The clinical studies in this application are focused on the pathophysiology of type 2 diabetes mellitus and specifically the alterations in islet B-cell function that characterize this disease process. Three specific objectives (with their experimental approaches) have been identified. 1. To determine whether subjects at high risk of developing type 2 diabetes (women with a history of gestational diabetes, individuals with a first degree relative with the disease and individuals with impaired glucose tolerance) have defects in B-cell function that can be exacerbated by increased secretory demand resulting in the development of hyperglycemia. Increased B-cell secretory demand will be produced by inducing experimental insulin resistance with nicotinic acid. 2. To determine whether the disproportionate pro-insulinemia observed in subjects with type 2 diabetes is due to a fundamental alteration in pro- insulin processing or whether it results from an increase in secretory demand with the premature release of B-cell secretory granules. Individuals with type 2 diabetes and healthy controls will be studied before and following 24 hours of islet B-cell result produced by an infusion of somatostatin. 3. To determine whether the disproportionate pro-insulinemia observed in subjects with type 2 diabetes is associated with disproportionate release of pro-islet amyloid polypeptide (proIAPP). An assay for proIAPP will be developed and measurements will be made in plasma from health subjects and subjects with type 2 diabetes to determine whether disproportionate release of proIAPP occurs in type 2 diabetes. The applicant has successfully trained a number of young investigators in the areas of patient-oriented and basic research and a plan to continue doing so is presented.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DK002654-04
Application #
6516729
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
1999-08-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
4
Fiscal Year
2002
Total Cost
$27,000
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Wander, Pandora L; Hayashi, Tomoshige; Sato, Kyoko Kogawa et al. (2018) Design and validation of a novel estimator of visceral adipose tissue area and comparison to existing adiposity surrogates. J Diabetes Complications 32:1062-1067
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Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M et al. (2016) Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years. Obes Res Clin Pract 10:624-632
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Wander, Pandora L; Boyko, Edward J; Leonetti, Donna L et al. (2013) Change in visceral adiposity independently predicts a greater risk of developing type 2 diabetes over 10 years in Japanese Americans. Diabetes Care 36:289-93
Faulenbach, Mirjam V; Wright, Lorena A; Lorenzo, Carlos et al. (2013) Impact of differences in glucose tolerance on the prevalence of a negative insulinogenic index. J Diabetes Complications 27:158-61
Smits, M M; Boyko, E J; Utzschneider, K M et al. (2012) Arm length is associated with type 2 diabetes mellitus in Japanese-Americans. Diabetologia 55:1679-84
Hsu, William C; Boyko, Edward J; Fujimoto, Wilfred Y et al. (2012) Pathophysiologic differences among Asians, native Hawaiians, and other Pacific Islanders and treatment implications. Diabetes Care 35:1189-98
McNeely, Marguerite J; Shofer, Jane B; Leonetti, Donna L et al. (2012) Associations among visceral fat, all-cause mortality, and obesity-related mortality in Japanese Americans. Diabetes Care 35:296-8

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