Type 2 Diabetes and the Brain in Adolescents

Not Applicable

Completed

• Conditions: Type 2 Diabetes Mellitus; Obesity; Pediatric Obesity; Insulin Resistance; Dysglycemia; Hyperglycemia
• Interventions: Procedure: Hyperglycemic clamp; Procedure: Hyperinsulinemic Euglycemic clamp

• Registration Number: NCT03461510
• Lead Sponsor: Nemours Children's Clinic

Brief Summary

This study evaluates differences in brain function and cognitive performance in adolescents with type 2 diabetes (T2D) compared to non diabetic controls (both obese and lean) and correlates these changes with obesity, insulin resistance, and glycemic control in youth with T2D.

Detailed Description

This is a cross-sectional study examining neurocognitive function and brain activity in resting state and during working memory and executive function tasks using blood oxygen level dependent (BOLD) functional MRI (fMRI) during hyperinsulinemic euglycemic and hyperglycemic clamps in obese adolescents with T2D compared to non-diabetic obese and lean controls. The investigators will measure glycemic control (acute hyperglycemia during clamps and glycemic variability) and insulin resistance to examine their association with neurocognitive metrics and brain functional activity.

There will be one screening visit and three study visits for subjects with T2D. One visit will consist of neurocognitive testing and dual energy X-ray absorptiometry (DEXA) of the whole body to assess body composition including fat mass. In the other two visits, subjects with T2D will undergo normal and high glucose clamps during fMRI.

Obese and lean control subjects will have one screening visit and two study visits, one for neurocognitive testing and DEXA and another for fMRI without glucose clamps. All subjects will have a blood sample obtained at the screening visit.

Only adolescents with type 2 diabetes will wear a continuous glucose monitor (CGM) for 6 days prior to neuroimaging to determine glycemic variability. A1C will be assessed at baseline.

Parents of subjects will also have abbreviated IQ testing.

Study Timeline

• Study Start: 2017-12-05
• Study First Submitted: 2018-01-04
• Study First Submitted QC: 2018-03-08
• Study First Posted: 2018-03-12
• Primary Completion: 2019-01-30
• Study Completion: 2019-01-30
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-05
• Last Update Posted: 2019-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Type 2 Diabetes:

• BMI ≥85th percentile
• A1c ≥ 8%
• Pubertal

Healthy Controls:

• BMI ≥85th percentile for Obese Controls
• BMI < 85th percentile for Lean Controls
• Pubertal
• Normal A1c & Fasting glucose

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Exclusion Criteria

• Significant developmental delay or learning disability
• Significant visual or auditory deficits
• Born <34 weeks gestation
• Neurologic disease
• Psychiatric disease requiring inpatient treatment
• Significant head trauma
• Malignancy
• Pregnancy
• Weight > 350lb (MRI weight limit)
• Metal in the body (including dental braces)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Type 2 Diabetes	Hyperglycemic clamp	Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp
Type 2 Diabetes	Hyperinsulinemic Euglycemic clamp	Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Primary Outcome Measures

Name	Time	Method
Brain Activity using functional MRI (fMRI)	Baseline	The investigators will examine functional connectivity of brain networks during cross sectional resting-state and task-related (working memory and response inhibition) BOLD-fMRI activation. fMRI activation in adolescents with T2D will be compared to age- and sex- matched, non-diabetic, healthy lean and obese controls.
Neurocognitive battery metrics including IQ as well as executive function and visual-spatial memory	Baseline	The investigators will evaluate cognitive performance by examining test scores from neurocognitive metrics which reflect global IQ, spatial recognition, episodic memory, executive function (includes response inhibition, working memory), academic achievement, and processing speed. Adolescents with T2D will be compared to controls to determine whether these differences are associated with glycemic control, obesity, and insulin resistance.
fMRI performance in relation to dysglycemia	Baseline	In adolescents with T2D, the investigators will examine BOLD-fMRI brain activation in relation to acute hyperglycemia during glucose clamping, chronic hyperglycemia, glycemic variability, and insulin resistance.

Trial Locations

Locations (1)

Nemours Children's Health System; 🇺🇸 Jacksonville, Florida, United States