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Clinical Research

Clinical research produces knowledge valuable for understanding human disease, preventing and treating illness, and promoting health.  We use the latest knowledge with patients to provide the best care, and we strive to use our clinical practice to increase our knowledge.   A large part of funding for clinical research in our Section comes from grants from the National Institutes of Health (NIH), but we also obtain funding from pharmaceutical companies.  Each research project is thoroughly reviewed by the university's  Institutional Review Board before it begins to ensure protection of participant rights and the welfare of human research participants.

Our section has been involved with clinical research for decades, but a series of studies stands out.  The TODAY studies were the first to understand which treatment works best for children and adolescents with Type 2 Diabetes.  Because of the success of the clinical trial, funding was awarded to observe these children and adolescents as they grew to become young adults - a span of up to 16 years.  We learned a great deal about how Type 2 diabetes advances over time as well as the development of complications.

What started as an NIH study tracking the risk of Type 1 diabetes in relatives of those with the disease, TrialNet has expanded to include clinical trials.  In our Section, medications are being studied to learn if they can prevent or delay Type 1 diabetes in those who are at highest risk.

In our work with pharmaceutical companies like AscendisNovo Nordisk, and Boehringer Ingelheim, clinical research seeks to address problems with growth and Type 2 diabetes.

Explore Our Research Work

The DISCOVERY Study

Based on seminal past research, including the TODAY StudiesSEARCH Study, and RISE Study, it became clear that the next step in Type 2 Diabetes research in youth needed to focus on understanding the early course of prediabetes and the risk factors for development of Type Diabetes in young people in order to design and test future prevention approaches and treatment efforts.

Higher prevalence of obesity in children has resulted in an increase in cases of prediabetes. Individuals with prediabetes are at higher risk of developing Type 2 Diabetes. Risk for development of Type 2 Diabetes is also influenced by puberty, which is characterized by significant hormonal  and metabolic changes. However, not every child has the same risk nor develops Type 2 Diabetes when they are at risk. The DISCOVERY Study will learn how to identify youth with the highest risk for Type 2 Diabetes by observing youth over a 2-4 year period who are at risk for developing Type 2 Diabetes. Some will be diagnosed with Type 2 Diabetes as it naturally occurs during the study. By comparing youth who are at risk but don't get Type 2 Diabetes with other youth at risk and are diagnosed with Type 2 Diabetes, we can learn a great deal how the development of Type 2 Diabetes actually happens and who are most likely to develop it.

Dr. Jeanie Tryggestad is the leading the OU Health Sciences Center site for the DISCOVERY Study, one of 15 clinical diabetes centers across the United States in a study funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). She and her team will recruit 240 obese youth at high risk for Type 2 Diabetes and who are in earlier stages of puberty. We will recruit participants from a variety of minority groups we already know are at higher risk (e.g., Native, Hispanic, and African Americans), rural and urban settings, and all overthe state of Oklahoma. Study participants will receive high quality monitoring for risk for Type 2 Diabetes with at least two in-person visits per year for up to four years. If study participants develop Type 2 Diabetes during the study, we will immediately connect them with a provider to manage their diabetes while they remain in the study until its conclusion. Study participants will also receive informational packets on health lifestyles, consistent with guidelines set by the American Academy of Pediatrics, and on symptoms of Type 2 Diabetes to help them identify early signs of Type 2 Diabetes that families, their providers, and the study need to know.

If you have questions or think you might want to participate, please send an email to our study team at discoverystudy@ou.edu or call 405-271-7554.

TODAY

Phase 1 - Intervention

Early in the 2000's, there was speculation that the growing epidemic of Type 2 Diabetes (DM2) in children and adolescents would lead to the largest public health crisis of the next generation. To that point, no effective treatment strategy had been demonstrated. The U.S. National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) sponsored TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) to address this need.  Our Section was one of 15 sites in the nation awarded this grant to participate.  Recruitment lasted from March, 2004 through February 2009, and the intervention phase of the study continued through February 28, 2011.

At the time, Metformin was the only oral medication approved by the U.S. Food and Drug Administration in the treatment of DM2 in youth. The primary aim of TODAY was to compare the safety and effectiveness of three treatments for DM2 in children ages 10 to 17: metformin + placebo, metformin + rosiglitazone (approved for DM2 in adults), and metformin + intensive lifestyle intervention.  All patients had to meet eligibility criteria, complete a run-in period (which includes standard diabetes education) prior to treatment, and to receive treatment for a total of 2-6 years.

We learned that the combined treatment worked better than either of the other treatments, and there we no serious safety problems in any of the treatments.  We also learned that other medical conditions were present in our young participants, including high blood pressure (risk factor for heart disease), high amounts of protein in the urine (risk factor for kidney disease), high amounts of LDL and triglycerides (risk factors for heart disease), and high levels of fat in the liver (risk factor for liver disease).  You can find more detailed information from the study results published in the New England Journal of Medicine, and you may view the official news release from the National Institutes of Health.  You can find a selection of additional publications here.

Phase 2 - Long-term Outcomes

After the clinical trial, from March 2011 through January 2020, we continued to observe these participants as they moved from childhood and adolescence to adulthood, which was something never done before.  We wanted to see how the treatments they received during TODAY impacted their diabetes in TODAY2.

We learned that complications were very common in these young adults, including high blood pressure (67.5%), high cholesterol and fats in the blood (51.6%), kidney disease (54.8%), nerve disease (32.4%), and eye disease (61.0%). At least one complication happened in 60.1% of participants, and two or more complications happened in 28.4%. Risk factors for developing complications included minority race or ethnic group, high blood sugars, high blood pressure, and high cholesterol and fats in the blood.

The data from TODAY2 show that complications are very common and serious. The longer term complications of Type 2 Diabetes in youth were worse and faster than typically seen with adults with Type 2 Diabetes or even youth with Type 1 Diabetes, frequently thought of before as the more severe disease. All of this points to the need for more approved medications to treat Type 2 Diabetes in youth. More importantly, we need to learn more about early risk factors for Type 2 Diabetes before it starts and how better to prevent it. 

Genetics

A separate set of TODAY study protocols relate to collecting blood and phenotypic information from more than 3,200 participants diagnosed with DM2 before age 18.  Our Section was one of 24 sites collecting this data, which will be used to explore relationships between candidate genes and DM2, obesity, insulin resistance, and cardiovascular complications of insulin resistance.

For information about the studies, call 405 271-6764 or visit the TODAY Study website.

Today Study Group

  • TODAY Study Group.  Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes.  Pediatric Diabetes 2007; 8:74-87. PMC2752327
  • TODAY Study Group.  Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study.  International Journal of Obesity 2010; 34:217–226. PMC2822093
  • Klingensmith GJ, Pyle L, Arslanian S, Copeland KC, Cuttler L, Kaufman F, Laffel L, Marcovina S, Tollefsen SE, Weinstock RS, Linder B, for the TODAY Study Group.  The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: Results from the TODAY study.  Diabetes Care 2010; 33(9):1970-1975. PMC2928346
  • TODAY Study Group.  Binge eating, mood, and quality of life in youth with type 2 diabetes: baseline data from the TODAY study.  Diabetes Care 2011; 34:858–860. PMC3064041
  • Copeland KC, Zeitler P, Geffner M, Guandalini C, Higgins J, Hirst K, Kaufman FR, Linder B, Marcovina S, McGuigan P, Pyle L, Tamborlane W, Willi S, for the TODAY Study Group.  Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. Journal of Clinical Endocrinology & Metabolism 2011; 96(1):159-167. PMC3038479
  • TODAY Study Group. A clinical trial to maintain glycemic control in youth with type 2 diabetes.  New England Journal of Medicine 2012; 366:2247-2256. PMC3478667
  • TODAY Study Group.  Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial.  Diabetes Care 2013; 36:1735–1741. PMC3661847
  • TODAY Study Group. Treatment effects on measures of body composition in the TODAY clinical trial. Diabetes Care 2013; 36:1742–1748. PMC3661839
  • TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and beta-cell function in TODAY. Diabetes Care 2013; 36:1749–1757.  PMC3661836
  • TODAY Study Group. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care 2013; 36:1758–1764. PMC3661790
  • TODAY Study Group. Safety and tolerability of the treatment of youth-onset type 2 diabetes: the TODAY experience. Diabetes Care 2013; 36:1765–1771. PMC3661822
  • TODAY Study Group. Retinopathy in youth with type 2 diabetes participating in the TODAY clinical trial.  Diabetes Care 2013; 36:1772–1774. PMC3661825
  • Kriska A, Delahanty L, Edelstein S, Amodei N, Chadwick N, Copeland K, Galvin B, El ghormli L,  Haymond M, Kelsey M, Lassiter C, Mayer-Davis E, Milaszewski K, Syme A.  Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes.  Pediatrics 2013; 131(3):e850-e856. PMC3581838
  • Delahanty L, Kriska A, Edelstein S, Amodei N, Chadwick JCopeland K, Galvin B, El ghormli L, Haymond M, Kelsey MG, Lassiter C, Milaszewski K, Syme A, Mayer-Davis E.  Self-reported dietary intake of youth with recent onset of type 2 diabetes:  results from the TODAY study.  Journal of the Academy of Nutrition and Dietetics 2013; 113:431-439. PMC3584416
  • Chadwick JQCopeland KCDaniel MRErb-Alvarez JAFelton BA, Khan SISaunkeah BR, Wharton DFPayan ML. Partnering in research: a national research trial exemplifying effective collaboration with American Indian Nations and the Indian Health Service. American Journal of Epidemiology 2014; 180(12):1202-1207. PMC4262439
  • TODAY Study Group. Alterations in left ventricular, left atrial, and right ventricular structure and function to cardiovascular risk factors in adolescents with type 2 diabetes participating in the TODAY clinical trial.  Pediatric Diabetes 2015; 16(1):39-47. PMC4107202
  • Zeitler P, Hirst K, Copeland KC, El ghormli L, Katz LL, Levitsky LL, Linder B, McGuigan P, White NH, Wilfley D for the TODAY Study Group. HbA1c after a short period of monotherapy with metformin identifies durable glycemic control among adolescents with type 2 diabetes. Diabetes Care 2015; 38:2285–2292. PMC4657618
  • Tryggestad JB and Willi SM. Complications and comorbidities of T2DM in adolescents: findings from the TODAY clinical trial. Journal of Diabetes Complications 2015; 29(2):307-312. PMC4333013
  • Weinstock RS, Trief P, El ghormli L, Goland R, McKay S, Milaszewski K, Preske J, Willi S, Yasuda P.   Parental characteristics associated with outcomes in youth with type 2 diabetes: results from the TODAY clinical trial. Diabetes Care 2015; 38:784-792. PMC4407755
  • Chernausek SD, Arslanian S, Caprio S, Copeland KC, El ghormli L, Kelsey MM, Koontz MB, Orsi CM, Wilfley D. Relationship between parental diabetes and presentation of metabolic and glycemic function in youth with type 2 diabetes: baseline findings from the TODAY trial. Diabetes Care 2016; 39(1):110-117. PMC4686846
  • Walders-Abramson N, Anderson B, Larkin ME, Chang N, Venditti E, Bzdick S, Tryggestad JB, Tan K,  Geffner ME, Hirst K. Benefits and barriers to participating in longitudinal research of youth-onset type 2 diabetes: results from the TODAY retention survey. Clinical Trials 2016; 13(2):240-243.  PMC4785072
  • Chadwick JQ, Van Buren DJ, Morales E, Timpson A, Abrams EL, Syme A, Preske J, Mireles G, Anderson B, Grover N, Laffel L. 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. Clinical Trials. 2017; 14(4):406-412. PMC5779851
  • Kriska A, El Ghormli L, Copeland KC, Higgins J, Ievers-Landis CE, Levitt Katz LE, Trief PM, Wauters AD, Yasuda PM, Delahanty, LM for the TODAY Study Group. Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes. Pediatric Diabetes 2018; 19(1):36-44. PMC5628101
  • Kleinberger JW, Copeland KC, Gandica RG, Haymond MW, Levitsky LL, Linder B, Shuldiner AR, Tollefsen S, White NH, Pollin TI.  Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes:  the TODAY clinical trial. Genetics in Medicine. 2018; 20:583-590. PMC5955780
  • Gidding S, Bacha F, Bjornstad P, El ghormli L, Katz L, Levitsky L, Lima J, Lynch J, Tryggestad J, Weinstock R for the TODAY Study Group. Cardiac biomarkers in youth with type 2 diabetes mellitus: results from the TODAY clinical trial. Journal of Pediatrics. 2018; 192:86-92. PMC5806514
  • Venditti EM, Delahanty N, Abramson N, Tryggestad J, Chang N, Yasuda P, Miranda N, McGinley G, Laffel L, Tan K for the TODAY Study Group. Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes. Diabetes Research and Clinical Practice. 2018; 139:24-31. PMC5955779
  • Shah AS, El ghormli L, Gidding SS, Bacha F, Nadeau KJ, Levitt Katz LE, Tryggestad JB, Leibel N, Hale DE, Urbina EM for the TODAY Study. Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: Relationships to glycemic control and other risk factors. Journal of Diabetes and its Complications. 2018; 32(8): 740-745. PMC6444355
  • Arslanian S, El ghormli L, Kim JY, Bacha F, Chan C, Ismail HM, Levitt Katz LE, Levitsky L, Tryggestad JB, White NH for the TODAY Study Group. The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in Beta-Cell Function in TODAY. Diabetes Care. 2018. PMC6300703
  • Chadwick JCopeland KBranam D, Erb-Alvarez JKhan SPeercy MRogers MSaunkeah BTryggestad JWharton D for the TODAY Study Group. Genomic research and American Indian tribal communities in Oklahoma: Learning from past research misconduct and building future trusting partnerships. American Journal of Epidemiology.2019; 188(7): 1206-1212. PMC6601530
  • Dhaliwal R, Shepherd J, El ghormli L, Copeland K, Geffner M, Higgins J, Levitsky L, Nadeau K, Weinstock R, White N for the TODAY Study Group. Changes in visceral and subcutaneous fat in youth with type 2 diabetes in the TODAY Study. Diabetes Care. 2019; 42(8): 1549-1559. PMC6647052
  • Shah A, El ghormli L, Vajravelu M, Bacha F, Farrell R, Gidding S, Levitt Katz L, Tryggestad J, White N, Urbina E for the TODAY Study Group. Heart rate variability and cardiac autonomic dysfunction: prevalence, risk actors and relationship to arterial stiffness in the treatment options for type 2 diabetes in adolescents and youth (TODAY) Study. Diabetes Care. 2019; 42(11):2143-2150. PMC6804614
  • Arslanian S, El Ghormli L, Haymond MH, Chan CL, Chernausek SD, Gandica RG, Gubitosi-Klug R, Levitsky LL, Siska M, Willi SM, TODAY Study Group. Beta Cell Function and Insulin Sensitivity in Obese Youth with Maturity Onset Diabetes of Youth Mutations vs Type 2 Diabetes in TODAY: Longitudinal Observations and Glycemic Failure. Pediatr Diabetes 2020 June;21(4):575-85. PMC32064729
  • Tryggestad JB, Shah RD, Braffett BH, Bacha F, Gidding SS, Gubitosi-Klug RA, Shah AS, Urbina EM, Levitt Katz LE, TODAY Study Group. Circulating Adhesion Molecules and Associations with HbA1c, Hypertension, Nephropathy, and Retinopathy in the Treatment Options for Type 2 Diabetes in Adolescent and Youth (TODAY) Study. Pediatr Diabetes 2020 June 5. PMC32501612
  • 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 June 5. PMC32498621

Contact Us

Department of Pediatrics

University of Oklahoma College of Medicine
1200 Children’s Ave., Ste. 14200
Oklahoma City, OK 73104
(405) 271-4401