Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both. DM can be classified as type 1 (characterized by insulin deficiency), the more common type 2 (characterized by insulin resistance with relative insulin deficiency), gestational diabetes mellitus (GDM) (a condition that occurs only during pregnancy), and other less common conditions (eg, monogenic DM). Laboratory evaluations used to screen for, diagnose, and monitor DM include a fasting plasma glucose (FPG) test, a hemoglobin A1c (A1c) test, and an oral glucose tolerance test (OGTT). Individuals diagnosed with DM or GDM require regular laboratory evaluation to assist in glycemic management and to monitor for the development of diabetes-related complications.
Quick Answers for Clinicians
Because hemoglobin A1c (A1c) testing measures the average amount of glucose attached to hemoglobin in red blood cells (RBCs) over approximately 3 months, conditions that affect RBC turnover can skew results. These conditions include hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, recent blood transfusions, drugs that stimulate erythropoiesis, end-stage kidney disease, and pregnancy. Hemoglobin variants (eg, the hemoglobin S [HbS] variant that causes the sickle cell trait) may also interfere with A1c results; A1c assays without interference, plasma blood glucose criteria, fructosamine, or 1,5-anhydroglucitol should be used in individuals with hemoglobin variants. For more information on hemoglobin variants, see the Hemoglobinopathies topic.
Once a diagnosis of type 1 diabetes mellitus (T1DM) has been made, autoantibody testing can be helpful in establishing an autoimmune etiology. Autoantibody testing may also help to exclude the diagnosis of T1DM in adults without traditional risk factors for type 2 diabetes mellitus (T2DM) and/or younger age. The American Diabetes Association (ADA) also recommends that pediatric patients who are overweight or obese and suspected of having T2DM have autoantibody testing performed to exclude the possibility of autoimmune T1DM.
As the prevalence of type 2 diabetes mellitus (T2DM) increases in children and adolescents, distinguishing type 1 diabetes mellitus (T1DM) from T2DM becomes more important because long-term management of the two types differs. Individuals with T1DM usually have absolute insulin deficiency, which often necessitates insulin therapy. Other treatments are recommended initially in those with T2DM, and insulin therapy is used only when all other treatments fail to reduce hemoglobin A1c levels.
Indications for Testing
- Screening adults ≥45 years of age, other at-risk individuals (eg, obese/overweight adolescents and adults ≤45 years of age), pregnant women, and women planning on becoming pregnant who are either overweight or have other risk factors
- Diagnosis of DM by confirmatory testing in the event of an abnormal test result or in patients who present with symptoms of hyperglycemia
- Monitoring for adherence to glycemic targets
The American Diabetes Association (ADA) recommends screening all asymptomatic adults for diabetes and the increased risk of developing diabetes (prediabetes) beginning at 45 years of age. Screening should be repeated at a minimum of every 3 years, unless initial results or risk status suggests that more frequent testing is appropriate. Risk-based screening should be considered in women who are planning a pregnancy and who are overweight or have additional risk factors. Additionally, screening should be considered in all overweight or obese adults who have more than one risk factor. Risk factors include a history of cardiovascular disease, hypertension, and high triglycerides or high-density lipoprotein (HDL) cholesterol levels; for a complete list of risk factors, see the ADA’s Standards of Medical Care in Diabetes.
Risk-based screening should also be considered in asymptomatic children or adolescents after the onset of puberty or beginning at 10 years of age (whichever comes first) who are overweight and have at least one additional risk factor. Risk factors include a maternal history of diabetes or GDM, a race/ethnicity associated with higher risk, and signs of insulin resistance; for a complete list of risk factors, see the ADA’s Standards of Medical Care in Diabetes. Children or adolescents with normal test results should be retested every 3 years; more frequent screenings are suggested if their body mass index (BMI) is increasing.
In pregnant women not previously known to have DM, testing for GDM should be performed at 24-28 weeks of gestation. - Testing for GDM can be performed using either a one-step or a two-step OGTT. Screening earlier in pregnancy using the same tests as those used for nonpregnant individuals may be considered in women at high risk for diabetes; those with a normal result should be screened again at 24-28 weeks.
Specific screening recommendations have been developed for certain patients, such as those with cystic fibrosis or those who have undergone organ transplantation. Refer to the ADA’s Standards of Medical Care in Diabetes for full screening recommendations, including risk factors.
Diabetes is diagnosed based on plasma blood glucose or A1c criteria. Generally, the FPG, OGTT, and A1c are equally appropriate tests for screening and diagnosis; however, the ADA does note that these tests may not detect diabetes in the same individuals (as explained below). The OGTT is required for screening and diagnosis of GDM.
Fasting Plasma Blood Glucose
An FPG test measures the amount of sugar in the blood without the effect of food intake and is a good indicator of glucose metabolism. Fasting is required for at least 8 hours. The concordance between the FPG and OGTT is imperfect; the OGTT tends to result in more diabetes diagnoses than either the FPG or A1c tests.
Oral Glucose Tolerance Test
The 2-hour plasma glucose (PG) OGTT is used to assess the body’s response to sugar and is performed using a glucose load containing the equivalent of 75 g of anhydrous glucose dissolved in water. The 2-hour PG OGTT is often referred to as the “one-step approach” for testing pregnant women for GDM at 24-28 weeks gestation. This approach is widely accepted; 95% of U.S. obstetricians prefer it as the universal screening tool. The more rigorous “two-step approach” involves administering a 50-g oral glucose solution followed by measurement of venous glucose after 1 hour. Women whose glucose levels meet or exceed an institution’s screening threshold then undergo a 3-hour diagnostic OGTT using 100 g of an oral glucose solution.
Random Plasma Glucose
A random plasma glucose (RPG) level does not take into account the time since the patient’s last meal and is affected by food eaten. An RPG test may be used in the diagnosis of type 1 diabetes mellitus (T1DM) when a patient presents with classic symptoms of hyperglycemia or is experiencing a hyperglycemic crisis.
The A1c test is used to assess glycemic control; the results reflect the average glycemia (glucose concentration) over approximately 3 months. It may be preferred when fasting is not feasible or for its preanalytic stability; however, the test has a lower sensitivity at the designated cut point and higher cost. Additionally, the correlation between the A1c concentration and the average glucose concentration is imperfect in some individuals. In individuals with hemoglobin variants, A1c assays without interference from those variants should be used to avoid skewed results. For those with conditions that cause an altered relationship between A1c and glycemia due to increased red blood cell turnover (eg, pregnancy, HIV, hemodialysis), only plasma blood glucose criteria should be used to diagnose diabetes.
Except in cases with a clear clinical diagnosis of diabetes (eg, hyperglycemic crisis or individuals with symptoms of hyperglycemia and an RPG ≥200 mg/dL), diagnosis requires two abnormal test results from the same sample or two separate samples. If two samples are tested, the second test should be performed promptly and may be either the same test that was performed on the initial sample or a different test.
|Laboratory Test||Diabetes Criteria Definition|
|FPG||≥126 mg/dL (7.0 mmol/L)|
|2-hr PG during OGTT||≥200 mg/dL (11.1 mmol/L)|
|A1c||≥6.5% (48 mmol/mol)|
|RPG||≥200 mg/dL (11.1 mmol/L)b|
aDefinitions of prediabetes (either impaired fasting glucose or impaired glucose tolerance) can be found in the ADA’s Standards of Medical Care in Diabetes.
bIn addition to classic symptoms of hyperglycemia or hyperglycemic crisis
AACE, American Association of Clinical Endocrinologist ; WHO, World Health Organization
|One-Step Approachb (mg/dL)||Two-Step Approachc (mg/dL)|
|Fasting||92||95 (CC) or 105 (NDDG)|
|1 hr||180||180 (CC) or 190 (NDDG)|
|2 hr||153||155 (CC) or 165 (NDDG)|
|3 hr||n/a||140 (CC) or 145 (NDDG)|
aPerformed at 24-28 weeks in women not previously diagnosed with diabetes.
bThe one-step approach is a 75-g OGTT with PG measurements at fasting, 1 hr, and 2 hrs. A diagnosis is made when any PG values are met or exceeded.
cThe two-step approach is a 50-g glucose load test (nonfasting) with PG measurement at 1 hr. If PG is ≥130 mg/dL, 135 mg/dL, or 140 mg/dL, a 100-g OGTT follows (step two). Either CC or NDDG cutoffs may be used.
ACOG. American Congress of Obstetricians and Gynecologists; CC, Carpenter-Coustan; n/a, not applicable; NDDG, National Diabetes Data Group
Differentiation between T1DM and T2DM is often made using patient factors (eg, age and weight), but the classic distinctions may not always be appropriate, given that some cases have overlapping features. Diabetes-related autoantibody testing can be helpful in establishing an autoimmune etiology in individuals with previously diagnosed T1DM and to exclude the diagnosis of T1DM in adults without traditional risk factors for T2DM and/or younger age. The ADA also recommends that pediatric patients who are overweight or obese and suspected of having T2DM have autoantibody testing to exclude the possibility of autoimmune T1DM.
Autoimmune markers, including islet cell antibodies (ICAs), insulin antibodies (IAs), glutamic acid decarboxylase antibodies (GADAs, or GAD 65), insulinoma-associated antigen 2, and zinc transporter (ZnT8) antibodies, may be present in cases of T1DM. The persistence of two or more of these autoantibodies predicts clinical DM. If pursuing antibody testing, at least two autoantibody tests should be ordered (in most cases, a GADA/GAD 65 test in combination with another test). However, the specificity of these tests is not perfect; some individuals with T1DM have no autoantibodies, and some individuals with latent autoimmune diabetes or T2DM may have one or more antibodies present.
Genetic testing is recommended in patients suspected of having monogenic diabetes syndromes, such as neonatal diabetes or maturity-onset diabetes of the young, to verify genetic etiology, establish treatment, and identify affected family members.
Routine Glycemic Control
The A1c concentration has strong predictive value for diabetes complications, and A1c testing should be performed routinely in all patients with diabetes. Clinicians should use judgment when using A1c to monitor patients with hemoglobin variants or conditions that affect red blood cells (RBCs). The ADA and the AACE recommend that an A1c test be performed at initial assessment and approximately every 3 months to determine whether glycemic targets have been reached and maintained. At that point, A1c should be measured at least twice a year in those with stable glycemic control. In individuals whose therapy has changed or who are not meeting glycemic goals, quarterly measurements are appropriate. Although A1c testing is the primary assessment tool for glycemic control, self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) is recommended in certain patients to help with self-management and medication adjustments, especially for hypoglycemia prevention. Other tests used to monitor glycemic control might include fructosamine and 1,5-anhydroglucitol, but the prognostic value of those tests is not as clear as it is for A1c.
The primary means of assessing glycemic control in pregnant women with GDM should be patient SMBG. CGM may help individuals with GDM achieve A1c targets, but it should be used in addition to SMBG and not as a substitute. A1c can be used as a secondary measure, as intraindividual results vary less. Additionally, because GDM may represent preexisting undiagnosed T2DM or T1DM, women with GDM should be tested 4-12 weeks postpartum with a 75-g PG OGTT. A1c testing is not recommended for this postpartum testing because increased RBC turnover related to pregnancy and/or blood loss at delivery can affect A1c results and because the OGTT is more sensitive at detecting glucose intolerance. If test results are normal, women should continue to be monitored for the development of diabetes every 1-3 years thereafter; more frequent testing should be considered based on risk factors (eg, family history). This ongoing evaluation can be performed with any recommended glycemic test.
The table below lists ideal A1c targets by population, but treatment goals should be determined and individualized based on patient circumstances. Refer to the ADA’s Standards of Medical Care in Diabetes for a full listing of glycemic targets for all individuals.
|Population||Ideal A1c Target (%)|
aMore stringent (<6.5%) or less stringent (<8%) targets may be used for select patients.
bAACE suggests ≤6.5% as a target goal and 7-8% for less stringent target goals.
cMore stringent (<6.5%) targets may be appropriate for select individuals if achievable without significant hypoglycemia.
dIf target cannot be achieved without significant hypoglycemia, adjust goal to <7%.
Individuals with DM usually have other cardiovascular disease risk factors, including dyslipidemia, and should be treated and monitored for dyslipidemia. For information on monitoring for dyslipidemia, see the Atherosclerotic Cardiovascular Disease Risk Markers ARUP Consult topic.
- Screen for diabetic kidney disease using urinary albumin and estimated glomerular filtration rate testing at least once a year in patients who have had T1DM for ≥5 years and in those with T2DM or comorbid hypertension.
- Consider screening patients with T1DM for autoimmune thyroid disease and celiac disease soon after diagnosis, as autoimmune diseases occur more frequently in individuals with T1DM.
- Consider screening for hypogonadism with a morning serum testosterone measurement in men with diabetes who have signs or symptoms of hypogonadism.
Individuals diagnosed with cystic fibrosis-related diabetes should be monitored annually for complications of diabetes beginning 5 years after the diagnosis.
ARUP Laboratory Tests
Quantitative Enzyme-Linked Immunosorbent Assay
May aid in monitoring glucose control for diabetes in specific disorders
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