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Endocrine Reviews 19 (4): 491-503
Copyright © 1998 by The Endocrine Society

The Genetic Basis of Type 2 Diabetes Mellitus: Impaired Insulin Secretion versus Impaired Insulin Sensitivity

John E. Gerich

University of Rochester, School of Medicine and Dentistry, Departments of Medicine, Physiology, and Pharmacology, Rochester, New York 14642

I. Introduction
A. General considerations
B. Diabetogenic vs. diabetes-related genes
C. Secondary impairment of insulin secretion and insulin sensitivity
D. Insulin deficiency vs. impaired insulin secretion
E. Misinterpretation of the Oral Glucose Tolerance Test (OGTT)
II. Strategy
III. Studies in Genetically Predisposed Individuals with NGT
A. First-degree relatives (excluding twins)
B. Identical twins discordant for type 2 diabetes
IV. Prospective Studies of Individuals Before Development of Type 2 Diabetes
V. Studies of Normal Glucose-Tolerant Women with a History of Gestational Diabetes
VI. Reversibility of Insulin Resistance and Impaired Insulin Secretion by Therapeutic Interventions
VII. Are all Type 2 Diabetics Insulin Resistant?
VIII. Hypothesis for Pathogenesis of Type 2 Diabetes
IX. Summary and Conclusion




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