TODAY2 Phase 2 Follow-up (T2P2)

Long-term Post-Intervention Follow-up of the TODAY Cohort (Treatment Options for Type 2 Diabetes in Youth and Adolescents)

The primary objective of T2P2 is to track the progression of T2D and related comorbidities and complications in the TODAY cohort as they transition to young adulthood. We hypothesize that:

• Youth-onset type 2 diabetes (T2D) will progress rapidly and result in high rates of diabetes-related medical complications and comorbidities.
• The rapid rate of progression is related to increased insulin resistance characteristic of puberty, worse β-cell function, degree of glycemic control, control of non-glycemic factors, and obesity itself.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: TODAY cohort

• Study Type: Observational
• Enrollment (Actual): 517

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Children's Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine Department of Pediatrics
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Naomi Berrie Diabetes Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate New York University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University Rainbow Babies and Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Science Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All subjects randomized into the TODAY study are eligible to participate in T2P2. There are no additional inclusion or exclusions criteria for participation in T2P2.

Description

Inclusion Criteria:

• Participated in TODAY clinical trial.

Exclusion Criteria:

-

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TODAY cohort; All subjects randomized to the TODAY clinical trial are eligible to participate in T2P2. The study performs long-term observation only and administers no treatment, care, or management.	Other: TODAY cohort; This protocol is observation only and involves no intervention, care, treatment, or management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diabetic retinopathy	a microvascular complication determined by fundus photography	year 4
microalbuminuria	a microvascular complication determined by urine albumin excretion >= 30 mg/day	every 12 months
overt diabetic nephropathy	a microvascular complication determined by glomerular filtration rate < 70 mL/min/1.73m2	every 12 months
peripheral diabetic neuropathy	a microvascular complication defined as the presence of Michigan Neuropathy Screening Instrument (MNSI) exam score >2 and <8 out of 10 appropriate responses to the Semmes-Weinstein monofilament (SW-MF) in either foot.	every 12 months
cardiac function	a macrovascular (cardiovascular) risk indicator determined by echocardiogram	year 2
arterial stiffness	a macrovascular (cardiovascular) risk indicator determined by pulse wave velocity	year 5
cardiovascular risk lipid values	a macrovascular (cardiovascular) risk indicator determined by abnormal lipid value for LDL (>= 130 mg/dL) or triglycerides (>= 300 mg/dL)	every 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glycemic control	determined by HbA1c (annual)	every 12 months
psychological disorder	determined by scores on the following participant self-report standard surveys: (a) the Beck Depression Inventory II (BDI-II), (b) the Patient Health Questionnaire (PHQ) scales for somatic symptoms, anxiety, and alcohol use; participants are also interviewed about emotional or mental health problems involving referral, treatment, or hospitalization, and psychiatric diagnoses made by a non-study source that can be confirmed according to standard study criteria from acquired medical records are also recorded	every 12 months
body composition	determined by body mass index (BMI) computed from physical measurements of height and weight	every 12 months
insulin sensitivity and beta cell function	determined by oral glucose tolerance test (at 6 and 9 years from randomization) to derive measures of insulin sensitivity (1/insulin0), insulin secretion (ΔC-peptide30-0/Δglucose30-0, Δinsulin30-0/Δglucose30-0 if not on insulin), and the oral disposition index (oDI = insulin sensitivity x insulin secretion)	participant years 6 and 9 from baseline
eating disorder	determined by score on participant self report questionnaire Eating Disorder Diagnostic Scale (EDDS)	every 12 months
health-related quality of life	determined by score on the participant self report questionnaire Pediatric Quality of Life Inventory version 4.0 with age-specific versions for teen (13-18), young adult (19-25), and adult (≥26)	every 12 months
blood pressure	determined by collection of blood pressure	every 12 months
sleep function	determined by scores on standard questionnaires and in-lab polysomnogram	years 2-3
life stress	determined by participant self report questionnaire based on the Yeaworth Adolescent Life Change Event Scale	every 12 months
healthcare usage	determined by participant self report about visits, referrals, treatments, tests, and procedures related to healthcare	every 6 months

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Eye Institute (NEI)
• Investigators: Principal Investigator: Sonia Caprio, MD, Yale University; Principal Investigator: Silva Arslanian, MD, University of Pittsburgh; Study Chair: Philip S Zeitler, MD PhD, University of Colorado Denver Children's Hospital; Principal Investigator: Jeanie B Tryggestad, MD, University of Oklahoma Health Science Center; Principal Investigator: Mitchell E Geffner, MD, Children's Hospital Los Angeles; Principal Investigator: Robin S Goland, MD, Columbia University Naomi Berrie Diabetes Center; Principal Investigator: Lorraine L Katz, MD, Children's Hospital of Philadelphia; Principal Investigator: Lori MB Laffel, MD, Joslin Diabetes Center; Principal Investigator: Jane L Lynch, MD, University of Texas Health Sciences Center at San Antonio; Principal Investigator: Siripoom V McKay, MD, Baylor College of Medicine; Principal Investigator: Rose Gubitosi-Klug, MD, Case Western Reserve University Rainbow Babies and Children's Hospital; Principal Investigator: Sherida E Tollefsen, MD, St. Louis University; Principal Investigator: Ruth S Weinstock, MD PhD, SUNY Upstate Medical Center; Principal Investigator: Neil H White, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Trief PM, Uschner D, Tung M, Marcus MD, Rayas M, MacLeish S, Farrell R, Keady J, Chao L, Weinstock RS. Diabetes Distress in Young Adults With Youth-Onset Type 2 Diabetes: TODAY2 Study Results. Diabetes Care. 2022 Mar 1;45(3):529-537. doi: 10.2337/dc21-1689.
• TODAY Study Group; Shah RD, Braffett BH, Tryggestad JB, Hughan KS, Dhaliwal R, Nadeau KJ, Levitt Katz LE, Gidding SS. Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes. J Diabetes Complications. 2022 Mar;36(3):108123. doi: 10.1016/j.jdiacomp.2021.108123. Epub 2022 Jan 3.
• TODAY Study Group. Health Care Coverage and Glycemic Control in Young Adults With Youth-Onset Type 2 Diabetes: Results From the TODAY2 Study. Diabetes Care. 2020 Oct;43(10):2469-2477. doi: 10.2337/dc20-0760. Epub 2020 Aug 10.
• TODAY Study Group. Longitudinal Changes in Cardiac Structure and Function From Adolescence to Young Adulthood in Participants With Type 2 Diabetes Mellitus: The TODAY Follow-Up Study. Circ Heart Fail. 2020 Jun;13(6):e006685. doi: 10.1161/CIRCHEARTFAILURE.119.006685. Epub 2020 Jun 5.
• TODAY Study Group; Bjornstad P, Drews KL, Caprio S, Gubitosi-Klug R, Nathan DM, Tesfaldet B, Tryggestad J, White NH, Zeitler P. Long-Term Complications in Youth-Onset Type 2 Diabetes. N Engl J Med. 2021 Jul 29;385(5):416-426. doi: 10.1056/NEJMoa2100165.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): January 17, 2020
• Study Completion (Actual): January 17, 2020

Study Registration Dates

• First Submitted: June 18, 2014
• First Submitted That Met QC Criteria: December 4, 2014
• First Posted (Estimate): December 8, 2014

Study Record Updates

• Last Update Posted (Actual): August 5, 2021
• Last Update Submitted That Met QC Criteria: July 29, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: insulin sensitivity; beta cell function; youth onset type 2 diabetes; macrovascular comorbidities; microvascular comorbidities
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: DK61230-T2P2; U01DK061230 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The TODAY/TODAY2 Study Group engages in a number of methods to disseminate and share resources.

• Findings are reported in manuscripts and presentations.
• An active Ancillary Studies Committee reviews proposals to access the study cohort, the central database, and stored biospecimens.
• Materials from the TODAY lifestyle intervention program and the standard diabetes education manual for adolescents developed by study experts are made available for public access on the website https://today.bsc.gwu.edu/web/today/home.
• The study group adheres to the policies of the NIDDK Central Repositories to make data available to other scientific investigators. A TODAY2 de-identified database will be prepared and transferred along with excess stored biospecimens. Appropriate informed consent is required to transfer stored biospecimens.
• TODAY establishes collaborative arrangements to work with other federally funded study groups.

• IPD Sharing Time Frame: Data will be prepared and provided to the NIDDK Data Repository in early 2022
• IPD Sharing Access Criteria: Currently with approval of the Ancillary Studies Committee and after 2022 as determined by the NIDDK Data Repository
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL