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BASICS

Description

  • Glucose intolerance is an intermediate stage between normal glucose metabolism and diabetes, resulting from progressive β-cell dysfunction.
  • Prediabetes includes:
  • Impaired fasting glucose (IFG): fasting glucose 100-125 mg/dL
  • Impaired glucose tolerance (IGT): 2-hour glucose 140-199 mg/dL post 75g OGTT
  • HbA1c: 5.7%-6.4%

Epidemiology

  • One in three U.S. adults ≥20 years had prediabetes as of 2010.
  • Estimated 88 million adults ≥18 years had prediabetes in the U.S. by 2020.
  • Only 11% of people with prediabetes are aware of their condition.
  • Prediabetes prevalence: 34.5% adults >18 years, 51% adults >65 years in the U.S.
  • Worldwide prevalence was 8% as of 2010.
  • Higher incidence in American Indians/Alaska Natives, non-Hispanic blacks, and Hispanics.

Etiology and Pathophysiology

  • Progressive loss of insulin secretion with underlying insulin resistance.
  • Genetic heterogeneity established; variants in multiple genes affect β-cell function.

Risk Factors

  • BMI ≥25 (≥23 for Asian Americans)
  • History of gestational diabetes mellitus (GDM)
  • Sedentary lifestyle
  • Medications (e.g., corticosteroids, β-blockers)

General Prevention

  • Lifestyle modification: weight loss and increased physical activity are key.
  • Pregnancy screening based on risk: high risk at first visit; average risk at 24-28 weeks.
  • Women with GDM require postpartum diabetes screening.

DIAGNOSIS

Who to Screen

  • BMI ≥25 (≥23 in Asian Americans)
  • Age ≥45 years
  • Family history of diabetes
  • Dyslipidemia: TG >250 mg/dL, HDL <35 mg/dL
  • Hypertension (BP >140/90 or on treatment)
  • History of GDM or cardiovascular disease
  • High-risk ethnicities (non-Hispanic black, Native American, Hispanic, Asian American, Pacific Islander)
  • Conditions associated with insulin resistance (PCOS, acanthosis nigricans)

History

  • Often asymptomatic
  • Possible polyuria, polydipsia, weight loss, blurred vision, polyphagia

Physical Exam

  • BMI measurement and general exam

Differential Diagnosis

  • Rare insulin resistance syndromes (Type A insulin resistance, Leprechaunism)
  • Endocrinopathies (Cushing, glucagonoma, pheochromocytoma, hyperthyroidism)
  • Drug-induced hyperglycemia (thiazides, β-blockers, corticosteroids, antipsychotics)

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests

  • Fasting glucose, 2-hour OGTT, or HbA1c are acceptable for diagnosis.
  • Repeat screening every 3 years if normal; sooner if risk factors present.

Follow-Up Tests

  • Fasting lipid profile
  • Creatinine and GFR
  • Urinalysis and microalbumin-to-creatinine ratio
  • Thyroid function tests
  • Vitamin B12 levels in long-term metformin users with anemia or neuropathy

TREATMENT

General Measures

  • Therapeutic lifestyle modification: diet and physical activity targeting 7% weight loss and ≥150 min/week moderate exercise.
  • Mediterranean diet and high-fiber foods recommended.
  • Interrupt prolonged sitting every 30 minutes with activity.

Medication

  • Metformin preferred for prevention in high-risk individuals (BMI >35, <60 years, history of GDM).
  • Other agents: acarbose, GLP-1 receptor agonists (not FDA-approved for prediabetes as of 2020).

Additional Therapies

  • Limited evidence for botanical supplements such as fenugreek, bitter melon, cinnamon.

ONGOING CARE

Follow-Up

  • Annual monitoring for diabetes development using fasting glucose, OGTT, or HbA1c.
  • Routine BP, lipid panel, microalbuminuria screening.
  • BMI monitoring.

Diet

  • Mediterranean diet with emphasis on vegetables, nuts, seeds, whole grains.
  • Limit high glycemic carbohydrates and sucrose.
  • Intermittent fasting shows benefit in improving glucose control.

PROGNOSIS

  • High risk of progression to type 2 diabetes (20-70% within 3-6 years without lifestyle change).
  • Lifestyle intervention reduces progression risk by ~58%; metformin by ~31%.
  • Increased risk of cardiovascular disease, stroke, and diabetic complications.

COMPLICATIONS

  • Cardiovascular disease, peripheral artery disease
  • Stroke (2-4 fold risk)
  • Ketoacidosis
  • Sexual dysfunction, gastroparesis, nephropathy, retinopathy, neuropathies

CLINICAL PEARLS

  • Educate patients on lifestyle modification to reduce diabetes risk.
  • Moderate exercise and weight loss are effective preventive measures.
  • Consider cardiovascular risk in comprehensive management.

REFERENCES

  1. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Suppl 1):S11-S24.
  2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014.
  3. Centers for Disease Control and Prevention. Awareness of prediabetes—United States, 2005-2010. MMWR Morb Mortal Wkly Rep. 2013;62(11):209-212.
  4. Centers for Disease Control and Prevention. Prediabetes. https://www.cdc.gov/diabetes/basics/prediabetes.html
  5. American Diabetes Association. 13. Management of diabetes in pregnancy. Diabetes Care. 2017;40(Suppl 1):S114-S119.
  6. American Diabetes Association. 5. Prevention or delay of type 2 diabetes. Diabetes Care. 2017;40(Suppl 1):S44-S47.
  7. Deng R. A review of the hypoglycemic effects of five commonly used herbal food supplements. Recent Pat Food Nutr Agric. 2012;4(1):50-60.
  8. Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers in those with type 2 diabetes: a pilot study. World J Diabetes. 2017;8(4):154-164.