Recurrent Hypoglycemia in Type 1 Diabetes (Aim 1)

Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 1)

Sponsors

Lead Sponsor: University of Minnesota

Source University of Minnesota
Brief Summary

This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Neurochemical profiles will be measured by high field MRS before and after induction of IAH. Subject glycemic variability for 2 weeks and activity/sleep for 1 week before each study will be monitored as all factors have been shown to alter responses to HG.

Detailed Description

The long-term goal of this project is to identify how recurrent hypoglycemia (HG) leads to the clinical syndrome of impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D). This study will test the hypothesis that recurrent HG in T1D leads to an upregulation in brain glucose transport and alterations in glutamatergic and GABAergic tone. The investigators will use MRS methodology that permits evaluation of cerebral cortex and hypothalamus in the same session to simultaneously evaluate the cerebral correlates/mediators of impaired awareness and impaired counterregulatory hormone responses (CRR). High MR data quality and reproducibility will be ensured by using high field MR scanners and technical advances (automated voxel placement, real-time voxel position, frequency, shim updates). Continuous glucose monitoring and actigraphy will be used to chronicle glucose variability and activity/exercise/sleep in the weeks before each experiment to assess the impact of these variables on IAH.

Overall Status Recruiting
Start Date May 24, 2018
Completion Date December 2023
Primary Completion Date December 2023
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Neurochemical response to HG before and after induction of IAH 240 Minutes
Secondary Outcome
Measure Time Frame
Antecedent glycemia concentration 16 days
Antecedent physical activity 16 days
Enrollment 50
Condition
Intervention

Intervention Type: Other

Intervention Name: Experimental hypoglycemia

Description: Experimental hypoglycemia with and without MRI

Arm Group Label: All Subjects

Eligibility

Criteria:

Inclusion Criteria:

- Type 1 diabetes diagnosed on clinical or laboratory grounds

- Diabetes duration 2 - 30 years

- Hemoglobin A1C <8.5%

Exclusion Criteria:

- Impaired awareness of hypoglycemia as determined by the Cox and Gold questionnaires

- Pregnant or plan to become pregnant during the study period

- Uncontrolled hypertension (blood pressure > 145/95 mmHg at screening)

- Evidence of autonomic neuropathy (presence of orthostatic hypotension or history of gastroparesis)

- Proliferative retinopathy

- Impaired kidney function (GFR < 45)

- History of myocardial infarction, stroke, seizures, neurosurgical procedures, major depression requiring hospitalization within the last 5 years, arrhythmias

- Current substance abuse

- Use of drugs that can alter glucose metabolism including but not limited to glucocorticoids and niacin, and excluding insulin and glucose lowering drugs used to treat diabetes, as determined by a clinician

- Inability to undergo MRI scanning, including but not limited to unable to remain still in an MRI scanner for more than 30 minutes, claustrophobia, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Elizabeth R Seaquist, MD Principal Investigator University of Minnesota
Overall Contact

Last Name: Anjali Kumar, PA-C

Phone: 612-301-7040

Email: [email protected]

Location
Facility: Status: Contact: Investigator: University of Minnesota Elizabeth R Seaquist, MD 612-624-9176 [email protected] Elizabeth R Seaquist, MD Principal Investigator Gulin Oz, PhD Sub-Investigator
Location Countries

United States

Verification Date

October 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: All Subjects

Type: Experimental

Description: Experimental hypoglycemia

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov