Type 2 Diabetes and the Brain in Adolescents

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03461510
• Other study ID #: 17-35
• Status: Completed
• Phase: N/A
• Start date: December 5, 2017
• Est. completion date: January 30, 2019

Study information

• Verified date: September 2019
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 30, 2019
• Est. primary completion date: January 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

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

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Dysglycemia
• Hyperglycemia
• Insulin Resistance
• Obesity
• Pediatric Obesity
• Type 2 Diabetes Mellitus

Intervention

Procedure:
• Hyperglycemic clamp
Subjects with T2D will receive IV Dextrose infusion to maintain plasma glucose at ~250 mg/dL during fMRI.
• Hyperinsulinemic Euglycemic clamp
Subjects with T2D will receive IV Dextrose and Insulin infusion to maintain plasma glucose at approximately 90 mg/dL during fMRI.

Locations

Country	Name	City	State
United States	Nemours Children's Health System	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nemours Children's Clinic

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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