Laboratory Testing for Diabetes Diagnosis, Risk Assessment, and Management

Laboratory Testing for Diabetes Diagnosis, Risk Assessment, and Management

This test guide discusses the use of laboratory tests for general screening and diagnosis of prediabetes and diabetes; it also provides additional information on diabetes risk assessment and monitoring glycemic control and complications in individuals with diabetes.

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Laboratory Testing for Diabetes Diagnosis, Risk Assessment, and Management

This Test Guide discusses the use of laboratory tests for general screening and diagnosis of prediabetes and diabetes primarily based on guidance provided by the American Diabetes Association® (ADA).1 Additional information is provided on diabetes risk assessment and monitoring glycemic control and complications in individuals with diabetes. This Test Guide is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician's education, clinical expertise, and assessment of the patient.

Diagnosis [return to contents]

Tests available for the general screening and diagnosis of prediabetes and diabetes include fasting plasma glucose (FPG) measurement (test code 484), oral glucose tolerance tests (OGTT, test codes 35181, 23475), and a standardized hemoglobin A1c (HbA1c, test code 496) assay (Table 1).1 Clinically significant glucose and HbA1c levels are shown in Table 2.1,2

Table 1. Tests Typically Used in Diabetes Screening and Diagnosis [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

General screening and diagnosis

484

Glucose, Plasma

  • Screen for and diagnose prediabetes and diabetes based on FPG

8917

Glucose, Random

  • Diagnose diabetes during a hyperglycemic crisis caused by use of certain therapies (Table 2)

35181

Glucose Tolerance Test, 2 Specimens (75g)

  • Screen for and diagnose diabetes based on fasting and 2-h (post 75-g glucose loading) specimens (2-h OGTT)

23475

Glucose Tolerance Test, 3 Specimens (75g)

  • Screen for and diagnose diabetes based on fasting, 1-, and 2-h (post 75-g glucose loading) specimens

 

496

Hemoglobin A1cb

  • Screen for and diagnose prediabetes and diabetes-determines long-term average blood glucose, expressed as a percentage

 

Gestational diabetes

8477

Glucose, Gestational Screen (50g), 135 Cutoff

  • Screen (without prior fasting) for gestational diabetes using a 1-h (post 50-g glucose loading) specimen (ADA- and ACOG-supported 1st step of 2-step evaluation); a cutoff of 135 mg/dL (test code 8477) or 140 mg/dL (test code 19833) indicates that the 2nd step (test code 6745) is necessary

 

 

19833

Glucose, Gestational Screen (50g), 140 Cutoff

18927

Glucose Tolerance Test, Gestational, 3 Specimens (75g)

  • Diagnose gestational diabetes (ADA-supported 1-step evaluation)

 

6745

Glucose Tolerance Test, Gestational, 4 Specimens (100g)

  • Diagnose gestational diabetes based on fasting, 1-, 2-, and 3-h (post 100-g glucose loading) specimens (ADA- and ACOG-supported 2nd step of 2-step evaluation)

Type 1 diabetes

13621

Diabetes Type 1 Autoantibody Panel

Includes GAD (34878), IA-2 (37933), insulin (36178), and ZnT8 (93022) autoantibodies.

  • Screen and assess risk for development of T1D in presymptomatic individuals
  • Diagnose T1D in symptomatic children and adults
  • Differentially diagnose T1D vs T2D
  • Determine eligibility for teplizumab therapy or clinical trials for new therapies that delay onset of clinical diabetes
ACOG, American College of Obstetricians and Gynecologists; ADA, American Diabetes Association; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; OGTT, oral glucose tolerance test; T1D, type 1 diabetes; T2D, type 2 diabetes.
a Panel components may be ordered separately.
b Determined using a National Glycohemoglobin Standardization Program (NGSP)-certified HbA1c method that is corrected for common hemoglobin variants.1
c This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

 

Table 2. Diagnostic Significance of Glucose and Hemoglobin A1c Concentrations [return to contents]

Individuals suitable for testing1,2

Marker: clinically significant levels1,a,b

Interpretation1

  • Nonpregnant individuals with diabetes risk factors or age ≥35 y
  • Individuals 3-6 mo following acute pancreatitis
  • Individuals with suspected monogenic diabetesd
  • Individuals prescribed medications known to increase diabetes riske
  • FPG: ≥126 mg/dL
  • 2-h OGTT (75 g): ≥200 mg/dL
  • HbA1c level: ≥6.5%
  • Diabetesc
  • FPG: 100-125 mg/dL
  • 2-h OGTT (75 g): 140-199 mg/dL
  • HbA1c level: 5.7%-6.4%
  • Prediabetes
  • Individuals experiencing a hyperglycemic crisis (eg, DKA or HHS)
  • Individuals with recurrent or long-term use of glucocorticoids
  • RPG: ≥200 mg/dL
  • Diabetes
  • Individuals prescribed ICIsf
  • RPG: ≥200 mg/dL
  • FPG: ≥126 mg/dL
  • Systemic anticancer therapy-induced diabetes
  • Individuals prescribed PI3Kαg or mTORh inhibitors
  • RPG: ≥200 mg/dL
  • FPG: ≥126 mg/dL
  • HbA1c level: ≥6.5%
  • Systemic anticancer therapy-induced diabetes
  • All individuals planning pregnancy
  • FPG: 100-125 mg/dL
  • HbA1c level: 5.9% to 6.4%
  • Increased risk for diabetes and adverse pregnancy and neonatal outcomes
  • Individuals with some hemoglobin variants, G6PD, HIV,i or abnormal red cell turnover
  • FPG: ≥126 mg/dL
  • Diabetesc
  • FPG: 100-125 mg/dL
  • Prediabetes
  • All pregnant individuals (24-28 wks of gestation)j
  • Individuals with CF age ≥10 ym
  • Individuals who have received an organ transplantn
  • 2-h OGTT (75 g)
  • Fasting: ≥92 mg/dL
  • 1 h: ≥180 mg/dL
  • 2 h: ≥153 mg/dL
  • Gestational diabetesk,l
  • CF-related diabetes
  • Posttransplantation diabetes
ACOG, American College of Obstetricians and Gynecologists; ADA, American Diabetes Association; CF, cystic fibrosis; DKA, diabetic ketoacidosis; FPG, fasting plasma glucose; G6PD, glucose-6-phosphate dehydrogenase deficiency; HbA1c, hemoglobin A1c; HHS, hyperosmolar hyperglycemic state; ICIs, immune checkpoint inhibitors; mTOR, mammalian target of rapamycin; OGTT, oral glucose tolerance test; PI3Kα, phosphoinositide 3-kinase alpha; RPG, random plasma glucose.
a If test results are in-range for healthy individuals, repeat testing at 3-year intervals, sooner if change in symptoms or risk (eg, weight gain).
b If test results are close to diagnostic thresholds, repeat testing in 3 to 6 months.
c Absent overt clinical signs of hyperglycemia (eg, polyuria, polydipsia, unexplained weight loss), diagnosis requires 2 clinically significant test results (either the same test using a new blood sample or 2 different tests). If 2 different tests (eg, HbA1c and FPG) are performed and 1 gives clinically significant results and the other does not, the test with clinically significant results should be repeated. If the repeat test result is also clinically significant, diabetes is diagnosed.
d If ≥1 of the following features is present, monogenic diabetes is suggested: HbA1c <7.5% at diagnosis, 1 parent with diabetes, clinical features consistent with a monogenic cause (eg, renal cysts, partial lipodystrophy, maternally inherited deafness, severe insulin resistance without obesity), or monogenic diabetes prediction model probability >5% (Exeter Diabetes App). Genetic testing options for monogenic diabetes are available through Athena Diagnostics.
e For example, glucocorticoids, statins, thiazide diuretics, and some HIV medications. For individuals prescribed 2nd-generation antipsychotic medications, screen for prediabetes and diabetes at baseline,12 to 16 weeks after initiation (sooner if clinically indicated); if test results are normal, repeat testing annually.
f For individuals prescribed ICIs: FPG or random plasma glucose at baseline, during each visit, or if signs of hyperglycemia develop during or after treatment cessation.
g For individuals prescribed PI3Kα inhibitors: FPG or random plasma glucose and HbA1c at baseline, random plasma glucose weekly for 2 weeks then every 4 weeks, and consider HbA1c every 3 months during treatment.
h For individuals prescribed mTOR inhibitors: FPG or random plasma glucose at baseline, during each visit, and consider HbA1c every 3 months during treatment.
i Screen before and 3 to 6 months after starting or changing antiretroviral therapy; if test results are normal, repeat testing annually.
j The 1-step strategy is listed; the alternative 2-step strategy involves a 1-h OGTT (50 g) screen in nonfasting individuals; if the indicated cutoff is met (ie, ≥135 mg/dL or ≥140 mg/dL), a 3-h OGTT (100 g) is performed with collection of 4 specimens (fasting, 1-, 2-, and 3-h). According to the ADA, gestational diabetes is diagnosed if 2 specimens meet or exceed the following glucose levels: fasting, 95 mg/dL; 1-h, 180 mg/dL; 2-h, 155 mg/dL; and 3-h, 140 mg/dL (ACOG requires only 1 elevated specimen for diagnosis of gestational diabetes).
k Only 1 of the 3 time points need to be elevated to make the diagnosis.
l Repeat 2-h OGTT 4 to 12 weeks postpartum and interpret results per nonpregnant individuals. Screen individuals with a history of GDM for prediabetes and diabetes every 1 to 3 years.
m If OGTT is not initially feasible, a 2-step screening strategy for CF–related diabetes is recommended involving HbA1c as the initial test. Only those with values between 5.5% and 6.4% should undergo an OGTT within 3 months.
n Stable on immunosuppressive therapy and free of acute infections.

 

Guidelines for testing

The ADA recommends using FPG, OGTT, and HbA1c for diagnosing diabetes and identifying increased diabetes risk (prediabetes). For individuals experiencing overt symptoms related to hyperglycemia, a random plasma glucose measurement (with a specimen collected any time of the day regardless of previous meal time, test code 8917) is recommended for diagnosis.1

Screening for prediabetes and/or T2D should be performed for all individuals beginning at age 35 years, earlier for those with risk factors (see “Risk Factor Assessment for Prediabetes and Type 2 Diabetes” in Section 2: Diagnosis and Classification of Diabetes | Clinical Diabetes | American Diabetes Association). For overweight or obese children or adolescents with ≥1 risk factor, screening should be considered after the onset of puberty or after 10 years of age, whichever occurs earlier.1

For individuals with prediabetes, annual monitoring for development of diabetes is recommended; frequency of monitoring may be modified based on an individual’s risk-to-benefit assessment.1 For those without diabetes or prediabetes, screening should be repeated every 3 years—earlier if their risk factors increase.1

Comparison of glycemic measures for screening and diagnosis

FPG, OGTT, and HbA1c are equally appropriate for diagnostic screening in the general population, although one may be more appropriate than another depending on an individual’s characteristics (eg, certain nondiabetic illnesses or pregnancy, Tables 1 and 2).1

FPG and OGTT tests are sensitive but measure glucose levels only in the short term, require fasting or glucose loading, and give variable results during stress and illness.1 In contrast, HbA1c assays reliably estimate average glucose levels over a longer term (2 to 3 months), do not require fasting or glucose loading, and have less variability during stress and illness.1

In some circumstances, HbA1c is a less reliable marker than plasma glucose. Examples include people with some hemoglobinopathies, altered red blood cell turnover (eg, caused by hemodialysis, recent blood cell loss/transfusion, erythropoietin-treatment, or anemia), HIV, glucose-6-phosphate dehydrogenase deficiency, or cystic fibrosis, as well as during pregnancy.1 In addition, primary prevention measures have proven more efficacious for individuals whose glycemic status is based on OGTT results compared with isolated FPG results or HbA1c results meeting the criteria for prediabetes.1

Quest Diagnostics uses an HbA1c assay (test code 496) that is unaffected by the presence of hemoglobin (Hb) variants (HbC, HbS, HbE, HbD) in heterozygous individuals (HbA1c cannot be measured in individuals who are homozygous or compound heterozygous for Hb variants). However, the assay is subject to interference by elevated HbF, which is present in conditions such as β-thalassemia, and a few rare Hb variants.3 The assay has no significant interference from high concentrations of lipids (including high triglycerides) and bilirubin. This method has been standardized against the approved International Federation of Clinical Chemistry (IFCC) reference method. Results are traceable to Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program (DCCP/NGSP).

When there is consistent and substantial discordance between glycemic measures for diagnosis and analytical issues have been eliminated as being a cause, the ADA recommends using alternative validated biomarkers, such as fructosamine (test code 8340), which is discussed in the "Management" section below.1

Gestational diabetes

ADA and American College of Obstetricians and Gynecologists (ACOG) recommendations for screening and diagnosis of gestational diabetes are provided in Table 2. Quest offers test codes 8477, 19833,18927, and 6745 for pregnant individuals and those planning pregnancy.

Type 1 diabetes

A hallmark of T1D is its association with autoantibodies targeting insulin, tyrosine phosphatase-related islet antigen 2 (IA-2), zinc transporter 8 (ZnT8), and glutamic acid decarboxylase-65 (GAD). Using these 4 antibodies together,4-7 T1D can be diagnosed in 93% to 98% of symptomatic patients.8-10 On this basis, the ADA recommends screening for T1D using these markers, especially among patients who are at risk (eg, family history of autoimmune diabetes).1 Consensus guidance has been provided for diagnosing and monitoring individuals with prestage-3 T1D and is based on the number of T1D autoantibodies and glycemic indices.11 Quest offers a panel comprising all these antibodies (test code 13621) for T1D screening, diagnosis, and treatment eligibility. For more information, see Diabetes Type 1 Autoantibody Panel | Test Summary | Quest Diagnostics.

 

Diabetes risk assessment [return to contents]

The ADA provides a calculator https://diabetes.org/diabetes-risk-test to estimate risk for diabetes, with scores ranging from 1 (low risk) to 10 (high risk) but otherwise, beyond identifying prediabetes, provides no guidance in calculating diabetes risk from laboratory results.1 Approaches offered by Quest for diabetes risk assessment include (a) using HbA1c in conjunction with other laboratory results and information from a clinical visit to estimate 8-year risk and (b) assessing the risk of insulin resistance as a predictor of onset of prediabetes and T2D using laboratory results alone. The latter approach allows prediction of diabetes risk before dysglycemia develops, as discussed below.

HbA1c

HbA1c results are used in combination with certain sociodemographic and anthropometric characteristics in predicting risk for prediabetes and T2D in asymptomatic individuals. Quest also provides panels that supplement HbA1c results with plasma glucose and lipid analysis with (test code 92027) or without (test code 91920) a calculated risk score for developing T2D over 8-years (Table 3).12 The risk score also uses patient age (30-79 years), sex, height, weight, blood pressure, family history of diabetes, and is most accurate when the patient is fasting 9-12 hours before blood collection. Because cardiovascular disease (CVD) is elevated with dysglycemia, concurrent monitoring of CVD risk factors is also recommended.13,14 Quest also offers a panel (test code 92062) with additional estimates of 10-year and lifetime risk of developing CVD.

Table 3. Tests Used in Diabetes Risk Assessment [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

36509

Cardio IQ® Insulin Resistance Panel With Scoreb

Includes intact insulin LC/MS/MS (93103), C-peptidec and calculated IR score.

  • Assess risk of insulin resistance and prediabetes

92062

Diabetes and ASCVD Risk Panel With Scoresd,e,f,g

Includes glucose (483); HbA1c (496); total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896) with reflex to direct LDL (8293); cholesterol/HDL ratio (calculated); non-HDL (calculated); 8-year risk of developing diabetes (calculated); and 10-year and lifetime ASCVD (calculated).

  • Screen for and diagnose prediabetes and diabetes
  • Calculate 8-year risk for developing T2D12 and 10-year and lifetime risk of developing ASCVD

92027

Diabetes Risk Panel With Scored,e,g

Includes glucose (483); HbA1c (496); total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896) with reflex to direct LDL (8293); cholesterol/HDL ratio (calculated); non-HDL (calculated); and 8-year risk of developing diabetes (calculated).

  • Screen for and diagnose prediabetes and diabetes
  • Calculate 8-year risk for developing T2D12

91920

Diabetes Risk Panel Without Scored

Includes glucose (483); HbA1c (496); total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896) with reflex to direct LDL (8293); cholesterol/HDL ratio (calculated); and non-HDL (calculated).

  • Screen for and diagnose prediabetes and diabetes
  • Assess risk for developing T2D

39447

Metabolic Risk Panel

Includes Cardio IQ apolipoprotein B (91726), HDL (91719) and total (91717) cholesterol, hemoglobin A1c (91732), insulin resistance panel with score (36509), triglycerides (91718), and non-HDL and calculated components.

  • Screen for and diagnose prediabetes and diabetes
  • Assess risk of insulin resistance and cardiovascular disease
ASCVD, atherosclerotic cardiovascular disease; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein; T2D, type 2 diabetes.
a Panel components may be ordered separately.
b This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c The C-peptide LC/MS/MS panel component cannot be ordered separately. C-peptide by immunoassay (test code 372) is not an equivalent test and cannot be used in calculation of the insulin resistance risk score.
d Reflex tests are performed at additional charge and are associated with an additional CPT® code.
e The diabetes risk score, expressed as a percentage, is calculated with an algorithm that incorporates levels of HbA1c, FPG, high-density lipoprotein (HDL) cholesterol, and triglycerides, as well as patient age and sex.12
f ASCVD risk calculator is available at ASCVD Risk Estimator +.
g Cardio IQ versions of these panels (test codes 92063 and 92026) are also available with a color-coded report to display progressive risk values versus goal using “optimal,” “moderate,” and “high-risk” categories.

 

Insulin resistance risk score

Emerging data also suggests that onset of prediabetes and T2D may be predicted by insulin resistance measured using an insulin resistance risk score (IRRS, test code 36509), even in normoglycemic individuals who are not overweight or obese or who do not have other risk factors.15 The score is calculated from fasting intact insulin and C-peptide blood levels measured using mass spectrometry16 standardized for consistent measurement over time.17

An IRRS ≥33% indicates a higher risk of having insulin resistance.18 Subsequent studies assessed the risk of developing T2D using the risk score and found that scores lower than 33% had clinical significance. Older individuals (median age 68 years) with an IRRS >20% had up to double the risk of developing T2D over 9 years compared to those with an IRRS <7%.19 Working age individuals (median age 43 years) with healthy, in-range HbA1c and FPG levels and an IRRS >20% had a 43% greater risk of developing prediabetes or T2D over 3 years compared to those with an IRRS <8%.15 Compared to lower IRRSs, higher IRRSs have also been associated with an increased risk of incident CVD and all-cause mortality20 and incident coronary heart disease (fatal and non-fatal myocardial infarction and coronary revascularization).21

For more information on the IRRS, see

Note: To assess insulin resistance, ADA 2026 guidelines only mention clinical presentation (eg, acanthosis nigricans, severe obesity, metabolic dysfunction-associated steatotic liver disease [MASLD], formerly nonalcoholic fatty liver disease [NAFLD]), with no reference to laboratory testing other than FPG, OGTT, and HbA1c for prediabetes and T2D.1

Management [return to contents]

Following a diagnosis of diabetes, a combination of laboratory and clinical tests can be used to monitor blood glucose control and predict treatment response (Table 4).1,13,22,23 Recommended testing frequency and target results for these tests can be found in Table 5.7,22-26 Different laboratory tests are available for monitoring blood glucose control over the short, long, and intermediate term to help evaluate the effectiveness of a management plan.

Table 4. Tests Used in Managing Diabetes [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

10378

1,5-Anhydroglucitol (1,5-AG), Intermediate Glycemic Controlb

  • Measure glycemic control over the short-to-intermediate term (1 to 2 weeks)

372

C-Peptide

  • Classify diabetes of uncertain type for individuals receiving insulin therapyd
  • Exclude severe insulin deficiency before discontinuing insulin therapy

15843

C-Peptide Response to Glucose, 2 Specimensc

15844

C-Peptide Response to Glucose, 3 Specimensc

15845

C-Peptide Response to Glucose, 4 Specimensc

31345

C-Peptide Response to Glucose, 5 Specimensc

15846

C-Peptide Response to Glucose, 6 Specimensc

15847

C-Peptide Response to Glucose, 7 Specimensc

15848

C-Peptide Response to Glucose, 8 Specimensc

15448

C-Peptide Response to Glucose, 9 Specimensc

8340

Fructosamine

  • Measure glycemic control over the intermediate term (2 to 3 weeks) and when there is discordance between other glycemic measures

16802

Hemoglobin A1c With eAGe

  • Determine long-term average blood glucose; expressed in percent HbA1c and eAG in conventional blood glucose units for more convenient comparison to BGM values1,22,23

10380

Hemoglobin A1c With Reflex to 1,5-Anhydroglucitol (1,5-AG)e,f

  • Measure glycemic control over the short-to-intermediate term (1 to 2 weeks) in moderately controlled diabetes (HbA1c ≥6.5% and ≤8.0%)

10379

Hemoglobin A1c With eAG With Reflex to 1,5-Anhydroglucitol (1,5-AG)e,f

7577

Protein, Total and Albumin

Includes albumin (223), globulin (calculated), albumin/globulin ratio (calculated), and total protein (754).

  • Used with fructosamine testing to assess plasma protein levels
1,5-AG, 1,5-anhydroglucitol; BGM, blood glucose monitoring; eAG, estimated average glucose; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; T1D, type 1 diabetes; T2D, type 2 diabetes.
a Panel components may be ordered separately.
b The analytical performance characteristics of this assay have been determined by Quest Diagnostics. The modifications have not been cleared or approved by the FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c Do not perform this test within 2 weeks of a hyperglycemic emergency.
d According to the ADA, a concurrent glucose and C-peptide measurement from a random specimen within 5 h of eating can replace a formal C-peptide stimulation test.
e Determined using a NGSP–certified HbA1c method that is corrected for common hemoglobin variants.1
f Reflex tests are performed at additional charge and are associated with an additional CPT code.

 

Table 5. Recommended Testing Frequency and Goals for Diabetes Management [return to contents]

Marker

Target levels in patients with diabetesa

Testing frequencyb

HbA1c test

HbA1c level

Nonpregnant adults without significant hypoglycemia24,c: <7.0%

Patients with a history of severe hypoglycemia, extensive comorbidities, or a long-standing diagnosis in whom lower targets are difficult to achieve: <8%24

  • Initial visit
  • Follow-up
  • Every 6 months for patients with stable glycemia who meet glycemic goals
  • Every 3 months or as needed for children and adolescents during periods of rapid growth, patients who have changed therapy and are not meeting glycemic goals, patients who experience frequent or severe hyper- or hypoglycemia or changes in health status
  • More frequently for patients with unstable glycemia and those undergoing intensive management (eg, pregnant women with T1D)

eAGd

<154 mg/dL (8.6 mmol/L)24

  • Same as for HbA1c level

Fructosamine

Fructosamine level

Target levels not establishede

  • As clinically indicated to monitor glucose control over 2 to 3 weeks

1,5-AG

1,5-AG level

≥8.0 μg/mL25

  • At time of HbA1c test if HbA1c levels are moderately or well-controlled to detect PPG excursions
  • As clinically indicated to monitor glucose control over 1 to 2 weeks
1,5-AG, 1,5-anhydroglucitol; BGM, blood glucose monitoring; eAG, estimated average glucose; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; T1D, type 1 diabetes; T2D, type 2 diabetes.
a Achieving glucose, HbA1c, eAG, and 1,5-AG goals should be balanced against risk of inducing hypoglycemia.
b Suggested testing frequency is generalized for routine monitoring and may vary depending on clinical condition and treatment regimen.
c Lower goals (<6%) may be appropriate for individuals with good health and low treatment risk; less stringent goals may be appropriate for individuals who are frail and in poor health for whom treatments risks are higher
d eAG values in mg/dL are calculated by converting HbA1c levels to eAG using the following formula22,23: eAG = HbA1c × 28.7 - 46.7. eAG values in mg/dL can be converted to mmol/L by dividing by 18.
e Fructosamine quantitation has not been standardized26; values from different assays cannot be easily compared. The assay that Quest offers (test code 8340) provides a reference range for healthy adults, but this is not a target for glycemic control for people with diabetes. Poorly controlled diabetes using this assay has been measured as mean a fructosamine of 396 μmol/L (range 228-563 μmol/L).7 In hydremic states, correcting fructosamine for total protein using the formula: Corrected fructosamine = 72 × [fructosamine μmol/L]/[total protein g/L] has been suggested.7

 

Comparison of testing methods for monitoring diabetes

Blood glucose monitoring (BGM) and continuous glucose monitoring (CGM) are useful for tracking short-term treatment responses in insulin-treated patients and identifying acute hypo- and hyperglycemic diabetic events.24,27 By contrast, the long-term HbA1c measure should be used as the primary test of glycemic control in all nonpregnant adults with diabetes24; lowering HbA1c levels by 1 percentage point reduces the risk of microvascular complications by approximately 40%.28

To help patients relate long-term glucose control to daily BGM and CGM measurements, HbA1c test results may be converted to conventional glucose units (mg/dL or mmol/L) and reported as the estimated average glucose (eAG, test code 16802).22-24 Although reporting eAG is approved by both the ADA and the American Association for Diagnostics & Laboratory Medicine, the ADA cautions that conversion to eAG relies on a 2008 study correlating HbA1c to older CGM technology.24

Alternatives to HbA1c testing for monitoring glycemic control over the short-to-intermediate term include fructosamine testing (2 to 3 weeks) and 1,5-anhydroglucitol (1,5-AG, 1 to 2 weeks) testing.

In addition to CGM, fructosamine testing (test code 8340) is particularly useful when HbA1c may not be a reliable marker,24 such as in hemodialysis patients with high red blood cell turnover, early responses to treatment changes, and pregnancy complicated by diabetes.29 The assay is a measure of glycated plasma proteins, which experience a faster turnover than intracellular HbA1c and better reflect short term glycemic variability.30 The assay is influenced by conditions in which serum albumin and total protein (test code 7577) concentrations are low because of disease (eg, liver cirrhosis, nephrotic syndrome, and protein-losing enteropathies) and hydremic states such as pregnancy, and is unreliable when albumin is <3.0 g/dL.26 Conditions with elevated protein (eg, polyclonal gammopathies and multiple myeloma) can also cause unreliable fructosamine results.26 Levodopa and oxytetracycline cause artificially high fructosamine results.7

Levels of 1,5-AG (test code 10378) are used to assess postprandial glucose excursions in individuals with moderately or well-controlled HbA1c levels (6.5% to 8.0%).25,29 A 2020 study proposes that 1,5-AG be used to increase physician awareness of steroid-induced hyperglycemia and poor short-term glycemic control, which is associated with poorer outcomes.31 Levels of 1,5-AG have been found to be predictive of microvascular complications, independent of HbA1c, in patients undergoing glucose and blood pressure-lowering therapy.32 In addition, lower 1,5-AG values are inversely correlated to higher coronary artery calcification and CVD risk.33 Quest offers 1,5-AG testing, which can be used as suggested in conjunction with HbA1c to identify individuals experiencing postprandial excursions over the short-to-intermediate term; these tests can be used as individual tests (Figure)25 or as reflex tests with (test code 10379) or without (test code 10380) eAG.

The 1,5-AG test is unreliable for patients taking SGLT2 inhibitors because of assay interference.34

Note: ADA 2026 guidelines do not provide recommendations on how 1,5-AG should be incorporated into clinical practice.24,29

For patients receiving insulin therapy, the ADA recommends C-peptide testing (Table 4) if (a) there is uncertainty regarding their type of diabetes or (b) discontinuation of insulin is being considered. Levels ≥1.8 ng/mL indicate T2D whereas level <0.24 ng/mL indicate T1D.1 Repeat testing may be required for intermediate C-peptide levels with concurrent glucose <70 mg/dL or if the patient may have been fasting.1

Testing methods for diabetic complications and comorbidities

Individuals with diabetes are at increased risk of retinopathy and neuropathy, as well as heart, liver, and kidney disease. In addition to routine eye and foot exams and blood pressure monitoring, tests for monitoring lipids, liver, and kidney function are recommended to detect the onset and monitor progression of these complications. Quest offers these tests individually and within panels (Table 6). For more information, see Laboratory Testing for Chronic Kidney Disease Diagnosis and Management and Cardiometabolic Disease Assessment (CMDA) Panel. Celiac disease screening (test codes 8821 and 539) and thyroid function testing (TSH, test code 899) are also recommended in the context of T1D and comorbid autoimmune disorders.13 Recommended testing frequency and target results for these tests can be found in Table 7.13,14,35,36

Table 6. Tests Used in Monitoring Diabetic Complications and Comorbidities [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

ASCVD

5224

Apolipoprotein Bb

  • Guide decisions on intensification of lipid-lowering therapy once LDL- and non-HDL-cholesterol goals have been achieved, particularly for patients with T2D and ASCVD, cardiovascular-kidney-metabolic syndrome, and/or elevated triglycerides37

7600(X)

Lipid Panel, Standardb

Includes total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896); cholesterol/HDL ratio (calculated); non-HDL (calculated).

  • Monitor dyslipidemia and thus risk of heart disease

Chronic kidney disease

94588

Cystatin C With Glomerular Filtration Rate, Estimated (eGFR)

  • Monitor chronic kidney disease in patients for whom creatinine-based results may lead to an incorrect diagnosisc

13581

Estimated Glomerular Filtration Rate (eGFR) With Creatinine and Cystatin C

Includes serum creatinine (375), cystatin C (94588), and eGFR calculation.

  • Monitor for chronic kidney disease (most accurate estimate for at-risk patients or for whom creatinine-based results may lead to an incorrect diagnosis)38,c

39165

Kidney Profile

Includes albumin, random urine with creatinine (6517) and serum creatinine (375) with calculated eGFR.

  • Monitor onset and progression of kidney disease

 

MASLD

10350

Enhanced Liver Fibrosis (ELF) Score

  • Assess likelihood that nonalcoholic steatohepatitis will progress to cirrhosis and liver-related clinical events; used for patients with indeterminant or high FIB-4 results13

30555

Liver Fibrosis, Fibrosis-4 (FIB-4) Index Panel

Includes ALT (823), AST (822), platelet count (723), and FIB-4 index (calculated).

  • Screen for fibrosis in individuals with prediabetes and CVD risk factors, T2D, or T1D (only if additional risk factors such as obesity, hepatic steatosis, or elevated liver aminotransferases are present); preferred option by the ADA13

T1D–associated conditions

539

IgA

  • Screen for IgA deficiency in people with T1D, which may lead to false positive tTG celiac screening (test code 8821)

8821

Tissue Transglutaminase (tTG) Antibody (IgA)

  • Screen for celiac disease in T1D

899

TSH

  • Assess thyroid function in T1D

Difficult-to-control diabetes

29391

Dexamethasone

  • Aid interpretation of DST (test code 6921)

6921

Dexamethasone Suppression Test (DST), 1 Specimen

  • Diagnose hypercortisolism in difficult-to-control T2D

Multiple conditions

14273

Cardiometabolic Disease Assessment (CMDA) Panel

Includes Cardio IQ apolipoprotein B (91726), HbA1c (91732), insulin resistance panel with score (36509), and lipid panel (91716); comprehensive metabolic panel with FIB-4 index (10372); kidney profile (39165); and TSH (899).

  • Identify early metabolic dysfunction in cardiometabolic disease in the context of measures of dyslipidemia and glycemic control
  • Assess common endocrine disorders that cause or are exacerbated by cardiometabolic dysfunction
  • Quantify downstream adverse effects of chronic cardiometabolic disease on end-organ dysfunction, including liver and kidney
ALT, alanine aminotransferase; ASCVD, atherosclerotic cardiovascular disease; AST, aspartate aminotransferase; DST, dexamethasone suppression test; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; IgA, immunoglobulin A; LDL, low-density lipoprotein; MASLD, metabolic dysfunction-associated steatotic liver disease; NAFLD, nonalcoholic fatty liver disease; T1D, type 1 diabetes; T2D, type 2 diabetes; TSH, thyroid stimulating hormone; tTG, tissue transglutaminase.
a Panel components may be ordered separately.
b Cardio IQ versions of apolipoprotein B (test code 91726) and the lipid panel (test code 91716) are also available with a color-coded report to display progressive risk values versus goal using “optimal,” “moderate-risk,” and “high-risk” categories.
c Pregnant women, patients with acute illness, patients with serious comorbid conditions, people with extremes of muscle mass (eg, bodybuilders, patients with amputation, paraplegia, muscle-wasting disease, or a neuromuscular disorder), patients suffering from malnutrition, those with a vegetarian or low-meat diet, and those taking creatine dietary supplements.

 

Table 7. Recommended Testing Frequency and Goals for Monitoring Diabetic Complications [return to contents]

Marker13

Target levels in patients with diabetes

Testing frequencya

ASCVD

Fasting lipid profile (LDL, HDL, TG)13,14

LDL: <70 mg/dL

HDL: ≥40 mg/dL(men); ≥50 mg/dL (women)

TG: <150 mg/dL

  • Initial visit and then annually (adults not taking statins); as needed to monitor adherence and efficacy of introducing statin therapy or for patients with ASCVD

Liver disease

FIB-4

Score: <1.3 (<F2)

  • Initial visit and then annually

Kidney disease

Creatinine level and eGFR

eGFR ≥60 mL/min/1.73 m2

  • Initial visit and then annually

Urine albumin/creatinine ratio

<30 μg/mg creatinine (normal)

  • Initial visit and then annually

Autoimmune disease

Tissue transglutaminase IgA35,b

<15.0 U/m (antibody not detected)

  • Initial visit for patients with T1D with gastrointestinal symptoms, signs, laboratory test results, or clinical suspicion

TSH

1-19 years: 0.50-4.30 mIU/L

≥20 years: 0.40-4.50 mIU/L

  • Initial visit and then annually for patients with T1D
ASCVD, atherosclerotic cardiovascular disease; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; T1D, type 1 diabetes; T2D, type 2 diabetes; TSH, thyroid stimulating hormone.
a Suggested testing frequency is generalized for routine monitoring and may vary depending on clinical condition and treatment regimen.
b May be performed with total IgA (test code 539) to detect false positives caused by IgA deficiency rather than celiac disease. IgA deficiency is relatively common in T1D; one study found about 1 in 10 children with T1D are affected.36

 

Testing methods for difficult-to-control T2D

In primary care settings, many patients with difficult-to-control T2D do not achieve glycemic goals despite taking multiple glucose-lowering medications.39,40 For some of these patients, other underlying conditions may be impairing glycemic control.40,41 In particular, hypercortisolism (excessive cortisol levels) may contribute to difficult-to-control T2D but is not typically assessed during T2D management.39-41 Quest offers several tests for initial evaluation of hypercortisolism including test codes 29391 and 6921. For more information, see Hypercortisolism in Difficult-to-Control Type 2 Diabetes Laboratory Support for Initial Evaluation.

Note: ADA 2026 guidelines do not mention hypercortisolism as a comorbidity that requires monitoring in the management of T2D.

References [return to contents]

  1. American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S27-S49. doi:10.2337/dc25-S002
  2. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. doi:10.1097/AOG.0000000000002501
  3. Little RR, La'ulu SL, Hanson SE, et al. Effects of 49 different rare Hb variants on HbA1c measurement in eight methods. J Diabetes Sci Technol. 2015;9(4):849-856. doi:10.1177/1932296815572367
  4. Glutamic Acid Decarboxylase (GAD) Autoantibody ELISA Kit. Package insert. KRONUS; December 2022.
  5. Insulin Autoantibody Radioimmunoassay Kit. Package insert. KRONUS; September 2009.
  6. IA-2 Autoantibody (IA-2Ab) ELISA Kit. Package insert. KRONUS; August 2021.
  7. FRA Fructosamine. Method sheet. cobas® Roche Diagnotics; August 2024.
  8. Andersson C, Vaziri-Sani F, Delli A, et al. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes. 2013;14(2):97-105. doi:10.1111/j.1399-5448.2012.00916.x
  9. Petruzelkova L, Ananieva-Jordanova R, Vcelakova J, et al. The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of type 1 diabetes mellitus. Diabet Med. 2014;31(2):165-171. doi:10.1111/dme.12308
  10. Wenzlau JM, Moua O, Sarkar SA, et al. SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann N Y Acad Sci. 2008;1150:256-259. doi:10.1196/annals.1447.029
  11. Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care. 2024;47(8):1276-1298. doi:10.2337/dci24-0042
  12. Leong A, Daya N, Porneala B, et al. Prediction of type 2 diabetes by hemoglobin A1c in two community-based cohorts. Diabetes Care. 2018;41(1):60-68. doi:10.2337/dc17-0607
  13. American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S61-S88. doi:10.2337/dc26-S004
  14. American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S216-S245. doi:10.2337/dc26-S010
  15. Louie JZ, Shiffman D, Meigs JB, et al. Insulin resistance is associated with incident prediabetes and type 2 diabetes in normoglycemic individuals. Diabetes Metab Syndr. 2026;20(1):103372. doi:10.1016/j.dsx.2025.103372
  16. Taylor SW, Clarke NJ, Chen Z, et al. A high-throughput mass spectrometry assay to simultaneously measure intact insulin and C-peptide. Clin Chim Acta. 2016;455:202-208. doi:10.1016/j.cca.2016.01.019
  17. Taylor SW, Clarke NJ, McPhaul MJ. Quantitative amino acid analysis in insulin and C-peptide assays. Clin Chem. 2016;62(8):1152-1153. doi:10.1373/clinchem.2016.256313
  18. Abbasi F, Shiffman D, Tong CH, et al. Insulin resistance probability scores for apparently healthy individuals. J Endocr Soc. 2018;2(9):1050-1057. doi:10.1210/js.2018-00107
  19. Shiffman D, Louie JZ, Meigs JB, et al. An insulin resistance score improved diabetes risk assessment in the Malmö Prevention Project-a longitudinal population-based study of older Europeans. Diabetes Care. 2021;44(10):e186-e187. doi:10.2337/dc21-1328
  20. Louie JZ, Shiffman D, McPhaul MJ, et al. Insulin resistance probability score and incident cardiovascular disease. J Intern Med. 2023;294(4):531-535. doi:10.1111/joim.13687
  21. Qian F, Guo Y, Li C, et al. Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial. Cardiovasc Diabetol. 2024;23(1):393. doi:10.1186/s12933-024-02470-1
  22. eAG/A1C conversion calculator. American Diabetes Association. Accessed February 24, 2026. http://professional.diabetes.org/diapro/glucose_calc.
  23. Nathan DM, Kuenen J, Borg R, et al. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008;31(8):1473-1478. doi:10.2337/dc08-0545
  24. American Diabetes Association Professional Practice Committee. 6. Glycemic goals, hypoglycemia, and hyperglycemic crises—2026. Diabetes Care. 2026;49(suppl 1):S132-S149. doi:10.2337/dc26-S006
  25. Dungan KM, Buse JB, Largay J, et al. 1,5-Anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes. Diabetes Care. 2006;29(6):1214-1219. doi:10.2337/dc06-1910
  26. Gounden V, Anastasopoulou C, Zubair M, et al. Clinical utility of fructosamine and glycated albumin In: StatPearls [Internet]. StatPearls Publishing; 2025. Updated September 15, 2025. Accessed February 24, 2026 https://www.ncbi.nlm.nih.gov/books/NBK470185/
  27. American Diabetes Association Professional Practice Committee. 7. Diabetes technology: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S150-S165. doi:10.2337/dc26-S007
  28. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412. doi:10.1136/bmj.321.7258.405
  29. Wright LA, Hirsch IB. Metrics beyond hemoglobin A1C in diabetes management: time in range, hypoglycemia, and other parameters. Diabetes Technol Ther. 2017;19(S2):S16-S26. doi:10.1089/dia.2017.0029
  30. Bergman M, Abdul-Ghani M, DeFronzo RA, et al. Review of methods for detecting glycemic disorders. Diabetes Res Clin Pract. 2020;165:108233. doi:10.1016/j.diabres.2020.108233
  31. Peabody J, Paculdo D, Acelajado MC, et al. Finding the clinical utility of 1,5-anhydroglucitol among primary care practitioners. J Clin Transl Endocrinol. 2020;20:100224. doi:10.1016/j.jcte.2020.100224
  32. Selvin E, Wang D, McEvoy JW, et al. Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial. Diabetes Obes Metab. 2019;21(8):2017-2023. doi:10.1111/dom.13755
  33. Onnis C, Virmani R, Kawai K, et al. Coronary artery calcification: current concepts and clinical implications. Circulation. 2024;149(3):251-266. doi:10.1161/CIRCULATIONAHA.123.065657
  34. JARDIANCE® (empagliflozin tablets). Package insert. Boehringer Ingelheim International GmbH. Updated February, 2022.
  35. Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023;118(1):59-76. doi:10.14309/ajg.0000000000002075
  36. Hogendorf A, Szymanska M, Krasinska J, et al. Clinical heterogeneity among pediatric patients with autoimmune type 1 diabetes stratified by immunoglobulin deficiency. Pediatr Diabetes. 2021;22(5):707-716. doi:10.1111/pedi.13208
  37. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia. JACC. Epub ahead of print. doi:10.1016/j.jacc.2025.11.016
  38. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314
  39. DeFronzo RA, Fonseca V, Aroda VR, et al. Inadequately controlled type 2 diabetes and hypercortisolism: improved glycemia with mifepristone treatment. Diabetes Care. 2025;48(12):2036-2044. doi:10.2337/dc25-1055
  40. Buse JB, Kahn SE, Aroda VR, et al. Prevalence of hypercortisolism in difficult-to-control type 2 diabetes. Diabetes Care. 2025;48(12):2012-2020. doi:10.2337/dc24-2841
  41. Nieman LK, Muniyappa R. Unmasking hypercortisolism in difficult-to-control type 2 diabetes: a useful paradigm shift? Diabetes Care. 2025;48(12):1994-1996. doi:10.2337/dci25-0038

Content reviewed 4/2026

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This test guide discusses the use of laboratory tests for general screening and diagnosis of prediabetes and diabetes; it also provides additional information on diabetes risk assessment and monitoring glycemic control and complications in individuals with diabetes.

Hereditary Cancer Test Selection Guide

Test Guide

 

Laboratory Testing for Diabetes Diagnosis, Risk Assessment, and Management

This Test Guide discusses the use of laboratory tests for general screening and diagnosis of prediabetes and diabetes primarily based on guidance provided by the American Diabetes Association® (ADA).1 Additional information is provided on diabetes risk assessment and monitoring glycemic control and complications in individuals with diabetes. This Test Guide is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician's education, clinical expertise, and assessment of the patient.

Diagnosis [return to contents]

Tests available for the general screening and diagnosis of prediabetes and diabetes include fasting plasma glucose (FPG) measurement (test code 484), oral glucose tolerance tests (OGTT, test codes 35181, 23475), and a standardized hemoglobin A1c (HbA1c, test code 496) assay (Table 1).1 Clinically significant glucose and HbA1c levels are shown in Table 2.1,2

Table 1. Tests Typically Used in Diabetes Screening and Diagnosis [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

General screening and diagnosis

484

Glucose, Plasma

  • Screen for and diagnose prediabetes and diabetes based on FPG

8917

Glucose, Random

  • Diagnose diabetes during a hyperglycemic crisis caused by use of certain therapies (Table 2)

35181

Glucose Tolerance Test, 2 Specimens (75g)

  • Screen for and diagnose diabetes based on fasting and 2-h (post 75-g glucose loading) specimens (2-h OGTT)

23475

Glucose Tolerance Test, 3 Specimens (75g)

  • Screen for and diagnose diabetes based on fasting, 1-, and 2-h (post 75-g glucose loading) specimens

 

496

Hemoglobin A1cb

  • Screen for and diagnose prediabetes and diabetes-determines long-term average blood glucose, expressed as a percentage

 

Gestational diabetes

8477

Glucose, Gestational Screen (50g), 135 Cutoff

  • Screen (without prior fasting) for gestational diabetes using a 1-h (post 50-g glucose loading) specimen (ADA- and ACOG-supported 1st step of 2-step evaluation); a cutoff of 135 mg/dL (test code 8477) or 140 mg/dL (test code 19833) indicates that the 2nd step (test code 6745) is necessary

 

 

19833

Glucose, Gestational Screen (50g), 140 Cutoff

18927

Glucose Tolerance Test, Gestational, 3 Specimens (75g)

  • Diagnose gestational diabetes (ADA-supported 1-step evaluation)

 

6745

Glucose Tolerance Test, Gestational, 4 Specimens (100g)

  • Diagnose gestational diabetes based on fasting, 1-, 2-, and 3-h (post 100-g glucose loading) specimens (ADA- and ACOG-supported 2nd step of 2-step evaluation)

Type 1 diabetes

13621

Diabetes Type 1 Autoantibody Panel

Includes GAD (34878), IA-2 (37933), insulin (36178), and ZnT8 (93022) autoantibodies.

  • Screen and assess risk for development of T1D in presymptomatic individuals
  • Diagnose T1D in symptomatic children and adults
  • Differentially diagnose T1D vs T2D
  • Determine eligibility for teplizumab therapy or clinical trials for new therapies that delay onset of clinical diabetes
ACOG, American College of Obstetricians and Gynecologists; ADA, American Diabetes Association; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; OGTT, oral glucose tolerance test; T1D, type 1 diabetes; T2D, type 2 diabetes.
a Panel components may be ordered separately.
b Determined using a National Glycohemoglobin Standardization Program (NGSP)-certified HbA1c method that is corrected for common hemoglobin variants.1
c This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

 

Table 2. Diagnostic Significance of Glucose and Hemoglobin A1c Concentrations [return to contents]

Individuals suitable for testing1,2

Marker: clinically significant levels1,a,b

Interpretation1

  • Nonpregnant individuals with diabetes risk factors or age ≥35 y
  • Individuals 3-6 mo following acute pancreatitis
  • Individuals with suspected monogenic diabetesd
  • Individuals prescribed medications known to increase diabetes riske
  • FPG: ≥126 mg/dL
  • 2-h OGTT (75 g): ≥200 mg/dL
  • HbA1c level: ≥6.5%
  • Diabetesc
  • FPG: 100-125 mg/dL
  • 2-h OGTT (75 g): 140-199 mg/dL
  • HbA1c level: 5.7%-6.4%
  • Prediabetes
  • Individuals experiencing a hyperglycemic crisis (eg, DKA or HHS)
  • Individuals with recurrent or long-term use of glucocorticoids
  • RPG: ≥200 mg/dL
  • Diabetes
  • Individuals prescribed ICIsf
  • RPG: ≥200 mg/dL
  • FPG: ≥126 mg/dL
  • Systemic anticancer therapy-induced diabetes
  • Individuals prescribed PI3Kαg or mTORh inhibitors
  • RPG: ≥200 mg/dL
  • FPG: ≥126 mg/dL
  • HbA1c level: ≥6.5%
  • Systemic anticancer therapy-induced diabetes
  • All individuals planning pregnancy
  • FPG: 100-125 mg/dL
  • HbA1c level: 5.9% to 6.4%
  • Increased risk for diabetes and adverse pregnancy and neonatal outcomes
  • Individuals with some hemoglobin variants, G6PD, HIV,i or abnormal red cell turnover
  • FPG: ≥126 mg/dL
  • Diabetesc
  • FPG: 100-125 mg/dL
  • Prediabetes
  • All pregnant individuals (24-28 wks of gestation)j
  • Individuals with CF age ≥10 ym
  • Individuals who have received an organ transplantn
  • 2-h OGTT (75 g)
  • Fasting: ≥92 mg/dL
  • 1 h: ≥180 mg/dL
  • 2 h: ≥153 mg/dL
  • Gestational diabetesk,l
  • CF-related diabetes
  • Posttransplantation diabetes
ACOG, American College of Obstetricians and Gynecologists; ADA, American Diabetes Association; CF, cystic fibrosis; DKA, diabetic ketoacidosis; FPG, fasting plasma glucose; G6PD, glucose-6-phosphate dehydrogenase deficiency; HbA1c, hemoglobin A1c; HHS, hyperosmolar hyperglycemic state; ICIs, immune checkpoint inhibitors; mTOR, mammalian target of rapamycin; OGTT, oral glucose tolerance test; PI3Kα, phosphoinositide 3-kinase alpha; RPG, random plasma glucose.
a If test results are in-range for healthy individuals, repeat testing at 3-year intervals, sooner if change in symptoms or risk (eg, weight gain).
b If test results are close to diagnostic thresholds, repeat testing in 3 to 6 months.
c Absent overt clinical signs of hyperglycemia (eg, polyuria, polydipsia, unexplained weight loss), diagnosis requires 2 clinically significant test results (either the same test using a new blood sample or 2 different tests). If 2 different tests (eg, HbA1c and FPG) are performed and 1 gives clinically significant results and the other does not, the test with clinically significant results should be repeated. If the repeat test result is also clinically significant, diabetes is diagnosed.
d If ≥1 of the following features is present, monogenic diabetes is suggested: HbA1c <7.5% at diagnosis, 1 parent with diabetes, clinical features consistent with a monogenic cause (eg, renal cysts, partial lipodystrophy, maternally inherited deafness, severe insulin resistance without obesity), or monogenic diabetes prediction model probability >5% (Exeter Diabetes App). Genetic testing options for monogenic diabetes are available through Athena Diagnostics.
e For example, glucocorticoids, statins, thiazide diuretics, and some HIV medications. For individuals prescribed 2nd-generation antipsychotic medications, screen for prediabetes and diabetes at baseline,12 to 16 weeks after initiation (sooner if clinically indicated); if test results are normal, repeat testing annually.
f For individuals prescribed ICIs: FPG or random plasma glucose at baseline, during each visit, or if signs of hyperglycemia develop during or after treatment cessation.
g For individuals prescribed PI3Kα inhibitors: FPG or random plasma glucose and HbA1c at baseline, random plasma glucose weekly for 2 weeks then every 4 weeks, and consider HbA1c every 3 months during treatment.
h For individuals prescribed mTOR inhibitors: FPG or random plasma glucose at baseline, during each visit, and consider HbA1c every 3 months during treatment.
i Screen before and 3 to 6 months after starting or changing antiretroviral therapy; if test results are normal, repeat testing annually.
j The 1-step strategy is listed; the alternative 2-step strategy involves a 1-h OGTT (50 g) screen in nonfasting individuals; if the indicated cutoff is met (ie, ≥135 mg/dL or ≥140 mg/dL), a 3-h OGTT (100 g) is performed with collection of 4 specimens (fasting, 1-, 2-, and 3-h). According to the ADA, gestational diabetes is diagnosed if 2 specimens meet or exceed the following glucose levels: fasting, 95 mg/dL; 1-h, 180 mg/dL; 2-h, 155 mg/dL; and 3-h, 140 mg/dL (ACOG requires only 1 elevated specimen for diagnosis of gestational diabetes).
k Only 1 of the 3 time points need to be elevated to make the diagnosis.
l Repeat 2-h OGTT 4 to 12 weeks postpartum and interpret results per nonpregnant individuals. Screen individuals with a history of GDM for prediabetes and diabetes every 1 to 3 years.
m If OGTT is not initially feasible, a 2-step screening strategy for CF–related diabetes is recommended involving HbA1c as the initial test. Only those with values between 5.5% and 6.4% should undergo an OGTT within 3 months.
n Stable on immunosuppressive therapy and free of acute infections.

 

Guidelines for testing

The ADA recommends using FPG, OGTT, and HbA1c for diagnosing diabetes and identifying increased diabetes risk (prediabetes). For individuals experiencing overt symptoms related to hyperglycemia, a random plasma glucose measurement (with a specimen collected any time of the day regardless of previous meal time, test code 8917) is recommended for diagnosis.1

Screening for prediabetes and/or T2D should be performed for all individuals beginning at age 35 years, earlier for those with risk factors (see “Risk Factor Assessment for Prediabetes and Type 2 Diabetes” in Section 2: Diagnosis and Classification of Diabetes | Clinical Diabetes | American Diabetes Association). For overweight or obese children or adolescents with ≥1 risk factor, screening should be considered after the onset of puberty or after 10 years of age, whichever occurs earlier.1

For individuals with prediabetes, annual monitoring for development of diabetes is recommended; frequency of monitoring may be modified based on an individual’s risk-to-benefit assessment.1 For those without diabetes or prediabetes, screening should be repeated every 3 years—earlier if their risk factors increase.1

Comparison of glycemic measures for screening and diagnosis

FPG, OGTT, and HbA1c are equally appropriate for diagnostic screening in the general population, although one may be more appropriate than another depending on an individual’s characteristics (eg, certain nondiabetic illnesses or pregnancy, Tables 1 and 2).1

FPG and OGTT tests are sensitive but measure glucose levels only in the short term, require fasting or glucose loading, and give variable results during stress and illness.1 In contrast, HbA1c assays reliably estimate average glucose levels over a longer term (2 to 3 months), do not require fasting or glucose loading, and have less variability during stress and illness.1

In some circumstances, HbA1c is a less reliable marker than plasma glucose. Examples include people with some hemoglobinopathies, altered red blood cell turnover (eg, caused by hemodialysis, recent blood cell loss/transfusion, erythropoietin-treatment, or anemia), HIV, glucose-6-phosphate dehydrogenase deficiency, or cystic fibrosis, as well as during pregnancy.1 In addition, primary prevention measures have proven more efficacious for individuals whose glycemic status is based on OGTT results compared with isolated FPG results or HbA1c results meeting the criteria for prediabetes.1

Quest Diagnostics uses an HbA1c assay (test code 496) that is unaffected by the presence of hemoglobin (Hb) variants (HbC, HbS, HbE, HbD) in heterozygous individuals (HbA1c cannot be measured in individuals who are homozygous or compound heterozygous for Hb variants). However, the assay is subject to interference by elevated HbF, which is present in conditions such as β-thalassemia, and a few rare Hb variants.3 The assay has no significant interference from high concentrations of lipids (including high triglycerides) and bilirubin. This method has been standardized against the approved International Federation of Clinical Chemistry (IFCC) reference method. Results are traceable to Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program (DCCP/NGSP).

When there is consistent and substantial discordance between glycemic measures for diagnosis and analytical issues have been eliminated as being a cause, the ADA recommends using alternative validated biomarkers, such as fructosamine (test code 8340), which is discussed in the "Management" section below.1

Gestational diabetes

ADA and American College of Obstetricians and Gynecologists (ACOG) recommendations for screening and diagnosis of gestational diabetes are provided in Table 2. Quest offers test codes 8477, 19833,18927, and 6745 for pregnant individuals and those planning pregnancy.

Type 1 diabetes

A hallmark of T1D is its association with autoantibodies targeting insulin, tyrosine phosphatase-related islet antigen 2 (IA-2), zinc transporter 8 (ZnT8), and glutamic acid decarboxylase-65 (GAD). Using these 4 antibodies together,4-7 T1D can be diagnosed in 93% to 98% of symptomatic patients.8-10 On this basis, the ADA recommends screening for T1D using these markers, especially among patients who are at risk (eg, family history of autoimmune diabetes).1 Consensus guidance has been provided for diagnosing and monitoring individuals with prestage-3 T1D and is based on the number of T1D autoantibodies and glycemic indices.11 Quest offers a panel comprising all these antibodies (test code 13621) for T1D screening, diagnosis, and treatment eligibility. For more information, see Diabetes Type 1 Autoantibody Panel | Test Summary | Quest Diagnostics.

 

Diabetes risk assessment [return to contents]

The ADA provides a calculator https://diabetes.org/diabetes-risk-test to estimate risk for diabetes, with scores ranging from 1 (low risk) to 10 (high risk) but otherwise, beyond identifying prediabetes, provides no guidance in calculating diabetes risk from laboratory results.1 Approaches offered by Quest for diabetes risk assessment include (a) using HbA1c in conjunction with other laboratory results and information from a clinical visit to estimate 8-year risk and (b) assessing the risk of insulin resistance as a predictor of onset of prediabetes and T2D using laboratory results alone. The latter approach allows prediction of diabetes risk before dysglycemia develops, as discussed below.

HbA1c

HbA1c results are used in combination with certain sociodemographic and anthropometric characteristics in predicting risk for prediabetes and T2D in asymptomatic individuals. Quest also provides panels that supplement HbA1c results with plasma glucose and lipid analysis with (test code 92027) or without (test code 91920) a calculated risk score for developing T2D over 8-years (Table 3).12 The risk score also uses patient age (30-79 years), sex, height, weight, blood pressure, family history of diabetes, and is most accurate when the patient is fasting 9-12 hours before blood collection. Because cardiovascular disease (CVD) is elevated with dysglycemia, concurrent monitoring of CVD risk factors is also recommended.13,14 Quest also offers a panel (test code 92062) with additional estimates of 10-year and lifetime risk of developing CVD.

Table 3. Tests Used in Diabetes Risk Assessment [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

36509

Cardio IQ® Insulin Resistance Panel With Scoreb

Includes intact insulin LC/MS/MS (93103), C-peptidec and calculated IR score.

  • Assess risk of insulin resistance and prediabetes

92062

Diabetes and ASCVD Risk Panel With Scoresd,e,f,g

Includes glucose (483); HbA1c (496); total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896) with reflex to direct LDL (8293); cholesterol/HDL ratio (calculated); non-HDL (calculated); 8-year risk of developing diabetes (calculated); and 10-year and lifetime ASCVD (calculated).

  • Screen for and diagnose prediabetes and diabetes
  • Calculate 8-year risk for developing T2D12 and 10-year and lifetime risk of developing ASCVD

92027

Diabetes Risk Panel With Scored,e,g

Includes glucose (483); HbA1c (496); total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896) with reflex to direct LDL (8293); cholesterol/HDL ratio (calculated); non-HDL (calculated); and 8-year risk of developing diabetes (calculated).

  • Screen for and diagnose prediabetes and diabetes
  • Calculate 8-year risk for developing T2D12

91920

Diabetes Risk Panel Without Scored

Includes glucose (483); HbA1c (496); total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896) with reflex to direct LDL (8293); cholesterol/HDL ratio (calculated); and non-HDL (calculated).

  • Screen for and diagnose prediabetes and diabetes
  • Assess risk for developing T2D

39447

Metabolic Risk Panel

Includes Cardio IQ apolipoprotein B (91726), HDL (91719) and total (91717) cholesterol, hemoglobin A1c (91732), insulin resistance panel with score (36509), triglycerides (91718), and non-HDL and calculated components.

  • Screen for and diagnose prediabetes and diabetes
  • Assess risk of insulin resistance and cardiovascular disease
ASCVD, atherosclerotic cardiovascular disease; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein; T2D, type 2 diabetes.
a Panel components may be ordered separately.
b This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c The C-peptide LC/MS/MS panel component cannot be ordered separately. C-peptide by immunoassay (test code 372) is not an equivalent test and cannot be used in calculation of the insulin resistance risk score.
d Reflex tests are performed at additional charge and are associated with an additional CPT® code.
e The diabetes risk score, expressed as a percentage, is calculated with an algorithm that incorporates levels of HbA1c, FPG, high-density lipoprotein (HDL) cholesterol, and triglycerides, as well as patient age and sex.12
f ASCVD risk calculator is available at ASCVD Risk Estimator +.
g Cardio IQ versions of these panels (test codes 92063 and 92026) are also available with a color-coded report to display progressive risk values versus goal using “optimal,” “moderate,” and “high-risk” categories.

 

Insulin resistance risk score

Emerging data also suggests that onset of prediabetes and T2D may be predicted by insulin resistance measured using an insulin resistance risk score (IRRS, test code 36509), even in normoglycemic individuals who are not overweight or obese or who do not have other risk factors.15 The score is calculated from fasting intact insulin and C-peptide blood levels measured using mass spectrometry16 standardized for consistent measurement over time.17

An IRRS ≥33% indicates a higher risk of having insulin resistance.18 Subsequent studies assessed the risk of developing T2D using the risk score and found that scores lower than 33% had clinical significance. Older individuals (median age 68 years) with an IRRS >20% had up to double the risk of developing T2D over 9 years compared to those with an IRRS <7%.19 Working age individuals (median age 43 years) with healthy, in-range HbA1c and FPG levels and an IRRS >20% had a 43% greater risk of developing prediabetes or T2D over 3 years compared to those with an IRRS <8%.15 Compared to lower IRRSs, higher IRRSs have also been associated with an increased risk of incident CVD and all-cause mortality20 and incident coronary heart disease (fatal and non-fatal myocardial infarction and coronary revascularization).21

For more information on the IRRS, see

Note: To assess insulin resistance, ADA 2026 guidelines only mention clinical presentation (eg, acanthosis nigricans, severe obesity, metabolic dysfunction-associated steatotic liver disease [MASLD], formerly nonalcoholic fatty liver disease [NAFLD]), with no reference to laboratory testing other than FPG, OGTT, and HbA1c for prediabetes and T2D.1

Management [return to contents]

Following a diagnosis of diabetes, a combination of laboratory and clinical tests can be used to monitor blood glucose control and predict treatment response (Table 4).1,13,22,23 Recommended testing frequency and target results for these tests can be found in Table 5.7,22-26 Different laboratory tests are available for monitoring blood glucose control over the short, long, and intermediate term to help evaluate the effectiveness of a management plan.

Table 4. Tests Used in Managing Diabetes [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

10378

1,5-Anhydroglucitol (1,5-AG), Intermediate Glycemic Controlb

  • Measure glycemic control over the short-to-intermediate term (1 to 2 weeks)

372

C-Peptide

  • Classify diabetes of uncertain type for individuals receiving insulin therapyd
  • Exclude severe insulin deficiency before discontinuing insulin therapy

15843

C-Peptide Response to Glucose, 2 Specimensc

15844

C-Peptide Response to Glucose, 3 Specimensc

15845

C-Peptide Response to Glucose, 4 Specimensc

31345

C-Peptide Response to Glucose, 5 Specimensc

15846

C-Peptide Response to Glucose, 6 Specimensc

15847

C-Peptide Response to Glucose, 7 Specimensc

15848

C-Peptide Response to Glucose, 8 Specimensc

15448

C-Peptide Response to Glucose, 9 Specimensc

8340

Fructosamine

  • Measure glycemic control over the intermediate term (2 to 3 weeks) and when there is discordance between other glycemic measures

16802

Hemoglobin A1c With eAGe

  • Determine long-term average blood glucose; expressed in percent HbA1c and eAG in conventional blood glucose units for more convenient comparison to BGM values1,22,23

10380

Hemoglobin A1c With Reflex to 1,5-Anhydroglucitol (1,5-AG)e,f

  • Measure glycemic control over the short-to-intermediate term (1 to 2 weeks) in moderately controlled diabetes (HbA1c ≥6.5% and ≤8.0%)

10379

Hemoglobin A1c With eAG With Reflex to 1,5-Anhydroglucitol (1,5-AG)e,f

7577

Protein, Total and Albumin

Includes albumin (223), globulin (calculated), albumin/globulin ratio (calculated), and total protein (754).

  • Used with fructosamine testing to assess plasma protein levels
1,5-AG, 1,5-anhydroglucitol; BGM, blood glucose monitoring; eAG, estimated average glucose; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; T1D, type 1 diabetes; T2D, type 2 diabetes.
a Panel components may be ordered separately.
b The analytical performance characteristics of this assay have been determined by Quest Diagnostics. The modifications have not been cleared or approved by the FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c Do not perform this test within 2 weeks of a hyperglycemic emergency.
d According to the ADA, a concurrent glucose and C-peptide measurement from a random specimen within 5 h of eating can replace a formal C-peptide stimulation test.
e Determined using a NGSP–certified HbA1c method that is corrected for common hemoglobin variants.1
f Reflex tests are performed at additional charge and are associated with an additional CPT code.

 

Table 5. Recommended Testing Frequency and Goals for Diabetes Management [return to contents]

Marker

Target levels in patients with diabetesa

Testing frequencyb

HbA1c test

HbA1c level

Nonpregnant adults without significant hypoglycemia24,c: <7.0%

Patients with a history of severe hypoglycemia, extensive comorbidities, or a long-standing diagnosis in whom lower targets are difficult to achieve: <8%24

  • Initial visit
  • Follow-up
  • Every 6 months for patients with stable glycemia who meet glycemic goals
  • Every 3 months or as needed for children and adolescents during periods of rapid growth, patients who have changed therapy and are not meeting glycemic goals, patients who experience frequent or severe hyper- or hypoglycemia or changes in health status
  • More frequently for patients with unstable glycemia and those undergoing intensive management (eg, pregnant women with T1D)

eAGd

<154 mg/dL (8.6 mmol/L)24

  • Same as for HbA1c level

Fructosamine

Fructosamine level

Target levels not establishede

  • As clinically indicated to monitor glucose control over 2 to 3 weeks

1,5-AG

1,5-AG level

≥8.0 μg/mL25

  • At time of HbA1c test if HbA1c levels are moderately or well-controlled to detect PPG excursions
  • As clinically indicated to monitor glucose control over 1 to 2 weeks
1,5-AG, 1,5-anhydroglucitol; BGM, blood glucose monitoring; eAG, estimated average glucose; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; T1D, type 1 diabetes; T2D, type 2 diabetes.
a Achieving glucose, HbA1c, eAG, and 1,5-AG goals should be balanced against risk of inducing hypoglycemia.
b Suggested testing frequency is generalized for routine monitoring and may vary depending on clinical condition and treatment regimen.
c Lower goals (<6%) may be appropriate for individuals with good health and low treatment risk; less stringent goals may be appropriate for individuals who are frail and in poor health for whom treatments risks are higher
d eAG values in mg/dL are calculated by converting HbA1c levels to eAG using the following formula22,23: eAG = HbA1c × 28.7 - 46.7. eAG values in mg/dL can be converted to mmol/L by dividing by 18.
e Fructosamine quantitation has not been standardized26; values from different assays cannot be easily compared. The assay that Quest offers (test code 8340) provides a reference range for healthy adults, but this is not a target for glycemic control for people with diabetes. Poorly controlled diabetes using this assay has been measured as mean a fructosamine of 396 μmol/L (range 228-563 μmol/L).7 In hydremic states, correcting fructosamine for total protein using the formula: Corrected fructosamine = 72 × [fructosamine μmol/L]/[total protein g/L] has been suggested.7

 

Comparison of testing methods for monitoring diabetes

Blood glucose monitoring (BGM) and continuous glucose monitoring (CGM) are useful for tracking short-term treatment responses in insulin-treated patients and identifying acute hypo- and hyperglycemic diabetic events.24,27 By contrast, the long-term HbA1c measure should be used as the primary test of glycemic control in all nonpregnant adults with diabetes24; lowering HbA1c levels by 1 percentage point reduces the risk of microvascular complications by approximately 40%.28

To help patients relate long-term glucose control to daily BGM and CGM measurements, HbA1c test results may be converted to conventional glucose units (mg/dL or mmol/L) and reported as the estimated average glucose (eAG, test code 16802).22-24 Although reporting eAG is approved by both the ADA and the American Association for Diagnostics & Laboratory Medicine, the ADA cautions that conversion to eAG relies on a 2008 study correlating HbA1c to older CGM technology.24

Alternatives to HbA1c testing for monitoring glycemic control over the short-to-intermediate term include fructosamine testing (2 to 3 weeks) and 1,5-anhydroglucitol (1,5-AG, 1 to 2 weeks) testing.

In addition to CGM, fructosamine testing (test code 8340) is particularly useful when HbA1c may not be a reliable marker,24 such as in hemodialysis patients with high red blood cell turnover, early responses to treatment changes, and pregnancy complicated by diabetes.29 The assay is a measure of glycated plasma proteins, which experience a faster turnover than intracellular HbA1c and better reflect short term glycemic variability.30 The assay is influenced by conditions in which serum albumin and total protein (test code 7577) concentrations are low because of disease (eg, liver cirrhosis, nephrotic syndrome, and protein-losing enteropathies) and hydremic states such as pregnancy, and is unreliable when albumin is <3.0 g/dL.26 Conditions with elevated protein (eg, polyclonal gammopathies and multiple myeloma) can also cause unreliable fructosamine results.26 Levodopa and oxytetracycline cause artificially high fructosamine results.7

Levels of 1,5-AG (test code 10378) are used to assess postprandial glucose excursions in individuals with moderately or well-controlled HbA1c levels (6.5% to 8.0%).25,29 A 2020 study proposes that 1,5-AG be used to increase physician awareness of steroid-induced hyperglycemia and poor short-term glycemic control, which is associated with poorer outcomes.31 Levels of 1,5-AG have been found to be predictive of microvascular complications, independent of HbA1c, in patients undergoing glucose and blood pressure-lowering therapy.32 In addition, lower 1,5-AG values are inversely correlated to higher coronary artery calcification and CVD risk.33 Quest offers 1,5-AG testing, which can be used as suggested in conjunction with HbA1c to identify individuals experiencing postprandial excursions over the short-to-intermediate term; these tests can be used as individual tests (Figure)25 or as reflex tests with (test code 10379) or without (test code 10380) eAG.

The 1,5-AG test is unreliable for patients taking SGLT2 inhibitors because of assay interference.34

Note: ADA 2026 guidelines do not provide recommendations on how 1,5-AG should be incorporated into clinical practice.24,29

For patients receiving insulin therapy, the ADA recommends C-peptide testing (Table 4) if (a) there is uncertainty regarding their type of diabetes or (b) discontinuation of insulin is being considered. Levels ≥1.8 ng/mL indicate T2D whereas level <0.24 ng/mL indicate T1D.1 Repeat testing may be required for intermediate C-peptide levels with concurrent glucose <70 mg/dL or if the patient may have been fasting.1

Testing methods for diabetic complications and comorbidities

Individuals with diabetes are at increased risk of retinopathy and neuropathy, as well as heart, liver, and kidney disease. In addition to routine eye and foot exams and blood pressure monitoring, tests for monitoring lipids, liver, and kidney function are recommended to detect the onset and monitor progression of these complications. Quest offers these tests individually and within panels (Table 6). For more information, see Laboratory Testing for Chronic Kidney Disease Diagnosis and Management and Cardiometabolic Disease Assessment (CMDA) Panel. Celiac disease screening (test codes 8821 and 539) and thyroid function testing (TSH, test code 899) are also recommended in the context of T1D and comorbid autoimmune disorders.13 Recommended testing frequency and target results for these tests can be found in Table 7.13,14,35,36

Table 6. Tests Used in Monitoring Diabetic Complications and Comorbidities [return to contents]

Test code

Test name (component tests)a

Primary clinical use and differentiating factors

ASCVD

5224

Apolipoprotein Bb

  • Guide decisions on intensification of lipid-lowering therapy once LDL- and non-HDL-cholesterol goals have been achieved, particularly for patients with T2D and ASCVD, cardiovascular-kidney-metabolic syndrome, and/or elevated triglycerides37

7600(X)

Lipid Panel, Standardb

Includes total (334), HDL (608), and LDL (calculated) cholesterol; triglycerides (896); cholesterol/HDL ratio (calculated); non-HDL (calculated).

  • Monitor dyslipidemia and thus risk of heart disease

Chronic kidney disease

94588

Cystatin C With Glomerular Filtration Rate, Estimated (eGFR)

  • Monitor chronic kidney disease in patients for whom creatinine-based results may lead to an incorrect diagnosisc

13581

Estimated Glomerular Filtration Rate (eGFR) With Creatinine and Cystatin C

Includes serum creatinine (375), cystatin C (94588), and eGFR calculation.

  • Monitor for chronic kidney disease (most accurate estimate for at-risk patients or for whom creatinine-based results may lead to an incorrect diagnosis)38,c

39165

Kidney Profile

Includes albumin, random urine with creatinine (6517) and serum creatinine (375) with calculated eGFR.

  • Monitor onset and progression of kidney disease

 

MASLD

10350

Enhanced Liver Fibrosis (ELF) Score

  • Assess likelihood that nonalcoholic steatohepatitis will progress to cirrhosis and liver-related clinical events; used for patients with indeterminant or high FIB-4 results13

30555

Liver Fibrosis, Fibrosis-4 (FIB-4) Index Panel

Includes ALT (823), AST (822), platelet count (723), and FIB-4 index (calculated).

  • Screen for fibrosis in individuals with prediabetes and CVD risk factors, T2D, or T1D (only if additional risk factors such as obesity, hepatic steatosis, or elevated liver aminotransferases are present); preferred option by the ADA13

T1D–associated conditions

539

IgA

  • Screen for IgA deficiency in people with T1D, which may lead to false positive tTG celiac screening (test code 8821)

8821

Tissue Transglutaminase (tTG) Antibody (IgA)

  • Screen for celiac disease in T1D

899

TSH

  • Assess thyroid function in T1D

Difficult-to-control diabetes

29391

Dexamethasone

  • Aid interpretation of DST (test code 6921)

6921

Dexamethasone Suppression Test (DST), 1 Specimen

  • Diagnose hypercortisolism in difficult-to-control T2D

Multiple conditions

14273

Cardiometabolic Disease Assessment (CMDA) Panel

Includes Cardio IQ apolipoprotein B (91726), HbA1c (91732), insulin resistance panel with score (36509), and lipid panel (91716); comprehensive metabolic panel with FIB-4 index (10372); kidney profile (39165); and TSH (899).

  • Identify early metabolic dysfunction in cardiometabolic disease in the context of measures of dyslipidemia and glycemic control
  • Assess common endocrine disorders that cause or are exacerbated by cardiometabolic dysfunction
  • Quantify downstream adverse effects of chronic cardiometabolic disease on end-organ dysfunction, including liver and kidney
ALT, alanine aminotransferase; ASCVD, atherosclerotic cardiovascular disease; AST, aspartate aminotransferase; DST, dexamethasone suppression test; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; IgA, immunoglobulin A; LDL, low-density lipoprotein; MASLD, metabolic dysfunction-associated steatotic liver disease; NAFLD, nonalcoholic fatty liver disease; T1D, type 1 diabetes; T2D, type 2 diabetes; TSH, thyroid stimulating hormone; tTG, tissue transglutaminase.
a Panel components may be ordered separately.
b Cardio IQ versions of apolipoprotein B (test code 91726) and the lipid panel (test code 91716) are also available with a color-coded report to display progressive risk values versus goal using “optimal,” “moderate-risk,” and “high-risk” categories.
c Pregnant women, patients with acute illness, patients with serious comorbid conditions, people with extremes of muscle mass (eg, bodybuilders, patients with amputation, paraplegia, muscle-wasting disease, or a neuromuscular disorder), patients suffering from malnutrition, those with a vegetarian or low-meat diet, and those taking creatine dietary supplements.

 

Table 7. Recommended Testing Frequency and Goals for Monitoring Diabetic Complications [return to contents]

Marker13

Target levels in patients with diabetes

Testing frequencya

ASCVD

Fasting lipid profile (LDL, HDL, TG)13,14

LDL: <70 mg/dL

HDL: ≥40 mg/dL(men); ≥50 mg/dL (women)

TG: <150 mg/dL

  • Initial visit and then annually (adults not taking statins); as needed to monitor adherence and efficacy of introducing statin therapy or for patients with ASCVD

Liver disease

FIB-4

Score: <1.3 (<F2)

  • Initial visit and then annually

Kidney disease

Creatinine level and eGFR

eGFR ≥60 mL/min/1.73 m2

  • Initial visit and then annually

Urine albumin/creatinine ratio

<30 μg/mg creatinine (normal)

  • Initial visit and then annually

Autoimmune disease

Tissue transglutaminase IgA35,b

<15.0 U/m (antibody not detected)

  • Initial visit for patients with T1D with gastrointestinal symptoms, signs, laboratory test results, or clinical suspicion

TSH

1-19 years: 0.50-4.30 mIU/L

≥20 years: 0.40-4.50 mIU/L

  • Initial visit and then annually for patients with T1D
ASCVD, atherosclerotic cardiovascular disease; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; T1D, type 1 diabetes; T2D, type 2 diabetes; TSH, thyroid stimulating hormone.
a Suggested testing frequency is generalized for routine monitoring and may vary depending on clinical condition and treatment regimen.
b May be performed with total IgA (test code 539) to detect false positives caused by IgA deficiency rather than celiac disease. IgA deficiency is relatively common in T1D; one study found about 1 in 10 children with T1D are affected.36

 

Testing methods for difficult-to-control T2D

In primary care settings, many patients with difficult-to-control T2D do not achieve glycemic goals despite taking multiple glucose-lowering medications.39,40 For some of these patients, other underlying conditions may be impairing glycemic control.40,41 In particular, hypercortisolism (excessive cortisol levels) may contribute to difficult-to-control T2D but is not typically assessed during T2D management.39-41 Quest offers several tests for initial evaluation of hypercortisolism including test codes 29391 and 6921. For more information, see Hypercortisolism in Difficult-to-Control Type 2 Diabetes Laboratory Support for Initial Evaluation.

Note: ADA 2026 guidelines do not mention hypercortisolism as a comorbidity that requires monitoring in the management of T2D.

References [return to contents]

  1. American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S27-S49. doi:10.2337/dc25-S002
  2. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. doi:10.1097/AOG.0000000000002501
  3. Little RR, La'ulu SL, Hanson SE, et al. Effects of 49 different rare Hb variants on HbA1c measurement in eight methods. J Diabetes Sci Technol. 2015;9(4):849-856. doi:10.1177/1932296815572367
  4. Glutamic Acid Decarboxylase (GAD) Autoantibody ELISA Kit. Package insert. KRONUS; December 2022.
  5. Insulin Autoantibody Radioimmunoassay Kit. Package insert. KRONUS; September 2009.
  6. IA-2 Autoantibody (IA-2Ab) ELISA Kit. Package insert. KRONUS; August 2021.
  7. FRA Fructosamine. Method sheet. cobas® Roche Diagnotics; August 2024.
  8. Andersson C, Vaziri-Sani F, Delli A, et al. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes. 2013;14(2):97-105. doi:10.1111/j.1399-5448.2012.00916.x
  9. Petruzelkova L, Ananieva-Jordanova R, Vcelakova J, et al. The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of type 1 diabetes mellitus. Diabet Med. 2014;31(2):165-171. doi:10.1111/dme.12308
  10. Wenzlau JM, Moua O, Sarkar SA, et al. SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann N Y Acad Sci. 2008;1150:256-259. doi:10.1196/annals.1447.029
  11. Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care. 2024;47(8):1276-1298. doi:10.2337/dci24-0042
  12. Leong A, Daya N, Porneala B, et al. Prediction of type 2 diabetes by hemoglobin A1c in two community-based cohorts. Diabetes Care. 2018;41(1):60-68. doi:10.2337/dc17-0607
  13. American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S61-S88. doi:10.2337/dc26-S004
  14. American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S216-S245. doi:10.2337/dc26-S010
  15. Louie JZ, Shiffman D, Meigs JB, et al. Insulin resistance is associated with incident prediabetes and type 2 diabetes in normoglycemic individuals. Diabetes Metab Syndr. 2026;20(1):103372. doi:10.1016/j.dsx.2025.103372
  16. Taylor SW, Clarke NJ, Chen Z, et al. A high-throughput mass spectrometry assay to simultaneously measure intact insulin and C-peptide. Clin Chim Acta. 2016;455:202-208. doi:10.1016/j.cca.2016.01.019
  17. Taylor SW, Clarke NJ, McPhaul MJ. Quantitative amino acid analysis in insulin and C-peptide assays. Clin Chem. 2016;62(8):1152-1153. doi:10.1373/clinchem.2016.256313
  18. Abbasi F, Shiffman D, Tong CH, et al. Insulin resistance probability scores for apparently healthy individuals. J Endocr Soc. 2018;2(9):1050-1057. doi:10.1210/js.2018-00107
  19. Shiffman D, Louie JZ, Meigs JB, et al. An insulin resistance score improved diabetes risk assessment in the Malmö Prevention Project-a longitudinal population-based study of older Europeans. Diabetes Care. 2021;44(10):e186-e187. doi:10.2337/dc21-1328
  20. Louie JZ, Shiffman D, McPhaul MJ, et al. Insulin resistance probability score and incident cardiovascular disease. J Intern Med. 2023;294(4):531-535. doi:10.1111/joim.13687
  21. Qian F, Guo Y, Li C, et al. Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial. Cardiovasc Diabetol. 2024;23(1):393. doi:10.1186/s12933-024-02470-1
  22. eAG/A1C conversion calculator. American Diabetes Association. Accessed February 24, 2026. http://professional.diabetes.org/diapro/glucose_calc.
  23. Nathan DM, Kuenen J, Borg R, et al. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008;31(8):1473-1478. doi:10.2337/dc08-0545
  24. American Diabetes Association Professional Practice Committee. 6. Glycemic goals, hypoglycemia, and hyperglycemic crises—2026. Diabetes Care. 2026;49(suppl 1):S132-S149. doi:10.2337/dc26-S006
  25. Dungan KM, Buse JB, Largay J, et al. 1,5-Anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes. Diabetes Care. 2006;29(6):1214-1219. doi:10.2337/dc06-1910
  26. Gounden V, Anastasopoulou C, Zubair M, et al. Clinical utility of fructosamine and glycated albumin In: StatPearls [Internet]. StatPearls Publishing; 2025. Updated September 15, 2025. Accessed February 24, 2026 https://www.ncbi.nlm.nih.gov/books/NBK470185/
  27. American Diabetes Association Professional Practice Committee. 7. Diabetes technology: standards of medical care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S150-S165. doi:10.2337/dc26-S007
  28. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412. doi:10.1136/bmj.321.7258.405
  29. Wright LA, Hirsch IB. Metrics beyond hemoglobin A1C in diabetes management: time in range, hypoglycemia, and other parameters. Diabetes Technol Ther. 2017;19(S2):S16-S26. doi:10.1089/dia.2017.0029
  30. Bergman M, Abdul-Ghani M, DeFronzo RA, et al. Review of methods for detecting glycemic disorders. Diabetes Res Clin Pract. 2020;165:108233. doi:10.1016/j.diabres.2020.108233
  31. Peabody J, Paculdo D, Acelajado MC, et al. Finding the clinical utility of 1,5-anhydroglucitol among primary care practitioners. J Clin Transl Endocrinol. 2020;20:100224. doi:10.1016/j.jcte.2020.100224
  32. Selvin E, Wang D, McEvoy JW, et al. Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial. Diabetes Obes Metab. 2019;21(8):2017-2023. doi:10.1111/dom.13755
  33. Onnis C, Virmani R, Kawai K, et al. Coronary artery calcification: current concepts and clinical implications. Circulation. 2024;149(3):251-266. doi:10.1161/CIRCULATIONAHA.123.065657
  34. JARDIANCE® (empagliflozin tablets). Package insert. Boehringer Ingelheim International GmbH. Updated February, 2022.
  35. Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023;118(1):59-76. doi:10.14309/ajg.0000000000002075
  36. Hogendorf A, Szymanska M, Krasinska J, et al. Clinical heterogeneity among pediatric patients with autoimmune type 1 diabetes stratified by immunoglobulin deficiency. Pediatr Diabetes. 2021;22(5):707-716. doi:10.1111/pedi.13208
  37. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia. JACC. Epub ahead of print. doi:10.1016/j.jacc.2025.11.016
  38. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314
  39. DeFronzo RA, Fonseca V, Aroda VR, et al. Inadequately controlled type 2 diabetes and hypercortisolism: improved glycemia with mifepristone treatment. Diabetes Care. 2025;48(12):2036-2044. doi:10.2337/dc25-1055
  40. Buse JB, Kahn SE, Aroda VR, et al. Prevalence of hypercortisolism in difficult-to-control type 2 diabetes. Diabetes Care. 2025;48(12):2012-2020. doi:10.2337/dc24-2841
  41. Nieman LK, Muniyappa R. Unmasking hypercortisolism in difficult-to-control type 2 diabetes: a useful paradigm shift? Diabetes Care. 2025;48(12):1994-1996. doi:10.2337/dci25-0038

Content reviewed 4/2026

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

The tests listed by specialty and category are a select group of tests offered. For a complete list of Quest Diagnostics tests, please adjust the filter options chosen, or refer to our Directory of Services.