Type 2 Diabetes and the Brain in Adolescents

Sponsor

Nemours Children's Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT03461510

Collaborator

(none)

Enrollment

Location

Arms

13.8

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Obesity Pediatric Obesity Insulin Resistance Dysglycemia Hyperglycemia	Procedure: Hyperglycemic clamp Procedure: Hyperinsulinemic Euglycemic clamp	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Dysglycemia & Obesity: Impact on the Brain in Adolescents With Type 2 Diabetes

Actual Study Start Date :

Dec 5, 2017

Actual Primary Completion Date :

Jan 30, 2019

Actual Study Completion Date :

Jan 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Type 2 Diabetes Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp	Procedure: Hyperglycemic clamp Subjects with T2D will receive IV Dextrose infusion to maintain plasma glucose at ~250 mg/dL during fMRI. Procedure: Hyperinsulinemic Euglycemic clamp Subjects with T2D will receive IV Dextrose and Insulin infusion to maintain plasma glucose at approximately 90 mg/dL during fMRI.
No Intervention: Lean Control Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp
No Intervention: Obese Control Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Arm

Intervention/Treatment

Experimental: Type 2 Diabetes

Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Procedure: Hyperglycemic clamp

Subjects with T2D will receive IV Dextrose infusion to maintain plasma glucose at ~250 mg/dL during fMRI.

Procedure: Hyperinsulinemic Euglycemic clamp

Subjects with T2D will receive IV Dextrose and Insulin infusion to maintain plasma glucose at approximately 90 mg/dL during fMRI.

No Intervention: Lean Control

Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

No Intervention: Obese Control

Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Outcome Measures

Primary Outcome Measures

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.