Impaired glucose tolerance in Pima Indians

Area of Science:

• Endocrinology
• Metabolic Diseases
• Human Genetics

Background:

• Pima Indians exhibit a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM).
• Non-insulin-dependent diabetes mellitus is preceded by impaired glucose tolerance (IGT).
• The underlying cause of IGT in this population, specifically beta-cell function versus insulin resistance, requires clarification.

Purpose of the Study:

• To test the hypothesis that elevated glucose levels in IGT are due to reduced beta-cell function.
• To determine if established relationships between glucose, insulin, and insulin resistance in normal glucose tolerance (NGT) hold true in IGT.
• To compare these relationships between Pima Indians and Caucasians with NGT and IGT.

Main Methods:

• Oral glucose tolerance test (OGTT)
• Intravenous glucose tolerance test (IVGTT)
• Underwater weighing for body composition
• Euglycaemic clamp studies
• Comparison between Pima Indians and Caucasians

Main Results:

• Insulin concentrations in Pima Indians with IGT were not lower than predicted by NGT relationships.
• Pima Indians demonstrated elevated insulin concentrations compared to Caucasians at equivalent levels of insulin resistance.
• Insulin resistance was identified as the primary factor in IGT development among Pima Indians.

Conclusions:

• Insulin resistance, rather than beta-cell failure, is the principal determinant of IGT in Pima Indians.
• Non-insulin-dependent diabetes mellitus arises when beta-cell failure occurs in the context of existing insulin resistance.
• The relative contribution of beta-cell failure to NIDDM development may vary across different ethnic groups.