patient with known diabetes (algorithm 1).

SCREENING FOR TYPE 2 DIABETES — 

Either A1C or fasting plasma glucose (FPG) are used to screen asymptomatic adults for type 2 diabetes (table 1). Although oral glucose tolerance testing remains a valid means of screening and diagnosis, it is now rarely used outside of pregnancy. A1C should be performed using methods certified by the National Glycohemoglobin Standardization Program (NGSP) and traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. A1C has several advantages, including increased patient convenience (since no special preparation or timing is required), and A1C levels are strongly linked to risk for retinopathy and other diabetes-specific complications. However, A1C is modestly more expensive than glucose and should be used with caution in some settings (eg, abnormal red cell turnover, abnormal hemoglobins, advanced chronic kidney disease treated with erythropoietin). The NGSP website contains current information about substances that interfere with A1C test results for specific assay methods. In these settings, diagnostic criteria using glucose testing (FPG, oral glucose tolerance testing) should be used to screen for diabetes (table 2). (See "Measurements of chronic glycemia in diabetes mellitus", section on 'Unexpected or discordant values'.)

A1C 5.7 to 6.4 percent — Individuals with A1C 5.7 to 6.4 percent (39 to 46 mmol/mol) are at high risk for developing diabetes, often termed prediabetes (table 3):

●Repeat A1C (or FPG) to confirm the presence of abnormal glucose metabolism. The confirmation should be performed as soon after the first test as possible.

●Refer patients to intensive lifestyle behavior change program (dietary changes and increased activity levels) aimed at weight loss. Metformin treatment may be indicated in some patients.

●Repeat A1C in one year.

(See "Prevention of type 2 diabetes mellitus", section on 'Our approach' and "Screening for type 2 diabetes mellitus and prediabetes".)

A1C ≥6.5 percent — Individuals with A1C ≥6.5 percent (48 mmol/mol) are likely to have diabetes (table 2). If two different tests (ie, FPG and A1C) are concordant for the diagnosis of diabetes, additional testing is not needed. Otherwise, repeat the A1C (or measure FPG) on a subsequent day to confirm the diagnosis of diabetes. The diagnosis of diabetes is confirmed if both the A1C and FPG are above their diagnostic thresholds, if two consecutive A1C levels are ≥6.5 percent, or if two consecutive FPG levels are ≥126 mg/dL (7.0 mmol/L).

If A1C and FPG are discordant, the test that is indicative of diabetes should be repeated to confirm the diagnosis. Additional testing may be warranted to understand the possible reason for discordance. Common reasons for discordance include those conditions that can interfere with either test results. For glucose, the conditions that can falsely lower levels include delayed or improper sample handling (samples should be collected in tubes that inhibit glycolysis and should not be left at room temperature prior to assay). Conditions that can transiently increase glucose levels include inadequate duration of fasting, recent illness or physical activity, acute stress, and certain medications. For A1C, factors that can influence test results include conditions that alter hemoglobin or red blood cell lifespan or some hemoglobin variants. (See "Measurements of chronic glycemia in diabetes mellitus", section on 'Unexpected or discordant values'.)

Evaluate for diabetes-related complications (table 4), cardiovascular risk factors, and, when indicated, for comorbid conditions (eg, sleep apnea, nonalcoholic fatty liver disease, depression). If not measured in the past one year, obtain:

●Fasting lipid profile

●Liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase)

●Serum creatinine (with estimation of glomerular filtration rate [eGFR])

●Urine albumin-to-creatinine ratio (spot urine)

Perform an annual assessment of risk factors for microvascular and cardiovascular disease (blood pressure, lipid profile, smoking history) to identify patients who might benefit from more intensive cardiovascular risk factor management. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Evaluation'.)

Additional evaluation and management of patients with newly diagnosed diabetes is discussed separately. (See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults", section on 'Evaluation' and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus".)

PATIENTS WITH DIABETES — 

Measurement of A1C is used to guide the management of glycemia in patients with diabetes (table 5). A1C reflects mean blood glucose over the lifespan of the red blood cell (approximately 90 to 120 days) and correlates best with mean blood glucose over the previous 8 to 12 weeks. (See "Measurements of chronic glycemia in diabetes mellitus", section on 'Glycated hemoglobin (A1C)'.)

Target A1C levels should be tailored to the individual, balancing the demonstrated reduction in risk of microvascular (and, in type 1 diabetes, macrovascular) complications with the increased risk of hypoglycemia. A reasonable goal is an A1C value <7 percent (53 mmol/mol) for most nonpregnant patients. Glycemic targets can be set higher (eg, <8 percent [63.9 mmol/mol]) for older adult patients with substantial comorbidities, a limited life expectancy, little likelihood of benefit from intensive therapy, or at high risk for adverse treatment outcomes, especially hypoglycemia. More stringent control (eg, A1C <6 percent [42.1 mmol/mol]) may be indicated for individual patients with type 1 diabetes and during pregnancy.

Obtain:

●A1C at least twice yearly in patients meeting their glycemic goals

●A1C every three months in patients whose therapy has changed or who are not meeting their glycemic goals

Patients with diabetes require ongoing surveillance for diabetes-related complications (table 4) and comorbid conditions (eg, sleep apnea, nonalcoholic fatty liver disease, depression). (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Diabetes-related complications'.)

REFERENCE RANGE — 

The normal range for A1C is typically 4 to 5.6 percent (20.2 to 37.7 mmol/mol) (calculator 1). Reference ranges can vary depending on the patient population and clinical laboratory. Interpretation of a specific abnormal test result should be based upon the reference range reported with that result.

CITATIONS — 

The supporting references for this content are accessible in the linked topics.