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Supplement

Obesity, Body Fat Distribution, Insulin Sensitivity and Islet -Cell Function as Explanations for Metabolic Diversity^{1 ,2}

Steven E. Kahn^*3, Ronald L. Prigeon^*, Robert S. Schwartz, Wilfred Y. Fujimoto, Robert H. Knopp^**, John D. Brunzell and Daniel Porte, Jr.^*

Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington and ^* Department of Veterans Affairs, Puget Sound Health Care System and ^** Harborview Medical Center, Seattle, WA 98108; and Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80267

³To whom correspondence should be addressed. E-mail: skahn{at}u.washington.edu.

Studies of metabolic processes have been enhanced by our understanding of the relationships among obesity, body fat distribution, insulin sensitivity and islet -cell function. Thus, we have learned that although insulin resistance is usually associated with obesity, even lean subjects can be insulin resistant due to the accumulation of visceral fat. Insulin sensitivity and -cell function are also intimately linked. The hyperbolic relationship between these two parameters explains why insulin-resistant individuals have markedly enhanced insulin responses, whereas subjects who are insulin sensitive exhibit very low responses. Failure to take into account this relationship will lead to erroneous conclusions. By accounting for this important interaction, it has been clearly demonstrated that subjects at high risk of developing type 2 diabetes (older individuals, women with a history of gestational diabetes or polycystic ovary syndrome, subjects with impaired glucose tolerance and first-degree relatives of individuals with type 2 diabetes) have impaired -cell function. Furthermore, the progression from normal glucose tolerance to impaired glucose tolerance and type 2 diabetes is associated with declining insulin secretion.

KEY WORDS: • obesity • intra-abdominal fat • impaired glucose tolerance • gestational diabetes • polycystic ovary syndrome

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