How to diagnose type 2 diabetes mellitus (DM)?

How to Diagnose Type 2 Diabetes Mellitus

Type 2 diabetes is diagnosed when any one of four laboratory criteria is met: fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during oral glucose tolerance test, hemoglobin A1C ≥6.5%, or random plasma glucose ≥200 mg/dL with classic hyperglycemic symptoms—and in most cases, abnormal results must be confirmed by repeat testing on a separate day. 1, 2

Diagnostic Criteria

The American Diabetes Association establishes four distinct pathways to diagnosis 1, 3:

Primary Laboratory Thresholds

• Fasting Plasma Glucose (FPG) ≥126 mg/dL after at least 8 hours without caloric intake 1, 2
• 2-hour Plasma Glucose ≥200 mg/dL during a 75-gram oral glucose tolerance test (OGTT) performed according to World Health Organization standards 1, 3
• Hemoglobin A1C ≥6.5% measured in a laboratory using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the Diabetes Control and Complications Trial (DCCT) assay 1, 3
• Random Plasma Glucose ≥200 mg/dL in a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, unintentional weight loss, blurred vision, fatigue) 2, 3

Confirmation Requirements: The Critical Two-Test Rule

You must obtain two abnormal test results to confirm the diagnosis, either from the same sample or on two separate days, unless the patient presents with unequivocal hyperglycemia and acute metabolic decompensation. 1, 2

Confirmation Algorithm

• If using two different tests (e.g., FPG and A1C) and both exceed diagnostic thresholds, the diagnosis is immediately confirmed 1
• If results are discordant between two different tests (one above, one below threshold), repeat the test that was above the diagnostic threshold 1, 3
• No confirmation is needed when a patient has classic hyperglycemic symptoms with random plasma glucose ≥200 mg/dL 1, 2
• A single random plasma glucose ≥200 mg/dL with typical symptoms is sufficient for diagnosis without further testing 2

When to Screen for Type 2 Diabetes

The American Diabetes Association recommends screening in these populations 2, 3:

• All adults aged 35 years and older (updated from previous age 45 threshold) 2
• Adults with BMI ≥25 kg/m² (or ≥23 kg/m² in Asian Americans) who have one or more additional risk factors at any age 2, 3
• Women with prior gestational diabetes should have lifelong testing at least every 3 years 2
• If screening tests are normal, repeat testing at minimum 3-year intervals 3
• In those with prediabetes, rescreen annually 2

Key Risk Factors Requiring Screening

Risk factors that trigger screening in overweight/obese adults include 2:

• First-degree relative with diabetes
• High-risk race/ethnicity (African American, Hispanic/Latino, Native American, Asian American, Native Hawaiian, Pacific Islander)
• History of cardiovascular disease
• Hypertension (≥140/90 mmHg or on antihypertensive therapy)
• HDL cholesterol <35 mg/dL and/or triglycerides >250 mg/dL
• Women with polycystic ovary syndrome
• Physical inactivity
• Other conditions associated with insulin resistance

Special Considerations for A1C Testing

A1C should NOT be used for diagnosis in conditions that affect red blood cell turnover. 1, 3

When A1C is Unreliable

In these conditions, use only plasma glucose criteria for diagnosis 1, 3:

• Hemoglobinopathies (sickle cell disease, thalassemia)
• Hemolytic anemias
• Pregnancy
• Recent blood loss or transfusion
• Hemodialysis
• Erythropoietin therapy

Marked discordance between measured A1C and plasma glucose levels should raise suspicion for hemoglobin variants interfering with the assay. 1

Prediabetes Identification

Prediabetes is diagnosed when test results fall within these intermediate ranges 1, 2:

• Impaired Fasting Glucose (IFG): FPG 100-125 mg/dL 1, 3
• Impaired Glucose Tolerance (IGT): 2-hour PG during OGTT 140-199 mg/dL 1, 3
• Elevated A1C: 5.7-6.4% 1, 3

Clinical Context and Pitfalls

Why Early Diagnosis Matters

Type 2 diabetes frequently goes undiagnosed for many years because hyperglycemia develops gradually and may not be severe enough initially to cause classic symptoms 4. Even undiagnosed patients are at increased risk of developing macrovascular and microvascular complications. 4, 2 The duration of glycemic burden is a strong predictor of adverse outcomes 4

Common Diagnostic Pitfalls to Avoid

• Relying on a single test without confirmation except when classic symptoms are present with random glucose ≥200 mg/dL 2
• Failing to recognize gradual onset: Type 2 diabetes often has a long presymptomatic phase, making screening essential 4
• Not considering type 1 diabetes in atypical presentations: Up to 40% of adults with new type 1 diabetes are initially misdiagnosed as having type 2 diabetes 1, 2. In patients without traditional risk factors and/or younger age, consider islet autoantibody testing to exclude type 1 diabetes 2
• Overlooking A1C limitations: Point-of-care A1C assays may be convenient for monitoring but require caution when used for diagnosis 1
• Ignoring ethnic-specific BMI thresholds: Asian Americans have increased diabetes risk at lower BMI levels (≥23 kg/m² vs ≥25 kg/m²) 4, 2
• Not accounting for test concordance: FPG, 2-hour PG, and A1C tests have imperfect concordance and do not necessarily detect diabetes in the same individuals 1, 3

Practical Diagnostic Algorithm

Step 1: Assess risk factors using the ADA Risk Test or clinical criteria 4, 2

Step 2: If screening is indicated, perform one of the following diagnostic tests 2, 3:

• Fasting plasma glucose (most practical)
• Hemoglobin A1C (convenient, no fasting required)
• 75-gram OGTT (most sensitive but least convenient)
• Random glucose if patient is symptomatic

Step 3: If results are abnormal and above diagnostic threshold 1, 2:

• With classic symptoms and random glucose ≥200 mg/dL: Diagnose immediately, no confirmation needed
• Without symptoms or with other test abnormalities: Confirm with repeat testing on a different day
• If using two different tests and both abnormal: Diagnosis confirmed
• If discordant results: Repeat the test that exceeded threshold

Step 4: If confirmed, diagnose type 2 diabetes and begin management 2

Step 5: If results indicate prediabetes, implement preventive measures and rescreen annually 2