Although type 2 diabetes mellitus (T2D) was formerly a disease exclusively of adulthood, youth-onset T2D now represents a substantial percentage of new cases of diabetes in children. When T2D onset occurs in youth (1) there is a substantial risk that diabetic complications will lead to major morbidity, mortality, economic loss, and reduced quality of life by young adulthood, (2) the consequences may disproportionately affect ethnic minorities, and (3) ?-cell failure and development of diabetes-related complications and comorbidities may be more rapid than in either adult-onset T2D or youth-onset T1D. Existing studies have been inadequate to draw definitive conclusions regarding rates of comorbidities, their long-term impact, and hard clinical endpoints. The TODAY clinical trial recruited 699 youth to address treatment modalities and start to document disease progression. Long-term observational follow-up (TODAY2) of this large, thoroughly characterized, cohort closely followed from near disease onset is an unparalleled opportunity to test the hypothesis that youth-onset T2D represents a more aggressive presentation of the disorder by direct comparison to equivalent longitudinal studies in adult-onset T2D and youth-onset T1D. In addition, the extensive phenotyping and close monitoring of this cohort from soon after diagnosis will address the question of whether the apparent difference in youth- onset T2D represents biological difference, is a consequence of poor metabolic control, or is related to the pubertal state. Longitudinal follow-up will also provide the opportunity to more fully understand the effects of puberty and transition out of puberty on youth-onset T2D, as well as the disease course of individuals who appear to have maintained durable control into the post-pubertal years. Finally, study of this cohort will add to our understanding of the challenges and burdens borne by individuals with youth-onset T2D as they transition into adulthood. To address these outcome questions, TODAY2 will follow the TODAY participants at annual in- person visits, semi-annual telephone contact, and quarterly telephone and electronic communications for a comprehensive and systematic approach to documenting outcomes indicating the progression of T2D, ?-cell function, and diabetes-related comorbidities and complications.

Public Health Relevance

For adolescents with T2D, there is a substantial risk that diabetic complications will occur in what should be their most productive period of life and will disproportionately affect ethnic minorities. The proposed research will address gaps in knowledge about this disease by continuing to follow a well-studied group of adolescents with T2D to identify causes and factors related to development of complications in young adulthood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01DK061230-13
Application #
9108586
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (J3)S)
Program Officer
Bremer, Andrew
Project Start
2001-09-30
Project End
2020-04-30
Budget Start
2016-08-01
Budget End
2017-04-30
Support Year
13
Fiscal Year
2016
Total Cost
$7,930,830
Indirect Cost
$675,537
Name
George Washington University
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
043990498
City
Washington
State
DC
Country
United States
Zip Code
20052
Kelsey, Megan M; Braffett, Barbara H; Geffner, Mitchell E et al. (2018) Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. J Clin Endocrinol Metab 103:2309-2318
Van Buren, Dorothy J; Wilfley, Denise E; Marcus, Marsha D et al. (2018) Depressive symptoms and glycemic control in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Res Clin Pract 135:85-87
Kleinberger, Jeffrey W; Copeland, Kenneth C; Gandica, Rachelle G et al. (2018) Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med 20:583-590
Berkowitz, Robert I; Marcus, Marsha D; Anderson, Barbara J et al. (2018) Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr Diabetes 19:191-198
Arslanian, Silva; El Ghormli, Laure; Kim, Joon Young et al. (2018) The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in ?-Cell Function in TODAY. Diabetes Care :
Bjornstad, Petter; Nehus, Edward; El Ghormli, Laure et al. (2018) Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial. Am J Kidney Dis 71:65-74
Kriska, Andrea; El Ghormli, Laure; Copeland, Kenneth C et al. (2018) Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes. Pediatr Diabetes 19:36-44
Venditti, E M; Tan, K; Chang, N et al. (2018) Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes. Diabetes Res Clin Pract 139:24-31
Gidding, Samuel S; Bacha, Fida; Bjornstad, Petter et al. (2018) Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study. J Pediatr 192:86-92.e5
Levitt Katz, Lorraine E; Bacha, Fida; Gidding, Samuel S et al. (2018) Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes. J Pediatr 196:208-216.e2

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