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

Purpose

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.

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

Eligibility

Eligible Ages
Between 12 Years and 17 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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).

Study Design

Phase
Study Type
Observational
Observational Model
Case-Control
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Normal Weight-Normal Glucose Tolerant (NW-NGT) (1) a group that is the normal weight (BMI<85th%) and has normal glucose tolerance (NW-NGT)
  • Other: Observational
    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)
  • Other: Observational
    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).
  • Other: Observational
    Investigators are observing brain health over time (21 months) in these groups

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University School of Medicine
St Louis, Missouri 63110
Contact:
Samantha Ranck, MSW, MA
314-362-6514
blankens@wustl.edu

More Details

NCT ID
NCT05277558
Status
Recruiting
Sponsor
Washington University School of Medicine

Study Contact

Mary Borgschulte, RN, BSN, CDE
314-952-8195
Mary.b@wustl.edu

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.