The Pima Indians have the highest reported prevalence and incident rate of non-insulin dependent diabetes mellitus (NIDDM) of any population of the world. The diabetes occurs more frequently in the offspring of diabetic mothers than in the offspring of non-diabetic parents. The reasons for this are unknown. In this project, we are longitudinally studying Pima Indians to determine the sequence of metabolic events that occurs with the development of NIDDM and also to isolate the predictor of the development of NIDDM. Studies are done on a yearly basis on the adult offspring of diabetic mothers and of non-diabetic parents to characterize their insulin and carbohydrate metabolism both in vivo and in vitro. Data collected to date has clearly demonstrated for the first time the relationships between degree of obesity as determined by careful body composition studies with insulin resistance. Obesity accounts at best for only about 50% of the variance in insulin resistance. Physical fitness, as determined by maximal oxygen uptake, appears to account for about 25% of the variance in insulin resistance. Most of insulin resistance appears to be due to a reduction in insulin-mediated glucose storage rather than a reduction in insulin-mediated glucose oxidation. Preliminary longitudinal analyses of the data so far have indicated that the development of impaired glucose tolerance is associated with weight gain, and decreased insulin action for glucose storage, but with little change in insulin action in isolated adipocytes from the same subjects. Approximately 14 subjects have developed diabetes and an equal number have developed impaired glucose tolerance. Statistical analyses are now underway to isolate the metabolic characteristic that is most predictive of these deteriorations of glucose tolerance.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Stumvoll, M; Bogardus, C (2009) Glucose allostasis: disrobing common wisdom. Diabetologia 52:779-80
Thearle, Marie S; Bunt, Joy C; Knowler, William C et al. (2009) Childhood predictors of adult acute insulin response and insulin action. Diabetes Care 32:938-43
Bogardus, Clifton (2009) Missing heritability and GWAS utility. Obesity (Silver Spring) 17:209-10
Koska, Juraj; Stefan, Norbert; Votruba, Susanne B et al. (2008) Distribution of subcutaneous fat predicts insulin action in obesity in sex-specific manner. Obesity (Silver Spring) 16:2003-9
Koska, Juraj; Stefan, Norbert; Permana, Paska A et al. (2008) Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals. Am J Clin Nutr 87:295-302
Mott, David M; Stone, Karen; Gessel, Mary C et al. (2008) Palmitate action to inhibit glycogen synthase and stimulate protein phosphatase 2A increases with risk factors for type 2 diabetes. Am J Physiol Endocrinol Metab 294:E444-50
Sahota, Puneet K C; Knowler, William C; Looker, Helen C (2008) Depression, diabetes, and glycemic control in an American Indian community. J Clin Psychiatry 69:800-9
Ortega, Emilio; Koska, Juraj; Pannacciulli, Nicola et al. (2008) Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals. Eur J Endocrinol 158:217-21
Le, Duc Son Nt; Pannacciulli, Nicola; Chen, Kewei et al. (2007) Less activation in the left dorsolateral prefrontal cortex in the reanalysis of the response to a meal in obese than in lean women and its association with successful weight loss. Am J Clin Nutr 86:573-9
Ortega, Emilio; Pannacciulli, Nicola; Bogardus, Clifton et al. (2007) Plasma concentrations of free triiodothyronine predict weight change in euthyroid persons. Am J Clin Nutr 85:440-5

Showing the most recent 10 out of 79 publications