Brain Health in Youth With Normal Weight, Overweight and Obesity at Risk for Type 2 Diabetes (T2D)

NCT ID: NCT05277558

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 117 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-24
• Study Completion Date: 2027-10-31

Brief Summary

Investigators propose to study youth across the spectrum of body mass index (BMI) and dysglycemia. This approach will allow investigators to disentangle the relationship of key features of type 2 diabetes (T2D) risk (e.g. obesity) with intermediary physiologic changes (e.g. insulin resistance, inflammation, β-cell dysfunction and dysglycemia) that pose a risk for the brain. Investigators will determine which of these factors are most associated with differences in brain structure and function among groups, over time, and how these effects differ from normal neurodevelopment.

Detailed Description

Investigators will study three groups of pubertal youth, ages 12-17 yrs old (n=31 each): a group with normal weight and normal glucose tolerance (NW-NGT), a group with overweight/obesity and normal glucose tolerance (O-NGT), and a group with overweight/obesity and dysglycemia (O-DG). Groups will be comparable in age, sex, race/ethnicity, and socio-economic status (SES). Brain structure and function will be examined in all groups using magnetic resonance imaging (MRI) and cognitive tests at study entry (time 1/baseline), and after 21 months (time 2), focusing on a limited number of key outcome variables known to be consistently impaired in obesity or T2D. Targeted MRI measures will be regional volumes (e.g. hippocampus), neuroinflammation via restricted ratio from diffusion basis spectrum imaging (DBSI); hippocampus and white matter tracts), whole-brain cerebral blood flow via arterial spin labeling (ASL). Targeted cognitive measures will be delayed memory, processing speed, and executive function. The ultimate goal of this study is to determine how metabolic factors during neurodevelopment set the stage for the potentially profound, long-term impact of T2D on the brain and its functions. Given that the disease occurs at a time when brains are undergoing dramatic developmental processes, the aggressive nature of youth-onset T2D progression and complications in other organ systems, these results may provide guidance and justification for longer follow-up, interventional and/or mechanistic studies, and have important clinical implications.

Conditions

Type2 Diabetes; Type 2 Diabetes Mellitus in Obese; Dysglycemia; Microvascular Complications; Brain Structure; Obesity, Childhood; Diabetes in Adolescence; Inflammation; Insulin Resistance; Overweight, Childhood; Cognitive Decline

Keywords

Brain, Health, Youth, Type 2 Diabetes Mellitus, overweight, obesity

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Normal Weight-Normal Glucose Tolerant (NW-NGT)

(1) a group that is the normal weight (BMI\<85th%) and has normal glucose tolerance (NW-NGT)

Observational

Intervention Type: OTHER

Investigators are observing brain health over time (21 months) in these groups

Overweight and/or obese and has normal glucose tolerance (O-NGT)

(2) a group that is overweight and/or obese (BMI \>85th%) and has normal glucose tolerance (O-NGT)

Observational

Intervention Type: OTHER

Investigators are observing brain health over time (21 months) in these groups

Overweight and/or Obese and has dysglycemia (O-DG)

(3) group that is overweight and/or obese (BMI \>85th%) and has dysglycemia (O-DG; fasting plasma glucose ≥100 mg/dl and/or 2-hour glucose ≥140 mg/dl oral glucose tolerance test (OGTT) and laboratory-based HbA1c ≥5.8 and ≤8.0%, if treatment naïve).

Observational

Intervention Type: OTHER

Investigators are observing brain health over time (21 months) in these groups

Interventions

Observational

Investigators are observing brain health over time (21 months) in these groups

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 12-17 yrs. old at visit 1, 12-19 yrs. old at visit 2, Tanner II or above (determined through an exam by a pediatric endocrinologist or certified nurse practitioner trained in pediatric endocrinology), otherwise healthy except for obesity, <450 lbs. (due to MRI scanner limits), able and willing to lie flat within the MRI scanner and do cognitive testing, fluent in English.

Exclusion Criteria

• Syndromic obesity, history of bariatric surgery, insulin treatment (metformin allowed if < 6 months) for T2D, contraindications for MRI (metal, claustrophobia), braces, pregnant (pregnancy test will be done on post-menarchal girls) or breastfeeding, inability to participate in cognitive testing due to sensory or language issues, intellectual disability, special education, pharmacologic treatment for Attention Deficit Hyperactivity Disorder (ADHD), prematurity (<36 weeks gestation), complications at birth, neurologic co-morbidities (e.g., seizures, stroke, head injury with >10 min loss of consciousness), significant psychiatric disorders (e.g., schizophrenia, bipolar disorder, current major depression), taking psychoactive medications (e.g., antipsychotics) that would interfere with testing or reporting illegal drug use. Self-reported smoking and alcohol use and length of time with obesity will be assessed by history (although these measures may not be fully reliable).

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tamara A Hershey, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Silva Arslanian, MD

Role: PRINCIPAL_INVESTIGATOR

UPMC Children's Hospital of Pittsburgh

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mary Borgschulte, RN, BSN, CDE

Role: CONTACT

Phone: 314-952-8195

Email: Mary.b@wustl.edu

Kaeli Spight

Role: CONTACT

Phone: 314-362-4721

Email: kspight@wustl.edu

Facility Contacts

Samantha Ranck, MSW, MA

Role: primary

Kaeli Spight

Role: backup

Angela Akar, BS, CCRC

Role: primary

Other Identifiers

1R01DK126826-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202107019

Identifier Type: -

Identifier Source: org_study_id