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

February 2, 2022 updated by: K. Sreekumaran Nair, Mayo Clinic

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

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?

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Structural MRI
Time Frame: 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.
baseline, 6 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2017

Primary Completion (Actual)

August 1, 2018

Study Completion (Actual)

July 5, 2019

Study Registration Dates

First Submitted

December 13, 2017

First Submitted That Met QC Criteria

January 2, 2018

First Posted (Actual)

January 8, 2018

Study Record Updates

Last Update Posted (Actual)

February 3, 2022

Last Update Submitted That Met QC Criteria

February 2, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-005244

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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