Diagnosing Type 2 Diabetes Mellitus
Diagnostic Criteria
Type 2 diabetes is diagnosed when any one of the following criteria is met: fasting plasma glucose ≥126 mg/dL, hemoglobin A1C ≥6.5%, random plasma glucose ≥200 mg/dL with symptoms of hyperglycemia, or 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test. 1, 2
Confirmation Requirements
- In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria must be confirmed by repeat testing on a different day 1
- A single random plasma glucose ≥200 mg/dL with typical symptoms (polyuria, polydipsia, unexplained weight loss) is sufficient for diagnosis without repeat testing 3
- The oral glucose tolerance test is not recommended for routine clinical use but may be required when diabetes is suspected despite normal fasting plasma glucose 1
Screening Recommendations
- Testing should begin at age 45 years in all individuals, particularly those with BMI ≥25 kg/m², and be repeated at 3-year intervals if normal 1
- Earlier and more frequent screening is indicated for individuals with risk factors including: 1, 3
- Physical inactivity
- First-degree relative with diabetes
- High-risk ethnicity (African-American, Latino, Native American, Asian-American, Pacific Islander)
- History of gestational diabetes or delivering a baby >9 lb
- Hypertension (≥140/90 mmHg)
- HDL cholesterol ≤35 mg/dL or triglycerides ≥250 mg/dL
- Polycystic ovary syndrome
- Previous impaired glucose tolerance or impaired fasting glucose
Treatment Algorithm for Type 2 Diabetes
Step 1: Foundation for All Patients
All patients must begin with comprehensive lifestyle modifications including diabetes self-management education, medical nutrition therapy, at least 150 minutes of moderate-intensity aerobic activity weekly, and resistance training twice per week 4, 5
- Weight loss of at least 5% is required for overweight/obese patients 4, 5
- Diabetes self-management education reduces A1C, mortality risk, and healthcare costs 4
- Medical nutrition therapy can reduce A1C by 0.3-2% in type 2 diabetes 4
Step 2: First-Line Pharmacologic Therapy
Metformin should be started at or soon after diagnosis in all patients without contraindications, beginning at a low dose and titrating gradually to a maximum of 2000 mg daily in divided doses 4, 5, 2, 6
- Metformin is preferred due to efficacy, safety, low cost, and potential cardiovascular benefits 4, 5, 2
- Metformin improves peripheral insulin sensitivity and reduces hepatic glucose production without causing hypoglycemia or weight gain 6
Step 3: Special Circumstances Requiring Different Initial Therapy
Insulin therapy must be initiated instead of metformin as first-line treatment in patients with: 5
- Ketosis or diabetic ketoacidosis
- Random blood glucose ≥250 mg/dL
- HbA1c >8.5%
- Symptomatic diabetes with polyuria, polydipsia, and weight loss
For patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, a GLP-1 receptor agonist or SGLT2 inhibitor should be added at diagnosis alongside metformin 4, 2
Step 4: Treatment Intensification
When metformin monotherapy at maximum tolerated dose does not achieve HbA1c target over 3 months, add a second agent: 5, 2
- SGLT2 inhibitors or GLP-1 receptor agonists are preferred second-line agents for patients with cardiovascular or kidney disease (12-26% cardiovascular risk reduction, 18-25% heart failure risk reduction, 24-39% kidney disease risk reduction) 2
- High-potency GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists produce weight loss >5% in most individuals, often exceeding 10% 2
- Alternative second-line options include DPP-4 inhibitors, thiazolidinediones, or sulfonylureas 5
- Approximately one-third of patients require insulin therapy during their lifetime 2
Step 5: Glycemic Targets and Monitoring
Target HbA1c <7% for most adults, with monitoring every 3 months until target is reached, then at least twice yearly 5
- More stringent targets (such as <6.5%) may be appropriate for selected individuals without significant hypoglycemia risk 5
- Intensive glucose-lowering strategies (HbA1c <7%) reduce microvascular disease by 3.5%, myocardial infarction by 3.3-6.2%, and mortality by 2.7-4.9% over 2 decades 2
Critical Safety Considerations
Hypoglycemia Management
- Severe or frequent hypoglycemia requires immediate modification of treatment regimens 4, 5
- Patients with hypoglycemia unawareness must increase glycemic targets for several weeks to partially reverse this condition 4, 5
- Hypoglycemia (plasma glucose <3.9 mmol/L or <70 mg/dL) is treated with 15-20g of rapid-acting glucose, with blood glucose rechecked after 15 minutes 5
Medication Reassessment
- Treatment regimens must be reassessed every 3-6 months and adjusted based on A1C, side effects, and patient factors 4
- Avoid aggressively targeting near-normal HbA1c levels in patients with advanced disease where such targets cannot be safely reached 5
Common Pitfalls
- Metformin is contraindicated in renal impairment; lactic acidosis risk is minimal when prescribing guidelines are followed 6
- Certain medications (glucocorticoids, thiazide diuretics, atypical antipsychotics) increase diabetes risk and should be considered when screening 1
- Gastrointestinal side effects with metformin are common but usually tolerated; starting at low doses and titrating gradually minimizes these effects 6