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A two-step model for development of non-insulin-dependent diabetes
M F Saad1, W C Knowler, D J Pettitt
1Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Arizona 85014.
The American Journal of Medicine
|February 1, 1991
Summary
Insulin resistance drives impaired glucose tolerance, while beta-cell dysfunction critically worsens it to non-insulin-dependent diabetes mellitus (NIDDM). This two-step model explains NIDDM development, observed in Pima Indians and other populations.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Diabetes Research
Background:
- Non-insulin-dependent diabetes mellitus (NIDDM) involves both insulin resistance and beta-cell dysfunction.
- The primary etiological factor in NIDDM pathogenesis remains debated.
- Pima Indians exhibit the world's highest NIDDM prevalence, offering a key study population.
Purpose of the Study:
- To propose a two-step model for NIDDM development.
- To elucidate the distinct roles of insulin resistance and beta-cell dysfunction in NIDDM progression.
- To validate the proposed model across diverse ethnic groups.
Main Methods:
- Longitudinal studies were conducted in the Pima Indian population.
- Analysis focused on the transition from normal glucose tolerance to impaired glucose tolerance.
- Further investigation examined the progression from impaired glucose tolerance to diabetes.
Main Results:
- Insulin resistance is the primary determinant for the initial step: progression from normal to impaired glucose tolerance.
- Beta-cell dysfunction plays a critical role in the second step: worsening from impaired glucose tolerance to overt diabetes.
- The proposed two-step model aligns with observations in various ethnic populations worldwide.
Conclusions:
- A sequential model of NIDDM pathogenesis is proposed, with distinct primary drivers at each stage.
- Insulin resistance precedes and facilitates the development of impaired glucose tolerance.
- Beta-cell dysfunction is crucial for the transition to established diabetes mellitus.