Type 2 Diabetes and the Brain in Adolescents

NCT03461510 | Completed DMC

• 1 other identifier: 17-35
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus; Obesity; Pediatric Obesity; Insulin Resistance; Dysglycemia; Hyperglycemia

Keywords

Cognition; MRI; Functional MRI; Pediatric Obesity; Type 2 Diabetes Mellitus; Adolescents; Continuous Glucose Monitoring; Insulin Clamp

Outcome Measures

Primary Outcomes (3)

• Brain Activity using functional MRI (fMRI)

  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.

  Baseline

• Neurocognitive battery metrics including IQ as well as executive function and visual-spatial memory

  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.

  Baseline

• fMRI performance in relation to dysglycemia

  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.

  Baseline

Study Arms (3)

Type 2 Diabetes

EXPERIMENTAL

Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Procedure: Hyperglycemic clamp; Procedure: Hyperinsulinemic Euglycemic clamp

Lean Control

NO INTERVENTION

Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Obese Control

NO INTERVENTION

Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp

Interventions

Hyperglycemic clamp PROCEDURE

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

Type 2 Diabetes

Hyperinsulinemic Euglycemic clamp PROCEDURE

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

Type 2 Diabetes

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Study Sites (1)

Nemours Children's Health System

Jacksonville, Florida, 32207, United States

Location

Related Publications (8)

• Mazaika PK, Weinzimer SA, Mauras N, Buckingham B, White NH, Tsalikian E, Hershey T, Cato A, Aye T, Fox L, Wilson DM, Tansey MJ, Tamborlane W, Peng D, Raman M, Marzelli M, Reiss AL; Diabetes Research in Children Network (DirecNet). Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes. 2016 Feb;65(2):476-85. doi: 10.2337/db15-1242. Epub 2015 Oct 28.

  PMID: 26512024 BACKGROUND

• Mauras N, Mazaika P, Buckingham B, Weinzimer S, White NH, Tsalikian E, Hershey T, Cato A, Cheng P, Kollman C, Beck RW, Ruedy K, Aye T, Fox L, Arbelaez AM, Wilson D, Tansey M, Tamborlane W, Peng D, Marzelli M, Winer KK, Reiss AL; Diabetes Research in Children Network (DirecNet). Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes. 2015 May;64(5):1770-9. doi: 10.2337/db14-1445. Epub 2014 Dec 8.

  PMID: 25488901 BACKGROUND

• Marzelli MJ, Mazaika PK, Barnea-Goraly N, Hershey T, Tsalikian E, Tamborlane W, Mauras N, White NH, Buckingham B, Beck RW, Ruedy KJ, Kollman C, Cheng P, Reiss AL; Diabetes Research in Children Network (DirecNet). Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes. Diabetes. 2014 Jan;63(1):343-53. doi: 10.2337/db13-0179. Epub 2013 Oct 29.

  PMID: 24170697 BACKGROUND

• Bruehl H, Sweat V, Tirsi A, Shah B, Convit A. Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions. Neurosci Med. 2011 Mar 1;2(1):34-42. doi: 10.4236/nm.2011.21005.

  PMID: 21691448 BACKGROUND

• Yau PL, Javier DC, Ryan CM, Tsui WH, Ardekani BA, Ten S, Convit A. Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia. 2010 Nov;53(11):2298-306. doi: 10.1007/s00125-010-1857-y. Epub 2010 Jul 30.

  PMID: 20668831 BACKGROUND

• Yau PL, Kang EH, Javier DC, Convit A. Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity. Obesity (Silver Spring). 2014 Aug;22(8):1865-71. doi: 10.1002/oby.20801. Epub 2014 May 28.

  PMID: 24891029 BACKGROUND

• Cui Y, Jiao Y, Chen YC, Wang K, Gao B, Wen S, Ju S, Teng GJ. Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes. 2014 Feb;63(2):749-60. doi: 10.2337/db13-0519. Epub 2013 Dec 18.

  PMID: 24353185 BACKGROUND

• Marder TJ, Flores VL, Bolo NR, Hoogenboom WS, Simonson DC, Jacobson AM, Foote SE, Shenton ME, Sperling RA, Musen G. Task-induced brain activity patterns in type 2 diabetes: a potential biomarker for cognitive decline. Diabetes. 2014 Sep;63(9):3112-9. doi: 10.2337/db13-1783. Epub 2014 Apr 4.

  PMID: 24705405 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Pediatric Obesity; Insulin Resistance; Hyperglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Study Officials

• Lydia Snyder, MD

  Nemours Children's Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: March 12, 2018
• Study Start: December 5, 2017
• Primary Completion: January 30, 2019
• Study Completion: January 30, 2019
• Last Updated: September 9, 2019

Record last verified: 2019-09

Locations

US (1)