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Principal Investigator: LORRAINE E LEVITT KATZ
Organization: CHILDREN'S HOSP OF PHILADELPHIA
Fiscal Year: 2024
Award: $865,708
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
ABSTRACT
While obesity, ancestry, family history of diabetes, insulin resistance, and puberty are all risk
factors for pediatric-onset type 2 diabetes (T2D), identifying the subset of youth at greatest risk of
advancing from “prediabetes” to T2D and the mechanisms underlying the deterioration remain
elusive. This lack of specificity defies the medical community's ability to 1) direct care to the youth
at greatest risk of pediatric onset T2D and 2) develop targeted interventions. The particularly
aggressive nature of pediatric T2D and the unique hormonal milieu of the adolescent suggest
while the mechanisms underlying adult-onset T2D in adults resonate in pediatric T2D, additional
perturbances are operative. Our team proposes to collaborate in a multi-center study, informed
by partnerships with family and community members, to define clinically accessible metrics of
increased diabetes risk as well as potential mechanisms that compromise the normal adaptations
to insulin resistance during adolescence. We propose a longitudinal study leveraging a 3-hour,
multi-sample oral glucose tolerance test performed at baseline, 18-months, and 36-months in
obese pubertal youth with pre-diabetes to 1) test the utility of the one-hour glucose in predicting
T2D and deterioration in insulin secretion, 2) perform extensive phenotyping for testing the
relationships of changes in insulin secretion (early phase and second phase), insulin sensitivity,
incretin secretion, glucagon suppression, hepatic glucose clearance, and free fatty flux with
emergence of T2D. The contributions of genetic variants, in utero environment, visceral adipose
accumulation, eating behaviors, mental health issues, social determinants of health, diet, physical
activity, sleep and COVID infection to perturbances in insulin secretion and sensitivity will be
tested. Home health care workers will provide additional critical insight into the home environment.
Glucose-potentiated arginine stimulation tests will be conducted in subsets of participants in
whom glucose homeostasis is preserved, worsens, or advances to T2D. This study is anticipated
to specify useful indicators of T2D risk and advance our understanding of the underpinnings of
progressive defects in insulin secretion and sensitivity to inform individualized programs aimed at
interrupting emergence of T2D.
Terms: <0-11 years old><12-20 years old><21+ years old><Acceleration><Adipose tissue><Adolescence><Adolescent><Adolescent Youth><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Algorithms><Antidiabetic Hormone><Arginine><Beta Cell><Biological Markers><Blood Plasma><Body Composition><COVID-19 infection><COVID-19 virus infection><COVID19 infection><Caring><Child><Child Youth><Childhood><Childhood diabetes><Children (0-21)><Children's Hospital><Clinical><Collaborations><Communication><Communities><Community Health Aides><Community Health Care><Community Healthcare><D-Glucose><DNA><Data><Data Collection><Defect><Deoxyribonucleic Acid><Deterioration><Development><Dextrose><Diabetes Mellitus><Diet><Disease><Disorder><Domiciliary Care><Eating Behavior><Eating Disorders><Education><Educational aspects><Emotional Depression><Environment><Evaluation><Exposure to><Family><Family Medical History><Family Medical History Epidemiology><Family history of><Fats><Fatty Tissue><Fatty acid glycerol esters><Fetal Growth Restriction><Fetal Growth Retardation><Fetal Macrosomia><Fetal Macrosomias><Future><Gene variant><Generalized Growth><Genetic Risk><Genomics><Genotype><Glucagon><Glucose><Glukagon><Goals><Growth><HG-Factor><Health Care Providers><Health Care Team><Health Personnel><Healthcare Providers><Healthcare Team><Healthcare worker><Hepatic><Home Care Services><Home environment><Hormonal><Hour><Human><Humulin R><Hyperglycemic-Glycogenolytic Factor><IUGR><Institution><Insulin><Insulin Cell><Insulin Resistance><Insulin Secreting Cell><Interruption><Intervention><Intervention Strategies><Intrauterine Growth Retardation><Ketosis-Resistant Diabetes Mellitus><L-Arginine><Life Style><Lifestyle><Long-term cohort><Longitudinal Studies><Longitudinal cohort><Longterm cohort><Maturity-Onset Diabetes Mellitus><Medical><Medical Care Team><Mental Health><Mental Hygiene><Metabolic><Methodology><Methods><Mission><Modern Man><Molecular><Multi-center studies><Multicenter Studies><NIDDM><Nature><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Non-Polyadenylated RNA><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Novolin R><OGTT><Obesity><Oral Glucose Tolerance Test><Participant><Patients><Pediatric Hospitals><Phase><Phenotype><Philadelphia><Physical activity><Physical assessment><Plasma><Plasma Serum><Population><Prediabetes><Prediabetes syndrome><Prediabetic State><Prevalence><Process><Prospective Studies><Protocol><Protocols documentation><Psychological Health><Psychosocial Factor><Puberty><RNA><RNA Gene Products><Regular Insulin><Reporting><Research><Research Design><Research Resources><Resources><Reticuloendothelial System, Serum, Plasma><Ribonucleic Acid><Risk><Risk Factors><SARS-CoV-2 infection><SARS-CoV2 infection><Sampling><Science><Secretory Cell><Secretory Rate><Severe acute respiratory syndrome coronavirus 2 infection><Sleep><Slow-Onset Diabetes Mellitus><Specific qualifier value><Specificity><Specified><Stable Diabetes Mellitus><Standardization><Study Type><T2 DM><T2D><T2DM><Teen><Teenagers><Testing><Tissue Growth><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Viral><Visceral><Youth><Youth 10-21><actigraph><actigraphy><adipocytokines><adipokines><adipose><adiposity><adolescence (12-20)><adult onset diabetes><adulthood><allele variant><allelic variant><anxiety symptoms><anxious symptom><base><bases><bio-markers><biobank><biologic marker><biomarker><biorepository><blood glucose regulation><clinical center><community based participatory research><community care><community health worker><community led research><community participatory research><community partnered participatory research><coronavirus disease 2019 infection><corpulence><depression symptom><depressive><depressive symptoms><design><designing><developmental><diabetes><diabetes during childhood><diabetes in childhood><diabetes in children><diabetes risk><diets><digital health><exposed in utero><fetal exposure><fetal overgrowth><genetic variant><genomic variant><glucose control><glucose homeostasis><glucose regulation><health care personnel><health care worker><health provider><health workforce><healthcare personnel><healthy weight><high risk><home health care><home healthcare><impaired fetal growth><in utero><in utero exposure><indexing><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innovate><innovation><innovative><insight><insulin resistant><insulin secretion><insulin sensitivity><insulin tolerance><interventional strategy><intra-uterine environment><intra-uterine environmental exposure><intra-uterine growth restriction><intra-uterine growth retardation><intrauterine environment><intrauterine environmental exposure><intrauterine growth restriction><intrauterine milieu><juvenile><juvenile human><ketosis resistant diabetes><kids><lack of physical activity><long-term study><longitudinal outcome studies><longterm study><maternal diabetes><maturity onset diabetes><medical personnel><member><ontogeny><open source><participatory action research><pediatric><pediatric diabetes><phenomics><physical inactivity><pre-diabetes><pre-diabetic><prediabetic><prenatal exposure><prenatal growth disorder><prenatally exposed><preservation><prevent><preventing><programs><psychosocial variables><recruit><screening><screenings><sleep health><sleep hygiene><social health determinants><study design><study population><teen years><teenage><tool><treatment provider><type 2 DM><type II DM><type two diabetes><white adipose tissue><yellow adipose tissue><youngster><β-cell><β-cells><βCell>