What is the best test to diagnose type 2 diabetes (Diabetes Mellitus Type 2) in adults over 45 years old with risk factors such as obesity, family history of diabetes, or a history of gestational diabetes?

Best Test to Diagnose Type 2 Diabetes

Fasting plasma glucose (FPG) ≥126 mg/dL is the best diagnostic test for type 2 diabetes in adults over 45 with risk factors, as it is faster, easier to perform, more convenient and acceptable to patients, less expensive, and more reproducible than alternatives. 1

Diagnostic Criteria

Three tests can diagnose type 2 diabetes, and any one of the following confirms the diagnosis 2:

• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) - fasting defined as no caloric intake for at least 8 hours 2
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during a 75-gram oral glucose tolerance test (OGTT) 2
• Hemoglobin A1C ≥6.5% - must be performed in a laboratory using an NGSP-certified method standardized to the DCCT assay 2

Why FPG is Preferred

FPG is the recommended first-line screening and diagnostic test because it offers superior practical advantages over the alternatives 1. The test is faster to complete, does not require the patient to consume a glucose solution and wait 2 hours (as with OGTT), and shows better reproducibility on repeat testing 1. Additionally, FPG is significantly less expensive than other options and more acceptable to patients who only need a single blood draw after an overnight fast 1.

Confirmation Requirements

In the absence of unequivocal hyperglycemia (symptoms plus random glucose ≥200 mg/dL), all abnormal results must be confirmed by repeat testing on a separate day 2, 1. Diabetes is confirmed if either the same test is repeated with both results exceeding the diagnostic threshold, or if two different tests both exceed their respective diagnostic thresholds 1.

When A1C Should NOT Be Used

Critical caveat: A1C is unreliable and should not be used for diagnosis in conditions with altered red blood cell turnover 2, 1:

• Pregnancy (second and third trimesters) 2
• Recent blood loss or transfusion 2, 3
• Hemolysis or hemoglobinopathies (e.g., sickle cell trait) 2
• Erythropoietin therapy 2, 3
• Hemodialysis 3

For patients with abnormal hemoglobin but normal red cell turnover (such as sickle cell trait), an A1C assay without interference from abnormal hemoglobins must be used, with an updated list available at www.ngsp.org/interf.asp 2. In these situations, only blood glucose criteria (FPG or OGTT) should be used 2.

Alternative Tests: When to Consider A1C or OGTT

While FPG is preferred, A1C and 2-hour OGTT are acceptable alternatives 2, 1. A1C offers the advantage of not requiring fasting, allowing appointments throughout the day rather than limiting them to mornings 4. The A1C result also reflects longer-term glycemia (2-3 months) and is less affected by recent physical or emotional stress 4.

However, A1C ≥6.5% as a sole diagnostic criterion misses a substantial number of people with type 2 diabetes 5, 6. In one study of 2,036 at-risk Caucasians, the 6.5% A1C cut-off correctly classified only 47% of diabetic individuals, missing 53% who were diagnosed by OGTT 6. Of those missed, 35% had elevated fasting glucose and 65% were only detected by their 2-hour glucose values 6. The two tests detect different populations of diabetic patients and cannot simply be exchanged 6.

Prediabetes Detection

For adults over 45 with risk factors (obesity, family history, gestational diabetes history), testing also identifies prediabetes 2:

• FPG 100-125 mg/dL (impaired fasting glucose) 2, 1
• 2-hour OGTT 140-199 mg/dL (impaired glucose tolerance) 2, 1
• A1C 5.7-6.4% 2, 1

Individuals with A1C 6.0-6.5% have a 5-year diabetes risk of 25-50%, representing a 20-fold higher risk than those with A1C 5.0% 2. Those with prediabetes should be tested annually rather than every 3 years 2, 1.

Screening Recommendations for Your Population

For adults over 45 with obesity, family history, or gestational diabetes history 2:

• Begin screening at age 35 years (updated from previous age 45 recommendation) 2
• Repeat testing every 3 years if normal 2, 1
• Test annually if prediabetes is detected 2, 1
• Women with prior gestational diabetes require lifelong testing at least every 1-3 years 2, 1

Common Pitfalls to Avoid

Do not mix different diagnostic methods without understanding their limitations 5. If an A1C result is discordant with the clinical picture or equivocal, perform plasma glucose testing 5. Combining A1C with plasma glucose measurements reduces the risk of systematic bias inherent in A1C testing alone 5.

Ensure proper sample handling for glucose measurements: the blood sample must be placed immediately in an ice-water bath and plasma separated from cells within 30 minutes to minimize glycolysis 7.

Do not delay confirmation testing: patients with results near diagnostic thresholds should be followed closely and retested in 3-6 months 2.