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)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: Experimental hypoglycemia

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Subjects; Experimental hypoglycemia	Other: Experimental hypoglycemia; Experimental hypoglycemia with and without MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurochemical response to HG before and after induction of IAH	The difference in neurochemical response (GABA, glutamate, and glucose) to HG during the first clamp study compared to the neurochemical response to HG after the induction of IAH as determined by the last clamp.	240 Minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antecedent glycemia concentration	The difference in antecedent glycemia concentration associated with the differences seen in the primary outcome.	16 days
Antecedent physical activity	The difference in antecedent physical activity associated with the differences seen in the primary outcome.	16 days

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Elizabeth R Seaquist, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2018
• Primary Completion (Actual): March 31, 2024
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 18, 2018
• First Posted (Actual): January 25, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: MED-2017-26317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No