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 funds to mitigate the effects of Hurricane Sandy and facilitate the successful completion of the Specific Aims of our proposal, which are:
Specific Aim I : To determine whether obese adolescents with insulin resistance have lower performance on memory and other cognitive domains relative to matched obese non-insulin resistant and lean adolescents.
Specific Aim II : To determine whether obese adolescents with insulin resistance have MRI-based hippocampal volume reductions, gray matter reductions, and white matter abnormalities.
Specific Aim III : To determine whether among obese adolescents markers of inflammation mediate the hypothesized links between insulin resistance and reductions in cognitive performance, hippocampal volume reductions, reductions in gray matter, and reductions in white matter integrity. Funds will be used for: - Salary of personnel for time spent either in lockout, damage assessment, re-establishing the laboratory, running additional subjects to complete the aims - Supplies costs that are needed to complete the aims; - Extra assays on stored samples needed to complete the aims We estimate that we will need 6 months to make up for the time lost due to Sandy.

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 #
3R01DK083537-04S2
Application #
8675057
Study Section
Program Officer
Jones, Teresa L Z
Project Start
2014-01-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2015-12-31
Support Year
4
Fiscal Year
2014
Total Cost
$199,588
Indirect Cost
$79,284
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
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
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
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
Cazettes, F; Tsui, W H; Johnson, G et al. (2011) Systematic differences between lean and obese adolescents in brain spin-lattice relaxation time: a quantitative study. AJNR Am J Neuroradiol 32:2037-42
Bruehl, Hannah; Sweat, Victoria; Tirsi, Aziz et al. (2011) Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions. Neurosci Med 2:34-42
Maayan, Lawrence; Hoogendoorn, Claire; Sweat, Victoria et al. (2011) Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction. Obesity (Silver Spring) 19:1382-7