The purpose of this study is to continue to follow participants in the TODAY clinical trial as they transition to non-blinded, non-randomized standard diabetes care and management with monitoring and follow-up for up to 24 months (phase 1), during which time the TODAY data are analyzed and findings interpreted to develop a long-term observational protocol (phase 2). Data are collected during phase 1 for descriptive purposes; there is no primary hypothesis.
TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multi-center study of the optimal approach to treatment of type 2 diabetes (T2D) in children and adolescents. The TODAY clinical trial of experimental interventions ended in February 2011. It is followed by TODAY2, a longitudinal study to continue the care and observation of the TODAY cohort beyond the end of the TODAY intervention trial. TODAY2 consists of two phases. 1. First is the immediate transition of TODAY participants to non-blinded, non-randomized standard diabetes care and management with monitoring and follow-up for up to 24 months. During this period, the findings of TODAY are analyzed and interpreted by the study group. 2. The second phase is a protocol for long-term longitudinal follow-up of the TODAY cohort, based on findings from TODAY. The primary objective of the first phase of TODAY2 is to continue to follow the TODAY subjects for up to 24 months in order to begin to: * understand the persistence of the effects of the different treatment regimens used in TODAY, * describe the continued evolution of beta cell function, and * describe the development of vascular complications and risk factors for complications.
Study Type
OBSERVATIONAL
Enrollment
550
Participants consenting to receive study-provided care may be treated with metformin, insulin, statin, and ace-inhibitor, as needed for glycemic control and for comorbid conditions.
Children's Hospital Los Angeles
Los Angeles, California, United States
University of Colorado Denver
Denver, Colorado, United States
effects of TODAY treatment assignment on long-term glycemic control
The primary objective of the first phase of TODAY2 is to begin to examine the persistence of effects of the TODAY treatment assignment on long-term glycemic control following discontinuation of randomized treatment. During this period, results of TODAY are produced and used to define additional outcomes for the second phase of TODAY2.
Time frame: observed for 2 years in phase 1
glycemic control
HbA1c is the designated measure of glycemic control during T2P1. Mean HbA1c levels for participants from the three original TODAY treatment arms are compared as measures of the degree and durability of glycemic control after discontinuation of initial randomized therapy. The overall target is to maintain HbA1c levels as close to the normal range as possible in order to reduce long-term diabetes complications. TODAY2 continues to use HbA1c \< 6% as the target.
Time frame: observed for 2 years in phase 1
safety
In TODAY2, subjects are treated with approved medications, i.e., metformin and/or insulin. No specific abnormalities are expected to develop in this cohort, given the well-documented safety record of these agents. However, abnormalities in laboratory tests (hemoglobin/hematocrit, liver function tests, calculated creatinine clearance), episodes of severe hypoglycemia, and incidence of side effects (e.g., gastrointestinal complaints) are tracked.
Time frame: observed for 2 years in phase 1
insulin sensitivity and secretion
An important component of TODAY2 is to continue to monitor insulin sensitivity and secretion in the TODAY cohort after discontinuation of randomized therapy to determine (1) the evolution of changes in insulin secretion and sensitivity as participants emerge from puberty and enter young adulthood and (2) the effect of each of the initial therapies on the progression of changes in insulin sensitivity and secretion. Insulin sensitivity and secretion are determined with fasting glucose, insulin, C-peptide, and proinsulin levels, OGTT-based indices, HOMA, and QUICKI measured annually.
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Yale University
New Haven, Connecticut, United States
George Washington University Biostatistics Center
Rockville, Maryland, United States
Massachusetts General Hospital Diabetes Center
Boston, Massachusetts, United States
Joslin Diabetes Center
Boston, Massachusetts, United States
Saint Louis University
St Louis, Missouri, United States
Washington University
St Louis, Missouri, United States
Columbia University Medical Center
New York, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
...and 6 more locations
Time frame: observed for 2 years in phase 1
cardiovascular risk factors
Both traditional and non-traditional CVD risk factors are measured in the first phase of TODAY2 and assessed overall as well as compared across initial treatment arms. Blood pressure is measured at every visit and specimens drawn annually for repeated measurements of lipids (free fatty acids, lipoprotein subclass levels, average LDL particle density, and total apoB level), fibrinogen, c-reactive protein, plasminogen activator inhibitor-1, homocysteine (vitamin B-12 to evaluate homocysteine levels), and interleukin-6.
Time frame: observed for 2 years in phase 1
microvascular complications
Quantitation of microalbuminuria is performed by obtaining spot urine measurements of microalbumin/creatinine ratio at annual visits. Abnormal values are confirmed with two additional samples within three months; diagnosis of microalbuminuria is made as a result of two out of three positive tests. Creatinine clearance (by calculation) is determined at annual visits. The presence of peripheral neuropathy is evaluated using the Michigan Neuropathy Screening Instrument (MNSI) performed annually.
Time frame: observed for 2 years in phase 1