What is coexisting impaired glucose tolerance?

Understanding Impaired Glucose Tolerance

Impaired glucose tolerance (IGT) is a metabolic condition characterized by blood glucose levels that are higher than normal but not high enough to be classified as diabetes, specifically defined as 2-hour post-load plasma glucose levels between 140-199 mg/dL (7.8-11.0 mmol/L) during an oral glucose tolerance test. 1, 2

Definition and Diagnostic Criteria

• IGT is diagnosed when 2-hour plasma glucose levels during a 75g oral glucose tolerance test (OGTT) are between 140-199 mg/dL (7.8-11.0 mmol/L), while fasting glucose remains below the diabetic threshold 1
• IGT often coexists with impaired fasting glucose (IFG), which is defined as fasting plasma glucose between 100-125 mg/dL (5.6-6.9 mmol/L) after at least 8 hours of fasting 2, 1
• The diagnosis should be confirmed with repeated testing, preferably using the same test on a different day 1

Clinical Significance

• IGT serves as an important risk factor for progression to type 2 diabetes, with approximately 20-50% of individuals developing diabetes over a 10-year period 3
• Individuals with IGT have significantly increased risk for cardiovascular disease, independent of whether they progress to diabetes 4
• IGT is often part of the broader metabolic syndrome, frequently coexisting with other cardiovascular risk factors such as obesity, hypertension, and dyslipidemia 1, 3
• In the Diabetes Prevention Program (DPP), individuals with IGT and elevated BMI had a crude incidence of diabetes of 11.0 cases per 100 person-years, with a cumulative 3-year incidence of 28.9% 1

Associated Risk Factors

• Risk factors for IGT include:
  • Overweight and obesity (particularly abdominal/visceral obesity) 1, 5
  • Physical inactivity 1
  • Family history of type 2 diabetes 5
  • Advanced age 3
  • History of gestational diabetes 1
  • Certain ethnic backgrounds (Black, Latin American, Native American, Asian-Pacific Islander) 5

Pathophysiology

• IGT is characterized by:
  • Impaired early insulin release, which is the most consistent defect 6
  • Insulin resistance, often attributable to obesity and decreased physical fitness 6
  • Impaired suppression of endogenous glucose release 6
  • Postprandial hyperglycemia with minimal elevations in fasting glucose 6

Screening Recommendations

• The U.S. Preventive Services Task Force recommends screening for abnormal blood glucose in adults aged 40-70 years who are overweight or obese 1, 2
• Screening can be done using HbA1c, fasting plasma glucose, or an oral glucose tolerance test 1
• Evidence suggests that rescreening every 3 years may be a reasonable approach for those with initially normal results 1

Clinical Management

• Lifestyle modifications are the cornerstone of management:
  • Weight loss of 5-7% of body weight 5
  • Moderate physical activity for at least 150 minutes per week 5
  • Dietary modifications focusing on reduced caloric intake 1
• Intensive behavioral interventions that combine counseling on healthful diet and physical activity have shown benefit in reducing progression to diabetes 1
• Pharmacological interventions with metformin or acarbose may delay or prevent diabetes onset, but are not as effective as lifestyle changes 5

Long-term Implications

• IGT is associated with both macrovascular and microvascular complications:
  • Increased risk of myocardial infarction, stroke, and large-vessel occlusive disease 4
  • Independent association with retinopathy, renal disease, and polyneuropathy 4
• Regression from IGT to normal glucose tolerance has been associated with lower risk of cardiovascular and microvascular disease over the long term 1

Clinical Pearls and Pitfalls

• IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, likely because it better reflects insulin resistance 4
• The oral glucose tolerance test is more sensitive but less convenient than fasting glucose for identifying prediabetes 2
• Not all individuals with IGT will progress to diabetes; approximately one-third may revert to normal glucose tolerance 1
• IGT should not be viewed simply as a pre-disease state but as a condition that independently increases cardiovascular risk 1, 4