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Principal Investigator: SILVA A ARSLANIAN
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $607,058
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Type 2 diabetes mellitus (T2D) is a significant public health problem affecting ~30 million American. Obesity,
insulin resistance, insulin deficiency (β cell dysfunction) and dysglycemia all precede the diagnosis of T2D and
are known to promote inflammation and ultimately lead to microvascular complications. More recently, research
has identified brain-related complications in adult-onset T2D, including reduced regional brain structure and
function, impaired cognition, and increased lifetime risk for Alzheimer’s disease. Alarmingly, an increasing
number of children and adolescents are being diagnosed with T2D, likely due to the growing prevalence and
earlier onset of obesity. Youth-onset T2D appears to have a more aggressive course than adult-onset T2D, with
earlier onset and more rapid progression of microvascular complications. In addition, studies of youth with
obesity and youth-onset T2D have reported robust differences in regional brain structure and cognition,
suggesting that brain effects may follow the same aggressive course as the more typical vascular complications.
Unfortunately, little is known about the factors associated with poor brain structure and function in youth with
T2D. To address this critical gap in knowledge, we propose to study youth across the spectrum of body mass
index (BMI) and metabolic dysfunction. This approach will allow us to disentangle the relationship of key features
of T2D risk (e.g. obesity) with intermediary physiologic changes that pose a risk for the brain (e.g. insulin
resistance, inflammation, β-cell dysfunction and dysglycemia) that may lead to reduced brain structure and
function in T2D. We will determine which of these factors are most associated with differences in brain structure
and function among groups, over time, and how these effects differ from normal neurodevelopment. Given that
the disease occurs at a time when brains are undergoing dramatic developmental processes, the aggressive
nature of youth-onset T2D progression and complications in other organ systems, these results may provide
guidance and justification for longer follow-up, interventional or mechanistic studies and have important clinical
implications.
Terms: <0-11 years old><21+ years old><Active Follow-up><Address><Adolescent><Adolescent Youth><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Affect><Age><Aggressive course><Alzheimer risk factor><Alzheimer's disease risk><American><Ammon Horn><BMI><BMI percentile><BMI z-score><Beta Cell><Blood Vessels><Body System><Body mass index><Brain><Brain Nervous System><Brain region><Cell Function><Cell Physiology><Cell Process><Cellular Function><Cellular Physiology><Cellular Process><Cerebrovascular Circulation><Child><Child Youth><Children (0-21)><Clinical><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cornu Ammonis><Delayed Memory><Developmental Process><Diagnosis><Diffusion><Disease><Disorder><Disturbance in cognition><Dysfunction><Encephalon><Ethnic Origin><Ethnicity><Functional disorder><Funding><Goals><Hippocampus><Hyperglycemia><Impaired cognition><Impairment><Inflammation><Insulin Cell><Insulin Resistance><Insulin Secreting Cell><Insulin deficiency><Intervention><Intervention Strategies><Ketosis-Resistant Diabetes Mellitus><Knowledge><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Maturity-Onset Diabetes Mellitus><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Metabolic><Metabolic dysfunction><Microvascular Dysfunction><NIDDK><NIDDM><NMR Imaging><NMR Tomography><National Institute of Diabetes and Digestive and Kidney Diseases><Nature><Neural Development><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nuclear Magnetic Resonance Imaging><Obesity><Organ System><Outcome><Over weight><Overweight><Persons><Physiologic><Physiological><Physiopathology><Predictive Factor><Prevalence><Probabilistic Models><Probability Models><Puberty><Public Health><Quetelet index><Race><Races><Reporting><Research><Risk><Risk Factors><Site><Slow-Onset Diabetes Mellitus><Socio-economic status><Socioeconomic Status><Stable Diabetes Mellitus><Statistical Models><Structure><Subcellular Process><T2 DM><T2D><T2DM><Time><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Weight><Youth><Youth 10-21><Zeugmatography><active followup><adiposity><adult onset diabetes><adulthood><ages><alzheimer risk><arterial spin labeling><arterial spin tagging><blood flow in brain><brain blood circulation><brain blood flow><brain health><cerebral blood flow><cerebral circulation><cerebrocirculation><cerebrovascular blood flow><cognitive assessment><cognitive dysfunction><cognitive loss><cognitive testing><corpulence><diffused><diffuses><diffusing><diffusions><early onset><early-onset obesity><executive control><executive function><follow up><follow-up><followed up><followup><glucose tolerance><hippocampal><hyperglycemic><impaired glucose tolerance><insulin resistant><insulin secretion><insulin tolerance><interventional strategy><juvenile><juvenile human><ketosis resistant diabetes><kids><life-time risk><lifetime risk><maturity onset diabetes><microvascular complications><microvascular disease><neural inflammation><neurodevelopment><neuroinflammation><neuroinflammatory><pathophysiology><processing speed><racial><racial background><racial origin><sex><small vessel disease><socio-economic position><socioeconomic position><spectral image><spectral imagery><spectrograph><spectrum image><spectrum imagery><statistical linear mixed models><statistical linear models><substantia alba><systemic inflammation><systemic inflammatory response><type 2 DM><type II DM><type two diabetes><vascular><weights><white matter><youngster><β-cell><β-cells><βCell>