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Type 2 Diabetes Mellitus (T2DM): Diagnosis & Treatment — Step by Step

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PART 1 — PATHOPHYSIOLOGY IN BRIEF

1. Insulin resistance — peripheral tissues (muscle, liver, adipose) fail to respond normally to insulin
2. Progressive β-cell dysfunction — the pancreas cannot compensate with sufficient insulin secretion

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PART 2 — WHO IS AT RISK? (Screen These Patients First)

The ADA recommends screening overweight/obese adults with any one risk factor above, and universal screening at age 35+ regardless of risk factors. — Henry's Clinical Diagnosis and Management by Laboratory Methods

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PART 3 — DIAGNOSTIC CRITERIA (ADA Standard)

"In a patient without classic symptoms, a single abnormal test result is not sufficient for diagnosis. A confirmatory test is required." — Tietz Textbook of Laboratory Medicine, 7th Ed

Prediabetes (High Risk — Not Yet Diabetes)

Prediabetes carries a 5-year cumulative diabetes incidence of 12–25% and also increases cardiovascular risk. — Tietz Textbook of Laboratory Medicine, 7th Ed

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PART 4 — INITIAL WORKUP AT DIAGNOSIS

• HbA1c (establishes baseline control)
• Fasting glucose

• Urine albumin-to-creatinine ratio (microalbuminuria)
• Serum creatinine + eGFR
• Lipid panel (LDL, HDL, TG, total cholesterol)
• Blood pressure

• Dilated retinal exam (diabetic retinopathy)
• Neurologic exam / monofilament test (peripheral neuropathy)
• ECG if cardiovascular risk is high
• Thyroid function (TSH) — commonly coexists

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PART 5 — TREATMENT: STEP-BY-STEP ALGORITHM

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STEP 1 — Lifestyle Modification (All Patients, Always)

• Medical Nutrition Therapy: Reduce refined carbohydrates, saturated fat; increase fiber; caloric deficit if obese
• Physical Activity: Minimum 150 min/week of moderate aerobic exercise (e.g., brisk walking)
• Weight Loss: Even 5–10% body weight reduction significantly improves insulin sensitivity
• Smoking cessation, alcohol moderation
• Diabetes education — self-monitoring of blood glucose (SMBG), foot care, hypoglycemia recognition

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STEP 2 — First-Line Pharmacotherapy: Metformin

• Mechanism: Decreases hepatic gluconeogenesis; increases insulin sensitivity via AMPK activation
• Dose: Start 500 mg once or twice daily with meals; titrate to 1000 mg twice daily
• Target: HbA1c ≤ 7% (individualized — may be stricter [6.5%] for young/newly diagnosed, or looser [8%] for elderly/frail)
• Advantages: Weight neutral to modest weight loss, no hypoglycemia, cardiovascular benefit (UKPDS), low cost
• Contraindications: eGFR < 30 mL/min/1.73m², active liver disease, alcohol excess, contrast dye procedures

"Metformin is generally accepted as the first-line treatment of type 2 diabetes and is the most commonly used oral agent." — Goodman & Gilman's, 14th Ed

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STEP 3 — Second Agent (If HbA1c Target Not Met)

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STEP 4 — Triple Therapy or Insulin

• Add a third oral/injectable agent, OR
• Initiate basal insulin (long-acting: glargine, detemir, degludec) — typically at bedtime, combined with oral agents
  • Start: 10 units/day (or 0.1–0.2 units/kg/day); titrate by 2 units every 3 days until fasting glucose 80–130 mg/dL
• As β-cell function declines, transition to basal-bolus insulin (basal + prandial doses at meals)

"Progressive insulin deficiency in type 2 diabetes often makes it increasingly difficult to achieve the glycemic goal solely with oral agents; thus, insulin is necessary in a substantial proportion." — Goodman & Gilman's

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GLYCEMIC TARGETS SUMMARY

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PART 6 — MONITORING & FOLLOW-UP

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PART 7 — COMPLICATION PREVENTION

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QUICK SUMMARY FLOWCHART

Screening (risk factors or age ≥35)
        ↓
Diagnostic Testing (FPG, HbA1c, OGTT)
        ↓
Confirm T2DM Diagnosis
        ↓
Baseline Workup (HbA1c, lipids, eGFR, urine albumin, retinal exam, neuro exam)
        ↓
STEP 1: Lifestyle + Metformin → Reassess HbA1c in 3 months
        ↓ (if not at goal)
STEP 2: Metformin + Second Agent (chosen by comorbidities)
        ↓ (if not at goal)
STEP 3: Triple Therapy or Add Basal Insulin
        ↓ (progressive disease)
STEP 4: Basal-Bolus Insulin ± Oral Agents

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