The rising prevalence of type 2 diabetes mellitus (T2DM) in obese children, particularly in minority ethnic groups, is an enormous public health problem. The early age of onset of T2DM in youth may particularly increase the risk of devastating complications which are known to be directly related to the degree and duration of hyperglycemia. There is strong evidence from studies in adults (UKPDS) that normalization of glucose greatly decreases the frequency of microvascular complications of T2DM. It is, therefore, imperative to aggressively treat T2DM in order to reach long-term glycemic control in youths. The UKPDS also showed that life style intervention or monotherapy with insulin or metformin alone is usually insufficient to maintain long-term diabetes control. We, hereby, propose to test the hypothesis that the combined use of therapeutic agents that reverses or improves insulin resistance and restores first phase insulin secretion VS monotherapy with metformin alone will serve to preserve B-cell function in youth with new onset T2DM and increase the likelihood of achieving and maintaining strict metabolic control of diabetes. We seek to serve for a clinical site for a multi center trial site for the treatment of T2DM in children and adolescents of different ethnic groups. At randomization patients will be allocated to 4 treatment strategies: 1) metformin alone; 2) metformin plus inhaled insulin; 3) metformin plus nateglinide and 4) piozlitazone plus metformin. The primary efficacy aim is: To examine and compare the effects of the treatments on overall diabetes control, as assessed by sequential HbA1c level less than or equal to 7.0 percent. Furthermore, to determine differences in the ability of treatments regimens to achieve and maintain target HbA1c levels less than or equal to 7 percent. Secondary efficacy aims: To examine and compare the effects of the treatment on macrovascular risk factors (lipid profiles, post-prandial hyperglycemia etc.); preservation of B-cell function as assessed by the C-peptide stimulation test; development and progression of microvascular complications and psychosocial well being. Safety aims are hypoglycemia; accelerated weight gain and known potential adverse effects of pharmacological agents. To accomplish these goals and to best perform as a clinical site in the multi center treatment trial of T2DM in youth, we have brought together a team of researchers with expertise in childhood obesity, T1 and T2DM in youth, pharmacological studies in children (Pediatric Pharmacology Research Unit, PPRU) and community based interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK061212-02
Application #
6525271
Study Section
Special Emphasis Panel (ZDK1-GRB-B (O1))
Program Officer
Linder, Barbara
Project Start
2001-09-30
Project End
2009-02-28
Budget Start
2003-03-01
Budget End
2004-02-28
Support Year
2
Fiscal Year
2003
Total Cost
$683,168
Indirect Cost
Name
Yale University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
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 :
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
Chadwick, Jennifer Q; Van Buren, Dorothy J; Morales, Elisa et al. (2017) Structure to utilize interventionists' implementation experiences of a family-based behavioral weight management program to enhance the dissemination of the standardized intervention: The TODAY study. Clin Trials 14:406-412
Arslanian, Silva; El Ghormli, Laure; Bacha, Fida et al. (2017) Adiponectin, Insulin Sensitivity, ?-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY. Diabetes Care 40:85-93
Rockette-Wagner, Bonny; Storti, Kristi L; Edelstein, Sharon et al. (2017) Measuring Physical Activity and Sedentary Behavior in Youth with Type 2 Diabetes. Child Obes 13:72-77

Showing the most recent 10 out of 47 publications