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Source: Triplitt CL, Reasner CA. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. Accessed July 16, 2012.

  • Adult onset diabetes mellitus (DM)
  • Non-insulin–dependent diabetes mellitus (NIDDM)

  • Disorder of carbohydrate regulation associated with:
    • Reduced pancreatic insulin production
    • Peripheral insulin resistance
    • Impaired regulation of hepatic glucose production

  • Excessive caloric intake, inadequate exercise, and obesity coupled with susceptible genotype.
  • Uncommon causes
  • Medications (glucocorticoids, pentamidine, niacin, alfa-interferon)

  • Usually characterized by insulin resistance and relative insulin deficiency.
  • Insulin resistance manifested by:
    • Increased lipolysis and free fatty acid production
    • Increased hepatic glucose production
    • Decreased skeletal muscle uptake of glucose
  • β-Cell dysfunction is progressive and contributes to worsening blood glucose control over time.
  • Microvascular complications:
    • Retinopathy
    • Neuropathy
    • Nephropathy
  • Macrovascular complications:
    • Coronary heart disease
    • Stroke
    • Peripheral vascular disease

  • Accounts for 90% of DM cases.
  • Affects 16 million individuals in Unites States; 30–40 million others have impaired glucose tolerance.
  • More prevalent among Hispanics, Native Americans, African Americans, and Asians/Pacific Islanders than in non-Hispanic Whites.

  • Prevention
    • Maintain healthy diet, increased physical activity, and appropriate body weight.
    • Medications (metformin) may help prevent progression to type 2 DM in individuals with impaired glucose tolerance.
  • Screening
    • Measure blood glucose at least every 3 years in people over age 45.

  • Age >45 years
  • Family history of diabetes
  • Impaired glucose tolerance
  • Obesity
  • Low physical activity level
  • Dyslipidemia
  • Diabetes during previous pregnancy
  • Polycystic ovarian syndrome
  • Acanthosis nigricans
  • Ethnicity (African Americans, Hispanic Americans, Asian Americans, Native Americans)

Signs and Symptoms

  • Often asymptomatic; may be diagnosed from unrelated blood testing.
  • Symptoms:
    • Lethargy
    • Polyuria
    • Nocturia
    • Polydipsia
    • Significant weight loss less common
  • Presence of complications (e.g., retinopathy, neuropathy, nephropathy) may indicate long-term disease presence.

Laboratory Tests

  • Criteria for diagnosis of DM include any one of the following:
    • A1C ≥6.5%
    • Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)
    • Two-hour plasma glucose ≥200 mg/dL (111.1 mmol/L) during oral glucose tolerance test (OGTT) using 75 g anhydrous glucose in water
    • Random plasma glucose concentration ≥200 mg/dL (111.1 mmol/L) with symptoms of hyperglycemia
  • In absence of unequivocal hyperglycemia, confirm criteria 1 through 3 by repeat testing.
  • Normal fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol/L).
  • Impaired fasting glucose defined as FPG of 100–125 mg/dL (5.6–6.9 mmol/L).
  • Impaired glucose tolerance diagnosed when 2-hour postload sample of OGTT between 140–199 mg per dL (7.8–11.0 mmol/L).

Differential Diagnosis

  • Ameliorate symptoms of hyperglycemia.
  • Reduce risk of complications.
  • Reduce mortality.
  • Improve quality of life.
  • Achieve desirable plasma glucose and A1C levels (Table 1).

Table 1. Glycemic Goals of Therapy

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