Overall Goal: Our major objective is to examine the role of metabolic factors in the development of insulin resistance and progression to beta- cell failure, and type 2 diabetes during puberty in Hispanic American adolescents. Rationale: The pubertal transition is a time during which rapid and dynamic changes occur in various metabolic systems, including insulin resistance. However, there is almost a complete lack of longitudinal studies on metabolic changes during puberty, especially among high risk ethnic groups, and especially with a focus on diabetes risk. Because of the unique metabolic events associated with the pubertal transition, the mechanism of insulin resistance and type 2 diabetes during adolescence cannot be inferred from adult studies.
Specific Aims & Approach: We will recruit a cohort of non-diabetic Hispanic American adolescents who are obese and have at least one first degree relative with type 2 diabetes for a longitudinal study. We will examine the time course of changes in insulin action, insulin secretion, beta-cell function, visceral versus subcutaneous abdominal fat, cardiovascular fitness, and endocrine factors using the most advanced clinical research techniques possible within the confines of a cohort study in adolescents. The patterns of change in these variables will be examined in those who progress to develop type 2 diabetes, versus those who do not. The application is based on compelling cross-sectional and longitudinal evidence from ongoing NIH supported cohort studies in children, young women and adults that support our hypothesis, and an extensive network of clinics providing diabetes care for Hispanic Americans from whom unaffected relatives will be recruited. Hypothesis: Our unifying hypothesis is that the progression to type 2 diabetes will be characterized by a sustained increase in insulin resistance, and a gradual deterioration in insulin secretion relative to the degree of insulin resistance, indicating a failure of beta-cell function. These events will be rapidly accelerated and confounded by puberty-related increases in insulin resistance, and requisite hypersecretion of insulin, as well as a puberty related increases in visceral fat and decreases in cardiovascular fitness that will further compound the puberty-related rise in insulin resistance. Summary: This study will establish the fundamental mechanism of type 2 diabetes in Hispanic adolescents and will clarify the role of body fat, physical activity and endocrine factors in relation to insulin resistance during puberty and progression to type 2 diabetes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZDK1-GRB-6 (O2))
Program Officer
Linder, Barbara
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University of Southern California
Public Health & Prev Medicine
Schools of Medicine
Los Angeles
United States
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Toledo-Corral, C M; Alderete, T L; Habre, R et al. (2018) Effects of air pollution exposure on glucose metabolism in Los Angeles minority children. Pediatr Obes 13:54-62
Alderete, Tanya L; Habre, Rima; Toledo-Corral, Claudia M et al. (2017) Longitudinal Associations Between Ambient Air Pollution With Insulin Sensitivity, ?-Cell Function, and Adiposity in Los Angeles Latino Children. Diabetes 66:1789-1796
Gyllenhammer, L E; Alderete, T L; Toledo-Corral, C M et al. (2016) Saturation of subcutaneous adipose tissue expansion and accumulation of ectopic fat associated with metabolic dysfunction during late and post-pubertal growth. Int J Obes (Lond) 40:601-6
Toledo-Corral, Claudia M; Alderete, Tanya L; Richey, Joyce et al. (2015) Fasting, post-OGTT challenge, and nocturnal free fatty acids in prediabetic versus normal glucose tolerant overweight and obese Latino adolescents. Acta Diabetol 52:277-84
House, B T; Shearrer, G E; Miller, S J et al. (2015) Increased eating frequency linked to decreased obesity and improved metabolic outcomes. Int J Obes (Lond) 39:136-41
Kayser, Brandon D; Toledo-Corral, Claudia M; Alderete, Tanya L et al. (2015) Temporal relationships between adipocytokines and diabetes risk in Hispanic adolescents with obesity. Obesity (Silver Spring) 23:1479-85
Alderete, Tanya L; Toledo-Corral, Claudia M; Goran, Michael I (2014) Metabolic basis of ethnic differences in diabetes risk in overweight and obese youth. Curr Diab Rep 14:455
Alderete, Tanya L; Toledo-Corral, Claudia M; Desai, Preeya et al. (2013) Liver fat has a stronger association with risk factors for type 2 diabetes in African-American compared with Hispanic adolescents. J Clin Endocrinol Metab 98:3748-54
Kim, Joon Young; Goran, Michael I; Toledo-Corral, Claudia M et al. (2013) One-hour glucose during an oral glucose challenge prospectively predicts ?-cell deterioration and prediabetes in obese Hispanic youth. Diabetes Care 36:1681-6
Walker, Ryan W; Sinatra, Frank; Hartiala, Jaana et al. (2013) Genetic and clinical markers of elevated liver fat content in overweight and obese Hispanic children. Obesity (Silver Spring) 21:E790-7

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