Diabetes Type 2

Saul Genuth, M.D.
Case Western Reserve University School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• A metabolic disorder characterized by hyperglycemia, insulin resistance, and relative insulin insufficiency

Classic Features

• Polyuria
• Polydipsia
• Polyphagia
• Weight loss

Other Presentations

• Hyperglycemia per screening tests
• Pain—peripheral neuropathy
• Weakness
• Blurred vision
• Central obesity
• Recurrent infections, e.g., vaginitis

Differential Diagnosis

• Type 1: insulin deficiency, beta cell destruction
• Type 2: insulin resistance and variable insulin deficiency
• Endocrine dysfunction (e.g., Cushing syndrome, acromegaly)

Best Tests

• Plasma glucose (fasting preferred): FPG ≥ 126 mg/dl or plasma glucose ≥ 200 2 hr after 75 g oral glucose load

Best Therapy

Nutritional Therapy and Exercise

• Caloric reduction (determine intake reduction based on degree of obesity and with dietitian's help)
• Addition of high-fiber foods
• Counting of carbohydrates to limit postprandial plasma glucose elevation
• Gradually increased aerobic exercise

Pharmacologic Therapy

• Begin with monotherapy; if response is not satisfactory by 3–6 mo, add additional drug

Oral monotherapy for type 2 diabetes

• Sulfonylureas: first choice for normal weight; hypoglycemia with monotherapy
  • Glyburide
    • Dose: lowest effective single dose, 1.25 mg; daily max, 10 mg
    • Cost/mo: $28.80
  • Micronized glyburide
    • Dose: lowest effective single dose, 1.5 mg; daily max, 6 mg
    • Cost/mo: $14.40
  • Glipizide
    • Dose: lowest effective single dose, 5 mg; daily max, 20 mg
    • Cost/mo: $12.66
  • Glipizide (GI therapeutic system)
    • Dose: lowest effective single dose, 5 mg; daily max, 20 mg
  • Glimepiride
    • Dose: lowest effective single dose, 0.5 mg; daily max, 8 mg
    • Cost/mo: $74.60
• Meglitinide
  • Repaglinide: hypoglycemia with monotherapy; each max. dose must be taken with meals
    • Dose: lowest effective single dose, 0.5 mg; daily max, 4 mg
    • Cost/mo: $227.99
• Biguanides
  • Metformin: first choice for obese
    • Dose: lowest effective single dose, 500 mg; daily max, 2,000 mg
    • Cost/mo: $67.98
• Thiazolidinediones
  • Rosiglitazone
    • Dose: lowest effective single dose, 2 mg; daily max, 8 mg
    • Cost/mo: $183.98
  • Pioglitazone
    • Dose: lowest effective single dose, 15 mg; daily max, 45 mg
    • Cost/mo: $257.97
• α-Glucosidase inhibitors: least effective; must be taken at start of meals
  • Acarbose
    • Dose: lowest effective single dose, 25 mg; daily max, 100 mg
    • Cost/mo: $113.98
  • Miglitol
    • Dose: lowest effective single dose, 25 mg; daily max, 100 mg
    • Cost/mo: $99.99

Combination Therapy

• Use same drugs as with monotherapy, beginning with the lowest suggested dose of each
  • Sulfonylurea + metformin
  • Sulfonylurea + thiazolidinedione
  • Metformin + thiazolidinedione
  • Metformin + repaglinide
  • Repaglinide + thiazolidinedione
  • Sulfonylurea + metformin + thiazolidinedione
  • Acarbose + any other drug except repaglinide
  • Miglitol + sulfonylurea
  • Insulin + any other drug

Best References

DeWitt: JAMA 289:2254, 2003

Gerich: Arch Intern Med 163:1306, 2003

Inzucchi: JAMA 287:360, 2002

Knowler, et al: N Engl J Med 346:393, 2002

Turner, et al: JAMA 281:2005, 1999

July 2004