Nutrition and Obesity Program

Clinical/Translational Research

Research within the Nutrition and Obesity Program involves many aspects of childhood diabetes and obesity. Our overall goals are to:

• Discover and understand the mechanisms contributing to obesity and its health consequences
• Develop strategies to reduce the burden of obesity and diabetes in children

Type 1 Diabetes

Research on Type 1 diabetes in our program focuses on two main areas:

• Preventing or reversing diabetes
• Improving treatment and outcome of patients with diabetes

TrialNet

TrialNet is a National Institutes of Health (NIH)-funded consortium of centers dedicated to the study, prevention and early treatment of type 1 diabetes (T1D). Our center has participated in TrialNet since its inception in 2001, screening more than 3,500 subjects for diabetes risk. We have also participated in multiple prevention and intervention studies, some with promising results, which have been published in multiple prestigious journals. Active studies include:

• Pathway to Prevention – A study screening family members of people with T1D to assess their risk for developing the condition. We test autoantibodies that are associated with the destruction of beta cells and progression to T1D. Family members are rescreened annually.
  • Eligible participants include:
    • First degree relatives (age 1-45 years)
    • Second and third degree relatives (age 1-20 years)
  • Screening visits take 15 minutes or less and involve a blood draw of ½ teaspoon.
  • Autoantibody positive participants are offered periodic monitoring visits, which include an HbA1c, HLA, and Oral Glucose Tolerance test.  
• CTLA4 Ig Prevention Trial – Participants who are at moderate risk of developing T1D based on their Pathway to Prevention results may be eligible for CTLA4 Ig Prevention trial, evaluating the efficacy of CTLA4 (Abatacept) infusions in preventing T1D. 
  • In an earlier study in newly diagnosed T1D individuals, those who received Abatacept had a 9.6 month delay in progression of insulin loss.
  • Abatacept is currently FDA approved for use in persons as young as 6 years with autoimmune arthritis.
• Long-Term Investigative Follow-Up Trial (LIFT) – Prior TrialNet participants (from the Pathway to Prevention trial, prevention studies, or new onset studies) who are diagnosed with T1D are evaluated every 6 months for the presence of residual beta cells. Information gathered in this study will provide participants and researchers important information about their diabetes that can only be learned in a long-term study.
• CGM Living Biobank Sub-study – A sub-study to Pathway to Prevention which investigates new metrics of interstitial glucose trends using continuous glucose monitoring (CGM). Information from this study will help researchers understand the nature of abnormal blood glucose values in participants with a high risk for T1D development. Interested Pathway to Prevention participants will wear a CGM for one week prior or following their monitoring visit at three consecutive semi-annual appointments. 

General Facts

• Relatives of people with type 1 diabetes are at a 15 times greater risk for developing the disease than the general population.
• For participants in type 1 diabetes research, the risk of DKA at diagnosis drops from 30% to less than 4%. 

TrialNet team: Roshanak Monzavi, MD, Debbie Miller, RN, and Dan Bisno.

For more information about TrialNet, please call 323-361-8641.

Select Publications

1. Sosenko JM, Skyler JS, DiMeglio LA, et al. A New Approach for Diagnosing Type 1 Diabetes in Autoantibody-positive Individuals Based on Prediction and Natural History.  Diabetes Care. 2015:38(2):271-6.
2. Orban T, Bundy B, Becker DJ, et al. Co-Stimulation Modulation with Abatacept in Patients with Recent-Onset Type 1 Diabetes: Follow-Up One Year After Cessation of Treatment. Diabetes Care. 2014 Apr;37(4):1069-75.
3. Orban T, Bundy B, Becker DJ, et al; Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011:378(9789):412-9.
4. Wherrett DK, Bundy B, Becker DJ, et al; Type 1 Diabetes TrialNet GAD Study Group. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomized double-blind trial. Lancet. 2011;378(9788):319-27. 

T1D Exchange

Children's Hospital Los Angeles participates in multicenter registry studies examining factors that predict health outcomes in children with type 1 diabetes. Learn more about the TD1 Exchange.

Investigator: Roshanak Monzavi, MD

Primary Coordinator: Brian Ichihara, (323)361-7615

Select Publications

1. Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, Maahs DM, Tamborlane WV, T1D Exchange Clinic Network. Current state of type 1 diabetes treatment in the U.S.:updated date from the T1D Exchange clinic registry. Diabetes Care. 2015;38(6):971-7
2. Wood JR, Miller KM, Maahs DM, et al; T1D Exchange Clinic Network. Most youth with type 1 diabetes in the T1D Exchange Clinic Registry do not meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes clinical guidelines. Diabetes Care. 2013;36(7):2035-7. PubMed Link.
3. Klingensmith GJ, Tamborlane WV, Wood J, et al; Pediatric Diabetes Consortium. Diabetic ketoacidosis at diabetes onset: still an all too common threat in youth. J Pediatr. 2013;162(2):330-4. PubMed Link.

YARDD (Young Adult Racial Disparities in Type 1 Diabetes) Study

The purpose of this study is to identify factors associated with poor health outcomes and care experiences in low-income minority young adults age 18-25 with type 1 diabetes. The primary objective of this study is to determine the prevalence and impact the barriers have on glycemic control in young adults with type 1 diabetes, based on minority race and socioeconomic status.

Investigator: Jennifer Raymond, MD, MCR and Roshanak Monzavi, MD

To learn more, contact Brian Ichihara at 323-361-7615

CITY (CGM Intervention in Teens and Young Adults with T1D) Study

This study will include adolescents and young adults with T1D and poor glycemic control (age 14-< 25 years, T1D duration >12 months, HbA1c 7.5-<11.0%, using an insulin pump or MDI)) will be randomly assigned to either CGM or BGM. The primary outcome assessment will be HbA1c after 6 months. Secondary outcomes will include HbA1c, CGM metrics (control group will wear blinded CGM at 13 and 24 weeks), and quality of life measures. The randomized trial will be followed by a 6-month extension study during which the RCT control group will initiate CGM and the RCT CGM group will continue CGM.Investigator: Roshanak Monzavi, MD and Jennifer Raymond, MD, MCR

To learn more, contact Brian Ichihara at 323-361-7615

Food Choices in Children with Type 1 Diabetes

This study is a summary of how children with type 1 diabetes with different body types choose what food to eat. Computer-based technology is used to help us better understand how children with type 1 diabetes process different attributes of food during dietary decision-making. 

Investigators: Mimi Kim, MD, MSc and Amy Seagroves, MD

For more information, please call (323)361-8848

Type 2 Diabetes

TODAY and TODAY2

The TODAY trials were designed to determine the best therapeutic approach for treatment of type 2 diabetes in adolescents. Our program has been a longstanding participant in this large, multicenter trial, funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Though not currently enrolling, this study is still following subjects to determine the effects of the interventions on outcomes.

TODAY team: Mitch Geffner, MD, Lynda K. Fisher, MD, Nancy Chang, MSN, FNP, and Jeralyn Duarte, BSN

To learn more, you can call us at 323-361-6327.

Select Publications

1. TODAY Study Group, Zeitler P, Hirst K, et al. A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes. N Engl J Med. 2012;366(24):2247-56. PubMed Link.
2. Laffel L, Chang N, Grey M, et al. Metformin monotherapy in youth with recent oncent type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study. Pediatr Diabetes. 2012;13(5):369-75. PubMed Link.
3. Copeland KC, Zeitler P, Geffner M, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159-67. PubMed Link.

Pediatric Diabetes Consortium 2

The Pediatric Diabetes Consortium (PDC) 2 is a network of 38 of the leading pediatric diabetes centers in the United States. PDC 2 maintains an active registry of pediatric patients with type 2 diabetes. One of the goals of the PDC network is to provide better access to a large, coordinated patient population for industry trials.

Investigator: Lynda Fisher, MD

WELKid DM

WELkid is a multi-center clinical trial to evaluate safety and efficacy of Colesevelam (Welchol®) Oral suspension as monotherapy or add-on to Metformin therapy in pediatric patients with type 2 diabetes. The primary objective of the study is to demonstrate the effects on colesevelam hydrochloride oral suspension on change in hemoglobin A1c from baseline over a 6-month treatment period in pediatric patients with type 2 diabetes.

Research Staff: Lynda Fisher, MD, Brian Miyazaki, MD, and Vanessa Guzman

To learn more, you can call us at 323-361-5553.

Sit-Up 289

A clinical trial to evaluate the safety and efficacy of a fixed dose combination tablet of Sitagliptin and extended release Metformin in pediatric patients with type 2 diabetes with inadequate glycemic control on Metformin and basal insulin.

Research Team: Lynda Fisher, MD, Mitchell Geffner, MD, Nancy Chang, MSN, FNP and Vanessa Guzman

To learn more, you can call us at 323-361-6327

Sit-up 083

A clinical trial to Evaluate the Safety and Efficacy of Sitagliptin versus a placebo in Pediatric Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on basal insulin only.

Investigator: Lynda Fisher, MD, Mitchell Geffner, MD, Nancy Chang, MSN, FNP, Jeralyn Duarte, BSN, and Vanessa Guzman

To learn more, you can call us at 323-361-6327.

CHAT2D (Children and Adolescents with Type 2 Diabetes) Study

CHAT2D is a multi-site clinical study that aims to assess the safety and efficacy of Exenatide (EQW) as a monotherapy and as an adjunct to oral antidiabetic agent and/or insulin therapy in patients with type 2 diabetes. EQW is a once weekly extended release, self-administered injection.

Research team: David Geller, MD, Lynda Fisher, MD Nancy Chang, MSN, FNP, PhD, Jeralyn Duarte, RN and Vanessa Guzman

To learn more about CHAT2D, please call (323)361-6327.

Obesity

Human Brown Adipose Tissue

Using the application of magnetic resonance imaging (MRI) techniques, this study examines the accumulation of fat within the human body, from abdominal depots to organs and muscles. MRI may be used to study the biological mechanisms underlying energy balance, nutrition, metabolism, Type 2 diabetes and obesity.

Investigators: Mimi Kim, MD, MSc

Kids N Fitness Junior

Kids N Fitness is designed to assist overweight children and their families make better lifestyle choices. The hospital’s Center for Endocrinology, Diabetes and Metabolism is conducting a research study of Kids N Fitness Junior, a six-week weight management program adapted for families with overweight and obese children ages 3-7 years.

Research Staff: Megan Lipton, MA, Brenda Manzanarez, MS, RD and Kelly Young.

For more information on Kids N Fitness Junior, call 323-361-3174.

 Select Publications

1. Monzavi R, Dreimane D, Geffner ME, Braun S, Conrad B, Klier M, Kaufman FR. Improvement in risk factors of metabolic syndrome and insulin resistance in overweight youth who are treated with lifestyle intervention. Pediatrics. 2006;117(6):e1111-8. PubMed Link.
2. Dreimane D, Safani D, MacKenzie M, et al. Feasibility of a hospital-based, family-centered intervention to reduce weight gain in overweight children and adolescents. Diabetes Res Clin Pract. 2007;75(2):159-68. PubMed Link. 

EMPOWER Telehealth Study

EMPOWER is piloting a new care delivery model for CHLA EMPOWER patients using group telehealth visits. This new communication technology is anticipated to help us connect with out patients and increase the likelihood of our patients achieving success. This model will allow patients to complete clinic visits from the comfort of their home. It will also encourage social interaction and support. The research study will assess the feasibility of using telehealth in this population and test the efficacy compared to regular in person visits. Eligible participants are patients age 14-18 who quality for the EMPOWER clinic.

Investigator: Claudia Borzutsky, MD

To learn more, contact Dalia Salazar at (323) 361-1920.

POWER (Pediatric Obesity and Weight Evaluation Registry)

We are participating in a multi-site pediatric weight evaluation registry along with more than 30 pediatric centers. The mission of POWER is to better understand and improve the health outcomes of children and adolescents with overweight and obesity who are participating in multi-component weight management programs. Patients in our Empower Weight Management Clinic are asked to enroll in POWER.

Investigator: Claudia Borzutzky, MD

Interested participants can call 323-361-7971

Food Choices in Childhood

This study evaluates how children decide what to eat. Computer-based technology may help us to better understand how the young brain processes different attributes of food during dietary decision-making. 

Investigators: Mimi Kim, MD, MSc and Amy Seagroves, MD

Obesity in Congenital Adrenal Hyperplasia

This study investigates reasons for obesity in an at-risk population of children, incorporating imaging technology to inform our understanding of this endocrine condition.

Investigators: Mimi Kim, MD, MSc and Mitchell Geffner, MD

An Addiction Approach Mobile Health Weight Loss Intervention in Obese Adolescents

Background: New and creative approaches are needed to address childhood obesity. Current strategies result in suboptimal outcomes and are intensive and costly. It has been theorized that overeating in some individuals may have addictive qualities, though few weight management interventions have tested therapeutic techniques founded in addiction medicine principles. Further, it is unknown whether mHealth platforms founded in behavioral theory may be a cost saving alternative to an in-clinic intervention for pediatric weight management.

Objective: To determine the efficacy of an addiction treatment approach mHealth weight loss intervention in adolescents.

Methods: Eighteen obese adolescents were recruited from an interdisciplinary weight management clinic (EMPOWER). Adolescents who exhibited signs of food addiction based on the Yale Food Addiction Scale, and who did not have signs of significant obesity comorbidities were enrolled in a six month pilot study of an interactive smartphone application (W8Loss2GO) with personalized coaching. The primary outcome was change in BMI z-score (zBMI) compared to baseline assessed at 3 and 6 months.

Results: All subjects completed the W8Loss2Go program. The W8Loss2Go participants had a significant decrease in zBMI compared to baseline assessed at 3 and 6 months and compared to the EMPOWER control group. There was a statistically significant difference in zBMI between W8Loss2GO and EMPOWER upon completion of the 6 month intervention (p=0.034). 

Conclusion: W8Loss2Go, an addiction medicine intervention, implemented as an mHealth platform, targeted for adolescents, appears to be useful in reducing zBMI and may be a cost-effective, timely and labor efficient method for weight management in adolescents.

Investigators: Alaina Vidmar, MD, Claudia Borzutsky, MD, Cassandra Fink

To learn more, please contact Alaina Vidmar at (323) 361-3385.