Reversibility of Brain Glucose Transport and Metabolism in T2DM: an Intervention Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- Yale University
- Locations
- 1
- Primary Endpoint
- Intracerebral concentrations of glucose
Study Overview
Brief Summary
This study is designed to test if there is a difference in brain glucose transport kinetics in poorly controlled T2DM individuals with short duration and long duration of diabetes, using non-invasive magnetic resonance spectroscopy (MRSI). Also, if these changes are reversible with improved glucose control will be tested. A better understanding of the impact of duration of diabetes on brain glucose transport function may have important implications for understanding the pathophysiology of brain complications in T2DM.
Detailed Description
Specific Aim 1: To compare brain glucose transport and metabolism in age, BMI, and HbA1c matched T2DM individuals with either long duration of diabetes or short duration of diabetes using brain 1H MRSI during hyperglycemic clamp
Hypothesis: T2DM individuals with chronic uncontrolled diabetes will have lower brain glucose levels as compared with age, BMI, and HbA1c matched T2DM individuals with shorter duration of diabetes.
Screening visit: Volunteers will be screened at the Yale New Haven Hospital (YNHH) Hospital Research Unit (HRU) or Yale Center for Clinical Investigation (YCCI) Church street Research Unit (CSRU) with a medical history and exam. Blood tests will be collected for A1C, ALT, TSH, Hgb and Creatinine. A urine pregnancy test will be performed on all women of childbearing potential, and women who are pregnant will be excluded.
Continuous Glucose Monitoring (CGM): Participants will wear for 14 days prior to the MRSI scanning sessions a CGM (FreeStyle Libre Pro glucose monitoring system) to continuously monitor their interstitial blood glucose levels. Given that this data is blinded, patients will be informed that it is not a replacement for self-monitoring of blood glucose. Subjects should continue their normal testing routine while wearing the sensor. CGM placement will take place at the HRU or CSRU. Those not already using CGM in their usual care will be trained in its proper use by experienced study staff. Patients already using CGM will be allowed to use their usual CGM, however, they will also be asked to wear a second blinded study sensor. Subjects will be provided with our contact information in the event that they have any questions, concerns or issues related to the CGM. Intense exercise may cause the sensor to loosen due to sweat or movement of the sensor. If the CGM sensor falls off while the subject is wearing it, subjects will be asked to return to the HRU or CSRU so that a new sensor can be re-inserted.
The CGM consists of a sensor that measures glucose levels from the interstitial tissue. The sensor is sterile and comes in an unopened package. It has a plastic wire-like tip that is placed under the skin and continuously measures the glucose levels. A trained study staff member will insert the CGM wirelike tip under the volunteer's skin with the use of the CGM sensor insertion kit. Each sensor is single use only and disposable. The FreeStyle Libre Pro does not require any calibration, as is the case with other CGM devices. This means that no finger sticks are required for its use.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Type 2 Diabetics with HbA1c > 7.5% with short duration of diabetes <5 years or
- •Type 2 Diabetics with HbA1c > 7.5% longer duration of diabetes >5 years
Exclusion Criteria
- •Patients treated with incretin-based therapies
- •Creatinine > 1.5 mg/dL
- •Hgb < 10 mg/dL
- •ALT > 3 X ULN
- •Untreated thyroid disease
- •Uncontrolled hypertension
- •Known neurological disorders
- •Untreated psychiatric disorders
- •Malignancy
- •Bleeding disorders
- •Current or recent steroid use in last 3 months
- •Illicit drug use
- •Women: pregnancy, actively seeking pregnancy, or breastfeeding
- •Inability to enter MRI/MRS (per standard MRI safety guidelines)
Arms & Interventions
Diabetic with short duration
Type 2 diabetics with HbA1c > 7.5 % with short duration of diabetes < 5 years
Intervention: Intensification of insulin regimen/Nutrition (Behavioral)
Diabetic with long duration
Type 2 diabetics with HbA1c > 7.5 % with short duration of diabetes > 5 years
Intervention: Intensification of insulin regimen/Nutrition (Behavioral)
Outcomes
Primary Outcomes
Intracerebral concentrations of glucose
Time Frame: Baseline
Intracerebral concentrations of glucose across multiple brain locations, including frontal and occipital, as measured by MRSI will be compared following hyperglycemic clamp in uncontrolled T2DM individuals with short duration of diabetes and long duration of diabetes
Intracerebral concentrations of glucose between T2DM patients
Time Frame: 12 Weeks
Intracerebral concentrations of glucose will be compared between T2DM patients before and after 12 weeks of intensification of their diabetes management
Secondary Outcomes
- Pattern Recognition Memory (PRM)(12 Week)
- Delayed Matching to Sample (DMS)(12 Week)
- Spatial Working Memory (SWM)(12 Week)
- Reaction Time (RTI)(12 Week)
- Rapid Visual Information Processing (RVP)(12 Week)
- Verbal Recognition Memory (VRM)(12 Week)
- Paired Associates Learning (PAL)(12 Week)
- Multitasking Test (MTT)(12 Week)
- Reaction Time (RTI)(Baseline)
- Verbal Recognition Memory (VRM)(Baseline)
- Paired Associates Learning (PAL)(Baseline)
- Spatial Working Memory (SWM)(Baseline)
- Pattern Recognition Memory (PRM)(Baseline)
- Delayed Matching to Sample (DMS)(Baseline)
- Rapid Visual Information Processing (RVP)(Baseline)
- Multitasking Test (MTT)(Baseline)