Insulin Deprivation on Brain Structure and Function in Humans With Type 1 Diabetes

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT03392441

Collaborator

(none)

Enrollment

Location

Arm

19.1

Actual Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

What are the effects of transient insulin deprivation on brain structure, blood flow, mitochondrial function, and cognitive function in T1DM patients?

What are the effects of transient insulin deprivation on circulating exosomes and metabolites in T1DM patients?

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1 Diabetes Diabetes Complications	Other: Insulin Deprivation in Type 1 Diabetic Patients	N/A

Detailed Description

Diabetes is associated with impaired cognition, abnormal brain development in children, and dementia in older adults, however the underlying mechanisms remain unclear. Little is known about the brain-specific effects of acute insulin deficiency. Our recent studies in diabetic mice show an overall down regulation of brain mitochondrial ATP production and up regulation of several key mitochondrial proteins, indicating that insulin withdrawal has a profound effect on brain mitochondria as well as proteins implicated in neurodegeneration. Hyperglycemia is known to alter cognitive function, but it is unclear if insulin deprivation independently alters cognitive function and has not been assessed in humans.

In order to investigate the effects of insulin deprivation on the human brain, we propose a study involving temporary insulin deprivation in adolescents and adults with type 1 diabetes (T1DM). We will perform brain MRI, phosphorus31 spectroscopy, cognitive testing, circulating blood exosome measurements, and proteomics from muscle biopsy; comparing these measures during insulin treatment and deprivation between diabetic patients and age-, sex-, BMI-matched controls.

Specific aim 1: Determine whether transient insulin deprivation in T1DM adults and adolescents alters brain structure, functions and blood flow as assessed by structural/functional MRI.

Specific aim 2: Determine whether transient insulin deprivation in T1DM adults and adolescents alters cognitive function.

Specific aim 3: Determine whether transient insulin deprivation in T1DM adults and adolescents alters the circulating blood exosome contents and metabolome that can potentially impact brain functions.

Specific aim 4: Determine whether transient insulin deprivation in T1DM adults alters the skeletal muscle proteome homeostasis especially those involved in fission and fusion

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Pilot Study to Evaluate the Effects of Insulin Deprivation on Brain Structure and Function in Humans With Type 1 Diabetes

Actual Study Start Date :

Nov 30, 2017

Actual Primary Completion Date :

Aug 1, 2018

Actual Study Completion Date :

Jul 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin Deprivation Insulin Deprivation in Type 1 Diabetic Patients will be performed for a short time period (4-6 hours). Changes to Age, Sex, and Gender matched controls will be compared.	Other: Insulin Deprivation in Type 1 Diabetic Patients Type 1 Diabetic Patients requiring insulin will have insulin stopped for a short period of time (4-6 hours)

Arm

Intervention/Treatment

Experimental: Insulin Deprivation

Insulin Deprivation in Type 1 Diabetic Patients will be performed for a short time period (4-6 hours). Changes to Age, Sex, and Gender matched controls will be compared.

Other: Insulin Deprivation in Type 1 Diabetic Patients

Type 1 Diabetic Patients requiring insulin will have insulin stopped for a short period of time (4-6 hours)

Outcome Measures

Primary Outcome Measures

Change in Structural MRI [baseline, 6 hours]
Structural magnetic resonance imaging (MRI) is a non-invasive technique for examining the anatomy and pathology of the brain (as opposed to using functional magnetic resonance imaging [fMRI] to examine brain activity. This produces images which can be used for clinical radiological reporting as well as for detailed analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

Male and females age 14-17 years, females must be post-menarcheal
Age 18-45 years
Able to provide written consent
Parents able to provide written consent
T1DM treated with CSII or MDI (not degludec)

Exclusion criteria:

BMI < 20 or > 30 kg/m2
BMI z-score <5th or >95th percentile
Celiac disease
Pregnancy
Smoking
Reported history of illicit substance use
History of active cardiovascular, cerebrovascular, or peripheral vascular disease
Active renal disease evidenced by estimated GFR < 50 mL/min/1.73 m2
History of traumatic brain injury
Dementia or any other neurologic disease
Psychiatric disease\
Any learning disability
Hemoglobin A1c > 8.5%
Hemoglobin A1c > 9%
T2DM, or impaired fasting glucose