Type 2 diabetes mellitus (T2DM) in middle-aged individuals has been consistently associated with deficits in recent memory, attention, executive function, and cognitive efficiency. Insulin resistance (IR) is a progressive pre-diabetic condition. We have strong preliminary evidence that similar cognitive problems are also present among obese adolescents with IR relative to matched non-insulin resistant groups. The purpose of the proposed study is to rigorously establish the nature of the cognitive impairments present among obese adolescents with IR and by means of a systematic and standardized neuropsychological and MRI-approach to further characterize the brain substrates for those abnormalities. In addition, we propose to ascertain whether, relative to matched lean adolescents, obese adolescents without insulin resistance have detectable cognitive impairments. Obesity and IR are associated with inflammation. Thus, we will also assess whether inflammation mediates some of the associations between IR (and/or obesity) and brain dysfunction in adolescence. We seek to critically examine, in three groups of adolescents, the hypotheses that in insulin resistance there are cross-sectional associations between measures of IR and measures of cognition and structural and functional brain integrity. We propose that obese adolescents with IR will have larger reductions than obese adolescents without IR relative to matched (other than on obesity) lean adolescents. In this effort we will study 180 individuals 16-21 years of age separated into three equal sized groups (obese insulin resistant individuals with normal fasting glucose levels, obese adolescents with normal fasting glucose levels and no evidence of significant insulin resistance, and lean adolescents with normal fasting glucose levels and normal insulin function). The two obese groups will be matched on obesity and, in addition, all three groups will be matched 1:1 on, age, education, ethnicity (race), socio-economic status, and gender. We will ensure that all participants are competent in English. All evaluations will use standardized and reliable methods. The proposed work will provide key data documenting brain involvement in metabolic disorders associated with obesity in childhood, which will serve as the foundation for future work.

Public Health Relevance

There are over 60 million obese individuals in the United States and the rate of obesity is rising at an alarming rate. The rate of overweight and obesity among children stands at over 30%. Obesity leads to insulin resistance, which is a progressive pre-diabetic condition, and there is emerging evidence that both type 2 diabetes and insulin resistance may damage the brain. The goal of this work is to carefully evaluate the nature of the brain abnormalities that may be related to obesity and insulin resistance among adolescents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK083537-04S1
Application #
8721605
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Jones, Teresa L Z
Project Start
2010-03-01
Project End
2015-08-31
Budget Start
2013-03-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$54,999
Indirect Cost
$22,551
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Varga, Andrew W; Ducca, Emma L; Kishi, Akifumi et al. (2016) Effects of aging on slow-wave sleep dynamics and human spatial navigational memory consolidation. Neurobiol Aging 42:142-9
Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C et al. (2016) Does Inflammation Mediate the Association Between Obesity and Insulin Resistance? Inflammation 39:994-1003
Ross, Naima; Yau, Po Lai; Convit, Antonio (2015) Obesity, fitness, and brain integrity in adolescence. Appetite 93:44-50
Yau, Po Lai; Kim, Minsung; Tirsi, Aziz et al. (2014) Retinal vessel alterations and cerebral white matter microstructural damage in obese adolescents with metabolic syndrome. JAMA Pediatr 168:e142815
Yau, Po Lai; Kang, Esther H; Javier, David C et al. (2014) Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity. Obesity (Silver Spring) 22:1865-71
Rusinek, Henry; Convit, Antonio (2014) Obesity: cerebral damage in obesity-associated metabolic syndrome. Nat Rev Endocrinol 10:642-4
Ha, Jenny; Cohen, Jessica I; Tirsi, Aziz et al. (2013) Association of obesity-mediated insulin resistance and hypothalamic volumes: possible sex differences. Dis Markers 35:249-59
Tirsi, Aziz; Duong, Michelle; Tsui, Wai et al. (2013) Retinal vessel abnormalities as a possible biomarker of brain volume loss in obese adolescents. Obesity (Silver Spring) 21:E577-85
Ursache, Alexandra; Wedin, William; Tirsi, Aziz et al. (2012) Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy. Psychoneuroendocrinology 37:1270-6
Cohen, Jessica I; Maayan, Lawrence; Convit, Antonio (2012) Preliminary evidence for obesity-associated insulin resistance in adolescents without elevations of inflammatory cytokines. Diabetol Metab Syndr 4:26

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